Prevalence and prognostic significance of hyperkalemia in hospitalized patients with cirrhosis.

PubMed

Maiwall, Rakhi; Kumar, Suman; Sharma, Manoj Kumar; Wani, Zeeshan; Ozukum, Mulu; Sarin, Shiv Kumar

2016-05-01

The prevalence and clinical significance of hyponatremia in cirrhotics have been well studied; however, there are limited data on hyperkalemia in cirrhotics. We evaluated the prevalence and prognostic significance of hyperkalemia in hospitalized patients with cirrhosis and developed a prognostic model incorporating potassium for prediction of liver-related death in these patients. The training derivative cohort of patients was used for development of prognostic scores (Group A, n = 1160), which were validated in a large prospective cohort of cirrhotic patients. (Group B, n = 2681) of cirrhosis. Hyperkalemia was seen in 189 (14.1%) and 336 (12%) in Group A and Group B, respectively. Potassium showed a significant association that was direct with creatinine (P < 0.001) and urea (P < 0.001) and inverse with sodium (P < 0.001). Mortality was also significantly higher in patients with hyperkalemia (P = 0.0015, Hazard Ratio (HR) 1.3, 95% confidence interval 1.11-1.57). Combination of all these parameters into a single value predictor, that is, renal dysfunction index predicted mortality better than the individual components. Combining renal dysfunction index with other known prognostic markers (i.e. serum bilirubin, INR, albumin, hepatic encephalopathy, and ascites) in the "K" model predicted both short-term and long-term mortality with an excellent accuracy (Concordance-index 0.78 and 0.80 in training and validation cohorts, respectively). This was also superior to Model for End-stage Liver Disease, Model for End-stage liver disease sodium (MELDNa), and Child-Turcott-Pugh scores. Cirrhotics frequently have impaired potassium homeostasis, which has a prognostic significance. Serum potassium correlates directly with serum creatinine and urea and inversely with serum sodium. The model incorporating serum potassium developed from this study ("K"model) can predict death in advanced cirrhotics with an excellent accuracy. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Diagnostic value of Doppler assessment of the hepatic and portal vessels and ultrasound of the spleen in liver disease.

PubMed

O'Donohue, John; Ng, Chaan; Catnach, Susan; Farrant, Patricia; Williams, Roger

2004-02-01

To investigate the clinical utility and the intra-observer and inter-observer variability of Doppler ultrasound assessment of the hepatic and portal vessels along with measurement of spleen size in the diagnosis of chronic liver disease and cirrhosis. Ultrasound measurements of portal vein diameter (PVD), portal vein velocity (PVV), hepatic arterial resistance index (HARI), hepatic vein profile (HVP), and spleen size were obtained in 49 controls and 45 patients with liver disease (23 with primary biliary cirrhosis, 22 with hepatitis C) by two experienced observers, who each performed three blinded measurements of each variable. Control values were derived from normal hospital workers. Percutaneous liver biopsies in 41 of the patients showed cirrhosis (14 patients), moderate/severe fibrosis (13 patients), and early disease (14 patients). Seventy-one percent of cirrhotic patients had splenomegaly (> 13.6 cm). The spleen size was significantly larger in cirrhotics (16.0 cm) than in non-cirrhotics (13.0 cm, P < 0.009) and healthy controls (10.7 cm, P < 0.00005), and was the only independent predictor of cirrhosis, with a threshold of 15 cm predicting cirrhosis with a specificity of 98%, positive predictive value of 93%, sensitivity of 57% and negative predictive value of 80%. HVP was abnormal in 76.9% of cirrhotics, 57.7% of non-cirrhotics and 2.1% of controls (P < 0.04). However, the mean PVV, PVD and HARI were no different between controls and patients or between cirrhotic and non-cirrhotic liver disease. There was significant inter-observer variability for PVV, but intra-observer and inter-observer variability was acceptable for the other measurements. Splenomegaly size and abnormal HVP are useful predictors of chronic liver disease and cirrhosis, and both can be measured reliably and reproducibly. However, Doppler measurements of PVV, PVD and HARI are not useful in distinguishing patients with chronic liver disease from normal controls.

Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit.

PubMed

Levesque, Eric; Hoti, Emir; Azoulay, Daniel; Ichaï, Philippe; Habouchi, Houssam; Castaing, Denis; Samuel, Didier; Saliba, Faouzi

2012-01-01

Cirrhotic patients admitted to an Intensive Care Unit (ICU) have a poor prognosis. Identifying patients in whom ICU care will be useful can be challenging. The aim of this study was to assess the predictive value of prognostic scores with respect to mortality and to identify mortality risk factors. Three hundred and seventy-seven cirrhotic patients admitted to a Liver ICU between May 2005 and March 2009 were enrolled in this study. Their average age was 55.5±11.4 years. The etiology of cirrhosis was alcohol (68%), virus hepatitis (18%), or mixed (5.5%). The main causes of hospitalization were gastrointestinal hemorrhage (43%), sepsis (19%), and hepatic encephalopathy (12%). ICU and in-hospital mortality rates were 34.7% and 43.0%, respectively. Infection was the major cause of death (81.6%). ROC curve analysis demonstrated that SOFA (0.92) and SAPS II (0.89) scores calculated within 24h of admission predicted ICU mortality better than the Child-Pugh score (0.79) or MELD scores with (0.79-0.82) or without the incorporation of serum sodium levels (0.82). Statistical analysis showed that the prognostic severity scores, organ replacement therapy, and infection were accurate predictors of mortality. On multivariate analysis, mechanical ventilation, vasopressor therapy, bilirubin level at admission, and infection were independently associated with ICU mortality. For cirrhotic patients admitted to the ICU, SAPS II, and SOFA scores predicted ICU mortality better than liver-specific scores. Mechanical ventilation or vasopressor therapy, bilirubin levels at admission and infection in patients with advanced cirrhosis were associated with a poor outcome. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Increased occurrence of native septic arthritis in adult cirrhotic patients: a population-based three-year follow-up study in Taiwan.

PubMed

Hung, Tsung-Hsing; Hsieh, Min-Hong; Lay, Chorng-Jang; Tsai, Chih-Chun; Tsai, Chen-Chi

2014-01-01

Due to impairment of immunity and metabolism, cirrhotic patients are prone to infection, osteoporosis, and osteonecrosis. However, it is unknown if cirrhotic patients are prone to native septic arthritis (NSA). To assess the occurrence of NSA between cirrhotic and non-cirrhotic patients. We used the Taiwan National Health Insurance Database to enrol 35,106 cirrhotic patients and 33,457 non-cirrhotic patients from January 1, 2004 to December 31, 2004. The medical record of each patient was individually followed for a 3-year period. There were 341 (0.5%) patients having NSA in a follow-up period of 3 years: 214 cirrhotic and 127 non-cirrhotic patients. The incidence density of hospitalisation for NSA was 2.03 episodes/1000 person-years in cirrhotic patients, and 1.27 episodes/1000 person-years in non-cirrhotic patients. After adjustment for age, gender, and other comorbid disorders, Cox's regression analysis showed that cirrhotic patients had a higher occurrence of NSA than non-cirrhotic patients(hazard ratio (HR) = 1.51, 95% confidence interval (CI) = 1.19-1.90; p = 0.001). The patients with complicated cirrhosis were more prone to have NSA than those with non-complicated cirrhosis (HR = 1.46, 95% CI = 1.09-1.96, p = 0.011). This analysis demonstrates that cirrhotic patients have a higher risk of NSA, particularly those with complicated cirrhosis.

Coding algorithms for identifying patients with cirrhosis and hepatitis B or C virus using administrative data.

PubMed

Niu, Bolin; Forde, Kimberly A; Goldberg, David S

2015-01-01

Despite the use of administrative data to perform epidemiological and cost-effectiveness research on patients with hepatitis B or C virus (HBV, HCV), there are no data outside of the Veterans Health Administration validating whether International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes can accurately identify cirrhotic patients with HBV or HCV. The validation of such algorithms is necessary for future epidemiological studies. We evaluated the positive predictive value (PPV) of ICD-9-CM codes for identifying chronic HBV or HCV among cirrhotic patients within the University of Pennsylvania Health System, a large network that includes a tertiary care referral center, a community-based hospital, and multiple outpatient practices across southeastern Pennsylvania and southern New Jersey. We reviewed a random sample of 200 cirrhotic patients with ICD-9-CM codes for HCV and 150 cirrhotic patients with ICD-9-CM codes for HBV. The PPV of 1 inpatient or 2 outpatient HCV codes was 88.0% (168/191, 95% CI: 82.5-92.2%), while the PPV of 1 inpatient or 2 outpatient HBV codes was 81.3% (113/139, 95% CI: 73.8-87.4%). Several variations of the primary coding algorithm were evaluated to determine if different combinations of inpatient and/or outpatient ICD-9-CM codes could increase the PPV of the coding algorithm. ICD-9-CM codes can identify chronic HBV or HCV in cirrhotic patients with a high PPV and can be used in future epidemiologic studies to examine disease burden and the proper allocation of resources. Copyright © 2014 John Wiley & Sons, Ltd.

[Analysis of the risk factors of hepatocellular carcinoma in cirrhotic patients with chronic hepatitis B].

PubMed

Zhang, Yuanqing; Peng, Lijun; Cao, Yirong; Zeng, Zhiping; Wu, Yujing; Shi, Hong; Chen, Shiyao; Guo, Jinsheng

2015-07-01

To identify risk factors of hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB). A total of 715 cirrhotic patients with CHB were recruited from the Zhongshan Hospital Affiliated to Fudan University and enrolled in this case-control study between January 2009 and September 2014. All participants were Chinese Han residing in Shanghai and the surrounding areas. The patients were divided into a cirrhosis group (n =281) and a HCC group (n=434). History of hepatitis B infection and HCC, as well as clinical data from serological, imaging and pathological examinations were collected for analysis.SPSS software, version 19.0, was used for all statistical comparisons. Single factor analysis indicated that development of HCC in cirrhotic patients with CHB was significantly associated with male sex, age of 50 years or more, family history of HCC, alcohol consumption,fatty liver, detectable levels of hepatitis B virus (HBV) DNA, and history of HBV infection without effective antiviral treatment. Multivariate logistic regression analysis indicated that age of 50 years or more (P =0.005, odds ratio [OR] =1.766), history of alcohol consumption (P =0.002, Or = 2.570), family history of HCC (P =0.014, Or = 2.268), fatty liver (P =0.023, Or = 3.390), and history of HBV infection without effective antiviral treatment (P < 0.001,Or = 5.389) were risk factors of HCC.The risk factors for development of HCC in cirrhotic patients with hepatitis B after achieving sustained virologic suppression (SVS) were family history of HBV infection (P =0.014, Or = 2.537), family history of HCC (P =0.037,Or = 3.339) and fatty liver (P =0.018, Or = 11.646). Risk factors of HCC in cirrhotic patients with CHB include age,drinking history,family history of HCC, fatty liver, and ineffective antiviral treatment of CHB.Family history of HBV infection or HCC, and fatty liver disease, were significantly associated with HCC development after SVS in patients with hepatitis B-related cirrhosis.

Coding algorithms for identifying patients with cirrhosis and hepatitis B or C virus using administrative data

PubMed Central

Niu, Bolin; Forde, Kimberly A; Goldberg, David S.

2014-01-01

Background & Aims Despite the use of administrative data to perform epidemiological and cost-effectiveness research on patients with hepatitis B or C virus (HBV, HCV), there are no data outside of the Veterans Health Administration validating whether International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes can accurately identify cirrhotic patients with HBV or HCV. The validation of such algorithms is necessary for future epidemiological studies. Methods We evaluated the positive predictive value (PPV) of ICD-9-CM codes for identifying chronic HBV or HCV among cirrhotic patients within the University of Pennsylvania Health System, a large network that includes a tertiary care referral center, a community-based hospital, and multiple outpatient practices across southeastern Pennsylvania and southern New Jersey. We reviewed a random sample of 200 cirrhotic patients with ICD-9-CM codes for HCV and 150 cirrhotic patients with ICD-9-CM codes for HBV. Results The PPV of 1 inpatient or 2 outpatient HCV codes was 88.0% (168/191, 95% CI: 82.5–92.2%), while the PPV of 1 inpatient or 2 outpatient HBV codes was 81.3% (113/139, 95% CI: 73.8–87.4%). Several variations of the primary coding algorithm were evaluated to determine if different combinations of inpatient and/or outpatient ICD-9-CM codes could increase the PPV of the coding algorithm. Conclusions ICD-9-CM codes can identify chronic HBV or HCV in cirrhotic patients with a high PPV, and can be used in future epidemiologic studies to examine disease burden and the proper allocation of resources. PMID:25335773

n-3 fatty acid-based parenteral nutrition improves postoperative recovery for cirrhotic patients with liver cancer: A randomized controlled clinical trial.

PubMed

Zhang, Binhao; Wei, Gang; Li, Rui; Wang, Yanjun; Yu, Jie; Wang, Rui; Xiao, Hua; Wu, Chao; Leng, Chao; Zhang, Bixiang; Chen, Xiao-Ping

2017-10-01

A new lipid emulsion enriched in n-3 fatty acid has been reported to prevent hepatic inflammation in patients following major surgery. However, the role of n-3 fatty acid-based parenteral nutrition for postoperative patients with cirrhosis-related liver cancer is unclear. We investigated the safety and efficacy of n-3 fatty acid-based parenteral nutrition for cirrhotic patients with liver cancer followed hepatectomy. A prospective randomized controlled clinical trial (Registered under ClinicalTrials.gov Identifier no. NCT02321202) was conducted for cirrhotic patients with liver cancer that underwent hepatectomy between March 2010 and September 2013 in our institution. We compared isonitrogenous total parenteral nutrition with 20% Structolipid and 10% n-3 fatty acid (Omegaven, Fresenius-Kabi, Germany) (treatment group) to Structolipid alone (control group) for five days postoperatively, in the absence of enteral nutrition. We enrolled 320 patients, and 312 (97.5%) were included in analysis (155 in the control group and 157 in the treatment group). There was a significant reduction of morbidity and mortality in the treatment group, when compared with the control group (total complications 78 [50.32%] vs. 46 [29.30%]; P < 0.001, total infective complications, 30 [19.35%] vs. 15 [9.55%]; P = 0.014), overall mortality (5 [3.23%] vs. 1 [0.64%]; P = 0.210), and hospital stay (12.56 ± 3.21 d vs. 10.17 ± 3.15 d; P = 0.018). We found that addition of n-3 fatty acid-based parenteral nutrition significantly improved postoperative recovery for cirrhotic patients with liver cancer following hepatectomy, with a significant reduction in overall mortality and length of hospital stay. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The relationship between a model of end stage liver disease score (MELD score) and the occurrence of spontaneous bacterial peritonitis in liver cirrhotic patients.

PubMed

Gayatri, A A Ayu Yuli; Suryadharma, I G A; Purwadi, N; Wibawa, I D N

2007-01-01

To determine relationship between MELD score and the occurrence of SBP, prevalence of SBP, pattern of bacterial culture and antibiotic susceptibility of causative bacteria of liver cirrhotic patients at Sanglah Hospital. Study design was a cross-sectional analytic study. The population in this study consists of liver cirrhotic patients admitted at Sanglah Hospital Denpasar from June 2005 to February 2006. This result confirmed that the MELD score is a reliable index of disease severity and that higher MELD scores had a significantly more frequent SBP prevalence in patients with a MELD score of 18 or more compared with that in patients with a MELD score of 17 or less (p=0.01; 95% CI = 1.379-15.537). Prevalence of SBP was 30.6%. Thirteen patients (68.4%) had monomicrobial positive culture of Aerob bacteria, consisting of Gram negative bacterias in 10 (77%), with Escherichia coli and Acinettobacter baumanii being the most frequent, and 3 (23%) had Gram positive bacteria. High sensitivity to Cefoperazone, Cefotaxim, Ceftazidime, Cefpirome, Ciprofloxacin, Fosfomicin, Meropenem, Streptomycin, Gentamycin, Trimethoprim/Sulphamethoxazole, were shown. Based on this study we concluded that severe liver cirrhosis with MELD score > or = 18 was associated with an increase risk of SBP, with a prevalence of 30.6%. Common causes of SBP mostly were Escherichia coli and Acinettobacter baumanii, which were sensitive to antibiotic treatment of Cefoperazone, Cefotaxime and Ciprofloxacin.

Natural history of patients with non cirrhotic portal hypertension: Comparison with patients with compensated cirrhosis.

PubMed

Gioia, Stefania; Nardelli, Silvia; Pasquale, Chiara; Pentassuglio, Ilaria; Nicoletti, Valeria; Aprile, Francesca; Merli, Manuela; Riggio, Oliviero

2018-01-31

The knowledge of natural history of patients with portal hypertension (PH) not due to cirrhosis is less well known than that of cirrhotic patients. To describe the clinical presentation and the outcomes of 89 patients with non-cirrhotic PH (25 with non-cirrhotic portal hypertension, INCPH, and 64 with chronic portal vein thrombosis, PVT) in comparison with 77 patients with Child A cirrhosis. The patients were submitted to a standardized clinical, laboratory, ultrasonographic and endoscopic follow-up. Variceal progression, incidence of variceal bleeding, portal vein thrombosis, ascites and survival were recorded. At presentation, the prevalence of varices, variceal bleeding and ascites was similar in the 3 groups. During follow-up, the rate of progression to varices at risk of bleeding (p < 0.0001) and the incidence of first variceal bleeding (p = 0.02) were significantly higher in non-cirrhotic then in cirrhotic patients. A PVT developed in 32% of INCPH patients and in 18% of cirrhotics (p = 0.02). In the patients with non-cirrhotic PH variceal progression is more rapid and bleeding more frequent than in cirrhotics. Patients with INCPH are particularly prompt to develop PVT. This observational study suggests that the management of patients with non-cirrhotic PH should take into consideration the natural history of portal hypertension in these patients and cannot be simply derived by the observation of cirrhotic patients. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Safety and efficacy of endoscopic retrograde cholangiopancreatography for common bile duct stones in liver cirrhotic patients.

PubMed

Li, De-min; Zhao, Jie; Zhao, Qiu; Qin, Hua; Wang, Bo; Li, Rong-xiang; Zhang, Min; Hu, Ji-fen; Yang, Min

2014-08-01

In order to investigate the safety and efficacy of endoscopic retrograde cholangiopancreatograpy (ERCP) in liver cirrhosis patients with common bile duct stones, we retrospectively analyzed data of 46 common bile duct stones patients with liver cirrhosis who underwent ERCP between 2000 and 2008. There were 12 cases of Child-Pugh A, 26 cases of Child-Pugh B, and 8 cases of Child-Pugh C. 100 common bile duct stones patients without liver cirrhosis were randomly selected. All the patients were subjected to ERCP for biliary stones extraction. The rates of bile duct clearance and complications were compared between cirrhotic and non-cirrhotic patients. The success rate of selective biliary cannulation was 95.6% in liver cirrhotic patients versus 97% in non-cirrhotic patients (P>0.05). The bile duct clearance rate was 87% in cirrhotic patients versus 96% in non-cirrhotic patients, but the difference was not statistically significant. Two liver cirrhotic patients (4.35%, 2/46) who were scored Child-Pugh C had hematemesis and melena 24 h after ERCP. The hemorrhage rate after ERCP in non-cirrhotic patients was 3%. The hemorrhage rate associated with ERCP in Child-Pugh C patients was significantly higher (25%, 2/8) than that (3%, 3/100) in non-cirrhotic patients (P<0.01%). There was no significant difference between these two groups in the rate of post-ERCP pancreatitis (PEP) and cholangitis. ERCP is safe and effective for Child-Pugh A and B cirrhotic patients with common bile duct stones. Hemorrhage risk in ERCP is higher in Child-Pugh C patients.

The impact of rifaximin in the prevention of bacterial infections in cirrhosis.

PubMed

Mariani, M; Zuccaro, V; Patruno, S F A; Scudeller, L; Sacchi, P; Lombardi, A; Vecchia, M; Columpsi, P; Marone, P; Filice, G; Bruno, R

2017-03-01

Bacterial infections are a leading factor in the progression from compensated to decompensated cirrhosis, with consequent worsening of the prognosis, and concerted efforts have been made to reduce infections and improve the survival rate of these patients. We retrospectively investigated the rate of infections in hospitalized cirrhotic patients under treatment with rifaximin. We enrolled 649 patients whose clinical and personal data, prescribed therapy, microbiological findings and laboratory tests were collected from previous discharge letters and our institution database. The efficacy of rifaximin in preventing several types infection was evaluated by comparing outcomes for rifaximin-treated patients vs patients receiving no antibiotic treatment. The risk of developing selected bacterial infections was significantly lower in patients treated with rifaximin (OR 0.29; 95% CI 0.20-0.40, p < 0.001). Continuous treatment with rifaximin may prevent bacterial infections in cirrhotic patients.

Second Infections Independently Increase Mortality in Hospitalized Cirrhotic Patients: The NACSELD Experience

PubMed Central

Bajaj, Jasmohan S; O’Leary, Jacqueline G; Reddy, K. Rajender; Wong, Florence; Olson, Jody C; Subramanian, Ram M; Brown, Geri; Noble, Nicole A; Thacker, Leroy R; Kamath, Patrick S

2012-01-01

Bacterial infections are an important cause of mortality in cirrhosis but there is a paucity of multi-center studies. The aim was to define factors predisposing to infection-related mortality in hospitalized cirrhotic patients. Methods A prospective, cohort study of cirrhotic patients with infections was performed at eight North American tertiary-care hepatology centers. Data were collected on admission vitals, disease severity [MELD and sequential organ failure (SOFA)] scores], first infection site, type [community-acquired, health care-associated (HCA) or nosocomial], and second infection occurrence during hospitalization. The outcome was mortality within 30 days. A multi-variable logistic regression model predicting mortality was created. Results 207 patients (55 years, 60% men, MELD 20) were included. Most first infections were HCA (71%), then nosocomial (15%) and community-acquired (14%). Urinary tract infections (52%), spontaneous bacterial peritonitis (SBP, 23%) and spontaneous bacteremia (21%) formed the majority of the first infections. Second infections were seen in 50 (24%) patients and were largely preventable: respiratory, including aspiration (28%), urinary, including catheter-related (26%), fungal (14%) and C. difficile (12%) infections. Forty-nine patients (23.6%) who died within 30 days had higher admission MELD (25 vs 18, p<0.0001), lower serum albumin (2.4g.dL vs. 2.8g/dL, p=0.002), and second infections (49% vs. 16%, p<0.0001) but equivalent SOFA scores (9.2 vs. 9.9, p=0.86). Case fatality rate was highest for C. difficile (40%), respiratory (37.5%) and spontaneous bacteremia (37%), and lowest for SBP (17%) and urinary infections (15%). The model for mortality included admission MELD (OR: 1.12), heart rate (OR:1.03) albumin (OR:0.5) and second infection (OR:4.42) as significant variables. Conclusions Potentially preventable second infections are predictors of mortality independent of liver disease severity in this multi-center cirrhosis cohort. PMID:22806618

Epidemiology, disease burden and outcomes of cirrhosis in a large secondary care hospital in South Auckland, New Zealand.

PubMed

Hsiang, J C; Bai, W W; Raos, Z; Stableforth, W; Upton, A; Selvaratnam, S; Gane, E J; Gerred, S J

2015-02-01

Liver cirrhosis is an important cause of morbidity and mortality; however, little is known about its impact in New Zealand. We aim to determine the disease burden, epidemiology and outcomes of cirrhotic patients. This is a retrospective study of cirrhosis patients under secondary public hospital care in a geographically defined region, between the years 2000 and 2011. Cirrhosis complications and mortality was recorded. Poisson log-linear regression analysis was performed for incidence rate ratio (IRR) and Cox regression analysis was used to analyse time-related events. Seven hundred and forty-six cirrhotic patients were analysed; most were European/Other (39.9%), Pacific islanders (21.6%), Southeast Asian/Chinese (17.8%) and Maori (12.3%). 68.4% were male. The common primary aetiologies for cirrhosis were chronic hepatitis B (CHB) cirrhosis (37.3%), alcoholic liver disease (ALD) cirrhosis (24.1%), chronic hepatitis C (CHC) cirrhosis (22.3%) and non-alcoholic fatty liver disease (NAFLD) cirrhosis (16.4%). The hepatocellular carcinoma (HCC) mortality rates were highest in NAFLD and CHB cirrhosis groups (3.0 and 3.1 per 100 patient-year respectively), compared with ALD and CHC groups (2.2 and 1.4 per 100 patient-year, all P < 0.05 respectively). Patients with ALD and NAFLD cirrhosis had the highest all-cause and non-HCC mortality rate compared with viral hepatitis cirrhosis groups. The IRR for HCC incidence, liver-related mortality and HCC mortality were 1.087, 1.098 and 1.114, respectively (all P < 0.001), suggesting increasing incidence and disease burden over the study period. The number of cirrhotic patients in secondary care is increasing steadily. Cirrhosis complications and mortality rates are also rising, particularly the incidence and mortality of HCC. © 2014 Royal Australasian College of Physicians.

Ischaemia-modified albumin: a marker of bacterial infection in hospitalized patients with cirrhosis.

PubMed

Giannone, Ferdinando A; Domenicali, Marco; Baldassarre, Maurizio; Bartoletti, Michele; Naldi, Marina; Laggetta, Maristella; Bertucci, Carlo; Colecchia, Antonio; Viale, Pierluigi; Bernardi, Mauro; Caraceni, Paolo

2015-11-01

Patients with cirrhosis present structural changes of human serum albumin (HSA) affecting non-oncotic functions. Ischaemia-modified albumin (IMA), which reflects the capacity to bind cobalt, has been associated to patient mortality during acute-on-chronic liver failure. This study aimed to assess whether circulating IMA is elevated in advanced cirrhosis and its relationship with severity of cirrhosis and specific complications. A total of 127 cirrhotic patients hospitalized for an acute complication of the disease and 44 healthy controls were enrolled. Plasma IMA and IMA to albumin ratio (IMAr) were measured with a cobalt-binding assay. HSA isoforms carrying post-transcriptional molecular changes were assessed with HPLC-ESI-MS. The effect of endotoxemia on IMA was evaluated in rats with CCl4 -cirrhosis. IMA/IMAr is significantly higher in cirrhotic patients than in controls, but no correlations were found with prognostic scores. IMA did not correlate with the altered HSA isoforms. Ascites, renal impairment and hepatic encephalopathy did not influence IMA/IMAr levels. In contrast, IMA/IMAr is significantly higher in infected than non-infected patients. ROC curves showed that IMA/IMAr had similar discriminating performances for bacterial infection as C-reactive protein (CRP). Moreover, CRP and IMA were independently associated with bacterial infection. Consistently, endotoxin injection significantly increased IMA in cirrhotic, but not in healthy rats. IMA is elevated in patients with advanced cirrhosis. The IMA level does not correlate with disease severity scores, but it is specifically associated to bacterial infection, showing a discriminating performance similar to CRP. Further investigations to assess IMA as a novel diagnostic test for bacterial infection are advocated. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Outcome of Cirrhotic Patients with Ascites Is Improved by the Normalization of the Serum Sodium Level by Tolvaptan

PubMed Central

Kogiso, Tomomi; Kobayashi, Mutsuki; Yamamoto, Kuniko; Ikarashi, Yuichi; Kodama, Kazuhisa; Taniai, Makiko; Torii, Nobuyuki; Hashimoto, Etsuko; Tokushige, Katsutoshi

2017-01-01

Objective Hyponatremia is frequently observed in patients with decompensated liver cirrhosis and it is also related to a poor prognosis. The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites and increases the serum sodium (Na) level. In this study, we investigated (i) whether or not correction of the Na level improves the prognosis of cirrhotic patients with ascites and (ii) predictors of normalization of the serum Na level after tolvaptan therapy. Methods This was a single-center retrospective study. A total of 95 Japanese cirrhotic patients (60 men, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites treatment. The serum Na level was monitored during the period of tolvaptan treatment. The laboratory data and survival rates of patients who achieved serum Na levels of <135 and ≥135 mEq/L after 1 week were compared. Results Patients showed serum Na levels of 136 (121-145) mEq/L, and 42.1% had a serum Na level of <135 mEq/L. Among patients with an initial serum Na level <135 mEq/L, 60.0% achieved a normal level after 1 week, and the survival rate was significantly higher in patients with a normalized serum Na level (p<0.01). The pretreatment brain natriuretic peptide (BNP) level was predictive of achieving a serum Na level of ≥135 mEq/L (odds ratio: 0.87, 95% confidence interval: 0.316-0.987, p<0.05). Conclusion Normalization of the Na level after one week was associated with a favorable outcome of tolvaptan therapy, and Na correction improved the prognosis. PMID:28943585

Intensive Care Management of Patients with Cirrhosis.

PubMed

Olson, Jody C

2018-06-01

Cirrhosis is a major worldwide health problem which results in a high level of morbidity and mortality. Patients with cirrhosis who require intensive care support have high mortality rates of near 50%. The goal of this review is to address the management of common complications of cirrhosis in the ICU. Recent epidemiological studies have shown an increase in hospitalizations due to advanced liver disease with an associated increase in intensive care utilization. Given an increasing burden on the healthcare system, it is imperative that we strive to improve our management cirrhotic patients in the intensive care unit. Large studies evaluating the management of patients in the intensive care setting are lacking. To date, most recommendations are based on extrapolation of data from studies in cirrhosis outside of the ICU or by applying general critical care principles which may or may not be appropriate for the critically ill cirrhotic patient. Future research is required to answer important management questions.

Upper gastrointestinal bleeding in patients with hepatic cirrhosis: clinical course and mortality prediction.

PubMed

Afessa, B; Kubilis, P S

2000-02-01

We conducted this study to describe the complications and validate the accuracy of previously reported prognostic indices in predicting the mortality of cirrhotic patients hospitalized for upper GI bleeding. This prospective, observational study included 111 consecutive hospitalizations of 85 cirrhotic patients admitted for GI bleeding. Data obtained included intensive care unit (ICU) admission status, Child-Pugh score, the development of systemic inflammatory response syndrome (SIRS), organ failure, and inhospital mortality. The performances of Garden's, Gatta's, and Acute Physiology and Chronic Health Evaluation (APACHE) II prognostic systems in predicting mortality were assessed. Patients' mean age was 48.7 yr, and the median APACHE II and Child-Pugh scores were 17 and 9, respectively. Their ICU admission rate was 71%. Organ failure developed in 57%, and SIRS in 46% of the patients. Nine patients had acute respiratory distress syndrome, and three patients had hepatorenal syndrome. The inhospital mortality was 21%. The APACHE II, Garden's, and Gatta' s predicted mortality rates were 39%, 24%, and 20%, respectively, and their areas under the receiver operating characteristic curve (AUC) were 0.78, 0.70, and 0.71, respectively. The AUC for Child-Pugh score was 0.76. SIRS and organ failure develop in many patients with hepatic cirrhosis hospitalized for upper GI bleeding, and are associated with increased mortality. Although the APACHE II prognostic system overestimated the mortality of these patients, the receiver operating characteristic curves did not show significant differences between the various prognostic systems.

Sero-prevalence and vaccination status of hepatitis A and hepatitis B among adults with cirrhosis in Sri Lanka: a hospital based cohort study.

PubMed

Niriella, Madunil Anuk; Kobbegala, Vipuli Jayendra; Karalliyadda, Hasnatha Nuwan; Ranawaka, Chamila Kumara; de Silva, Arjuna Priyadarshin; Dassanayake, Anuradha Supun; de Silva, Hithanadura Janaka

2017-07-21

As acute viral hepatitis can be fatal in patients with cirrhosis, vaccination against hepatitis A (HAV) and hepatitis B (HBV) is recommended for non-immune patients. With increasing affluence the incidence of hepatitis A in childhood has decreased leading to a significant proportion of non-immune adults. As part of their routine investigation, hepatitis A IgG antibodies (anti-HAV IgG), hepatitis B surface antigen (HBsAg) and anti-HCV antibodies was checked and immunization status was assessed among consenting newly diagnosed cirrhotic patients presenting to a tertiary referral center. Out of 135 patients, 107 [79.3%; males 91; mean age (SD) at presentation: 55.5 (11.6) years] with complete data were included for analysis. Most patients had either cryptogenic cirrhosis (62.6%) or alcoholic cirrhosis (29.9%); 2 (1.9%) had HBV cirrhosis, none had hepatitis C (HCV) cirrhosis. None of the patients had received vaccination against hepatitis A, while 71 (67.6%) had been vaccinated against HBV. The majority [62 (58%)] were negative for anti-HAV IgG. Most cirrhotic patients in this cohort were not immune to hepatitis A. None had been vaccinated against HAV, while a third of patients had not been vaccinated against HBV. Cirrhotic patients should be routinely investigated for immunity against HAV and HBV, and vaccination offered to those found to be non-immune.

Increased survival of cirrhotic patients with septic shock.

PubMed

Sauneuf, Bertrand; Champigneulle, Benoit; Soummer, Alexis; Mongardon, Nicolas; Charpentier, Julien; Cariou, Alain; Chiche, Jean-Daniel; Mallet, Vincent; Mira, Jean-Paul; Pène, Frédéric

2013-04-19

The overall outcome of septic shock has been recently improved. We sought to determine whether this survival gain extends to the high-risk subgroup of patients with cirrhosis. Cirrhotic patients with septic shock admitted to a medical intensive care unit (ICU) during two consecutive periods (1997-2004 and 2005-2010) were retrospectively studied. Forty-seven and 42 cirrhotic patients presented with septic shock in 1997-2004 and 2005-2010, respectively. The recent period differed from the previous one by implementation of adjuvant treatments of septic shock including albumin infusion as fluid volume therapy, low-dose glucocorticoids, and intensive insulin therapy. ICU and hospital survival markedly improved over time (40% in 2005-2010 vs. 17% in 1997-2004, P = 0.02 and 29% in 2005-2010 vs. 6% in 1997-2004, P = 0.009, respectively). Furthermore, this survival gain in the latter period was sustained for 6 months (survival rate 24% in 2005-2010 vs. 6% in 1997-2004, P = 0.06). After adjustment with age, the liver disease stage (Child-Pugh score), and the critical illness severity score (SOFA score), ICU admission between 2005 and 2010 remained an independent favorable prognostic factor (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.02-0.4, P = 0.004). The stage of the underlying liver disease was also independently associated with hospital mortality (Child-Pugh score: OR 1.42 per point, 95% CI 1.06-1.9, P = 0.018). In the light of advances in management of both cirrhosis and septic shock, survival of such patients substantially increased over recent years. The stage of the underlying liver disease and the related therapeutic options should be included in the decision-making process for ICU admission.

Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF).

PubMed

Cordoba, Juan; Ventura-Cots, Meritxell; Simón-Talero, Macarena; Amorós, Àlex; Pavesi, Marco; Vilstrup, Hendrik; Angeli, Paolo; Domenicali, Marco; Ginés, Pere; Bernardi, Mauro; Arroyo, Vicente

2014-02-01

In spite of the high incidence of hepatic encephalopathy (HE) in cirrhosis, there are few observational studies. We performed an analysis to define the characteristics of HE and associated features using the database of the Canonic Study. Clinical, laboratory and survival data of 1348 consecutive cirrhotic patients admitted with an acute decompensation were compared according to the presence (n=406) or absence of HE and of acute-on-chronic liver failure (ACLF) (n=301). HE development was independently associated with previous HE episodes; survival probabilities worsen in relation to the presence and grade of HE. There were marked differences between HE associated (n=174) and not associated (n=286) to ACLF. HE not associated with ACLF occurred in older cirrhotics, inactive drinkers, without severe liver failure or systemic inflammatory reaction and in relation to diuretic use. In contrast, HE associated with ACLF occurred in younger cirrhotics, more frequently alcoholics, with severe liver failure and systemic inflammatory reaction, and in relation to bacterial infections, active alcoholism and/or dilutional hyponatremia. Prognosis was relatively preserved in the first and extremely poor in the second group. Independent risk factors of mortality in patients with HE were age, bilirubin, INR, creatinine, sodium, and HE grade. In cirrhosis, previous HE identifies a subgroup of patients that is especially vulnerable for developing new episodes of HE. The course of HE appears to be different according to the presence of ACLF. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Are total prostate-specific antigen serum levels in cirrhotic men different from those in normal men?

PubMed

Vicentini, Fabio C; Botelho, Luiz A A; Hisano, Marcelo; Ebaid, Gustavo X; Lucon, Marcos; Lucon, Antonio M; Srougi, Miguel

2009-05-01

To determine the serum total prostate-specific antigen (tPSA) levels in cirrhotic men and compare them with those in noncirrhotic men. We prospectively evaluated 113 cirrhotic patients listed for liver transplantation using the serum tPSA, total testosterone level, and Child-Pugh liver function score according to age and severity of liver disease. The tPSA levels were compared with those of 661 healthy men. The Mann-Whitney U test was used for statistical analysis, with a significance level of .05. The median age of the cirrhotic and noncirrhotic patients was 55 years (range 28-70) and 58 years (range 46-70), respectively (P < .01). However, when stratified by age group (<49, 50-59, and >60 years), this difference was not significant. The median serum tPSA level was 0.3 ng/mL (range 0.04-9.9) and 1.3 ng/mL (range 0.04-65.8) in the cirrhotic and noncirrhotic group, respectively (P < .0001). Stratifying both groups according to age, the cirrhotic patients had significantly lower tPSA levels than did the noncirrhotic patients. According to the Child-Pugh score (A, B, and C), Child-Pugh class C patients had significantly lower tPSA levels than did Child-Pugh class A patients and also had lower testosterone levels than did Child-Pugh class A and B patients. The tPSA levels correlated significantly with the testosterone levels in the cirrhotic patients (P = .028). The results of our study have shown that cirrhotic patients have approximately 4 times lower serum tPSA levels than noncirrhotic men. Patients with more severe liver disease have lower tPSA and testosterone levels than patients less affected. The tPSA levels in cirrhotic men are affected by the total testosterone levels.

Origin, Clinical Characteristics and 30-Day Outcomes of Severe Hematochezia in Cirrhotics and Non-cirrhotics

PubMed Central

Khungar, Vandana; Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas O.; Jutabha, Rome; Ghassemi, Kevin A.; Machicado, Gustavo A.; Dulai, Gareth S.

2017-01-01

Background The sites of origin, causes and outcomes of severe hematochezia have not been compared between cirrhotics and non-cirrhotics. In cirrhotics versus non-cirrhotics presenting with severe hematochezia, we aimed at (1) identifying the site and etiology of gastro-intestinal bleeding and independent predictors of bleeding from the upper gastrointestinal tract versus small bowel or the colon, (2) comparing 30-day clinical outcomes, and (3) proposing an algorithm for management of severe hematochezia. Methods In this cohort study from two university-based medical centers, 860 consecutive patients with severe hematochezia admitted from 1995 to 2011 were prospectively enrolled with 160 (18.6 %) cirrhotics. We studied (a) general clinical and laboratory characteristics of cirrhotics versus non-cirrhotics, (b) predictors of bleeding sites in each patient group by multiple variable regression analysis, and compared (c) 30-day outcomes, including rebleeding, surgery and deaths. Results Cirrhosis independently predicted an upper gastrointestinal source of bleeding (OR 3.47; 95 % CI 2.01–5.96) as well as history of hematemesis, melena in the past 30 days, positive nasogastric aspirate, prior upper gastrointestinal bleeding or use of aspirin or non-steroidal anti-inflammatory. The most prevalent diagnoses were esophageal varices (20 %) in cirrhotics and colon diverticular bleeding (27.1 %) in non-cirrhotics. Thirty-day rates of rebleeding, surgical interventions and deaths were 23.1 versus 15 % (P = 0.01), 14.4 versus 6.4 % (P < 0.001), and 17.5 versus 4.1 % (P < 0.001), in cirrhotics versus non-cirrhotics, respectively. Conclusions Cirrhosis predicted an upper gastrointestinal site of bleeding in patients presenting with severe hematochezia. The 30-day rates of rebleeding, surgery, and death were significantly higher in cirrhotics than in non-cirrhotics. PMID:27286877

Nitro-oxidative stress, VEGF and MMP-9 in patients with cirrhotic and non-cirrhotic portal hypertension.

PubMed

Muti, Leon Adrian; Pârvu, Alina Elena; Crăciun, Alexandra M; Miron, Nicolae; Acalovschi, Monica

2015-01-01

Nitro-oxidative stress may have pathophysiological consequences. The study aimed to assess the nitro-oxidative stress, the vascular growth factor, and metalloproteinase-9 levels in patients with noncirrohic and cirrhotic portal hypertension. Patients with noncirrhotic portal hypertension (n=50) and cirrhotic portal hypertension (n=50) from the 3rd Medical Clinic in Cluj-Napoca Romania were prospectively enrolled between October 2004 and October 2006. A control group of healthy volunteers (n=50) was also evaluated. Nitro-oxidative stress was assessed by measuring serum concentration of nitrites and nitrate, 3-nitrotyrosine, total oxidative status, total antioxidant reactivity, and oxidative stress index. Serum vascular growth factor and matrix metalloproteinase-9 were also determined. Serum nitrites and nitrate levels significantly increased in both noncirrhotic (p<0.001) and cirrhotic portal hypertension (p=0.057). 3-nitrotyrosine also increased in noncirrhotic (p=0.001) and cirrhotic portal hypertension patients (p=0.014). Total oxidative status showed a significant increase in noncirrhotic (p<0.001) and in cirrhotic portal hypertension (p<0.001), but total antioxidant reactivity did not change significantly. The oxidative stress index increased in both noncirrhotic (p <0.001) and cirrhotic portal hypertension (p<0.001), as well as the serum vascular growth factor (p=0.005 and p=0.01, respectively). In NCPHT patients serum MMP-9 was significantly lower than in the healthy controls (p=0.03) and CPHT patients (p=0.05). In patients with noncirrhotic and cirrhotic portal hypertension a significant systemic nitro-oxidative stress was found, correlated with an increase of VEGF. MMP-9 decreased in noncirrhotic portal hypertension.

Risk of Depressive Disorder following Non-Alcoholic Cirrhosis: A Nationwide Population-Based Study

PubMed Central

Hu, Li-Yu; Yeh, Chiu-Mei; Chen, Mu-Hong; Tsai, Chia-Fen; Chiang, Huey-Ling; Hung, Yi-Ping; Su, Vincent Yi-Fong; Hu, Yu-Wen; Su, Tung-Ping; Chen, Pan-Ming; Hung, Jeng-Hsiu; Liu, Chia-Jen; Huang, Min-Wei

2014-01-01

Background & Aims To evaluate the risk of depressive disorders among non-alcoholic patients by using the Taiwan National Health Insurance Research Database (NHIRD). Methods We conducted a retrospective study of a matched cohort of 52 725 participants (10 545 non-alcoholic cirrhotic patients and 42 180 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 11 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in cirrhotic patients. Results During the 11-year follow-up period, 395 (3.75%) non-alcoholic cirrhotic patients and 1 183 (2.80%) control patients were diagnosed with depressive disorders. The incidence risk ratio of depressive disorders between non-alcoholic cirrhotic patients and control patients was 1.76 (95% CI, 1.57–1.98, P<.001). After adjusting for age, sex, and comorbidities, non-alcoholic cirrhotic patients were 1.75 times more likely to develop depressive disorders (95% CI, 1.56–1.96, P<.001) compared with the control patients. The hazard ratios for patients younger than 60 years old (1.31) and female (1.25) indicated that each is an independent risk factor for depressive disorders in non-alcoholic cirrhotic patients. Conclusions The likelihood of developing depressive disorders is greater among non-alcoholic cirrhotic patients than among patients without cirrhosis. Symptoms of depression should be sought in patients with cirrhosis. PMID:24533141

Relevance of plasma malondialdehyde level and severity of portal hypertension in cirrhotic patients.

PubMed

Wang, Sheng-Lan; Zhu, Xin-Yan; Zhang, Dong-Wei; Zhang, Zhao-Jie; Gao, Heng-Jun; Yang, Chang-Qing

2015-01-01

Portal hypertension is one of the death reasons for the liver cirrhosis patients. The oxidative stress is related to the occurrence and development of portal hypertension in cirrhosis. Malondialdehyde (MDA), one of the lipid peroxides, increases substantially in cirrhotic patients. To evaluate the relevance between the MDA level and portal hypertension in cirrhotic patients. 60 liver cirrhotic patients and 30 healthy controls were enrolled. The plasma MDA level and general blood tests including ALT, AST, ALB, total bilirubin, and platelet were measured. All people enrolled accepted endoscopic examination and B-Ultrasound check to evaluate the severity of portal hypertension. The MDA plasma level of cirrhotic patients was significantly higher than the controls (P<0.001) and increased significantly accompanied by the severity of liver fibrosis and portal hypertension (P<0.01). Further, the plasma MDA level of cirrhotic patients was significantly correlated with Child-Pugh classification of cirrhosis (r=0.820, P<0.001), the degree of esophageal varices (r=0.857, P<0.001) and the width of portal vein (r=0.652, P<0.001). The ROC curve analyses showed that the plasma MDA level is a strong predictor of liver cirrhosis and portal hypertension. Plasma MDA level may correlate with the severity of portal hypertension in cirrhotic patients.

Mortality Following Catheter Drainage Versus Thoracentesis in Cirrhotic Patients with Pleural Effusion.

PubMed

Hung, Tsung-Hsing; Tseng, Chih-Wei; Tsai, Chen-Chi; Hsieh, Yu-Hsi; Tseng, Kuo-Chih; Tsai, Chih-Chun

2017-04-01

Pleural effusion is an abnormal collection of body fluids that may cause related morbidity or mortality in cirrhotic patients. There are insufficient data to determine the optimal method of drainage, for symptomatic relief in cirrhotic patients with pleural effusion. In this study, we compare the mortality outcomes of catheter drainage versus thoracentesis in cirrhotic patients. The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify cirrhotic patients with pleural effusion requiring drainage between January 1, 2007, and December 31, 2010. In all, 2556 cirrhotic patients with pleural effusion were selected for the study and divided into the two groups (n = 1278/group) after propensity score matching. The mean age was 61.0 ± 14.3 years, and 68.9% (1761/2556) were men. The overall 30-day mortality was 21.0% (538/2556) and was higher in patients treated with catheter drainage than those treated with thoracentesis (23.5 vs. 18.6%, respectively, P < 0.001 by log-rank test). After Cox proportional hazard regression analysis adjusted by patient sex, age, and comorbid disorders, the risk of 30-day mortality was significantly higher in cirrhotic patients who accepted catheter drainage compared to thoracentesis (hazard ratio 1.30, 95% confidence interval 1.10-1.54, P = 0.003). Old age, hepatic encephalopathy, bleeding esophageal varices, hepatocellular carcinoma, ascites, and pneumonia were associated with higher risks for 30-day mortality. In cirrhotic patients with pleural effusion requiring drainage, catheter drainage is associated with higher mortality compared to thoracentesis.

Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis.

PubMed

Bajaj, Jasmohan S; Acharya, Chathur; Fagan, Andrew; White, Melanie B; Gavis, Edith; Heuman, Douglas M; Hylemon, Phillip B; Fuchs, Michael; Puri, Puneet; Schubert, Mitchell L; Sanyal, Arun J; Sterling, Richard K; Stravitz, R Todd; Siddiqui, Mohammad S; Luketic, Velimir; Lee, Hannah; Sikaroodi, Masoumeh; Gillevet, Patrick M

2018-06-06

Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis. Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90-days post-discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross-sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral-origin taxa analysis vis-à-vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral-origin taxa was performed pre/post-intervention. Readmissions study: 343 inpatients (151 on admission PPI) were enrolled. 21 were withdrawn and 45 were initiated on PPI resulting in a PPI use increase of 21%. PPIs were associated with higher 30 (p = 0.002) and 90-day readmissions (p = 0.008) independent of comorbidities, medications, MELD and age. Cross-sectional microbiota: 137 cirrhotics (59 on PPI) and 45 controls (17 on PPI) were included. PPI users regardless of cirrhosis had higher oral-origin microbiota while cirrhotics on PPI had lower autochthonous taxa compared to the rest. Longitudinal studies: Fifteen decompensated cirrhotics tolerated omeprazole initiation with an increase in oral-origin microbial taxa compared to baseline. PPIs were withdrawn from an additional 15 outpatients, which resulted in a significant reduction of oral-origin taxa compared to baseline. PPIs modulate readmission risk and microbiota composition in cirrhosis, which responds to withdrawal. The systematic withdrawal and judicious use of PPIs is needed from a clinical and microbiological perspective in decompensated cirrhosis.

Characteristic risk factors in cirrhotic patients for posthepatectomy complications: comparison with noncirrhotic patients.

PubMed

Itoh, Shinji; Uchiyama, Hideaki; Kawanaka, Hirofumi; Higashi, Takahiro; Egashira, Akinori; Eguchi, Daihiko; Okuyama, Toshiro; Tateishi, Masahiro; Korenaga, Daisuke; Takenaka, Kenji

2014-02-01

There seemed to be characteristic risk factors in cirrhotic patients for posthepatectomy complications because these patients have less hepatic reserve as compared with noncirrhotic patients. The aim of the current study was to identify these characteristic risk factors in cirrhotic patients. We performed 419 primary hepatectomies for hepatocellular carcinoma. The patients were divided into the cirrhotic group (n = 198) and the noncirrhotic group (n = 221), and the risk factors for posthepatectomy complications were compared between the groups. Thirty-six cirrhotic patients (18.2%) experienced Clavien's Grade III or more complications. Tumor size, intraoperative blood loss, duration of operation, major hepatectomy (two or more segments), and necessity of blood transfusion were found to be significant risk factors in univariate analyses. Multivariate analysis revealed that major hepatectomy and intraoperative blood loss were independent risk factors for posthepatectomy complications in patients with cirrhosis. On the other hand, the duration of operation was only an independent risk factor for posthepatectomy complication in noncirrhotic patients. Cirrhotic patients should avoid a major hepatectomy and undergo a limited resection preserving as much liver tissue as possible and meticulous surgical procedures to lessen intraoperative blood loss are mandatory to prevent major posthepatectomy complications.

Gender-Specific Differences in Baseline, Peak, and Delta Serum Creatinine: The NACSELD Experience.

PubMed

O'Leary, Jacqueline G; Wong, Florence; Reddy, K Rajender; Garcia-Tsao, Guadalupe; Kamath, Patrick S; Biggins, Scott W; Fallon, Michael B; Subramanian, Ram M; Maliakkal, B; Thacker, Leroy; Bajaj, Jasmohan S

2017-03-01

Women have lower serum creatinine values than men for similar renal function. We aimed to determine the differential effect of baseline, peak, and delta creatinine between genders on outcomes in infected hospitalized cirrhotic patients. North American Consortium for the Study of End-Stage Liver Disease is a 15-center consortium of tertiary care hepatology centers prospectively enrolling infected cirrhotic inpatients. Baseline, peak, and delta creatinine during hospitalization were compared between genders, and their impact on overall survival, transplant-free survival, probability of transplantation, and need for renal replacement therapy (RRT) was analyzed. In total, 532 patients with cirrhosis (males = 59% median admission MELD = 20) had significantly lower median baseline (1.07 vs. 1.30 mg/dL, p < 0.0001) and peak creatinine (1.47 vs. 1.59 mg/dL, p = 0.024) in women than men during hospitalization for an infection, but both genders had similar delta creatinine levels (0.30 vs. 0.30 mg/dL, p = 0.957). Thirty-day mortality was similar between genders. RRT was not used more often in women (19 vs. 12%, p = 0.050), and women were 1.8 times more likely than men to receive RRT at the same creatinine (p = 0.028). Both peak and delta creatinine significantly predicted 6-month overall and transplant-free survival (p < 0.0001), but the probability of liver transplantation was affected by the interaction between gender and both peak and delta creatinine. Infected hospitalized cirrhotic women are significantly more likely than men to receive RRT at similar creatinine levels. Gender-specific differences in baseline, peak, and delta creatinine need further investigation to determine whether women need acute kidney injury treatment at lower creatinine thresholds than men.

Serum Leptin Is a Biomarker of Malnutrition in Decompensated Cirrhosis

PubMed Central

Rachakonda, Vikrant; Borhani, Amir A.; Dunn, Michael A.; Andrzejewski, Margaret; Martin, Kelly; Behari, Jaideep

2016-01-01

Background and Aims Malnutrition is a leading cause of morbidity and mortality in cirrhosis. There is no consensus as to the optimal approach for identifying malnutrition in end-stage liver disease. The aim of this study was to measure biochemical, serologic, hormonal, radiographic, and anthropometric features in a cohort of hospitalized cirrhotic patients to characterize biomarkers for identification of malnutrition. Design In this prospective observational cohort study, 52 hospitalized cirrhotic patients were classified as malnourished (42.3%) or nourished (57.7%) based on mid-arm muscle circumference < 23 cm and dominant handgrip strength < 30 kg. Anthropometric measurements were obtained. Appetite was assessed using the Simplified Nutrition Appetite Questionnaire (SNAQ) score. Fasting levels of serum adipokines, cytokines, and hormones were determined using Luminex assays. Logistic regression analysis was used to determine features independently associated with malnutrition. Results Subjects with and without malnutrition differed in several key features of metabolic phenotype including wet and dry BMI, skeletal muscle index, visceral fat index and HOMA-IR. Serum leptin levels were lower and INR was higher in malnourished subjects. Serum leptin was significantly correlated with HOMA-IR, wet and dry BMI, mid-arm muscle circumference, skeletal muscle index, and visceral fat index. Logistic regression analysis revealed that INR and log-transformed leptin were independently associated with malnutrition. Conclusions Low serum leptin and elevated INR are associated with malnutrition in hospitalized patients with end-stage liver disease. PMID:27583675

Bacterial infections in patients with liver cirrhosis: clinical characteristics and the role of C-reactive protein.

PubMed

Deutsch, Melanie; Manolakopoulos, Spilios; Andreadis, Ioannis; Giannaris, Markos; Kontos, George; Kranidioti, Hariklia; Pirounaki, Maria; Koskinas, John

2018-01-01

The diagnosis of bacterial infection in cirrhotic patients may be difficult, because of the absence of classical signs such as fever and raised white blood cell count. The role of C-reactive protein (CRP) in this context has not been clearly defined. Clinical and laboratory characteristics of 210 consecutive cirrhotic patients with (n=100) or without (n=110) bacterial infection were compared with a control group of non-cirrhotic patients with infection (n=106). Significantly fewer patients with cirrhosis had a body temperature ≥37°C when presenting with bacterial infection (56% cirrhotic vs. 85.5% non-cirrhotic patients, P=0.01). Mean leukocyte count was 6.92 × 10 3 /mm 3 in patients with cirrhosis and infection, 5.75 × 10 3 /mm 3 (P=0.02) in cirrhotic patients without infection, and 11.28 × 10 3 /mm 3 in non-cirrhotic patients with infection (P<0.001). Multivariate analysis revealed that CRP level and model for end-stage liver disease score were significantly associated with the presence of infection in patients with cirrhosis. A cutoff level of CRP>10 mg/L indicated the presence of infection with a sensitivity of 68%, a specificity of 84.5% and an area under the receiver operating characteristic curve of 0.8197. CRP cutoff level differed according to the severity of the liver disease: Child-Pugh score (CPS) A: 21.3 mg/L, B: 17 mg/L, and C: 5.78 mg/L. CRP at admission could help diagnose infection in cirrhotic patients. Since the severity of liver disease seems to affect the CRP values, lower CRP levels might indicate infection. Clinical suspicion is necessary to avoid delay in diagnosis and initiate antibiotic treatment.

The long-term outcomes of cirrhotic patients with pleural effusion.

PubMed

Hung, Tsung-Hsing; Tseng, Chih-Wei; Tsai, Chih-Chun; Tsai, Chen-Chi; Tseng, Kuo-Chih; Hsieh, Yu-Hsi

2018-01-01

A pleural effusion is an abnormal collection of fluid in the pleural space and may cause related morbidity or mortality in cirrhotic patients. Currently, there are insufficient data to support the long-term prognosis for cirrhotic patients with pleural effusion. In this study, we investigated the short- and long-term effects of pleural effusion on mortality in cirrhotic patients and evaluated the benefit of liver transplantation in these patients. The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify 3,487 cirrhotic patients with pleural effusion requiring drainage between January 1, 2007 and December 31, 2010. The proportional hazards Cox regression model was used to control for possible confounding factors. The 30-day, 90-day, 1-year, and 3-year mortalities were 20.1%, 40.2%, 59.1%, and 75.9%, respectively, in the cirrhotic patients with pleural effusion. After Cox proportional hazard regression analysis adjusted by patient gender, age, complications of cirrhosis and comorbid disorders, old age, esophageal variceal bleeding, hepatocellular carcinoma, hepatic encephalopathy, pneumonia, renal function impairment, and without liver transplantation conferred higher risks for 3-year mortality in the cirrhotic patients with pleura effusion. Liver transplantation is the most important factor to determine the 3-year mortalities (HR: 0.17, 95% CI 0.11- 0.26, P < 0.001). The 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year mortalities were 5.7%, 13.4%, 20.4%, and 21.7% respectively, in the liver transplantation group, and 20.5%, 41.0%, 61.2%, and 77.5%, respectively, in the non-liver transplantation group. In cirrhotic patients, the presence of pleural effusion predicts poor long-term outcomes. Liver transplantation could dramatically improve the survival and should be suggested as soon as possible.

Decreased Serum Hepcidin Concentration Correlates with Brain Iron Deposition in Patients with HBV-Related Cirrhosis

PubMed Central

Liu, Jian-Ying; He, Yi-Feng; Dai, Zhi; Chen, Cai-Zhong; Cheng, Wei-Zhong; Zhou, Jian; Wang, Xin

2013-01-01

Purpose Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level. Methods Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters. Results Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients. Conclusions Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential. PMID:23776499

High mortality in cirrhotic patients following hemorrhagic stroke.

PubMed

Hung, Tsung-Hsing; Hsieh, Yu-Hsi; Tseng, Kuo-Chih; Tseng, Chih-Wei; Lee, Hsing-Feng; Tsai, Chih-Chun; Tsai, Chen-Chi

2015-06-01

The impact of hemorrhagic stroke (HS) on the mortality of cirrhotic patients is unknown. To evaluate the morality risk of HS in cirrhotic patients, we used the Taiwan National Health Insurance Database to evaluate cirrhotic patients with HS who were discharged between 1 January and 31 December 2007. In total, there were 321 cirrhotic patients with HS. We randomly selected 3210 cirrhotic patients without HS as a comparison group. The 30 and 90 day mortality rates were 29.6% and 43.0% in the HS group, and 9.1% and 17.7% in the comparison group, respectively (p<0.001). After Cox proportional hazard regression model adjustment of patients' sex, age, and other comorbid disorders, the hazard ratio (HR) for 90 day mortality in the HS group was 3.89 (95% confidence interval [CI] 3.20-4.71, p<0.001), compared to the comparison group. In the subgroup analysis, the HR for 90 day mortality in the subarachnoid hemorrhage and other HS groups were 7.93 (95% CI 5.23-12.0, p<0.001) and 3.51 (95% CI 2.85-4.32, p<0.001), respectively, compared to the comparison group. In conclusion, HS is associated with a very high 90 day mortality risk in cirrhotic patients, in whom subarachnoid hemorrhage can also increase the risk of mortality eight-fold. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-variceal upper gastrointestinal bleeding in cirrhotic patients in Nile Delta.

PubMed

Gabr, Mamdouh Ahmed; Tawfik, Mohamed Abd El-Raouf; El-Sawy, Abd Allah Ahmed

2016-01-01

Acute upper gastrointestinal bleeding (AUGIB) in cirrhotic patients occurs mainly from esophageal and gastric varices; however, quite a large number of cirrhotic patients bleed from other sources as well. The aim of the present work is to determine the prevalence of non-variceal UGIB as well as its different causes among the cirrhotic portal hypertensive patients in Nile Delta. Emergency upper gastrointestinal (UGI) endoscopy for AUGIB was done in 650 patients. Out of these patients, 550 (84.6%) patients who were proved to have cirrhosis were the subject of the present study. From all cirrhotic portal hypertensive patients, 415 (75.5%) bled from variceal sources (esophageal and gastric) while 135 (24.5%) of them bled from non-variceal sources. Among variceal sources of bleeding, esophageal varices were much more common than gastric varices. Peptic ulcer was the most common non-variceal source of bleeding. Non-variceal bleeding in cirrhosis was not frequent, and sources included peptic ulcer, portal hypertensive gastropathy, and erosive disease of the stomach and duodenum.

Septic Shock due to Vibrio alginolyticus in a Cirrhotic Patient: The First Case in Korea

PubMed Central

Lee, Dong-Young; Moon, Soo-Youn; Lee, Sang-Oh; Yang, Hee-Young; Lee, Hee-Joo

2008-01-01

We describe a case of septic shock due to Vibrio alginolyticus presenting with fever and bilateral leg pain. Despite intensive management with antibiotics and inotropic agents, the patient died from septic shock 1 day after hospitalization. V. alginolyticus was isolated from both leg wounds and a blood culture. To the best of our knowledge, this is the first reported case of V. alginolyticus bacteremia in Korea. PMID:18452273

Sleep disorders in cirrhotics; how can we detect ?

PubMed

Gencdal, Genco; Gunsar, Fulya; Meral, Cenk E; Salman, Esin; Gürsel, Berna; Oruç, Nevin; Karasu, Zeki; Ersöz, Galip; Akarca, Ulus Salih

2014-09-01

Sleep disorders (SDs) are common in cirrhotics and are often associated with hepatic encephalopathy. SDs negatively affect patients' daily activities and work efficiency. For this reason, early diagnosis is important. The methods used for diagnosis of SDs are not practical and need longer periods of application and evaluation. In this study, we aimed to investigate sleep disorders and related clinical parameters in cirrhosis and also wanted to investigate the using of Sleep Timing and Sleep Quality Screening questionnaire (STSQS), a simple form with a short application time, for diagnosis of SDs and its correlation with Pittsburg Sleep Quality Index (PSQI) form. Cirrhotic patients and age-matched healthy volunteers were enrolled. Patients were excluded from this study if they had neuropsychiatric disease or used excessive alcohol or drugs known to affect sleep. Both groups completed validated Turkish form of PSQI and STSQS. SD was defined as PSQI score (0-21) of >5 or STSQS ≥5. One hundred and thirty-one cirrhotic patients and 18 healthy volunteers were enrolled. SDs in cirrhotics and control group were detected 56.5% and 27.8% by PSQI, 49.6% and 16.7% by STSQS respectively. SDs are the most frequent in the Child C patients, and the least frequent in the Child A patients (P > 0.05). No correlation was found between the MELD score and SDs. SDs were more common in cirrhotic patients with hypoalbuminaemia and low haemoglobin levels. In addition, the patients with decompensated cirrhosis had more frequently SDs than the patients with compensated cirrhosis. In the patient group, sleep latency and total sleep time, sleep parameters were correlated with SDs. STSQS had statistical significant correlation with PSQI for diagnosis of SDs. SDs are common in cirrhotics and STSQS could be an appropriate and practical method for diagnosis of SDS in these patients. We can use it in cirrhotic patients at outpatient clinics. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A cost analysis of a broad-spectrum antibiotic therapy in the empirical treatment of health care-associated infections in cirrhotic patients

PubMed Central

Lucidi, Cristina; Di Gregorio, Vincenza; Ceccarelli, Giancarlo; Venditti, Mario; Riggio, Oliviero; Merli, Manuela

2017-01-01

Background Early diagnosis and appropriate treatment of infections in cirrhosis are crucial. As new guidelines in this context, particularly for health care-associated (HCA) infections, would be needed, we performed a trial documenting whether an empirical broad-spectrum antibiotic therapy is more effective than the standard one for these infections. Because of the higher daily cost of broad-spectrum than standard antibiotics, we performed a cost analysis to compare: 1) total drug costs, 2) profitability of hospital admissions. Methods This retrospective observational analysis was performed on patients enrolled in the trial NCT01820026, in which consecutive cirrhotic patients with HCA infections were randomly assigned to a standard vs a broad-spectrum treatment. Antibiotic daily doses, days of treatment, length of hospital stay, and DRG (diagnosis-related group) were recorded from the clinical trial medical records. The profitability of hospitalizations was calculated considering DRG tariffs divided by length of hospital stay. Results We considered 84 patients (42 for each group). The standard therapy allowed to obtain a first-line treatment cost lower than in the broad-spectrum therapy. Anyway, the latter, being related to a lower failure rate (19% vs 57.1%), resulted in cost saving in terms of cumulative antibiotic costs (first- and second-line treatments). The mean cost saving per patient for the broad-spectrum arm was €44.18 (−37.6%), with a total cost saving of about €2,000. Compared to standard group, we observed a statistically significant reduction in hospital stay from 17.8 to 11.8 days (p<0.002) for patients treated with broad-spectrum antibiotics. The distribution of DRG tariffs was similar in the two groups. According to DRG, the shorter length of hospital stay of the broad-spectrum group involved a higher mean profitable daily cost than standard group (€345.61 vs €252.23; +37%). Conclusion Our study supports the idea that the use of a broad-spectrum empirical treatment for HCA infections in cirrhosis would be cost-saving and that hospitals need to be aware of the clinical and economic consequences of a wrong antibiotic treatment in this setting. PMID:28721080

A cost analysis of a broad-spectrum antibiotic therapy in the empirical treatment of health care-associated infections in cirrhotic patients.

PubMed

Lucidi, Cristina; Di Gregorio, Vincenza; Ceccarelli, Giancarlo; Venditti, Mario; Riggio, Oliviero; Merli, Manuela

2017-01-01

Early diagnosis and appropriate treatment of infections in cirrhosis are crucial. As new guidelines in this context, particularly for health care-associated (HCA) infections, would be needed, we performed a trial documenting whether an empirical broad-spectrum antibiotic therapy is more effective than the standard one for these infections. Because of the higher daily cost of broad-spectrum than standard antibiotics, we performed a cost analysis to compare: 1) total drug costs, 2) profitability of hospital admissions. This retrospective observational analysis was performed on patients enrolled in the trial NCT01820026, in which consecutive cirrhotic patients with HCA infections were randomly assigned to a standard vs a broad-spectrum treatment. Antibiotic daily doses, days of treatment, length of hospital stay, and DRG (diagnosis-related group) were recorded from the clinical trial medical records. The profitability of hospitalizations was calculated considering DRG tariffs divided by length of hospital stay. We considered 84 patients (42 for each group). The standard therapy allowed to obtain a first-line treatment cost lower than in the broad-spectrum therapy. Anyway, the latter, being related to a lower failure rate (19% vs 57.1%), resulted in cost saving in terms of cumulative antibiotic costs (first- and second-line treatments). The mean cost saving per patient for the broad-spectrum arm was €44.18 (-37.6%), with a total cost saving of about €2,000. Compared to standard group, we observed a statistically significant reduction in hospital stay from 17.8 to 11.8 days ( p <0.002) for patients treated with broad-spectrum antibiotics. The distribution of DRG tariffs was similar in the two groups. According to DRG, the shorter length of hospital stay of the broad-spectrum group involved a higher mean profitable daily cost than standard group (€345.61 vs €252.23; +37%). Our study supports the idea that the use of a broad-spectrum empirical treatment for HCA infections in cirrhosis would be cost-saving and that hospitals need to be aware of the clinical and economic consequences of a wrong antibiotic treatment in this setting.

[Open cholecystectomy in cirrhotic patients. Experience at the Salvador Zubirán National Institute of Nutrition].

PubMed

Carmona, R; Suazo, J; Mercado, M A; Orozco, H

1996-01-01

To inform the morbidity and mortality observed in cirrhotic patients who underwent open cholecystectomy. We reviewed the clinical records of 31 cirrhotics that underwent open cholecystectomy and they were compared with a control group of the same age and sex. Despite administration of plasma or vitamin K or both, bleeding and transfusions during surgery were observed more frequently in cirrhotics. The morbidity was 13% in the controls and 42% in the cases. Renal failure, cardiac failure and upper gastrointestinal bleeding were present only in the cirrhotics. Mortality was 16% in this group (one Child A patient and four Child B-C patients). The variable related with major morbimortality was Child B or C classification. Open cholecystectomy was associated with high morbimortality. The valoration and preparation before surgery must be careful, and the indication from this procedure needs to be made with caution.

Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease

PubMed Central

Leung, Christopher; Yeoh, Sern Wei; Patrick, Desmond; Ket, Shara; Marion, Kaye; Gow, Paul; Angus, Peter W

2015-01-01

AIM: To determine characteristics and prognostic predictors of patients with hepatocellular carcinoma (HCC) in association with non-alcoholic fatty liver disease (NAFLD). METHODS: We reviewed the records of all patients with NAFLD associated HCC between 2000 and 2012. Data collected included demographics; histology; presence or absence of cirrhosis, size and number of HCC, alpha-fetoprotein, body mass index (BMI), and the presence of diabetes, hypertension, or dyslipidaemia. RESULTS: Fifty-four patients with NAFLD associated HCC were identified. Mean age was 64 years with 87% male. Fifteen percent (8/54) were not cirrhotic. 11%, 24% and 50% had a BMI of < 25 kg/m2, 25-29 kg/m2 and ≥ 30 kg/m2 respectively. Fifty-nine percent were diabetic, 44% hypertensive and 26% hyperlipidaemic. Thirty-four percent of the patients had ≤ 1 of these risk factors. Non-cirrhotics had a significantly larger mean tumour diameter at diagnosis than cirrhotics (P = 0.041). Multivariate analysis did not identify any other patient characteristics that predicted the size or number of HCC. CONCLUSION: HCC can develop in NAFLD without cirrhosis. At diagnosis such tumours are larger than those in cirrhotics, conferring a poorer prognosis. PMID:25632192

Efficacy and safety of endometrial ablation for treating abnormal uterine bleeding in pre- and postmenopausal women with liver cirrhosis.

PubMed

Liu, Qing; Li, Xiu-Lan; Liu, Ji-Juan; Song, Xiao-Hong; Jiang, Xiao-Ying; Li, Wei; Zhang, Hua; Pan, Calvin Q

2016-12-01

Abnormal uterine bleeding (AUB) occurs in 10-30% of women of reproductive age and up to 61% of cirrhotic women. We evaluated the efficacy and safety of endometrial ablation (NovaSure therapy) for AUB in cirrhotic women. This prospective, two-arm, observational study enrolled patients for NovaSure treatment, and they were followed for 12 months. Primary measurements were the amenorrhea rate and changes of pictorial blood loss assessment chart (PBLAC) scores at 1-month post-therapy. Key secondary end-points included the longevity of amenorrhea at 12 months, safety profile, and progression of cirrhosis. Among 88 women, 26 were cirrhotic and 62 were non-cirrhotic. At 1-month post-NovaSure treatment, a significant reduction of mean PBLAC scores was observed in cirrhotic patients compared to those at baseline (0.4 ± 1.3 vs 215.2 ± 410.9, P < 0.001), and the amenorrhea rate was 88.5%. The efficacy outcomes of the PBLAC scores and amenorrhea rate were maintained until the end of the 12-month follow-up. A significant improvement in quality of life scores was observed 1-month post-therapy compared to those at baseline (5.4 ± 3.1 vs 20.5 ± 5.5, P < 0.001). Patients' satisfaction rates were 100% and 92.31% at 6 and 12 months, respectively. The aforementioned outcomes were comparable with those in non-cirrhotic patients. No significant progression of cirrhosis or safety concern was reported. Cirrhotic patients on NovaSure therapy had a high rate of amenorrhea 1-month post-treatment, which maintained longevity for 12 months. The safety profile was similar to that in non-cirrhotic patients. © 2016 Japan Society of Obstetrics and Gynecology.

Stimulation of insulin secretion by medium-chain triglycerides in patients with cirrhosis 1

PubMed Central

McCullough, Frank S.; Tzagournis, Manuel; Greenberger, Norton J.; Linscheer, Willem G.

1971-01-01

Oral medium-chain triglycerides were given to 10 normal volunteers, 12 cirrhotics (group I) without and 28 cirrhotics (group II) with abnormal portal systemic communications (ascites, splenomegaly, oesophageal varices, or surgically-created portacaval shunts). After 30 ml of medium-chain triglyceride oil there was no appreciable change in serum glucose levels in any of the three groups nor in serum insulin levels in the normals and in cirrhotics in group I. However, there was a significant increase in serum insulin levels in the cirrhotic patients in group II. It is suggested that the rise in serum insulin levels after medium-chain triglycerides noted in the cirrhotics with shunts is due to shunting of insulin-containing portal blood around the liver (anatomical shunts) and to a diminished hepatic cell mass capable of extracting insulin (functional shunt). This differential response of serum insulin levels to medium-chain triglycerides may prove to be of value in detecting the presence of abnormal portal systemic communications in cirrhotic patients. PMID:5548559

Liver Cirrhosis is Independently Associated With 90-Day Mortality in ARDS Patients.

PubMed

Gacouin, Arnaud; Locufier, Maxime; Uhel, Fabrice; Letheulle, Julien; Bouju, Pierre; Fillatre, Pierre; Le Tulzo, Yves; Tadié, Jean Marc

2016-01-01

In a few studies, cirrhosis has been associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). These studies were, however, conducted mostly before 2000. Over the last 15 years, the prognosis of cirrhotic patients admitted to the intensive care unit (ICU) seems to have improved and major changes in the management of mechanical ventilation (MV) of ARDS have appeared. The aim of this study was to determine whether cirrhosis remains a factor for poor prognosis despite improvements in MV techniques and supportive therapies for ARDS. Retrospective analysis of data recorded from 232 patients (42 with cirrhosis and 290 without cirrhosis) who received lung-protective ventilation for ARDS defined according to American-European Consensus Conference criteria and admitted from 2006 to 2013. Alcohol was the most common aetiology of the cirrhosis. The end point was mortality at day-90 from the diagnosis of ARDS, survival was calculated using the Kaplan-Meier method, and we used a Cox-proportional hazard model to determine whether cirrhosis remained independently associated with mortality after adjustment for other prognostic variables for ARDS described previously. Organ dysfunctions were assessed based on the Sequential Organ Failure Assessment (SOFA) criteria, pulmonary and nonpulmonary dysfunctions were distinguished and compared between cirrhotic and non-cirrhotic patients on the first 3 days of VM. Comparison of survival curves showed that cirrhotic patients had a poorer 90-day prognosis than non-cirrhotic patients (P = 0.03 by the log-rank test). After adjusted analysis, cirrhosis remained independently associated with mortality at day 90 (adjusted hazard ratio 2.09, 95% CI, 1.27-3.45, P = 0.004). Non-pulmonary SOFA scores were significantly higher in cirrhotic patients than in non-cirrhotic patients on day 1 (P < 0.001), day 2 (P = 0.003), and day 3 (P = 0.002) of MV for ARDS whereas pulmonary SOFA scores did not differ significantly. Despite improvements in the management of cirrhotic patients admitted to the ICU and in the management of MV for the treatment of ARDS, cirrhosis remained associated with a poorer prognosis in ARDS patients. The prognosis of cirrhotic patients with ARDS appears related to extrapulmonary organ dysfunctions rather than pulmonary dysfunction.

[Evaluation and treatment of the critically ill cirrhotic patient].

PubMed

Fernández, Javier; Aracil, Carles; Solà, Elsa; Soriano, Germán; Cinta Cardona, Maria; Coll, Susanna; Genescà, Joan; Hombrados, Manoli; Morillas, Rosa; Martín-Llahí, Marta; Pardo, Albert; Sánchez, Jordi; Vargas, Victor; Xiol, Xavier; Ginès, Pere

2016-11-01

Cirrhotic patients often develop severe complications requiring ICU admission. Grade III-IV hepatic encephalopathy, septic shock, acute-on-chronic liver failure and variceal bleeding are clinical decompensations that need a specific therapeutic approach in cirrhosis. The increased effectiveness of the treatments currently used in this setting and the spread of liver transplantation programs have substantially improved the prognosis of critically ill cirrhotic patients, which has facilitated their admission to critical care units. However, gastroenterologists and intensivists have limited knowledge of the pathogenesis, diagnosis and treatment of these complications and of the prognostic evaluation of critically ill cirrhotic patients. Cirrhotic patients present alterations in systemic and splanchnic hemodynamics, coagulation and immune dysfunction what further increase the complexity of the treatment, the risk of developing new complications and mortality in comparison with the general population. These differential characteristics have important diagnostic and therapeutic implications that must be known by general intensivists. In this context, the Catalan Society of Gastroenterology and Hepatology requested a group of experts to draft a position paper on the assessment and treatment of critically ill cirrhotic patients. This article describes the recommendations agreed upon at the consensus meetings and their main conclusions. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Disrupted metabolic and functional connectivity patterns of the posterior cingulate cortex in cirrhotic patients: a study combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging.

PubMed

Lu, Li; Wang, Junpeng; Zhang, Longjiang; Zhang, Zhiqiang; Ni, Ling; Qi, Rongfeng; Kong, Xiang; Lu, Mengjie; Sami, Muhammad U; Xu, Kai; Lu, Guangming

2018-06-26

The association between metabolic activity and functional coupling of the posterior cingulate cortex (PCC) in cirrhotic patients remains undefined. Therefore, this study aimed to assess the association of functional coupling with metabolic patterns of PCC in resting cirrhotic patients. Twenty-six cirrhotic patients, including 10 with hepatic encephalopathy (HE) and 16 without HE, were assessed, alongside 21 control participants. Single-voxel proton magnetic resonance spectroscopy (MRS) of the PCC and resting-state functional MRI (rs-fMRI) were performed on a 3.0-T MR scanner. The ratios of all metabolites to creatine (Cr) and rs-fMRI parameters [including amplitude of low-frequency fluctuation (ALFF), node degree (Ki), and betweenness centrality (Bi)] were evaluated by analysis of variance. Associations of metabolite ratios with rs-fMRI parameters and venous ammonia were determined by Pearson's correlation analysis. Lower chlorine (Cho)/Cr (0.6±0.2 vs. 0.9±0.1, P<0.001) and higher ALFF (1.3±0.5 vs. 1.1±0.3, P=0.01) were found in cirrhotic patients in comparison with controls. In cirrhotic patients, the ALFF values correlated negatively with Cho/Cr (r=-0.397, P=0.044). Meanwhile, Bi values showed positive associations with glutamine+glutamate/Cr (r=0.500, P=0.009) and N-acetyl aspartate/Cr (r=0.581, P=0.006). In the HE subgroup, Ki correlated positively with Cho/Cr (r=0.867, P=0.001). In cirrhotic patients without HE, Bi values showed a high positive correlation with glutamate+glutamine/Cr (r=0.690, P=0.013). These findings suggest a close association between metabolic activity and functional coupling of the PCC in cirrhotic patients, especially those with HE, whose node degree of the PCC shows an overt positive correlation with Cho/Cr.

L-ornithine-L-aspartate infusion efficacy in hepatic encephalopathy.

PubMed

Ahmad, Irfan; Khan, Anwaar A; Alam, Altaf; Dilshad, Akif; Butt, Arshad Kamal; Shafqat, Farzana; Malik, Kashif; Sarwar, Shahid

2008-11-01

To determine the efficacy of L-ornithine-L-aspartate in treatment of hepatic encephalopathy. Randomized, placebo-controlled trial. Department of Gastroenterology and Hepatology, Sheikh Zayed Hospital, Lahore, from February to August 2005. Cirrhotic patients with hyperammonemia and overt hepatic encephalopathy were enrolled. Eighty patients were randomized to two treatment groups, L-ornithine-L-aspartate (20 g/d) or placebo, both dissolved in 250 mL of 5% dextrose water and infused intravenously for four hours a day for five consecutive days with 0.5 g/kg dietary protein intake at the end of daily treatment period. Outcome variables were postprandial blood ammonia and mental state grade. Adverse reactions and mortality were also determined. Both treatment groups were comparable regarding age, gender, etiology of cirrhosis, Child-Pugh class, mental state grade and blood ammonia at baseline. Although, improvement occurred in both groups, there was a greater improvement in L-ornithine-L-aspartate group with regard to both variables. Four patients in the placebo group and 2 in L-ornithine-L-aspartate group died. L-ornithine-L-aspartate infusions were found to be effective in cirrhotic patients with hepatic encephalopathy.

Diastolic dysfunction characterizes cirrhotic cardiomyopathy

PubMed Central

Somani, Piyush O.; contractor, Qais; Chaurasia, Ajay S.; Rathi, Pravin M.

2014-01-01

Aim Present study aims to study the occurrence of cirrhotic cardiomyopathy and its correlation to hepatorenal syndrome by assessing the cardiac status in patients with cirrhosis of liver and healthy controls. Methods Thirty alcoholic cirrhotic, thirty non-alcoholic cirrhotic and thirty controls were enrolled for the study. Cardiac parameters were assessed by color doppler echocardiography. Patients were followed up for twelve months period for development of hepatorenal syndrome. Results Mild diastolic dysfunction was present in 18 cirrhotic patients (30%): grade I in fifteen patients and grade II in three. Diastolic dysfunction was unrelated to age; sex and etiology of cirrhosis. Among all the echocardiographic parameters, only deceleration time was found to be statistically significant. Echocardiographic parameters in systolic and diastolic function were not different in compensated vs decompensated patients in different Child-Pugh classes or cirrhosis aetiologies. At one year follow-up, no significant differences were found in survival between patients with or without diastolic dysfunction. Hepatorenal syndrome developed in only two patients and its correlation with diastolic dysfunction was not statistically significant. Conclusions Present study shows that although diastolic dysfunction is a frequent event in cirrhosis, it is usually of mild degree and does not correlate with severity of liver dysfunction. There are no significant differences in echocardiographic parameters between alcoholic and non-alcoholic cirrhosis. HRS is not correlated to diastolic dysfunction in cirrhotic patients. There is no difference in survival at one year between patients with or without diastolic dysfunction. Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS. PMID:25634400

[Umbilical and inguinal hernioplasty in cirrhotic patients].

PubMed

Zepeda, R; Herrera, M F; Mercado, M A

1994-01-01

The overall results of surgical treatment of abdominal wall hernias in patients with hepatic cirrhosis were assessed by a retrospective study in 41 cirrhotic patients. They underwent 22 umbilical and 22 inguinal herniorrhapies between 1982 and 1992. Sixteen patients were classified as Child-Pugh A, 16 as B and 9 as C. Clinical evidence of ascitis was documented in 19 patients. The operative mortality was 5% (two Child-Pugh C cases). Postoperative complications occurred in 10 patients, most of them related to the surgical wound. We recommend herniorraphy in symptomatic cirrhotic patients but with fairly good hepatic function.

Complications Requiring Hospital Admission and Causes of In-Hospital Death over Time in Alcoholic and Nonalcoholic Cirrhosis Patients.

PubMed

Kim, Hee Yeon; Kim, Chang Wook; Choi, Jong Young; Lee, Chang Don; Lee, Sae Hwan; Kim, Moon Young; Jang, Byoung Kuk; Wo, Hyun Young

2016-01-01

Data on the epidemiology of alcoholic cirrhosis, especially in Asian countries, are limited. We compared the temporal evolution of patterns of alcoholic and nonalcoholic cirrhosis over the last decade. We retrospectively examined the inpatient datasets of five referral centers during 2002 and 2011. The study included patients who were admitted due to specific complications of liver cirrhosis. We compared the causes of hospital admissions and in-hospital deaths between patients with alcoholic and nonalcoholic cirrhosis. Among the included 2,799 hospitalizations (2,165 patients), 1,496 (1,143 patients) were from 2002, and 1,303 (1,022 patients) were from 2011. Over time, there was a reduction in the rate of hepatic encephalopathy (HE) as a cause of hospitalization and an increase in the rate of hepatocellular carcinoma. Deaths that were attributable to HE or spontaneous bacterial peritonitis (SBP) significantly decreased, whereas those due to hepatorenal syndrome (HRS) significantly increased over time in patients with alcoholic cirrhosis. However, in patients with nonalcoholic cirrhosis, hepatic failure and HRS remained the principal causes of in-hospital death during both time periods. The major causes of in-hospital deaths have evolved from acute cirrhotic complications, including HE or SBP to HRS in alcoholic cirrhosis, whereas those have remained unchanged in nonalcoholic cirrhosis during the last decade.

Assessment of Body Composition Using Dual Energy X-Ray Absorptiometry in Patients with Liver Cirrhosis: Comparison with Anthropometry

PubMed Central

Jeong, Seong Han; Lee, Jeong A; Kim, Jin A; Lee, Mun Woo; Chae, Hee Bok; Choi, Won Jun; Shin, Hyoung Shik; Lee, Ki Hyeong; Youn, Sei Jin; Koong, Sung Soo; Park, Seon Mee

1999-01-01

Objectives The aim of this study was to evaluate changes of body composition in cirrhotic patients. Dual energy x-ray absorptiometry (DEXA) and anthropometry were used, and the values obtained were compared. Methods Mid-arm fat and muscle areas were calculated by anthropometry in 66 cirrhotic patients and 94 healthy controls. In 37 of the cirrhotic patients and 39 of the controls, fat mass, lean soft tissue mass and bone mineral contents were measured with DEXA. Results The number of cirrhotic patients with measured values below the fifth percentile of normal controls was 21 (31.8%) by mid-arm fat area, six (9.1%) by mid-arm muscle area, 15 (40.5%) by fat mass and 0 (0%) by lean soft tissue mass. The fat mass in cirrhotic patients was less than in controls, whereas lean soft tissue mass and bone mineral content were not different. Fat depletion was severe in Child-class C patients and with severe ascites. Mid-arm fat area and fat mass showed close correlation (r = 0.85, p<0.01), but mid-arm muscle area and lean soft tissue mass showed poor correlation (r = 0.32, p<0.05). Conclusion Cirrhotic patients showed lower fat component, with preserved lean soft tissue mass and bone mineral content. In clinical practice, the measurement of mid-arm fat area was useful for the assessment of fat mass. PMID:10461427

Outcome of sublay mesh repair in non-complicated umbilical hernia with liver cirrhosis and ascites.

PubMed

Hassan, Ahmed Mohamed Abdelaziz; Salama, Asaad Fayrouz; Hamdy, Hussam; Elsebae, Magdy Mohamed; Abdelaziz, Ayman Mohamed; Elzayat, Wessam Abdelrahman

2014-01-01

Umbilical hernia repair is often accompanied by complications in patients with liver cirrhosis and ascites. It appears that the early elective repair of umbilical hernias in these patients is safer and can be considered for selected patients. The objective of this study is to evaluate the feasibility, safety, complications and technical aspects of sublay mesh repair of umbilical hernia in cirrhotic patients with ascites. Between October 2010 and April 2013, 70 patients with non-complicated umbilical hernia, liver cirrhosis and ascites were enrolled in this study. All patients underwent sublay mesh repair. Demographic data, preoperative variables, peri-operative course, and postoperative complications were recorded and analyzed. A total of 38 women and 32 men underwent operation at an average age 51.24 years. The patients mean MELD score was 18 (range 12-25). The mean operative time was 67.45 min and the average hospital stay was 3.8 days. 2 patients had wound infection, 3 patients developed seroma and 1 patient had an ascitic fistula. Recurrence occurred in 1 (1.4%) patient and no mortality related to the procedure. elective sublay umbilical hernia mesh repair is a safe approach and feasible technique in selected non-complicated cirrhotic patients with ascites. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Serum lipopolysaccharide-binding protein prediction of severe bacterial infection in cirrhotic patients with ascites.

PubMed

Albillos, Agustín; de-la-Hera, Antonio; Alvarez-Mon, Melchor

2004-05-15

Serum lipopolysaccharide-binding protein is increased in a subset of non-infected ascitic cirrhotic patients, a finding previously related to bacterial passage from the gut to the circulation without overt infection. We prospectively analysed the risk factors associated with a first episode of severe bacterial infection in 84 ascitic cirrhotics, followed up for a median of 46 weeks. The cumulative probability of such infection in patients with raised and normal lipopolysaccharide-binding protein was 32.4% and 8.0% (p=0.004), respectively. Increased lipopolysaccharide-binding protein was the only factor independently associated with severe bacterial infection in a multivariate analysis (relative risk 4.49, 95% CI 1.42-14.1). Monitoring of serum lipopolysaccharide-binding protein could, therefore, help to target cirrhotic patients with ascites for antibiotic prophylaxis.

What proportions of focal liver lesions detected by unenhanced ultrasound are inconclusive?

PubMed Central

Willits, Iain; Burn, Julie; Cole, Helen; Hoare, Tim

2014-01-01

In August 2012, the National Institute for Health and Care Excellence produced positive diagnostics guidance on the ultrasound contrast agent SonoVue®, but recommended further research involving an estimation of the proportion of unenhanced ultrasound scans reporting, but not characterising, focal liver lesions, particularly in cirrhotic livers. Patient records from the Radiology Information System of an acute hospital trust were progressively filtered based on categorical fields and keywords in the free text reports, to obtain ultrasound records including the liver that were appropriate for manual analysis. In total, 21,731 records referred from general practice or out-patient clinics were analysed. Patients described as having cirrhosis were analysed as a subgroup. After automatic exclusion of records considered likely to be negative, 5812 records were manually read and categorised as focal liver lesion inconclusive, benign or malignant. In the general practice cohort of 9175 records, 746 reported the presence of one or more focal liver lesions, with 18.4% (95% CI 15.7% to 21.3%) of these records mentioning an inconclusive focal liver lesion. In the out-patient cohort of 12,556 records, 1437 reported one or more focal liver lesions, and 29.4% (95% CI 26.9% to 32.0%) of these were inconclusive. Cirrhosis was reported in 10.8% of the out-patient scans that also reported a focal liver lesion, and 47.4% (95% CI 39.3% to 55.6%) of these scans had an inconclusive focal liver lesion, compared with 27.3% (95% CI 24.9% to 29.8%) that were inconclusive in non-cirrhotic livers (odds ratio 2.4; 95% CI 1.7 to 3.4). This retrospective study indicates that unenhanced ultrasound scans, in which a focal liver lesion is detected, are frequently inconclusive, with the probability of an inconclusive scan being greater in out-patient than general practice referrals. Inconclusive focal liver lesions were also reported in greater proportions of cirrhotic than non-cirrhotic livers. The results of this research will inform future updates of National Institute for Health and Care Excellence diagnostics guidance. PMID:25949268

Incidence of bacteremia in cirrhotic patients undergoing upper endoscopic ultrasonography.

PubMed

Fernández-Esparrach, Gloria; Sendino, Oriol; Araujo, Isis; Pellisé, Maria; Almela, Manel; González-Suárez, Begoña; López-Cerón, María; Córdova, Henry; Sanabria, Erwin; Uchima, Hugo; Llach, Josep; Ginès, Àngels

2014-01-01

The incidence of bacteremia after endoscopic ultrasonography (EUS) or EUS-guided fine-needle aspiration (EUS-FNA) is between 0% and 4%, but there are no data on this topic in cirrhotic patients. To prospectively assess the incidence of bacteremia in cirrhotic patients undergoing EUS and EUS-FNA. We enrolled 41 cirrhotic patients. Of these, 16 (39%) also underwent EUS-FNA. Blood cultures were obtained before and at 5 and 30 min after the procedure. When EUS-FNA was used, an extra blood culture was obtained after the conclusion of radial EUS and before the introduction of the sectorial echoendoscope. All patients were clinically followed up for 7 days for signs of infection. Blood cultures were positive in 16 patients. In 10 patients, blood cultures grew coagulase-negative Staphylococcus, Corynebacterium species, Propionibacterium species or Acinetobacterium Lwoffii, which were considered contaminants (contamination rate 9.8%, 95% CI: 5.7-16%). The remaining 6 patients had true positive blood cultures and were considered to have had true bacteremia (15%, 95% CI: 4-26%). Blood cultures were positive after diagnostic EUS in five patients but were positive after EUS-FNA in only one patient. Thus, the frequency of bacteremia after EUS and EUS-FNA was 12% and 6%, respectively (95% CI: 2-22% and 0.2-30%, respectively). Only one of the patients who developed bacteremia after EUS had a self-limiting fever with no other signs of infection. Asymptomatic Gram-positive bacteremia developed in cirrhotic patients after EUS and EUS-FNA at a rate higher than in non-cirrhotic patients. However, this finding was not associated with any clinically significant infections. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Liver surgery in cirrhosis and portal hypertension.

PubMed

Hackl, Christina; Schlitt, Hans J; Renner, Philipp; Lang, Sven A

2016-03-07

The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis.

Rifaximin Decreases the Incidence and Severity of Acute Kidney Injury and Hepatorenal Syndrome in Cirrhosis.

PubMed

Dong, Tien; Aronsohn, Andrew; Gautham Reddy, K; Te, Helen S

2016-12-01

While the effects of rifaximin have been shown to be protective against acute kidney injury (AKI) and hepatorenal syndrome (HRS) in alcohol-induced cirrhosis, its long-term effects on the renal function of other cirrhotic patients are unknown. To examine the long-term effects of rifaximin on the renal function of patients with cirrhosis from various etiologies. In a retrospective study, we examined cirrhotic patients at the University of Chicago Liver Clinic from January 1, 2011, to December 31, 2014. The study enrolled patients on rifaximin for ≥90 days, who were then matched by age, gender, and MELD score to a control group. Patients with malignancy and renal replacement therapy (RRT) at baseline were excluded. Data were censored at the last follow-up, termination of rifaximin therapy, initiation of RRT, death, or liver transplant. Eighty-eight rifaximin cases were identified and matched to 88 control cases. Baseline characteristics were similar, with the exceptions of more prevalent long-term midodrine use (≥90 days) (17.0 vs 4.5 %, p = 0.01) and baseline ascites (37.5 vs 23.8 %, p = 0.05) in the rifaximin group. There was no difference in the frequency of infections, deaths, liver transplants, or hospitalizations. After controlling for cofounders, the incidence rate ratio of AKI (IRR 0.71, p = 0.02) and HRS (IRR 0.21, p = 0.02), as well as the risk of requiring RRT (OR 0.23, p = 0.01), was lower in the rifaximin group. Long-term use of rifaximin is associated with a decrease incidence of AKI and HRS and a decrease risk of requiring RRT in a general population of cirrhotic patients.

Impact of different sofosbuvir based treatment regimens on the biochemical profile of chronic hepatitis C genotype 4 patients.

PubMed

Elsharkawy, Aisha; Eletreby, Rasha; Fouad, Rabab; Soliman, Zeinab; Abdallah, Mohamed; Negm, Mohamed; Mohey, Mohammad; Esmat, Gamal

2017-08-01

Huge efforts have been made to control chronic HCV in Egypt with introduction of Direct-Acting Antivirals (DAAs). Current study aims at evaluating effect of various DAA regimens on liver biochemical profile and haematological indices during treatment. 272 patients with chronic HCV genotype 4 treated by different DAA regimens (SOF/RBV, SOF/DAC ± RBV, SOF/SIM) for a duration of 12 or 24 weeks in Kasr Alainy Viral Hepatitis Center, Cairo University were followed up for serum bilirubin (BIL), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), prothrombin concentration, international normalized ratio (INR), and CBC at baseline, week-4 and end of treatment. Mean age was 54 years. Males comprised 64.7%, 72.4% were treatment-naïve, 39% were cirrhotic. Overall SVR12 rate was (93.4%). With all regimens, ALT and AST declined after treatment. In cirrhotics, there was a rise in BIL and INR; with no change in ALB and a decrease in White blood cells. Drop in Hemoglobin and platelets in cirrhotic patients were noted with SOF/RBV, while SOF/SIM showed rise in BIL. DAAs are safe and effective in genotype 4 chronic HCV patients. It improves liver necro-inflammatory markers in cirrhotics and non-cirrhotics. Cirrhotic patients require careful observation being more vulnerable for treatment related complications.

Association of umbilical hernia with volume of ascites in liver cirrhosis: a retrospective observational study.

PubMed

Wang, Ran; Qi, Xingshun; Peng, Ying; Deng, Han; Li, Jing; Ning, Zheng; Dai, Junna; Hou, Feifei; Zhao, Jiancheng; Guo, Xiaozhong

2016-11-01

Umbilical hernia is a common abdominal complication in cirrhotic patients with ascites. Our study aimed to evaluate the correlation of umbilical hernia with the volume of ascites. Cirrhotic patients that underwent axial abdominopelvic computed tomography (CT) scans at our hospital between June 2012 and June 2014 were eligible. All CT images were reviewed to confirm the presence of umbilical hernia. The volume of ascites was estimated by five-point method. One hundred and fifty-seven patients were enrolled into this study. Among them, 101 patients had ascites and 6 patients had umbilical hernia. Alkaline phosphatase (AKP) and serum sodium were significantly lower in patients with umbilical hernia (P = 0.008, P = 0.011, respectively). Child-Pugh scores and the volume of ascites were significantly higher in patients with umbilical hernia (P = 0.03, P < 0.0001, respectively). Correlation analysis demonstrated that the volume of ascites, Child-Pugh scores, and blood ammonia had positive correlations with umbilical hernia (r = 0.4579, P < 0.0001; r = 0.175, P = 0.03; r = 0.342, P = 0.001, respectively) and that serum sodium had a negative correlation with umbilical hernia (r = -0.203, P = 0.011). In patients with ascites ≥2000 mL, only AKP was significantly associated with umbilical hernia (P = 0.0497). No variables were significantly associated with umbilical hernia in a subgroup analysis of patients matched according to the volume of ascites. The volume of ascites has a positive correlation with umbilical hernia. However, the factors associated with umbilical hernia in patients with severe ascites remain unclear. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity.

PubMed

Chen, Hua-Jun; Zhang, Ling; Jiang, Long-Feng; Chen, Qiu-Feng; Li, Jun; Shi, Hai-Bin

2016-08-01

It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients.

Portal hypertensive gastropathy: association with Child-Pugh score in liver cirrhosis

NASA Astrophysics Data System (ADS)

Sungkar, T.; Zain, L. H.; Siregar, G. A.

2018-03-01

Portal Hypertensive Gastropathy (PHG) occurs as a complication of cirrhotic or non-cirrhotic portal hypertension. The association between the severity of portal hypertensive gastropathy and the hepatic function, as assessed by the Child-Pugh score in patients with liver cirrhosis are poorly defined. We evaluated association between PHG and Child-Pugh score in patients with liver cirrhosis. Adults liver cirrhosis patients admitted at Adam Malik Hospital Medan during January 2016-December 2016, were included in this study. Endoscopic PHG grade, Child-Pugh score were assessed. A total of 49 patients were enrolled. Majority of cases of liver cirrhosis are due to chronic viral hepatitis B infections (65.3 %). Portal hypertensive gastropathy were observed in 46 cases; twenty-five patients (51%) showed severe portal hypertensive gastropathy. The overall prevalence of PHG and the proportion of patients with severe PHG differ about the Child-Pugh classification. PHG was present in 66.7 % of patients from Child-Pugh class A, 96 % of patients with class B, and 95.2 % of those from class C, and severe forms were present in 0 %, 36 %, and 76.2 %, respectively (P< 0.000). In conclusions, the present data suggest that the severity of portal hypertensive gastropathy is related to Child-Pugh score.

Hepatocellular Carcinoma Surveillance Rates in Commercially Insured Patients with Non-Cirrhotic Chronic Hepatitis B

PubMed Central

Goldberg, David S.; Valderrama, Adriana; Kamalakar, Rajesh; Sansgiry, Sujit S; Babajanyan, Svetlana; Lewis, James D.

2015-01-01

AASLD and EASL guidelines recommend biannual hepatocellular carcinoma (HCC) screening for non-cirrhotic patients with chronic hepatitis B infection (HBV), yet there are no data estimating surveillance rates or factors associated with surveillance. We performed a retrospective cohort study of U.S. patients using the Truven Health Analytics databases from 2006-2010, and identified patients with non-cirrhotic chronic HBV. Surveillance patterns were characterized using categorical and continuous outcomes, with the continuous measure of the proportion of time “up-to-date” with surveillance (PUTDS), with the six-month interval following each ultrasound categorized as “up-to-date.” During a median follow-up of 26.0 (IQR: 16.2-40.0) months among 4,576 non-cirrhotic patients with chronic HBV (median age: 44 years, IQR: 36-52), only 306 (6.7%) had complete surveillance (one ultrasound every 6-month interval), 2,727 (59.6%) incomplete (≥1 ultrasound), and 1,543 (33.7%) none. The mean PUTDS was 0.34 ± 0.29, and the median was 0.32 (IQR: 0.03-0.52). In multinomial logistic regression models, patients diagnosed by a non-gastroenterologist were significantly less likely to have complete surveillance (p<0.001), as were those co-infected with HBV/HIV (p<0.001). In linear regression models, non-gastroenterologist provider, health insurance subtype, HBV/HIV co-infection, rural status, and metabolic syndrome were independently associated with decreased surveillance. Patients with HIV had an absolute decrease in the PUTDS of 0.24, while patients in less populated rural areas had an absolute decrease of 0.10. HCC surveillance rates in non-cirrhotic patients with chronic HBV in the United States are poor, and lower than reported rates of HCC surveillance in cirrhotic patients. PMID:25581816

[Acute liver ischaemia after gastro-oesophageal variceal bleeding].

PubMed

Senosiain Lalastra, Carla; Arribas Anta, Julia; Moreira Vicente, Víctor; Martínez González, Javier; Maroto Castellanos, Maite; García Sánchez, María Concepción; Zaera de la Fuente, Celia; López Durán, Sergio; Cañete Ruiz, Ángel; Albillos Martínez, Agustín

2016-11-01

Variceal upper gastrointestinal bleeding (UGIB) can trigger acute hypoxic hepatitis (AHH). The aim of this study was to analyse the incidence, associated risk factors and mortality of AHH after variceal UGIB. Retrospective study of cirrhotic patients with variceal UGIB, classified into 2 groups according to the development of AHH. AHH was diagnosed when AST and ALT reached levels 10 times above the upper limit of normal, after ruling out other causes of hepatitis. The standard initial treatment consisted of haemodynamic support, emergency endoscopy with rubber band ligation, somatostatin and antibiotics. In the case of failure of primary haemostasis, a transjugular intrahepatic portosystemic shunt (TIPS) was implanted. Both groups (AHH and non-AHH) were compared. Sixty-eight cirrhotic patients with variceal UGIB admitted to the gastroenterology department of Hospital Ramón y Cajal between January 2007 and March 2012 were analysed. Eleven of these patients (16.2%) developed AHH. Univariate analysis showed the following items as risk factors: diabetes (OR: 7.5; CI: 1.9-29), shock (OR: 8.5; CI: 2.06-34) and persistent bleeding (OR: 9.0, CI: 1.6-49, P=.03). However, multivariate analysis confirmed only diabetes (OR: 8.61; CI: 1.4-52.5) and shock (OR: 7.58; CI: 1.26-45.51) as risk factors. Mortality rate in the AHH group was 45%, compared to 10.5% in the non-HAA group (P=.012). AHH after variceal UGIB occurred in 16.2% of cirrhotic patients and was associated with a poorer prognosis, with a mortality rate of 45%. Our findings suggest that diabetes and shock are risk factors for the development of AHH. Early identification of at-risk patients could therefore help prevent AHH. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Intestinal microbiota assessment in cirrhotic patients from a Mexican mestizo population.

PubMed

Pérez-Monter, C; Escalona-Nandez, I; Estanes-Hernández, A; Noriega-López, L G; Torre-Delgadillo, A

2018-06-11

The intestinal microbiota is significantly altered in cirrhotic patients, but the composition of the intestinal microbiota in Mexican patients with the pathology has not been reported. The present study is an attempt to determine the type of intestinal microbiota in healthy subjects and in patients of Mexican mestizo origin that present with cirrhosis of the liver. Biochemical liver function parameters (ALT, AST, GGT, BIL-T, etc.) were determined in 23 cirrhotic patients and 21 control subjects. The intestinal microbiota was established through 16S ribosomal RNA gene sequencing. The cirrhotic patients had elevated levels of ALT, AST, GGT (105.2±77.7 vs. 20.99±8.5UI/L, 110±68.6 vs. 23.39±5.2, and 119.1±79.1 vs. 19.3±15.2UI/L, respectively), IL-6 (1.64±0.38pg/ml, P<.001), or TNFα (1.78±0.3, P<.05). The intestinal microbiota of the cirrhotic patients was less diverse, compared with that of the control subjects. At the level of the phylum, there was a significant increase in Proteobacteria and Bacteroidetes in the patients with cirrhosis, compared with the controls (6.2 vs. 4.9% and 44 vs. 46%, respectively, P<.01). In contrast, there was a decrease in Firmicutes, Actinobacteria, and Fusobacteria in the cirrhotic patients. There was an increase in the Campylobacter and Gemella families in the cirrhotic patients, whereas Streptococcus and Veillonella had a positive association with serum ALT or AST levels. To the best of our knowledge, the present study is the first to demonstrate the type of intestinal microbiota in Mexican patients with cirrhosis of the liver. The extension of the findings in a larger cohort of subjects and the metagenome analysis will enable the creation of data that can have relevant treatment implications for this group of patients in Mexico. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

[2-3 diphosphoglycerate and tissue oxygenation in the cirrhotic].

PubMed

Vendemiale, G; Altomare, E; Stufano, N; Procacci, V; Albano, O

1985-01-30

Increased 2-3 Diphosphoglycerate levels in cirrhotic patients have been reported. Previous studies did not show significant changes in 2-3 DPG in anaemic cirrhotic patients when compared to non anaemic cirrhotic patients, but the role played by alkalosis and/or hypoxia has not been investigated. To study this question, haematic 2-3 DPG was measured in 8 male patients with liver cirrhosis (histologically diagnosed) together with PO2, PCO2, pH and Hct. 2-3 DPG was also measured in 6 healthy male volunteers. We found a significant increase in blood 2-3 DPG of cirrhotic patients compared to control subjects (5,55 +/- 0,4 vs 2,18 +/- 0,3 mmol/l erythrocytes respectively, p less than 0,001) in agreement with previous studies. PO2 levels and Hct value did not show important changes, whereas PCO2 and pH resulted to be very altered when compared to normal values, even though we could not correlate these values with blood 2-3 DPG. We conclude that the genesis of 2-3 DPG increase is multifactorial, however an alteration in acid-base equilibrium seems to play a more important role than hypoxia.

Prospective study of bacteremia rate after elective band ligation and sclerotherapy with cyanoacrylate for esophageal varices in patients with advanced liver disease.

PubMed

Bonilha, Danielle Queiroz; Correia, Lucianna Motta; Monaghan, Marie; Lenz, Luciano; Santos, Marcus; Libera, Ermelindo Della

2011-01-01

Band ligation (BL) is the most appropriate endoscopic treatment for acute bleeding or prophylaxis of esophageal variceal bleeding. Sclerotherapy with N-butyl-2-cyanoacrylate (CY) can be an alternative for patients with advanced liver disease. Bacteremia is an infrequent complication after BL while the bacteremia rate following treatment with CY for esophageal varices remains unknown. To evaluate and compare the incidence of transient bacteremia between cirrhotic patients submitted to diagnostic endoscopy, CY and BL for treatment of esophageal varices. A prospective study comprising the period from 2004 to 2007 was conducted at Hospital of Universidade Federal de São Paulo, UNIFESP, SP, Brazil. Cirrhotic patients with advanced liver disease (Child-Pugh B or C) were enrolled. The patients were divided into two groups according treatment: BL Group (patients undergoing band ligation, n = 20) and CY Group (patients receiving cyanoacrylate injection for esophageal variceal, n = 18). Cirrhotic patients with no esophageal varices or without indication for endoscopic treatment were recruited as control (diagnostic group n = 20). Bacteremia was evaluated by blood culture at baseline and 30 minutes after the procedure. After 137 scheduled endoscopic procedures, none of the 58 patients had fever or any sign suggestive of infection. All baseline cultures were negative. No positive cultures were observed after CY or in the control group - diagnostic endoscopy. Three (4.6 %) positive cultures were found out of the 65 sessions of band ligation (P = 0.187). Two of these samples were positive for coagulase-negative staphylococcus, which could be regarded as a contaminant. The isolated microorganism in the other case was Klebsiella oxytoca. The patient in this case presented no evidence of immunodeficiency except liver disease. There was no significant difference in bacteremia rate between these three groups. BL or CY injection for non-bleeding esophageal varices may be considered as low-risk procedures regarding bacteremia even when performed on patients with advanced liver disease.

Albumin reduces paracentesis-induced circulatory dysfunction and reduces death and renal impairment among patients with cirrhosis and infection: a systematic review and meta-analysis.

PubMed

Kwok, Chun Shing; Krupa, Lukasz; Mahtani, Ash; Kaye, Duncan; Rushbrook, Simon M; Phillips, Martin G; Gelson, William

2013-01-01

Studies have suggested that albumin has a value in cirrhotic patients undergoing paracentesis but its value in infection and sepsis is less clear. We planned to perform a meta-analysis of the risk of adverse outcomes in cirrhotic patients with and without albumin use. We searched MEDLINE and EMBASE in January 2013 for randomized studies of cirrhotic patients that reported the risk of adverse events and mortality with albumin and no albumin exposure. We performed random effects meta-analysis and assessed heterogeneity using the I² statistic. Our review included 16 studies covering 1,518 patients. The use of albumin in paracentesis was associated with significantly reduced risk of paracentesis-induced circulatory dysfunction (OR 0.26 95%, CI 0.08-0.93) and there was a nonsignificant difference in death, encephalopathy, hyponatraemia, readmission, and renal impairment. Compared to the other volume expanders, albumin use showed no difference in clinical outcomes. In cirrhotic patients with any infection, there was a significant reduction in mortality (OR 0.46 95%, CI 0.25-0.86) and renal impairment (OR 0.34 95%, CI 0.15-0.75) when albumin was used. The use of albumin in cirrhotic patients is valuable in patients with any infection and it reduces the risk of circulatory dysfunction among patients undergoing paracentesis.

Albumin Reduces Paracentesis-Induced Circulatory Dysfunction and Reduces Death and Renal Impairment among Patients with Cirrhosis and Infection: A Systematic Review and Meta-Analysis

PubMed Central

Krupa, Lukasz; Mahtani, Ash; Kaye, Duncan; Rushbrook, Simon M.; Phillips, Martin G.

2013-01-01

Background. Studies have suggested that albumin has a value in cirrhotic patients undergoing paracentesis but its value in infection and sepsis is less clear. We planned to perform a meta-analysis of the risk of adverse outcomes in cirrhotic patients with and without albumin use. Methods. We searched MEDLINE and EMBASE in January 2013 for randomized studies of cirrhotic patients that reported the risk of adverse events and mortality with albumin and no albumin exposure. We performed random effects meta-analysis and assessed heterogeneity using the I2 statistic. Results. Our review included 16 studies covering 1,518 patients. The use of albumin in paracentesis was associated with significantly reduced risk of paracentesis-induced circulatory dysfunction (OR 0.26 95%, CI 0.08–0.93) and there was a nonsignificant difference in death, encephalopathy, hyponatraemia, readmission, and renal impairment. Compared to the other volume expanders, albumin use showed no difference in clinical outcomes. In cirrhotic patients with any infection, there was a significant reduction in mortality (OR 0.46 95%, CI 0.25–0.86) and renal impairment (OR 0.34 95%, CI 0.15–0.75) when albumin was used. Conclusion. The use of albumin in cirrhotic patients is valuable in patients with any infection and it reduces the risk of circulatory dysfunction among patients undergoing paracentesis. PMID:24222902

Liver surgery in cirrhosis and portal hypertension

PubMed Central

Hackl, Christina; Schlitt, Hans J; Renner, Philipp; Lang, Sven A

2016-01-01

The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis. PMID:26973411

Single-centre validation of the EASL-CLIF consortium definition of acute-on-chronic liver failure and CLIF-SOFA for prediction of mortality in cirrhosis.

PubMed

Silva, Pedro E Soares E; Fayad, Leonardo; Lazzarotto, César; Ronsoni, Marcelo F; Bazzo, Maria L; Colombo, Bruno S; Dantas-Correa, Esther B; Narciso-Schiavon, Janaína L; Schiavon, Leonardo L

2015-05-01

The idea of acute-on-chronic liver failure (ACLF) has emerged to identify those subjects with organ failure and high mortality rates. However, the absence of a precise definition has limited the clinical application and research related to the ACLF concept. We sought to validate the ACLF definition and the CLIF-SOFA Score recently proposed by the EASL-CLIF Consortium in a cohort of patients admitted for acute decompensation (AD) of cirrhosis. In this prospective cohort study, patients were followed during their hospital stay and thirty and 90-day mortality was evaluated by phone call, in case of hospital discharge. All subjects underwent laboratory evaluation at admission. Between December 2010 and November 2013, 192 cirrhotic patients were included. At enrollment, 46 patients (24%) met the criteria for ACLF (Grades 1, 2 and 3 in 18%, 4% and 2% respectively). The 30-day mortality was 65% in ACLF group and 12% in the remaining subjects (P < 0.001). Logistic regression analysis showed that 30-day mortality was independently associated with ascites and ACLF at admission. The Kaplan-Meier survival probability at 90-day was 92% in patients without ascites or ACLF and only 22% for patients with both ascites and ACLF. The AUROC of CLIF-SOFA in predicting 30-day mortality was 0.847 ± 0.034, with sensitivity of 64%, specificity of 90% and positive likelihood ratio of 6.61 for values ≥9. In our single-centre experience the CLIF-SOFA and the EASL-CLIF Consortium definition of ACLF proved to be strong predictors of short-term mortality in cirrhotic patients admitted for AD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Flow cytometric DNA analysis of cirrhotic liver cells in patients with hepatocellular carcinoma can provide a new prognostic factor.

PubMed

Ruà, S; Comino, A; Fruttero, A; Torchio, P; Bouzari, H; Taraglio, S; Torchio, B; Capussotti, L

1996-09-15

DNA flow cytometry of hepatocellular carcinoma (HCC) cells has been investigated in many studies, but, to the best of our knowledge, there are no data on DNA analysis of cirrhotic parenchyma around the HCC. In this study, cell kinetics and ploidy of parenchymal cells around HCC were performed to ascertain if this would predict the possibility of recurrence in the cirrhotic areas. The DNA content of 93 cases of HCC and of cirrhotic liver around the tumor nodules was analyzed by flow cytometry. Ploidy and proliferative index of HCC and cirrhotic liver were compared with macroscopic, histologic, and clinical features of each case and linked with the behavior of these tumors. Survival curves were assessed according to the Kaplan-Meier method. A multivariate analysis based on Cox proportional hazards regression model was performed on cases of diploid cirrhosis cells in which the S-phase fraction was evaluable. The univariate analysis of survival suggested significant roles for age, number of intrahepatic nodules, Edmondson-Steiner's classification, portal invasion, vascular invasion, presence of necrosis, hepatitis B surface antigen, alpha-feto-protein, Child's score, ploidy, and S-phase fraction of HCC cells. The DNA analysis of the cirrhotic cells showed that polyploidy was dramatically reduced in patients with HCC, compared with normal hepatocytes, and aneuploid clones were present among diploid cells. High S-phase fraction of cirrhotic cells and Child-Pugh classification were the strongest independent parameters affecting the tumor behavior in this study. The results of this study suggest that S-phase fraction of cirrhotic liver parenchyma may be employed as a new parameter in the prognostic evaluation of HCC patients.

Prognostic Value of Metabolic Liver Function Tests: a Study on 711 Cirrhotic Patients.

PubMed

Lebossé, Fanny; Guillaud, Olivier; Forestier, Julien; Ecochard, Marie; Boillot, Olivier; Roman, Sabine; Mion, François; Dumortier, Jérôme

2016-09-01

The prognosis of cirrhotic patients is usually assessed by Child-Pugh and MELD scores. Metabolic liver function tests such as aminopyrine breath test (ABT) and indocyanine green clearance (IGC) have been shown to reveal hepatocellular dysfunction. The aim of this retrospective study was to compare the prognostic value of the MELD score, Child-Pugh score, ABT and IGC in a large cohort of cirrhotic patients. Between January 1996 and June 2008, 711 cirrhotic patients were included and the primary endpoint was survival without LT. The ROC curves with c-statistics, correlation coefficient and survival were calculated. Metabolic function tests and scores were strongly correlated. At the time of evaluation, 111 patients had died and 520 had received a transplant. Prognostic ability (estimated by the AUROC curve) to predict survival without LT at 6 months was 0.662, 0.691, 0.738 and 0.715 for ABT, IGC, Child-Pugh score and MELD score, respectively. Similarly, at 1 year, AUROC was 0.738 for Child-Pugh score, 0.716 for MELD score, 0.693 for IGC clearance and 0.651 for ABT. Our results strongly confirm that IGC and ABT have a high prognostic value in cirrhotic patients, similar to Child-Pugh and MELD scores. They could be developed to routinely evaluate the prognosis of patients in addition to clinical and biochemical data.

Nutritional status in patients with hepatitis C.

PubMed

Ismail, Faisal Wasim; Khan, Rustam A; Kamani, Lubna; Wadalawala, Ashfaq A; Shah, Hasnain Ali; Hamid, Saeed S; Jafri, Wasim

2012-03-01

To assess the nutritional status via the SGA (subjective global assessment) screening tool of patients at all stages of hepatitis C virus (HCV) liver disease. Descriptive study. Out-patient Clinics of the Aga Khan University Hospital, Karachi, conducted from October 2009 to January 2011. Patients with hepatitis C virus infection and their HCV-negative attendants were enrolled from the outpatient clinics, and categorized into 4 groups of 100 patients each: healthy controls (HC), those with chronic hepatitis C infection (CHC), compensated cirrhotics (CC) and decompensated cirrhotics (DC). The validated subjective global assessment (SGA) tool was used to assess nutritional status. A total of 400 patients were enrolled. Most of the patients in the HC group were class 'A' (best nutritional status). In contrast, the majority (64%) in the DC group were in the class 'C' (worst status). The compensated cirrhosis (CC) group showed that 90% of patients were malnourished, while 98% of all patients were malnourished in the DC group, predominantly class 'C'. Most importantly, 14% of patients with chronic hepatitis C (CHC) also scored a 'B' on the SGA; which when compared to HC was statistically significant (p=0.005). As the groups progressed in their disease from CHC to DC, the transition in nutritional status from 'A' to 'C' between groups was statistically significant. Malnutrition occurs early in the course of HCV, and progresses relentlessly throughout the spectrum of HCVdisease.

Predictive factors for rebleeding and death in alcoholic cirrhotic patients with acute variceal bleeding: a multivariate analysis.

PubMed

Krige, Jake E J; Kotze, Urda K; Distiller, Greg; Shaw, John M; Bornman, Philippus C

2009-10-01

Bleeding from esophageal varices is a leading cause of death in alcoholic cirrhotic patients. The aim of the present single-center study was to identify risk factors predictive of variceal rebleeding and death within 6 weeks of initial treatment. Univariate and multivariate analyses were performed on 310 prospectively documented alcoholic cirrhotic patients with acute variceal hemorrhage (AVH) who underwent 786 endoscopic variceal injection treatments between January 1984 and December 2006. All injections were administered during the first 6 weeks after the patients were treated for their first variceal bleed. Seventy-five (24.2%) patients experienced a rebleed, 38 within 5 days of the initial treatment and 37 within 6 weeks of their initial treatment. Of the 15 variables studied and included in a multivariate analysis using a logistic regression model, a bilirubin level >51 mmol/l and transfusion of >6 units of blood during the initial hospital admission were predictors of variceal rebleeding within the first 6 weeks. Seventy-seven (24.8%) patients died, 29 (9.3%) within 5 days and 48 (15.4%) between 6 and 42 days after the initial treatment. Stepwise multivariate logistic regression analysis showed that six variables were predictors of death within the first 6 weeks: encephalopathy, ascites, bilirubin level >51 mmol/l, international normalized ratio (INR) >2.3, albumin <25 g/l, and the need for balloon tube tamponade. Survival was influenced by the severity of liver failure, with most deaths occurring in Child-Pugh grade C patients. Patients with AVH and encephalopathy, ascites, bilirubin levels >51 mmol/l, INR >2.3, albumin <25 g/l and who require balloon tube tamponade are at increased risk of dying within the first 6 weeks. Bilirubin levels >51 mmol/l and transfusion of >6 units of blood were predictors of variceal rebleeding.

Machine Learning Classification of Cirrhotic Patients with and without Minimal Hepatic Encephalopathy Based on Regional Homogeneity of Intrinsic Brain Activity.

PubMed

Chen, Qiu-Feng; Chen, Hua-Jun; Liu, Jun; Sun, Tao; Shen, Qun-Tai

2016-01-01

Machine learning-based approaches play an important role in examining functional magnetic resonance imaging (fMRI) data in a multivariate manner and extracting features predictive of group membership. This study was performed to assess the potential for measuring brain intrinsic activity to identify minimal hepatic encephalopathy (MHE) in cirrhotic patients, using the support vector machine (SVM) method. Resting-state fMRI data were acquired in 16 cirrhotic patients with MHE and 19 cirrhotic patients without MHE. The regional homogeneity (ReHo) method was used to investigate the local synchrony of intrinsic brain activity. Psychometric Hepatic Encephalopathy Score (PHES) was used to define MHE condition. SVM-classifier was then applied using leave-one-out cross-validation, to determine the discriminative ReHo-map for MHE. The discrimination map highlights a set of regions, including the prefrontal cortex, anterior cingulate cortex, anterior insular cortex, inferior parietal lobule, precentral and postcentral gyri, superior and medial temporal cortices, and middle and inferior occipital gyri. The optimized discriminative model showed total accuracy of 82.9% and sensitivity of 81.3%. Our results suggested that a combination of the SVM approach and brain intrinsic activity measurement could be helpful for detection of MHE in cirrhotic patients.

Soluble Klotho and Brain Atrophy in Alcoholism.

PubMed

González-Reimers, Emilio; Romero-Acevedo, Lucía; Espelosín-Ortega, Elisa; Martín-González, M Candelaria; Quintero-Platt, Geraldine; Abreu-González, Pedro; José de-la-Vega-Prieto, María; Martínez-Martínez, Daniel; Santolaria-Fernández, Francisco

2018-05-26

Fibroblast growth factor (FGF-23) and α-Klotho (Klotho) levels may be altered in inflammatory conditions, possibly as compensatory mechanisms. Klotho exerts a protective effect on neurodegeneration and improves learning and cognition. No data exist about the association of Klotho and FGF-23 levels with brain atrophy observed in alcoholics. The aim of this study is to explore these relationships. FGF-23 and Klotho levels are altered in inflammation, possibly as compensatory mechanisms. Klotho enhances learning, but its role in ethanol-mediated brain atrophy is unknown. We found higher FGF-23 and lower Klotho levels in 131 alcoholics compared with 41 controls. Among cirrhotics, Klotho was higher and inversely related to brain atrophy. The study was performed on 131 alcoholic patients (54 cirrhotics) and 41 age- and sex-matched controls, in whom a brain computed tomography (CT) was performed and several indices were calculated. Marked brain atrophy was observed among patients when compared with controls. Patients also showed higher FGF-23 and lower Klotho values. However, among cirrhotics, Klotho values were higher. Klotho was inversely related to brain atrophy (for instance, ventricular index (ρ = -0.23, P = 0.008)), especially in cirrhotics. Klotho was also directly related to tumor necrosis factor (TNF) alpha (ρ = 0.22; P = 0.026) and inversely to transforming growth factor (TGF)-β (ρ = -0.34; P = 0.002), but not to C-reactive protein (CRP) or malondialdehyde levels. FGF-23 was also higher among cirrhotics but showed no association with CT indices. Klotho showed higher values among cirrhotics, and was inversely related to brain atrophy. FGF-23, although high among patients, especially cirrhotics, did not show any association with brain atrophy. Some inflammatory markers or cytokines, such as CRP or TGF-β were related to brain atrophy.

Use of concomitant variceal embolization and prophylactic antiplatelet/anticoagulative in transjugular intrahepatic portosystemic shunting: A retrospective study of 182 cirrhotic portal hypertension patients.

PubMed

Tang, Yingmei; Zheng, Sheng; Yang, Jinhui; Bao, Weimin; Yang, Lihong; Li, Yingchun; Xu, Ying; Yang, Jing; Tong, Yuyun; Gao, Jinhang; Tang, Chengwei

2017-12-01

Transjugular intrahepatic portosystemic shunting (TIPS) is an effective treatment modality for refractory variceal bleeding and ascites in patients with cirrhotic portal hypertension (CPH). Variceal rebleeding and shunt dysfunction are major post-TIPS morbidities. This study aimed to retrospectively evaluate the effectiveness and safety of use of concomitant variceal embolization and prophylactic antiplatelet/anticoagulative in patients with CPH undergoing TIPS. Between October 2006 and October 2011, 182 patients with CPH were retrospectively and consecutively hospitalized for elective TIPS with Fluency stenting. Concomitant variceal embolization was given after establishing the shunt. Subcutaneous heparin was given after TIPS and replaced by oral clopidogrel, aspirin, or warfarin for at least 6 months. Main outcome measures included shunt patency rate, recurrence of CPH (rebleeding and/or refractory ascites), hepatic encephalopathy (HE) frequency, and post-TIPS survival. The cumulative primary patency rate was 96%, 94%, 90%, 88%, and 88% at 6, 12, 24, 36, and 48 months, respectively. Shunt stenosis occurred in 16 (9%) patients, gastrointestinal (GI) rebleeding in 32 (17.5%) patients, recurrence of refractory ascites 44 (48%) patients, HE in 42 (23%) patients, and death in 36 (20%) patients during the follow-up period. Use of concomitant variceal embolization and prophylactic antiplatelet/anticoagulative was associated with a favorable shunt patency and a low risk of GI rebleeding.

Risk of progression of Barrett's esophagus in patients with cirrhosis

PubMed Central

Apfel, Tehilla; Lopez, Rocio; Sanaka, Madhusudhan R; Thota, Prashanthi N

2017-01-01

AIM To study Barrett’s esophagus (BE) in cirrhosis and assess progression to esophageal adenocarcinoma (EAC) compared to non-cirrhotic BE controls. METHODS Cirrhotic patients who were found to have endoscopic evidence of BE confirmed by the presence of intestinal metaplasia on histology from 1/1/2000 to 12/1/2015 at Cleveland Clinic were included. Cirrhotic patients were matched 1:4 to BE controls without cirrhosis. Age, gender, race, BE length, hiatal hernia size, Child-Pugh (CP) class and histological findings were recorded. Cases and controls without high-grade dysplasia (HGD)/EAC and who had follow-up endoscopies were studied for incidence of dysplasia/EAC and to assess progression rates. Univariable conditional logistic regression was done to assess differences in baseline characteristics between the two groups. RESULTS A total of 57 patients with cirrhosis and BE were matched with 228 controls (BE without cirrhosis). The prevalence of dysplasia in cirrhosis and controls were similar with 8.8% vs 12% with low grade dysplasia (LGD) and 12.3 % vs 19.7% with HGD or EAC (P = 0.1). In the incidence cohort of 44 patients with median follow-up time of 2.7 years [interquartile range 1.0, 4.8], there were 7 cases of LGD, 2 cases of HGD, and 2 cases of EAC. There were no differences in incidence rates of HGD/EAC in nondysplastic BE between cirrhotic cases and noncirrhotic controls (1.4 vs 1.1 per 100 person- years, P = 0.8). In LGD, cirrhotic patients were found to have higher rates of progression to HGD/EAC compared to control group though this did not reach statistical significance (13.7 vs 8.1 per 100 person- years, P = 0.51). A significant association was found between a higher CP class and neoplastic progression of BE in cirrhotic patients (HR =7.9, 95%CI: 2.0-30.9, P = 0.003). CONCLUSION Cirrhotics with worsening liver function are at increased risk of progression of BE. More frequent endoscopic surveillance might be warranted in such patients. PMID:28566888

Risk Factors for Hepatocellular Carcinoma in Cirrhotic Patients with Chronic Hepatitis B.

PubMed

Zhang, Yuan-Qing; Peng, Li-Jun; Cao, Yi-Rong; Zeng, Zhi-Ping; Wu, Yu-Jing; Shi, Hong; Cheng, Shi-Yao; Wang, Ji-Yao; Friedman, Scott L; Sninsky, John J; Guo, Jin-Sheng

2016-09-01

To investigate the clinical and genetic risk factors associated with hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB). Nine hundred forty-nine Chinese Han patients with CHB were studied, including noncirrhotic patients without HCC (N = 234), cirrhotic patients without (N = 281) and with HCC (N = 434). Patients were genotyped for 10 candidate single nucleotide polymorphisms (SNPs) by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. By multivariate logistic regression analysis adjusted for Child-Pugh scores, noneffective antiviral treatment, drinking history, family history of HCC, and age ≥50 years old were associated with HCC risk (odds ratio [OR] = 5.923, 2.456, 2.241, 1.955, respectively). Sixty-two of 170 cirrhotic patients who achieved sustained virological suppression by antiviral treatment developed HCC, with fatty liver disease, family history of HCC, and family history of hepatitis B virus (HBV) infection as the risk factors (OR = 11.646, 3.339, 2.537, respectively). The SNPs associated with HCC risk in patients with cirrhosis and CHB were rs11536889 in TLR4 and rs2853744 in SPP1. Polymorphisms of TLR4 rs2149356, AP3S2 rs2290351, STXBP5L rs2169302, MLEC rs7976497, and SOCS3 rs4969168 were associated with HCC risk in specific stratified analyses with gender, age, and drinking history in the cirrhotic patients. Inadequate antiviral treatment, family history of HCC, drinking history, and age ≥50 years old are risk factors for HCC. Sustained suppression of HBV does not eliminate the risk of HCC. Specific host genetic factors may impact HCC development in Han Chinese cirrhotic patients with CHB, including SNPs in TLR4, SPP1, AP3S2, STXBP5L, MLEC, and SOCS3, which warrant further validation in additional cohorts.

Efficacy and safety of direct antiviral agents in a cohort of cirrhotic HCV/HIV-coinfected patients.

PubMed

Navarro, Jordi; Laguno, Montserrat; Vilchez, Helem Haydee; Guardiola, Jose M; Carrion, Jose A; Force, Luis; Cairó, Mireia; Cifuentes, Carmen; Vilaró, Josep; Cucurull, Josep; Marco, Andrés; Roget, Mercè; Erice, Eva; Crespo, Manuel

2017-10-01

New direct-acting antiviral agents (DAAs) have shown great efficacy and tolerability in clinical trials and real-life cohorts. However, data are scarce regarding efficacy and safety in cirrhotic HCV/HIV-coinfected patients. A multicentre prospective analysis was performed in 13 Spanish hospitals, including all cirrhotic HCV/HIV-coinfected patients starting DAA combinations from January to December 2015. Sustained virological response 12 weeks after treatment (SVR12) was analysed. Withdrawal due to toxicity and/or hepatic decompensation and change in liver stiffness measurement (LSM) after HCV treatment were evaluated. Patients (n = 170) were mostly male (n = 125; 74.3%) with the following HCV genotype (Gt) distribution: Gt-1a, 68 (40%); Gt-1b, 21 (12.4%); Gt-4, 47 (27.6%); and Gt-3, 26 (15.3%). Baseline median LSM was 20.6 kPa (IQR 16.1-33.7) and log10 HCV-RNA 6.1 IU/mL (IQR 5.7-6.5). Most patients had a Child-Pugh class A score (n = 127; 74.7%) and 28 (16.5%) had prior hepatic decompensation. There were 89 (52.4%) pretreated patients with 40.4% (n = 36) of null responders. Preferred regimens were as follows: sofosbuvir/ledipasvir + ribavirin, 43 (25.3%) patients; sofosbuvir + simeprevir + ribavirin, 34 (20%); sofosbuvir/ledipasvir, 26 (15.3%) and sofosbuvir + daclatasvir + ribavirin, 25 (14.7%). Overall SVR12 was 92.9% (158/170), without differences between genotypes. Pretreated patients had lower SVR12 rates compared with naive (88.8% versus 97.5%; P = 0.026). Treatment failures were as follows: 7 (4.1%) relapses; 2 (1.2%) lost to follow-up; 1 (0.6%) toxicity-related discontinuation; 1 (0.6%) hepatic decompensation; and 1 (0.6%) viral breakthrough. On-treatment hepatic decompensation was recorded in four (2.4%) patients (encephalopathy and ascites, two each). Paired LSM in 33 patients showed a decrease of 5.6 kPa (95% CI 1.8-9.2; P = 0.004). In our cohort of cirrhotic HCV/HIV-coinfected patients, DAAs were highly safe and efficacious. Viral eradication was associated with a significant decrease in liver stiffness. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

APTR is a prognostic marker in cirrhotic patients with portal hypertension during TIPS procedure.

PubMed

Yu, Shanshan; Qi, Yanhua; Jiang, Jue; Wang, Hua; Zhou, Qi

2018-03-01

Portal hypertension is a major cause of mortality and morbidity in cirrhotic patients. In this study, we aimed to analyze the clinical characteristics of Alu-mediated p21 transcriptional regulator (APTR) during transjugular intrahepatic portosystemic shunt (TIPS) procedure. Portal and hepatic venous blood was drawn from 84 patients with liver cirrhosis and portal hypertension before and after TIPS treatment. Then, we detected biochemical, hemodynamic parameters and APTR expression before and after TIPS treatment. Indeed, TIPS treatment could markedly ameliorate the serum blood urea nitrogen (BUN) level and portal vein hemodynamics in cirrhotic patients. We found that portal venous levels of APTR was significantly decreased after TIPS treatment and its aberrant expression levels were positively correlated with Model for End Stage Liver Disease (MELD), portal hepatic venous pressure gradient (PHPG) in patients. Higher APTR expression in portal vein was associated with poor prognosis. APTR level in portal vein was an independent predictors of mortality. Our data indicated that APTR may serve as a novel biomarker for cirrhotic patients with portal hypertension before and after receiving TIPS. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers.

PubMed

Ali, Ahmed; Farid, Samar; Amin, Mona; Kassem, Mohamed; Al-Garem, Nouman; Al-Ghobashy, Medhat

2016-02-01

Midodrine is an α-agonist prodrug of desglymidodrine used for the management of hypotension, and can also be used for hepatorenal syndrome and cirrhotic patients with tense ascites. The objective of the present work was to study the clinical pharmacokinetic parameters of midodrine and its active metabolite desglymidodrine in cirrhotic patients with tense ascites, which may help in dose selection and improve treatment outcome. This was a prospective, open-label, single-dose, parallel-group study. At first, a pilot study was performed on one healthy volunteer by taking serial blood samples at scheduled time intervals to validate the method of analysis and sampling times. The full study was then conducted by selecting 12 cirrhotic patients with tense ascites in one group and taking nine blood samples. We also selected five healthy volunteers as the control group and took 11 blood samples. Statistically significant differences were observed between the healthy volunteer group and the patients group in the area under the concentration versus time curve (AUC0-t) and maximum plasma concentration (Cmax) values of midodrine and desglymidodrine. Based on the results of the pharmacokinetic analysis, the patient group was further subdivided into those receiving the interacting drug ranitidine (five patients) and those not receiving the interacting drug (seven patients). Pharmacokinetic parameters of midodrine can differ significantly in cirrhotic patients with tense ascites from those in healthy individuals. Drug monitoring, dose adjustments, and drug-drug interactions should all be considered during therapy in this vulnerable patient group.

Eight-week ledipasvir/sofosbuvir in non-cirrhotic, treatment-naïve hepatitis C genotype-1 patients with hepatitis C virus-RNA < 6 million: Single center, real world effectiveness and safety.

PubMed

Latt, Nyan L; Yanny, Beshoy T; Gharibian, Derenik; Gevorkyan, Rita; Sahota, Amandeep K

2017-07-14

To evaluate sustained viral response (SVR) of 8-wk ledipasvir/sofosbuvir therapy among non-cirrhotic, genotype-1 hepatitis C virus (HCV) patients with RNA < 6 million IU/mL. We performed a retrospective cohort study to examine SVR rates, predictors of treatment failure and safety analysis of 8-wk ledipasvir/sofosbuvir (LDV/SOF) therapy among non-cirrhotic, genotype 1 HCV patients with viral load < 6 million IU/mL. Primary outcome was an achievement of SVR at 12 wk after treatment. Secondary outcomes were identifying predictors of treatment failure and adverse events during treatment. Total 736 patients: 55% males, 51% Caucasians and 65% were genotype 1a. Non-cirrhotic state of 53% was determined by clinical judgment (imaging, AST, platelet count) and 47% had documented liver fibrosis testing (biopsy, vibration-controlled transient elastography, serum biomarkers). Overall SVR12 was 96%. No difference in SVR12 was seen between patients whose non-cirrhotic state was determined by clinical judgment and patients who had fibrosis testing. Age groups, gender, ethnicity and genotype 1 subtype did not predict SVR. Non-cirrhotic state determined by clinical judgment based on simple, non-invasive tests were not associated with lower SVR [OR = 1.02, 95%CI: 0.48-2.17, P = 0.962]. The AUROC for hepatitis C RNA viral load was 0.734 ( P < 0.001, 95%CI: 0.66-0.82). HCV RNA 2.2 million IU/mL was identified as the cutoff value with sensitivity 73% and specificity 64%. HCV RNA < 2.2 million IU/mL was associated with significantly higher SVR 98% with OR = 0.22 (95%CI: 0.1-0.49, P < 0.001) compared to SVR 92% in HCV RNA ≥ 2.2 million IU/mL. No death or morbidities were reported. Our outcomes validate safety and effectiveness of 8-wk LDV/SOF therapy in non-cirrhotic, untreated HCV genotype 1 patients with HCV RNA < 6 million IU/mL.

Eight-week ledipasvir/sofosbuvir in non-cirrhotic, treatment-naïve hepatitis C genotype-1 patients with hepatitis C virus-RNA < 6 million: Single center, real world effectiveness and safety

PubMed Central

Latt, Nyan L; Yanny, Beshoy T; Gharibian, Derenik; Gevorkyan, Rita; Sahota, Amandeep K

2017-01-01

AIM To evaluate sustained viral response (SVR) of 8-wk ledipasvir/sofosbuvir therapy among non-cirrhotic, genotype-1 hepatitis C virus (HCV) patients with RNA < 6 million IU/mL. METHODS We performed a retrospective cohort study to examine SVR rates, predictors of treatment failure and safety analysis of 8-wk ledipasvir/sofosbuvir (LDV/SOF) therapy among non-cirrhotic, genotype 1 HCV patients with viral load < 6 million IU/mL. Primary outcome was an achievement of SVR at 12 wk after treatment. Secondary outcomes were identifying predictors of treatment failure and adverse events during treatment. RESULTS Total 736 patients: 55% males, 51% Caucasians and 65% were genotype 1a. Non-cirrhotic state of 53% was determined by clinical judgment (imaging, AST, platelet count) and 47% had documented liver fibrosis testing (biopsy, vibration-controlled transient elastography, serum biomarkers). Overall SVR12 was 96%. No difference in SVR12 was seen between patients whose non-cirrhotic state was determined by clinical judgment and patients who had fibrosis testing. Age groups, gender, ethnicity and genotype 1 subtype did not predict SVR. Non-cirrhotic state determined by clinical judgment based on simple, non-invasive tests were not associated with lower SVR [OR = 1.02, 95%CI: 0.48-2.17, P = 0.962]. The AUROC for hepatitis C RNA viral load was 0.734 (P < 0.001, 95%CI: 0.66-0.82). HCV RNA 2.2 million IU/mL was identified as the cutoff value with sensitivity 73% and specificity 64%. HCV RNA < 2.2 million IU/mL was associated with significantly higher SVR 98% with OR = 0.22 (95%CI: 0.1-0.49, P < 0.001) compared to SVR 92% in HCV RNA ≥ 2.2 million IU/mL. No death or morbidities were reported. CONCLUSION Our outcomes validate safety and effectiveness of 8-wk LDV/SOF therapy in non-cirrhotic, untreated HCV genotype 1 patients with HCV RNA < 6 million IU/mL. PMID:28765697

Safety and effectiveness of umbilical hernia repair in patients with cirrhosis.

PubMed

Hew, S; Yu, W; Robson, S; Starkey, G; Testro, A; Fink, M; Angus, P; Gow, P

2018-03-27

Umbilical hernia is a common complication in patients with cirrhosis. Early studies have reported a high morbidity and mortality associated with hernia repair. The traditional approach has been to non-operatively manage umbilical hernias in patients with cirrhosis. There are emerging data suggesting that an elective repair is a preferable approach. This study examined the outcomes of umbilical hernia repair in patients with advanced liver disease and compared this with a control group of non-cirrhotic patients. Prospective data were collected regarding the outcome of umbilical hernia repairs performed between 2004 and 2013 at the Austin Hospital, Melbourne, Australia. Outcomes at 90 days were compared between patients with and without cirrhosis. 79 patients with cirrhosis and 249 controls were analysed. Of the patients with cirrhosis, 9% were classified as Child-Pugh A, 61% were Child-Pugh B and 30% were Child-Pugh C. Emergency repairs for complicated hernias was undertaken in 18% of the cirrhosis population and 10% in controls (P = 0.10). Post-operative complications occurred more commonly in patients with cirrhosis (26%) compared with controls (11%) (P < 0.01). Emergency hernia repairs were associated with a higher complication rate in both patients with cirrhosis (62%) and controls (20%) (P = 0.01). There was no significant difference in the rate of hernia recurrence as assessed by clinical examination between patients with cirrhosis (2.7%) and controls (6.8%) (P = 0.17) nor in 90-day mortality between patients with cirrhosis (n = 1, 1.3%) and the controls (n = 0) (P = 0.43). Within the limitations of a small study cohort and therefore an underpowered study, elective surgical repair of umbilical hernias in patients with cirrhosis, including decompensated cirrhosis, may not be associated with a significant increase in mortality when compared to a control cohort. Whilst complications are higher in cirrhotic patients, there is no difference in the rate of hernia recurrence. Emergency repairs of umbilical hernias are associated with a high complication rate in cirrhotic patients.

Repeated courses of transarterial embolization with polyvinyl alcohol particles: 'long life elixir' in a cirrhotic patient with unresectable hepatocellular carcinoma.

PubMed

Marelli, Laura; Shusang, Vibhakorn; Senzolo, Marco; Cholongitas, Evangelos; Goode, Antony; Yu, Dominic; Patch, David W; Burroughs, Andrew K

2007-04-01

Chemoembolization improves survival in selected cirrhotic patients with hepatocellular carcinoma, but prolonged survival is unusual. In this study, a 70-year-old cirrhotic patient, who had a histologically proven hepatocellular carcinoma of 5 cm diameter, embolization with polyvinyl alcohol particles alone, without chemotherapeutic agent, has resulted in continued survival, of 5 years to date, with virtual elimination of residual hypervascularity following 10 sessions of embolization, and with continued patency of the injected branch of the hepatic artery. Provided liver function is maintained, embolization alone appears a feasible long term and effective therapy for unresectable hepatocellular carcinoma.

Optimization of direct anti-viral agent treatment schedule: Focus on HCV genotype 3.

PubMed

Morisco, Filomena; Granata, Rocco; Camera, Silvia; Ippolito, Antonio; Milella, Michele; Conti, Fabio; Masetti, Chiara; Smedile, Antonella; Tundo, Paolo; Santantonio, Teresa; Valvano, Maria Rosa; Termite, Antonio; Gatti, Pietro; Messina, Vincenzo; Iacobellis, Angelo; Librandi, Marta; Caporaso, Nicola; Andriulli, Angelo

2018-03-01

Direct antiviral agents (DAAs) have led to high sustained virological responses (SVR) in hepatitis C virus (HCV) patients. However, genotype 3 patients respond to treatment in a suboptimal way. This study aims to identify which of the several treatment schedules recommended for genotype 3 would constitute the best option. Twenty-four Italian centers were involved in this real-life study of HCV genotype 3 patients treated with DAAs. To expand the number of cases, we conducted a systematic review of the literature on the outcome of genotype 3 patients treated with DAAs. A total of 233 patients with HCV genotype 3 were enrolled. Cirrhotic patients accounted for 83.7%. Overall, the SVR12 rate was achieved by 205 patients (88.0%); the SVR rates were 78.8% after sofosbuvir/ribavirin, 92.5% after sofosbuvir/daclatasvir ± ribavirin, and 100% after sofosbuvir/ledipasvir (seven patients). No difference in rate of SVR was observed in cirrhotic and non-cirrhotic patients (92.2 vs 94.4) using a combination regimen of NS5A and NS5B inhibitors.The systematic review of the literature provided data of 3311 patients: The mean weighted SVR12 rate was 84.4% (CI: 80.4-87.8); the rates varied from 79.0% (CI: 70.9-85.3) with sofosbuvir/ribavirin, to 83.7% (CI: 66.2-93.1) with sofosbuvir/ledispavir, and to 88.2% (CI: 83.3-91.7) with sofosbuvir/daclatasvir. Our results reinforce the concept that patients with HCV genotype 3 should no longer be considered difficult-to-treat individuals. The optimal therapeutic regimen for these patients appears to be the combination sofosbuvir/daclatasvir, administered for 12 weeks without the use of RBV in non-cirrhotic patients. In cirrhotics the meta-analytic approach suggests extending therapy to 24 weeks.

Endoscopic treatment of bleeding gastric varices with histoacryl (N-butyl-2-cyanoacrylate): a South European single center experience.

PubMed

Monsanto, Pedro; Almeida, Nuno; Rosa, Albano; Maçôas, Fernanda; Lérias, Clotilde; Portela, Francisco; Amaro, Pedro; Ferreira, Manuela; Gouveia, Hermano; Sofia, Carlos

2013-07-01

Endoscopic injection of N-butyl-2-cyanoacrylate is the current recommended treatment for gastric variceal bleeding. Despite the extensive worldwide use, there are still differences related to the technique, safety, and long term-results. We retrospectively evaluated the efficacy and safety of cyanoacrylate in patients with gastric variceal bleeding. Between January 1998 and January 2010, 97 patients with gastric variceal bleeding underwent endoscopic treatment with a mixture of N-butyl-2-cyanoacrylate and Lipiodol(TM). Ninety-one patients had cirrhosis and 6 had non-cirrhotic portal hypertension. Child-Pugh score at presentation for cirrhotic patients was A-12.1 %; B-53.8 %; C-34.1 % and median MELD score at admission was 13 (3-26). Successful hemostasis, rebleeding rate and complications were reviewed. Median time of follow up was 19 months (0.5-126). A median mixture volume of 1.5 mL (0.6 to 5 mL), in 1 to 8 injections, was used, with immediate hemostasis rate of 95.9 % and early rebleeding rate of 14.4 %. One or more complications occurred in 17.5 % and were associated with the use of Sengstaken-Blakemore tube before cyanoacrylate and very early rebleeding (p < 0.05). Hospital mortality rate during initial bleeding episode was 9.3 %. Very early rebleeding was a strong and independent predictor for in-hospital mortality (p < 0.001). Long-term mortality rate was 58.8 %, in most of the cases secondary to hepatic failure. N-butyl-2-cyanoacrylate is a rapid, easy and highly effective modality for immediate hemostasis of gastric variceal bleeding with an acceptable rebleeding rate. Patients with very early rebleeding are at higher risk of death.

Bacterial infections in alcoholic and nonalcoholic liver cirrhosis.

PubMed

Sargenti, Konstantina; Prytz, Hanne; Nilsson, Emma; Bertilsson, Sara; Kalaitzakis, Evangelos

2015-09-01

Longitudinal, population-based data on the occurrence, localization, and severity of bacterial infections over time in patients with alcoholic compared with nonalcoholic cirrhosis are limited. All patients with incident cirrhosis diagnosed in 2001-2010 (area of 600,000 inhabitants) were retrospectively identified. All bacterial infections resulting in or occurring during an inpatient hospital episode during this period were registered. The etiology of cirrhosis (alcoholic vs. nonalcoholic), infection localization, and outcome as well as bacterial resistance patterns were analyzed. Patients were followed until death, transplant, or the end of 2011. In all, 633 cirrhotics (363 alcoholic, 270 nonalcoholic) experienced a total of 398 infections (2276 patient-years). Among patients diagnosed with cirrhosis each year from 2001 to 2010, increasing trends were noted in the occurrence of infection (from 13 to 27%, P<0.001) and infection-related in-hospital mortality (from 2 to 7%, P=0.05), the latter mainly in the alcoholic group. Although alcoholic etiology was related to the occurrence of more frequent infection (Kaplan-Meier, P<0.001), this relationship was not significant after adjustment for confounders in Cox regression analysis (P=0.056). Resistance to piperacilin-tazobactam and carbapenems was more common in infections occurring in alcoholic versus nonalcoholic cirrhosis (13 vs. 5%, P=0.057 and 12 vs. 2%, P=0.009). Alcoholic etiology predicted pneumonia and infections caused by Gram-positive bacteria in multivariate analysis (P<0.05 for both). In a population-based cirrhotic cohort, bacterial infections increased over time, which, in the case of alcoholic cirrhosis, was associated with pneumonia and bacterial resistance to antibiotics. However, alcoholic etiology was not related indepedently to the occurrence of bacterial infections.

Postoperative complications in cirrhotic pediatric deceased donor liver transplantation: Focus on transfusion therapy.

PubMed

Nacoti, M; Cazzaniga, S; Colombo, G; Corbella, D; Fazzi, F; Fochi, O; Gattoni, C; Zambelli, M; Colledan, M; Bonanomi, E

2017-12-01

Intraoperative transfusions seem associated with patient death and graft failure after PLTx. A retrospective analysis of recipients' and donors' characteristics and transplantation data in a cohort of patients undergoing PLTx from 2002 to 2013 at the Bergamo General Hospital was performed. A two-stage hierarchical Cox proportional hazard regression with forward stepwise selection was used to identify the main risk factors for major complications. In addition, propensity score analysis was used to adjust risk estimates for possible selection biases in the use of blood products. Over the 12-year period, 232 pediatric cirrhotic patients underwent PLTx. One-year patient and graft survival rates were 92.3% and 83.7%, respectively. The Kaplan-Meier shows that the main decrease in both graft and patient survival occurs during the first months post-transplantation. At the same time, it appears that most of the complications occur during the first month post-transplantation. One-month and 1-year patient complication-free survival rates were 24.8% and 12.1%, respectively. Our study shows that intraoperative red blood cells and platelet transfusions are independent risk factors for developing one or more major complications in the first year after PLTx. Decreasing major complications will improve the health status and overall long-term patient survival after pediatric PLTx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neuropsychological and neurophysiological evaluation in cirrhotic patients with minimal hepatic encephalopathy undergoing liver transplantation.

PubMed

Senzolo, M; Amodio, P; D'Aloiso, M C; Fagiuoli, S; Del Piccolo, F; Canova, D; Masier, A; Bassanello, M; Zanus, G; Burra, P

2005-03-01

Cirrhotic patients without overt hepatic encephalopathy may have cerebral function alterations called minimal hepatic encephalopathy (MHE). Our goal was to evaluate the role of partial pressure of ammonia (pNH3), neuropsychological, and neurophysiological assessment in detecting cognitive changes in cirrhotic patients awaiting liver transplantation. Fourteen cirrhotic patients listed for liver transplant were studied. All patients underwent the neuropsychological battery called PSE. Neurophysiological assessment including spectral EEG (sEEG), evoked potential P300 and pNH3 and venous and arterial ammonia levels was performed in all patients. Four patients were transplanted. Liver disease etiology was alcoholic in four patients, viral in six mixed in two, and cryptogenic in two. PSE scores revealed MHE in 8 patients; sEEG was altered in 6, and P300 in 1. No correlations were detected between P300, sEEG, and PSE. pNH3 and arterial ammonia levels were significantly higher in the subgroup of patients with altered sEEG and were correlated with theta band increase in sEEG but not with pathological PSE scores or P300 wave abnormalities. The combination of sEEG and PSE, and possibly also pNH3 and arterial ammonia, is useful in detecting cerebral function alterations in cirrhotic patients with no apparent encephalopathy, whereas P300 is not. The diagnosis of MHE obtained using the multimodal approach adopted in this study may enable the adequate treatment of these patients prior to surgery, which includes advising them not to drive and adjusting their priority on the waiting list for OLTx in the light of a condition that cannot be evaluated by Child Pugh score and MELD score.

Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids

PubMed Central

Nakamura, Ikuo

2014-01-01

It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids (BCAA) on innate immune responses. We already reported that phagocytic function of neutrophils was significantly improved by 3-mo BCAA supplementation. In addition, the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation. Also, Fisher’s ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation. Therefore, administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host. In addition, it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients. The mechanisms of the effects will also be discussed in this review article. PMID:24966600

Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition

PubMed Central

Kim, Hee Yeon; Sinn, Dong Hyun; Yoon, Eileen L.; Kim, Chang Wook; Jung, Young Kul; Suk, Ki Tae; Lee, Sang Soo; Lee, Chang Hyeong; Kim, Tae Hun; Kim, Jeong Han; Choe, Won Hyeok; Yim, Hyung Joon; Kim, Sung Eun; Baik, Soon Koo; Lee, Byung Seok; Jang, Jae Young; Suh, Jeong Ill; Kim, Hyoung Su; Nam, Seong Woo; Kwon, Hyeok Choon; Kim, Young Seok; Kim, Sang Gyune; Chae, Hee Bok; Yang, Jin Mo; Sohn, Joo Hyun; Lee, Heon Ju; Park, Seung Ha; Han, Byung Hoon; Choi, Eun Hee; Kim, Chang H.; Kim, Dong Joon

2016-01-01

Background & Aim To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions. Methods We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea. Results Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001). Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192). Patients with previous acute decompensation (AD) within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001). Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391). Conclusions The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF. PMID:26789409

Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: a randomized controlled trial.

PubMed

Stanca, Carmen M; Montazem, Andre H; Lawal, Adeyemi; Zhang, Jin X; Schiano, Thomas D

2010-01-01

Cirrhotic patients waiting for liver transplantation who need dental extractions are given fresh frozen plasma and/or platelets to correct coagulopathy. This is costly and may be associated with transfusion reactions and fluid overload. We evaluated the efficacy of intranasal desmopressin as an alternative to transfusion to correct the coagulopathy of cirrhotic patients undergoing dental extraction. Cirrhotic patients with platelet counts of 30,000 to 50,000/microL and/or international normalized ratio (INR) 2.0 to 3.0 were enrolled in a prospective, controlled, randomized clinical trial. Blood transfusion (fresh frozen plasma 10 mL/kg and/or 1 unit of single donor platelets, respectively) or intranasal desmopressin (300 microg) were given before dental extraction. A standard oral and maxillofacial surgical treatment protocol was performed by the same surgeon. Patients were followed for postextraction bleeding and side-effects over the next 24 to 48 hours. No significant differences were noted between the 2 groups in gender, age, INR, platelet count, creatinine, total bilirubin, ALT, albumin, MELD score, or number of teeth removed (median 3 vs 4). The number of teeth removed ranged between 1 and 31 in the desmopressin group and 1 and 22 in the transfusion group. No patients in desmopressin group required rescue blood transfusion after extraction. One patient in the transfusion group had bleeding after the procedure and required an additional transfusion. Another patient experienced an allergic reaction at the end of transfusion, which was effectively treated with diphenhydramine. Treatment associated average costs were lower for desmopressin ($700/patient) compared with transfusion ($1,173/patient). Intranasal desmopressin was as effective as blood transfusion in achieving hemostasis in cirrhotic patients with moderate coagulopathy undergoing dental extraction. Intranasal desmopressin was much more convenient, less expensive, and well tolerated.

Phosphatidylserine on blood cells and endothelial cells contributes to the hypercoagulable state in cirrhosis.

PubMed

Wu, Xiaoming; Yao, Zhipeng; Zhao, Lu; Zhang, Yan; Cao, Muhua; Li, Tao; Ding, Wenbo; Liu, Yan; Deng, Ruijuan; Dong, Zengxiang; Chen, He; Novakovic, Valerie A; Bi, Yayan; Kou, Junjie; Tian, Ye; Zhou, Jin; Shi, Jialan

2016-12-01

The mechanism of thrombogenicity in cirrhosis is largely unknown. Our objective was to study the relationship between phosphatidylserine on blood cells and endothelial cells and the hypercoagulable state in cirrhotic patients. Patients with cirrhosis and healthy controls were studied. Lactadherin was used to quantify phosphatidylserine exposure on blood cells and endothelial cells. Procoagulant activity of cells was evaluated using clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. Phosphatidylserine exposure, fibrin strands and FVa/Xa binding on cells were observed using confocal microscopy. Our study showed that phosphatidylserine exposure on erythrocytes, platelets and leucocytes in cirrhotic patients increased progressively with Child-Pugh categories. In addition, we found that endothelial cells treated with cirrhotic serum in vitro exposed more phosphatidylserine than those exposed to healthy serum. The exposed phosphatidylserine supported a shorter coagulation time and increased FXa, thrombin and fibrin formation. Notably, phosphatidylserine + erythrocytes also promoted shorter coagulation times and more fibrin generation in cirrhotic microparticle-depleted plasma, regardless of Child-Pugh categories. Confocal microscopy data showed that the FVa/FXa complex and fibrin fibrils colocalized with phosphatidylserine on endothelial cells. Lactadherin significantly inhibited FXa and thrombin generation and consequently decreased fibrin production in normal or cirrhotic plasma. These results lead us to believe that exposed phosphatidylserine on activated or injured erythrocytes, platelets, leucocytes and endothelial cells plays an important role in the hypercoagulable state in cirrhotic patients. Thus, blocking phosphatidylserine binding sites might be a new therapeutic target for preventing thrombosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Can the tyrosine kinase inhibitors trigger metabolic encephalopathy in cirrhotic patients?

PubMed

Brandi, Giovanni; de Rosa, Francesco; Calzà, Laura; Girolamo, Stefania Di; Tufoni, Manuel; Ricci, Carmen Serena; Cirignotta, Fabio; Caraceni, Paolo; Biasco, Guido

2013-03-01

Sorafenib is the standard treatment of advanced hepatocarcinoma (HCC) in cirrhotic patients with preserved liver function. It shares many adverse effects with other tyrosine-kinase (TK) inhibitors and antiangiogenic drugs. TK inhibitors could have a direct toxicity on CNS, both by interfering with TK-related pathways and by inhibiting angiogenesis. The aim of this study was to investigate whether sorafenib administration can be associated to metabolic encephalopathy in patients with cirrhosis. We retrospectively reviewed medical records of all cirrhotic patients treated with sorafenib for HCC afferent at our Department from January 2009 to December 2011. Among 62 patients, we identified 10 patients with clinically significant cognitive impairment. Seven of these were clearly diagnosed with overt hepatic encephalopathy (HE), one with brain metastases and two with drug-related toxic-metabolic encephalopathy. These last two cases were characterized by severe cognitive impairment, mood alteration and memory deficit. Clinical exam, blood tests and brain CT excluded organic causes of encephalopathy and precipitating factors of HE. Sorafenib discontinuation was associated with complete reversal of the syndrome, which recurred on drug re-administration in one case. Our study suggests that sorafenib may be a precipitating factor of metabolic encephalopathy in cirrhotic patients with advanced HCC. This neurological syndrome appears to be not responsive to the conventional treatment for HE, but it is fully reversible by drug discontinuation. It can be speculated that the potential direct neuronal action of sorafenib may represent a trigger for the onset of metabolic encephalopathy in a subset of cirrhotic patients. © 2012 John Wiley & Sons A/S.

Large splenic volume may be a useful predictor for partial splenic embolization-induced liver functional improvement in cirrhotic patients.

PubMed

Hayashi, Hiromitsu; Beppu, Toru; Masuda, Toshiro; Okabe, Hirohisa; Imai, Katsunori; Hashimoto, Daisuke; Ikuta, Yoshiaki; Chikamoto, Akira; Watanabe, Masayuki; Baba, Hideo

2014-01-01

Partial splenic embolization (PSE) for cirrhotic patients has been reported not only to achieve an improvement in thrombocytopenia and portal hypertension, but also to induce PSE-associated fringe benefit such as individual liver functional improvement. The purpose of this study was to clarify the predictive marker of liver functional improvement due from PSE in cirrhotic patients. From April 1999 to January 2009, 83 cirrhotic patients with hypersplenism-induced thrombocytopenia (platelet count <10 × 10(4)/μl) underwent PSE. Of them, 71 patients with follow-up for more than one year after PSE were retrospectively investigated. In liver tissues after PSE, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were remarkably increased, speculating that PSE induced liver regenerative response. Indeed, serum albumin and cholinesterase levels increased to 104 ± 14% and 130 ± 65% each of the pretreatment level at one year after PSE. In a multiple linear regression analysis, preoperative splenic volume was extracted as the predictive factor for the improvement in cholinesterase level after PSE. Cirrhotic patients with preoperative splenic volume >600 ml obtained significantly higher serum albumin and cholinesterase levels at one year after PSE compared to those with less than 600 ml (P-values were 0.029 in both). A large preoperative splenic volume was the useful predictive marker for an effective PSE-induced liver functional improvement. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

The International Normalized Ratio does not Reflect Bleeding Risk in Esophageal Variceal Hemorrhage

PubMed Central

Hshieh, Tammy T.; Kaung, Aung; Hussain, Syed; Curry, Michael P.; Sundaram, Vinay

2015-01-01

Background/Aims: The international normalized ratio (INR) has not been validated as a predictor of bleeding risk in cirrhotics. The aim of this study was to determine whether elevation in the INR correlated with risk of esophageal variceal hemorrhage and whether correction of the INR prior to endoscopic therapy affects failure to control bleeding. Patients and Methods: Patient records were retrospectively reviewed from January 1, 2000 to December 31, 2010. Cases were cirrhotics admitted to the hospital due to bleeding esophageal varices. Controls were cirrhotics with a history of non-bleeding esophageal varices admitted with ascites or encephalopathy. All variceal bleeders were treated with octreotide, antibiotics, and band ligation. Failure to control bleeding was defined according to the Baveno V criteria. Results: We analyzed 74 cases and 74 controls. The mean INR at presentation was lower in those with bleeding varices compared to non-bleeders (1.61 vs 1.74, P = 0.03). Those with bleeding varices had higher serum sodium (136.1 vs 133.8, P = 0.02), lower hemoglobin (9.59 vs 11.0, P < 0.001), and lower total bilirubin (2.47 vs 5.50, P < 0.001). Multivariable logistic regression showed total bilirubin to inversely correlate with bleeding (OR = 0.74). Bleeders received a mean of 1.14 units of fresh frozen plasma (FFP) prior to endoscopy (range 0-11 units). Of the 14 patients (20%) with failure to control bleeding, median INR (1.8 vs 1.5, P = 0.02) and median units of FFP transfused (2 vs 0, P = 0.01) were higher than those with hemostasis after the initial endoscopy. Conclusions: The INR reflects liver dysfunction, not bleeding risk. Correction of INR with FFP has little effect on hemostasis. PMID:26228370

Occult HCV Infection (OCI) Diagnosis in Cirrhotic and Non-cirrhotic Naïve Patients by Intra-PBMC Nested Viral RNA PCR.

PubMed

Abd Alla, Mohamed Darwish Ahmed; Elibiary, Saleh Ahmed; Wu, George Y; El-Awady, Mostafa Kamel

2017-12-28

Background and Aims: Occult HCV infections (OCIs) include IgG antibody seronegative cryptogenic (COCIs), as well as seropositive secondary naïve (SNOCIs) and experienced (SEOCIs) cases. We used peripheral-blood-mononuclear-cell (PBMC)-PCR to evaluate COCIs and SNOCIs prevalence, serum HCV spontaneous disappearance (SCSD) in naïve cirrhotics and non-cirrhotics, intra-PBMC HCV-RNA strands in relation to cirrhosis density in naïve non-viremia cases, and HCV-RNA seroconversion after 1 year of solitary naïve intra-PBMC infection. Methods: The anti-HCV IgG antibody-positive naïve-patients ( n = 785) were classified into viremic ( n = 673) and non-viremic [ n = 112, including non-cirrhotics ( n = 55) and cirrhotics ( n = 57)], and 62 controls without evidence of HCV-infection. Controls and post-HCV non-viremia cases ( n = 62+112 = 174) were submitted to hepatic Fibroscan-Elastography evaluation. All subjects ( n = 847) were screened for intra-PBMC HCV-RNA sense and antisense strands by nested-PCR. Results: Naïve-OCI cases (4.84%) that were diagnosed by PBMC-PCR significantly raised the total numbers of HCV-infection to 714 ( p = 0.01). The percent positivity of SNOCIs (34.82%) was significantly higher than for asymptomatic-COCIs (3.125%, p = 0.0001). Comparing PBMC-PCR with single-step-reverse-transcription (SRT)-PCR for identification of SCSD in naïve IgG antibody-positive non-viremia patients ( n = 112) revealed a decline in SCSD prevalence by PBMC-PCR (from 14.27% to 9.3%), regardless of presence of hepatic cirrhosis ( p = 0.03). SCSD was found to be higher by PBMC-PCR in non-cirrhotics compared to cirrhotics ( p = 0.0001), with an insignificant difference when using SRT-PCR ( p = 0.45). Intra-PBMC HCV-RNA infection was significantly more frequent in cirrhotics compared to both non-cirrhotics and controls ( p < 0.0005). An increased hepatic fibrosis density was recognized in intra-PBMC HCV-RNA infection with sense ( p = 0.0001) or antisense strand ( p = 0.003). HCV-RNA seroconversion was associated with intra-PBMC infection when both sense and antisense strands were detected ( p = 0.047). Conclusions: Intracellular HCV-RNA evaluation is crucial for diagnosing OCIs and addressing relapse probability.

Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients

PubMed Central

Sood, Siddharth; Yu, Lijia; Visvanathan, Kumar; Angus, Peter William; Gow, Paul John; Testro, Adam Gareth

2016-01-01

AIM To investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODS Adult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1st February 2014. RESULTS Cirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient’s immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM < 214 IU/mL was associated with HR = 4.1 (P = 0.01) for infection. A very low QFM < 30 IU/mL was significantly associated (P = 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6). CONCLUSION QFM is lower in cirrhotics, allowing objective determinations of an individual’s unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection. PMID:28050238

[Extracellular fluid, plasma and interstitial volume in cirrhotic patients without clinical edema or ascites].

PubMed

Noguera Viñas, E C; Hames, W; Mothe, G; Barrionuevo, M P

1989-01-01

Extracellular fluid volume (E.C.F.) and plasma volume (P.V.), were measured with sodium sulfate labeled with 35I and 131I human serum albumin, respectively, by the dilution technique in control subjects and in cirrhotic patients without clinical ascites or edema, renal or hepatic failure, gastrointestinal bleeding or diuretics. Results are expressed as mean +/- DS in both ml/m2 and ml/kg. In normal subjects E.C.F. (n = 8) was 7,533 +/- 817 ml/m2 (201.3 +/- 182 ml/kg), P.V. (n = 11) 1,767 +/- 337 ml/m2 (47.2 +/- 9.3 ml/kg), and interstitial fluid (I.S.F.) (n = 7) 5,758 +/- 851 ml/m2 (Table 2). In cirrhotic patients E.C.F. (n = 11) was 10,318 +/- 2,980 ml/m2 (261.7 +/- 76.8 ml/kg), P.V. (n = 12) 2,649 +/- 558 ml/m2 (67.7 +/- 15.6 ml/kg) and I.S.F. (n = 11) 7,866 +/- 2,987 ml/m2 (Table 3). Cirrhotic patients compared with normal subjects have hypervolemia due to a significant E.C.F. and P.V. expansion (p less than 0.02 and less than 0.001 respectively) (Fig. 1). Reasons for E.C.F. and P.V. abnormalities in cirrhotic patients may reflect urinary sodium retention related to portal hipertension which stimulates aldosterone release or enhanced renal tubular sensitivity to the hormone. However, it is also possible that these patients, in the presence of hypoalbuminemia (Table 1), have no clinical edema or ascites due to increased glomerular filtration, suppressed release of vasopressin, increased natriuretic factor, and urinary prostaglandin excretion, in response to the intravascular expansion, all of which increased solute and water delivery to the distal nephron and improved renal water excretion. We conclude that in our clinical experience cirrhotic patients without ascites or edema have hypervolemia because of a disturbance in E.C.F.

Antibiotic stewardship and empirical antibiotic treatment: How can they get along?

PubMed

Zuccaro, Valentina; Columpsi, Paola; Sacchi, Paolo; Lucà, Maria Grazia; Fagiuoli, Stefano; Bruno, Raffaele

2017-06-01

The aim of this review is to focus on the recent knowledge on antibiotic stewardship and empiric antibiotic treatment in cirrhotic patients. The application of antimicrobial stewardship (AMS) rules appears to be the most appropriate strategy to globally manage cirrhotic patients with infectious complications: indeed they represent a unique way to provide both early diagnosis and appropriate therapy in order to avoid not only antibiotic over-prescription but, more importantly, selection and spread of antimicrobial resistance. Moreover, cirrhotic patients must be considered "frail" and susceptible to healthcare associated infections: applying AMS policies would assure a cost reduction and thus contribute to the improvement of public health strategies. Copyright © 2017. Published by Elsevier Ltd.

Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease.

PubMed

Li, Jin-Ping; Zhao, De-Li; Jiang, Hui-Jie; Huang, Ya-Hua; Li, Da-Qing; Wan, Yong; Liu, Xin-Ding; Wang, Jin-E

2011-02-01

Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor rim was significantly higher than that in the controls. HBF, HBV, HAI, HAP and HPP, but not MTT and PS, were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.

Unexpected disappearance of portal cavernoma on long-term anticoagulation.

PubMed

Silva-Junior, Gilberto; Turon, Fanny; Hernandez-Gea, Virginia; Darnell, Anna; García-Criado, Ángeles; García-Pagán, Juan Carlos

2014-08-01

Idiopathic non-cirrhotic portal hypertension is a rare disease of unknown etiology. Patients with idiopathic non-cirrhotic portal hypertension have an increased risk of developing portal vein thrombosis and this is especially prevalent when HIV is also present. We describe a unique case of a patient with idiopathic non-cirrhotic portal hypertension associated to HIV, who developed acute portal vein thrombosis that despite anticoagulation transformed in portal cavernoma and disappeared completely after five years of follow-up on continuous anticoagulation. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Transient Elastography (Fibroscan) in Patients with Non-cirrhotic Portal Fibrosis.

PubMed

Sharma, Praveen; Agarwal, Rachit; Dhawan, Shashi; Bansal, Naresh; Singla, Vikas; Kumar, Ashish; Arora, Anil

2017-09-01

Non-cirrhotic portal hypertension (NCPH) is a common cause of variceal bleed in developing countries. Transient elastography (TE) using Fibroscan is a useful technique for evaluation of fibrosis in patients with liver disease. There is a paucity of studies evaluating TE in patients with Non-cirrhotic portal fibrosis (NCPF) and none in Asian population. Aim of this study was to evaluate role of TE in NCPF. Retrospective data of consecutive patients of NCPF as per Asian pacific association for the study of liver (APASL) guidelines were noted. All patients had liver biopsy, TE, computed tomography of abdomen and hepatic venous pressure gradient (HVPG). Twenty age and gender matched healthy subjects and forty age matched patients with cirrhosis with Child's A were taken as controls. A total of 20 patients with age [median 29.5 (13-50) years], Male:Female = 11:9 with a diagnosis of NCPF were enrolled from January 2011 to December 2015. Of 20 patients 18 patients had variceal bleed and required endoscopic band ligation. There was no difference in haemoglobin and platelet count between patients with cirrhosis and NCPF, but total leucocyte count was significantly lower in patients with NCPF compared to patients with cirrhosis (3.2 vs 6.7 × 10 3 /cumm, P  = 0.01). TE (Fibroscan) was high in patients with NCPF compared to healthy controls (6.8 vs 4.7 kPa, P  = 0.001) but it was significantly low compared to cirrhotic patients (6.8 vs 52.3 kPa, P  = 0.001). HVPG is significant low in patients with NCPF compared to patients with cirrhosis (5.0 vs 16.0 mmHg, P  = 0.001). Transient elastography (Fibroscan) is significantly low in patients with NCPF compared to patients with cirrhosis. It is a very useful non-invasive technique to differentiate between Child's A cirrhosis and non-cirrhotic portal fibrosis.

Assessment of health utilities and quality of life in patients with non-alcoholic fatty liver disease

PubMed Central

Sayiner, Mehmet; Stepanova, Maria; Pham, Huong; Noor, Bashir; Walters, Mercedes; Younossi, Zobair M

2016-01-01

Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease associated with increased liver-related mortality. Additionally, NAFLD could potentially impair health-related quality of life. Although an approved treatment for NAFLD does not exist, a number of new drugs for treatment of NAFLD are being developed. As the efficacy and safety of these regimens are being established, their cost-effectiveness, which requires the use of quality of life metrics and health utility scores to quality-adjusted outcomes, must also be assessed. The aim of this study was to report quality of life and health utilities in patients with NAFLD with and without cirrhosis for future use. Methods Patients with NAFLD were seen in an outpatient clinic setting. Each patient had extensive clinical data and completed the Short Form-36 (SF-36 V.1) questionnaire. The SF-6D health utility scores were calculated. Results There were 89 patients with the spectrum of NAFLD completed the SF-36 questionnaire: 59 with non-cirrhotic NAFLD and 30 with cirrhosis. Patients with NAFLD had significantly lower quality of life and health utility scores than the general population (all p<0.0001). Furthermore, patients with cirrhosis had lower quality of life and utility scores than non-cirrhotic NAFLD patients: SF-6D 0.660±0.107 in non-cirrhotic NAFLD vs 0.551±0.138 in cirrhotic NAFLD (p=0.0003). Conclusions Health utilities and quality of life scores are impaired in patients with cirrhotic NAFLD. These values should be used in cost-effectiveness analysis of the upcoming treatment regimens for advanced NAFLD. PMID:27648297

Short-Term Outcome of Patients with Cirrhosis and Concurrent Portal Cavernoma Presenting with Acute Variceal Bleeding.

PubMed

Luo, Xuefeng; Wang, Wanqin; Fan, Xiaoli; Zhao, Ying; Wang, Xiaoze; Yang, Jinlin; Yang, Li

2018-01-01

The outcome of cirrhotic patients with main portal vein occlusion and portal cavernoma after the first episode of acute variceal bleeding (AVB) is unknown. We compared short-term outcomes after AVB in cirrhotic patients with and without portal cavernoma. Between January 2009 and September 2014, 28 patients with cirrhosis and portal cavernoma presenting with the first occurrence of AVB and 56 age-, sex-, and Child-Pugh score-matched cirrhotic patients without portal cavernoma were included. The primary endpoints were 5-day treatment failure and 6-week mortality. The 5-day treatment failure rate was higher in the cavernoma group than in the control group (32.1% versus 12.5%; p = 0.031). The 6-week mortality rate did not differ between the cavernoma and control group (25% versus 12.5%, p = 0.137). Multivariable Cox proportional hazard regression analyses revealed that 5-day treatment failure (HR = 1.223, 95% CI = 1.082 to 1.384; p = 0.001) independently predicted 6-week mortality. Cirrhotic patients with AVB and portal cavernoma have worse short-term prognosis than patients without portal cavernoma. The 5-day treatment failure was an independent risk factor for 6-week mortality in patients with cirrhosis and portal cavernoma.

Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients.

PubMed

Qi, Xingshun; Han, Guohong; Ye, Chun; Zhang, Yongguo; Dai, Junna; Peng, Ying; Deng, Han; Li, Jing; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Zhang, Xintong; Wang, Ran; Guo, Xiaozhong

2016-07-19

BACKGROUND Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. MATERIAL AND METHODS All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152-61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247-276.949; clinically significant PVST: OR=40.415, 95%CI=3.895-419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953-0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895-0.980; clinically significant PVST: OR=0.935, 95%CI=0.891-0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909-0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. CONCLUSIONS Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction.

Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients

PubMed Central

Qi, Xingshun; Han, Guohong; Ye, Chun; Zhang, Yongguo; Dai, Junna; Peng, Ying; Deng, Han; Li, Jing; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Zhang, Xintong; Wang, Ran; Guo, Xiaozhong

2016-01-01

Background Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. Material/Methods All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Results Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152–61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247–276.949; clinically significant PVST: OR=40.415, 95%CI=3.895–419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953–0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895–0.980; clinically significant PVST: OR=0.935, 95%CI=0.891–0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909–0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. Conclusions Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction. PMID:27432511

Partial spleen embolization reduces the risk of portal hypertension-induced upper gastrointestinal bleeding in patients not eligible for TIPS implantation.

PubMed

Buechter, Matthias; Kahraman, Alisan; Manka, Paul; Gerken, Guido; Dechêne, Alexander; Canbay, Ali; Wetter, Axel; Umutlu, Lale; Theysohn, Jens M

2017-01-01

Upper gastrointestinal bleeding (UGIB) is a severe and life-threatening complication among patients with portal hypertension (PH). Covered transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for patients with refractory or recurrent UGIB despite pharmacological and endoscopic therapy. In some patients, TIPS implantation is not possible due to co-morbidity or vascular disorders. Spleen embolization (SE) may be a promising alternative in this setting. We retrospectively analyzed 9 patients with PH-induced UGIB who underwent partial SE between 2012 and 2016. All patients met the following criteria: (i) upper gastrointestinal hemorrhage with primary or secondary failure of endoscopic interventions and (ii) TIPS implantation not possible. Each patient was followed for at least 6 months after embolization. Five patients (56%) suffered from cirrhotic PH, 4 patients (44%) from non-cirrhotic PH. UGIB occured in terms of refractory hemorrhage from gastric varices (3/9; 33%), hemorrhage from esophageal varices (3/9; 33%), and finally, hemorrhage from portal-hypertensive gastropathy (3/9; 33%). None of the patients treated with partial SE experienced re-bleeding episodes or required blood transfusions during a total follow-up time of 159 months, including both patients with cirrhotic- and non-cirrhotic PH. Partial SE, as a minimally invasive intervention with low procedure-associated complications, may be a valuable alternative for patients with recurrent PH-induced UGIB refractory to standard therapy.

Review article: scoring systems for assessing prognosis in critically ill adult cirrhotics.

PubMed

Cholongitas, E; Senzolo, M; Patch, D; Shaw, S; Hui, C; Burroughs, A K

2006-08-01

Cirrhotic patients admitted to intensive care units (ICU) still have poor outcomes. Some current ICU prognostic models [Acute Physiology and Chronic Health Evaluation (APACHE), Organ System Failure (OSF) and Sequential Organ Failure Assessment (SOFA)] were used to stratify cirrhotics into risk categories, but few cirrhotics were included in the original model development. Liver-specific scores [Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD)] could be useful in this setting. To evaluate whether ICU prognostic models perform better compared with liver-disease specific ones in cirrhotics admitted to ICU. We performed a structured literature review identifying clinical studies focusing on prognosis and risk factors for mortality in adult cirrhotics admitted to ICU. We found 21 studies (five solely dealing with gastrointestinal bleeding) published during the last 20 years (54-420 patients in each). APACHE II and III, SOFA and OSF had better discrimination for correctly predicting death compared with the CTP score. The MELD score was evaluated only in one study and had good predictive accuracy [receiver operator characteristic (ROC) curve: 0.81). Organ dysfunction models (OSF, SOFA) were superior compared with APACHE II and III (ROC curve: range 0.83-0.94 vs. 0.66-0.88 respectively). Cardiovascular, liver and renal system dysfunction were more frequently independently associated with mortality. General-ICU models had better performance in cirrhotic populations compared with CTP score; OSF and SOFA had the best predictive ability. Further prospective and validation studies are needed.

Laparoscopic umbilical hernia repair in a cirrhotic patient with a peritoneovenous shunt.

PubMed

Umemura, Akira; Suto, Takayuki; Sasaki, Akira; Fujita, Tomohiro; Endo, Fumitaka; Wakabayashi, Go

2015-05-01

A 62-year-old Japanese woman who had developed massive cirrhotic ascites was referred to our hospital for a peritoneovenous shunt implant. However, CT examination revealed an umbilical hernia that had not been observed before the peritoneovenous shunt was implanted. We decided to perform laparoscopic umbilical hernia repair to keep carbon dioxide from flowing backward into the central circulatory system. We first clamped the catheter and set the upper limit of the pneumoperitoneum pressure to 6 mmHg. The central venous pressure was also measured simultaneously. Mesh was then applied over the hernia and fixed by the double-crown technique. Finally, 1000-mL physiological saline was infused into the abdominal cavity while the pneumoperitoneum was slowly released. In this case, we safely performed laparoscopic umbilical hernia repair while making some alterations, specifically catheter clamping, reducing pneumoperitoneum pressure, monitoring central venous pressure, and infusing physiological saline. © 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

Spider angiomas in patients with liver cirrhosis: Role of vascular endothelial growth factor and basic fibroblast growth factor

PubMed Central

Li, Chung-Pin; Lee, Fa-Yauh; Hwang, Shinn-Jang; Lu, Rei-Hwa; Lee, Wei-Ping; Chao, Yee; Wang, Sung-Sang; Chang, Full-Young; Whang-Peng, Jacqueline; Lee, Shou-Dong

2003-01-01

AIM: To investigate whether vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) are associated with spider angiomas in patients with liver cirrhosis. METHODS: Eighty-six patients with liver cirrhosis were enrolled and the number and size of the spider angiomas were recorded. Fifty-three healthy subjects were selected as controls. Plasma levels of VEGF and bFGF were measured in both the cirrhotics and the controls. RESULTS: Plasma VEGF and bFGF were increased in cirrhotics compared with controls (122 ± 13 vs. 71 ± 11 pg/mL, P = 0.003 for VEGF; 5.1 ± 0.5 vs. 3.4 ± 0.5 pg/mL, P = 0.022 for bFGF). In cirrhotics, plasma VEGF and bFGF were also higher in patients with spider angiomas compared with patients without spider angiomas (185 ± 28 vs. 90 ± 10 pg/mL, P = 0.003 for VEGF; 6.8 ± 1.0 vs. 4.1 ± 0.5 pg/mL, P = 0.017 for bFGF). Multivariate logistic regression showed that young age and increased plasma levels of VEGF and bFGF were the most significant predictors for the presence of spider angiomas in cirrhotic patients (odds ratio [OR] = 6.64, 95% confidence interval [CI] = 2.02-21.79, P = 0.002; OR = 4.35, 95%CI = 1.35-14.01, P = 0.014; OR = 5.66, 95%CI = 1.72-18.63, P = 0.004, respectively). CONCLUSION: Plasma VEGF and bFGF are elevated in patients with liver cirrhosis. Age as well as plasma levels of VEGF and bFGF are significant predictors for spider angiomas in cirrhotic patients. PMID:14669345

Abnormalities of Lipoprotein Levels in Liver Cirrhosis: Clinical Relevance.

PubMed

Privitera, Graziella; Spadaro, Luisa; Marchisello, Simona; Fede, Giuseppe; Purrello, Francesco

2018-01-01

Progressive lipoprotein impairment occurs in liver cirrhosis and is associated with increased morbidity and mortality. The present review aims to summarize the current evidence regarding the prognostic value of lipoprotein abnormalities in liver cirrhosis and to address the need of a better prognostic stratification of patients, including lipoprotein profile assessment. Low levels of lipoproteins are usual in cirrhosis. Much evidence supports the prognostic role of hypolipidemia in cirrhotic patients. In particular, hypocholesterolemia represents an independent predictor of survival in cirrhosis. In cirrhotic patients, lipoprotein impairment is associated with several complications: infections, malnutrition, adrenal function, and spur cell anemia. Alterations of liver function are associated with modifications of circulating lipids. Decreased levels of lipoproteins significantly impact the survival of cirrhotic patients and play an important role in the pathogenesis of some cirrhosis-related complications.

Clearance of hepatitis C viral RNA in cirrhotic patients with antiviral therapy.

PubMed

Ono, S K; da Silva, L C; Carrilho, F J; da Fonseca, L E; Mendes, L C; Madruga, C L; Farias, A de Q; Laudanna, A A

1996-01-01

Interferon is indicated in chronic infection by hepatitis C virus (HCV), however, cirrhosis has been reported as a bad response factor to the therapy. Fifteen cirrhotic patients with HCV, undergoing treatment with recombinant interferon-alpha, ribavirin and/or ursodeoxycholic acid were studied. They were followed-up and evaluated with dosages of alanine aminotransferase and HCV RNA investigation by PCR technique. Of the 15 cirrhotic patients, seven were negative for HCV RNA after antiviral treatment, however ALT was normal in only three of them. Of the eight patients who were not negative, two had normal ALT. Biochemical-virological discrepancy in the follow-up of the patients after antiviral treatment observed in this study has also been reported by other authors. These reports show that the criteria for response to the treatment is to be established.

Total and acylated ghrelin in liver cirrhosis: correlation with clinical and nutritional status.

PubMed

El-Shehaby, Amal M; Obaia, Eman M; Alwakil, Sahar S; Hiekal, Ahmed A

2010-07-01

The pathogenesis of anorexia in cirrhotic patients is complex and the appetite-modulating hormone ghrelin could be involved. Acylated ghrelin is the biologically active form that modifies insulin sensitivity and body composition. The aim of the present study was to compare acylated and total ghrelin concentration in patients with liver cirrhosis and to investigate the possible relationship between ghrelin and clinical and nutritional parameters. Sixty patients with viral liver cirrhosis who did not have hepatocellular carcinoma or acute infections were studied. Twenty healthy volunteers were recruited after matching for age, gender, and body mass index with the patients and served as controls. Fasting levels of total, acylated ghrelin, leptin, TNF-alpha and insulin were measured in all subjects, in addition, clinical and nutrition parameters were assessed. In cirrhotic patients, plasma levels of both acylated and total ghrelin were significantly higher than those in the controls. The mean plasma acylated ghrelin levels were significantly higher in Child C cirrhosis compared to Child A and B. Ghrelin (total and acylated) were negatively correlated with leptin in cirrhotic patients confirming the fact that leptin acts as a physiological counterpart of ghrelin. Nutritional and metabolic abnormalities in cirrhotic patients may be dependent on the changes in the ghrelin/leptin systems, mainly the acylated form of ghrelin.

Seroprevalence of hepatitis A,B, and C viruses in Turkish alcoholic cirrhotics and the impact of hepatitis B on clinical profile.

PubMed

Tekin, Fatih; Gunsar, Fulya; Erdogan, Elvan Isik; Sertoz, Ruchan Yazan; Karasu, Zeki; Ersoz, Galip; Ozutemiz, Omer; Akarca, Ulus

2015-03-15

The aims of this study were to detect the seroprevalence of hepatitis A, B, and C viruses in Turkish alcoholic cirrhotics, and to evaluate the impact of hepatitis B infection on clinical profile at first admittance. Serological markers for hepatitis A, B, and C viruses in 300 alcoholic cirrhotics diagnosed between January 1994 and December 2012 were retrospectively reviewed. Among them, 148 eligible patients were divided into group 1 (HBsAg positive, n = 43) and group 2 (HBsAg and anti-HBc negative, n = 105). Clinical characteristics at first admittance of groups 1 and 2 were compared. The seroprevalence of anti-HAV total, HBsAg, and anti-HCV was found to be 91.5%, 16.3%, and 8.2%, respectively. The prevalence of hepatocellular carcinoma was higher in the HbsAg-positive group compared to HbsAg- and anti-HBc-negative group (16.3% vs. 2.9%, p = 0.007). Other clinical features were similar in the two groups. Alcoholic cirrhotics have higher frequencies of HBsAg and anti-HCV than the general population. These patients should be investigated for coexistent HBV and HCV infections, and HBV vaccination should not be neglected. Alcoholic cirrhotic patients with concomitant HBV infection should be closely screened for hepatocellular carcinoma.

Effect of Post-Traumatic Stress Disorder on Cognitive Function and Covert Hepatic Encephalopathy Diagnosis in Cirrhotic Veterans.

PubMed

Burroughs, Thomas K; Wade, James B; Ellwood, Michael S; Fagan, Andrew; Heuman, Douglas M; Fuchs, Michael; Bajaj, Jasmohan S

2018-02-01

In veterans, post-traumatic stress disorder (PTSD) is often associated with substance abuse, which in turn can lead to cirrhosis. Cirrhotic patients are prone to cognitive impairment, which is typically due to covert hepatic encephalopathy (CHE), but can also be affected by PTSD. The aim was to define the impact of PTSD on cognitive performance and the diagnosis of CHE in cirrhotic patients. Outpatient veterans with cirrhosis underwent two separate modalities for CHE cognitive testing [Psychometric Hepatic Encephalopathy Scale (PHES) and Inhibitory Control Test (ICT)]. ICT tests for inhibitory control and response inhibition, while PHES tests for attention and psychomotor speed. Comparisons were made between patients with/without PTSD. Multivariable logistic regression with CHE on PHES and CHE on ICT as dependent variables including prior OHE, demographics, PTSD and psychotropic medications was performed. Of 402 patients with cirrhosis, 88 had evidence of PTSD. Fifty-five of these were on psychoactive medications, 15 were undergoing psychotherapy, while no specific PTSD-related therapy was found in 28 patients. Cirrhotic patients with/without PTSD were statistically similar on demographics and cirrhosis severity, but cirrhotic subjects with PTSD had a higher frequency of alcoholic cirrhosis etiology and psychotropic drug use. PTSD cirrhosis had higher ICT lure and switching errors (NCT-B response), but on regression, there was no significant impact of PTSD on CHE diagnosis using either the ICT or PHES. Veterans with cirrhosis and PTSD have a higher frequency of psychotropic drug use and alcoholic cirrhosis etiology. CHE diagnosis using PHES or ICT is not affected by concomitant PTSD.

Diagnostic Value of Glypican3, Heat Shock Protein 70 and Glutamine Synthetase in Hepatocellular Carcinoma Arising in Cirrhotic and Non-Cirrhotic Livers.

PubMed

Uthamalingam, Preithy; Das, Ashim; Behra, Arunanshu; Kalra, Naveen; Chawla, Yogesh

2018-06-01

Histopathological distinction of various nodular lesions in liver with sufficient sensitivity and specificity is a challenge even in an expert set up. The panel of immunohistochemical markers composed of glutamine synthetase (GS), Glypican3 (GPC3) and heat shock protein 70 (HSP70) was recommended by the International Consensus Group for Hepatocellular Neoplasia group for the differentiation of high grade dysplastic nodule and early hepatocellular carcinoma (HCC). The panel has been extensively validated in the western population. This study aims to test this panel on Indian population on resected, explanted and autopsy cirrhotic and non-cirrhotic liver specimens of HCC. This study was conducted on 39 such liver specimens (12 cirrhotic, 12 pre-cirrhotic and 11 non-cirrhotic, non-fibrotic livers), including 35 cases of HCC over a period of 12 years. Immunohistochemistry was performed with antibodies against GS, GPC3 and HSP70 on the sections containing both malignant and dysplastic nodules. The diagnostic yield depended upon the nature of background liver pathology and was found to be high for only those HCCs arising in cirrhotic background, when positivity of any two markers was taken to be in favor of HCC (sensitivity-58.33%; specificity-100%). GS had a sensitivity and Negative predictive value of 100% for HCCs arising in cirrhotic livers. Strong positivity for GS is a highly sensitive marker for HCC in a cirrhotic background regardless of the differentiation of the tumor in Indian population. This may be due to preferential activation of Wnt pathway in Indian patients with cirrhosis. The sensitivity of the panel was too low for detecting HCCs arising in non-cirrhotic livers, even in the pre-cirrhotic chronically inflamed livers, even though the specificity was high. GPC3 and HSP70 appear to be useful as individual markers for HCCs arising in non-cirrhotic livers.

Transjugular intrahepatic portosystemic shunt creation for cirrhotic portal hypertension is well tolerated among patients with portal vein thrombosis.

PubMed

Merola, Jonathan; Fortune, Brett E; Deng, Yanhong; Ciarleglio, Maria; Amirbekian, Smbat; Chaudhary, Noami; Shanbhogue, Alampady; Ayyagari, Rajasekhara; Rodriguez-Davalos, Manuel I; Teperman, Lewis; Charles, Hearns W; Sigal, Samuel H

2018-06-01

Portal vein thrombosis (PVT) develops in cirrhotic patients because of stagnation of blood flow. Transjugular intrahepatic portosystemic shunt (TIPS) creates a low-resistance conduit that restores portal venous patency and blood flow. The effect of PVT on transplant-free survival in cirrhotic patients undergoing TIPS creation was evaluated. A multicenter, retrospective cohort study of patients who underwent TIPS creation for cirrhotic portal hypertension was carried out. A Cox model with propensity score adjustment was developed to evaluate the effect of PVT on 90-day and 3-year transplant-free survival. A subgroup analysis examining mortality of those with superior and inferior PVT was also carried out. A total of 252 consecutive TIPS creations were assessed, including 65 in patients with PVT. Survival of patients with high Model for End-stage Liver Disease scores (≥18) and PVT was not statistically different compared with patients with low Model for End-stage Liver Disease scores (<18) and no PVT at 90 days (P=0.46) and 3 years (P=0.42). Those with superior PVT had improved 90-day and 3-year survival both compared with patients with a inferior PVT and those without a PVT (P<0.01, all cases). The presence of PVT does not impair the prognosis of patients following TIPS creation, particularly in patients with superior portal occlusion.

Budesonide as first-line therapy for non-cirrhotic autoimmune hepatitis in children: a decision analysis.

PubMed

Mohammad, Saeed

2016-01-01

Therapy for autoimmune hepatitis has been prednisone based for decades; however, budesonide may be equally effective with fewer side effects. Our aim was to evaluate quality-adjusted life years and health care costs of three different treatment regimens. Treatment using prednisone, budesonide or a combination of both over a three-year period in newly diagnosed children with type I autoimmune hepatitis were simulated with a Markov model. Transition probabilities were calculated over consecutive three-month period. Costs were determined from a hospital database and health utilities were estimated from the literature. A Monte Carlo probabilistic sensitivity analysis was used to simulate the outcomes of 5000 patients in each treatment arm. Compared to standard therapy, budesonide leads to a gain of 0.09 quality-adjusted life years, costing $17,722 per QALY over a three-year period. Standard therapy led to significantly lower QALY's compared to other strategies (p < 0.001). Health utilities of patients in remission in each treatment group had the greatest impact on the model. Budesonide remained the treatment of choice if the probability of inducing remission was 55% or greater. Budesonide therapy in non-cirrhotic, treatment naïve patients with type I autoimmune hepatitis yielded greater QALY's compared to the current standard therapy with an acceptable increase in costs.

Hepatic encephalopathy in patients with non-cirrhotic portal hypertension: Description, prevalence and risk factors.

PubMed

Nicoletti, Valeria; Gioia, Stefania; Lucatelli, Pierleone; Nardelli, Silvia; Pasquale, Chiara; Nogas Sobrinho, Stefano; Pentassuglio, Ilaria; Greco, Francesca; De Santis, Adriano; Merli, Manuela; Riggio, Oliviero

2016-09-01

Hepatic encephalopathy (HE) is a common complication of cirrhosis but it is less studied in patients with non-cirrhotic portal hypertension (NCPH). To describe the prevalence of cognitive impairment (overt and covert HE) in NCPH patients and to identify the risk factors for its development. 51 patients with NCPH, 35 with chronic portal vein thrombosis (PVT) and 16 with idiopathic non-cirrhotic portal hypertension (INCPH), were evaluated for the presence of previous or present overt HE (OHE). The psychometric hepatic encephalopathy score and the SCAN battery were used to detect the presence of covert HE (CHE). 34 compensated cirrhotic patients were used as control. In NCPH patients, abdominal scans were performed to detect the presence of shunts. None of the patients experienced OHE at evaluation while 5.7% of PVT and 12.5% of INCPH patients referred at least one documented episode of previous OHE, similarly to patients with cirrhosis (14.7%). Even if lower than in patients with cirrhosis (64.7%), a considerable proportion of patients with chronic PVT (34.3%) and INCPH (25%) had CHE (p=0.008). The presence of a large portal-systemic shunt was the only factor significantly correlated to cognitive impairment in NCPH patients. HE is a tangible complication of NCPH and is mainly related to the presence of portal-systemic shunts. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Is administrating branched-chain amino acid-enriched nutrition achieved symptom-free in malnourished cirrhotic patients?

PubMed

Tsuda, Yasuhiro; Fukui, Hideo; Sujishi, Tetsuya; Ohama, Hideko; Tsuchimoto, Yusuke; Asai, Akira; Fukunisi, Shinya; Higuchi, Kazuhide

2014-01-01

Administration of branched-chain amino acids (BCAA) has been reported to improve liver function, quality of life (QOL). However, in some malnourished patients, serum albumin levels do not improve in response to BCAA granules. In this study, we examined the effects of BCAA-enriched enteral nutrition in patients unresponsive to BCAA granules. Thirty-two decompensated cirrhotic patients at Osaka Medical College were enrolled in this study. Since all patients showed no improvement in serum albumin levels despite 3 months of BCAA granule administration, they were administered 50 g of a flavored BCAA-enriched enteral nutrient twice daily, i.e., during the daytime and late evening. Serum albumin levels and major cirrhotic symptoms were examined 1, 3, and 5 months after treatment initiation. Serum albumin levels improved significantly 3 months after treatment initiation (3.14 ± 0.32 g/dl vs 3.5 ± 0.31 g/dl, p<0.01), and Child-Pugh scores decreased significantly (p<0.01). In the majority (53-80%) of patients, muscles cramps, fatigue, fatigability, edema, and sleep disturbance improved within 3 months after therapy initiation. Moreover, approximately 90% of the patients became symptom-free 5 months after treatment initiation. These results indicate that switching to BCAA-enriched nutrients improves QOL of cirrhotic patients unresponsive to BCAA granules.

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage.

PubMed

Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

2014-10-14

To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT.

Preliminary report of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) score.

PubMed

Baskin-Bey, Edwina S; Stewart, Charmaine A; Mitchell, Mary M; Bida, John P; Rosenthal, Theodore J; Nyberg, Scott L

2008-01-01

Audiovisual simulations of real-life driving (ie, driving simulators) have been used to assess neurologic dysfunction in a variety of medical applications. However, the use of simulated driving to assess neurologic impairment in the setting of liver disease (ie, hepatic encephalopathy) is limited. The aim of this analysis was to develop a scoring system based on simulated driving performance to assess mild cognitive impairment in cirrhotic patients with hepatic encephalopathy. This preliminary analysis was conducted as part of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) pilot study. Cirrhotic volunteers initially underwent a battery of neuropsychological tests to identify those cirrhotic patients with mild cognitive impairment. Performance during an audiovisually simulated course of on-road driving was then compared between mildly impaired cirrhotic patients and healthy volunteers. A scoring system was developed to quantify the likelihood of cognitive impairment on the basis of data from the simulated on-road driving. Mildly impaired cirrhotic patients performed below the level of healthy volunteers on the driving simulator. Univariate logistic regression and correlation models indicated that several driving simulator variables were significant predictors of cognitive impairment. Five variables (run time, total map performance, number of collisions, visual divided attention response, and average lane position) were incorporated into a quantitative model, the HEADS scoring system. The HEADS score (0-9 points) showed a strong correlation with cognitive impairment as measured by area under the receiver-operator curve (.89). The HEADS system appears to be a promising new tool for the assessment of mild hepatic encephalopathy.

Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis.

PubMed

Weil, Delphine; Levesque, Eric; McPhail, Marc; Cavallazzi, Rodrigo; Theocharidou, Eleni; Cholongitas, Evangelos; Galbois, Arnaud; Pan, Heng Chih; Karvellas, Constantine J; Sauneuf, Bertrand; Robert, René; Fichet, Jérome; Piton, Gaël; Thevenot, Thierry; Capellier, Gilles; Di Martino, Vincent

2017-12-01

The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown. We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores). In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36-0.59; p < 0.001) and higher in patients with SOFA > 19 at baseline (OR 8.54; 95% CI 2.09-34.91; p < 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64-3.65; p < 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47-3.22; p < 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07-27.63; p < 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11-17.24; p < 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02-10.27; p < 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32-23.96; p < 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68-9.42; p < 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22-3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mortality without heterogeneity. In ICU survivors, eight markers of liver and renal failure predicted 6-month mortality, including Child-Pugh stage C (OR 2.43; 95% CI 1.44-4.10; p < 0.001; PPV = 0.57), baseline MELD > 26 (OR 3.97; 95% CI 1.92-8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24-17.64; p = 0.022; PPV = 0.88). Prognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child-Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality.

An Insight into Antibiotic Resistance to Bacterial Infection in Chronic Liver Disease.

PubMed

Jain, Mayank; Varghese, Joy; Michael, Tom; Kedarishetty, Chandan Kumar; G, Balajee; Swaminathan, Subramanian; Venkataraman, Jayanthi

2017-12-01

End stage liver disease leads to immune dysfunction which predisposes to infection. There has been a rise in antibiotic resistant infections in these patients. There is scanty data f from India or idea regarding the same. The present study was undertaken to determine the type of infection acquired and the prevalence of antibiotic resistant infections in cirrhotic patients at a tertiary referral center in South India. In this retrospective study, all consecutive cirrhotic patients hospitalized between 2011 and 2013 with a microbiologically-documented infection were enrolled. Details of previous admission and antibiotics if received were noted. In culture positive infections, the source of infection (ascites, skin, respiratory tract: sputum/endotracheal tube aspirate, pleural fluid; urine and blood) and microorganisms isolated and their antibiotic susceptibility was noted. A total of 92 patients had 240 culture positive samples in the study period. Majority were Klebseilla followed by Escherichia coli and Enterococcus in nosocomial and health care associated infections. However, Enteroccocus was followed by E. coli and Klebsiella in community acquired infections. The antibiotic sensitivity pattern was analyzed for the major causative organisms such as E. coli , Klebsiella and Enterococcus . Most common resistant strains were extended spectrum beta lactamase producing enterobacteriacae (ESBL) followed by carbapenemase producing Klebsiella and methicillin resistant Staphylococcus aureus . Noscomial infection is the most common type, with Klebsiella and E. coli and there is significant rise in ESBL producing organism.

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.

PubMed

Mariño, Zoe; Pascasio-Acevedo, Juan M; Gallego, Adolfo; Diago, Moisés; Baliellas, Carme; Morillas, Rosa; Prieto, Martín; Moreno, José M; Sánchez-Antolín, Gloria; Vergara, Mercedes; Forné, Montserrat; Fernández, Inmaculada; Castro, María A; Pascual, Sonia; Gómez, Alexandra; Castells, Lluis; Montero, José L; Crespo, Javier; Calleja, José L; García-Samaniego, Javier; Carrión, Jose A; Arencibia, Ana C; Blasco, Alejandro; López-Núñez, Carmen; Sánchez-Ruano, Juan J; Gea-Rodríguez, Francisco; Giráldez, Álvaro; Cabezas, Joaquín; Hontangas, Vanessa; Torras, Xavier; Castellote, Jose; Romero-Gómez, Manuel; Turnes, Juan; de Artaza, Tomás; Narváez, Isidoro; Cuervas-Mons, Valentín; Forns, Xavier

2017-12-01

Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×10 9 /L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%. In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transjugular local thrombolysis with/without TIPS in patients with acute non-cirrhotic, non-malignant portal vein thrombosis.

PubMed

Klinger, Christoph; Riecken, Bettina; Schmidt, Arthur; De Gottardi, Andrea; Meier, Benjamin; Bosch, Jaime; Caca, Karel

2017-12-01

Therapeutic anticoagulation is the standard treatment in patients with acute non-cirrhotic portal vein thrombosis (PVT). In critically ill patients, anticoagulation only may not suffice to achive rapid and stable recanalization. This study evaluates efficacy and safety of transjugular interventional therapy in acute non-cirrhotic PVT. This retrospective study includes 17 consecutive patients with acute noncirrhotic, non-malignant PVT. Main indication for interventional therapy was imminent intestinal infarction (n=10). Treatment consisted of a combination of transjugular thrombectomy, local fibrinolysis and - depending on thrombus resolution - transjugular intrahepatic portosystemic shunt. Recanalization was successful in 94.1%. One- and two-year secondary PV patency rates were 88.2%. Major complications (n=3) resolved spontaneously in all but one patient (heparin induced thrombocytopenia type 2 with intestinal infarction). Symptoms improved in all patients. However, segmental bowel resection had to be performed in two (11.8%). During a median follow-up of 28.6 months, no patient experienced portal hypertensive complications. Presence of JAK2 V617F mutation predicted both short-term and long-term technical success. Transjugular recanalization is safe and effective in patients with acute non-cirrhotic, non-malignant PVT. It should be considered especially in patients with imminent bowel infarction and low likelihood of recanalization following therapeutic anticoagulation. Patients with JAK2 mutation ought to be followed meticulously. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Laparoscopic cholecystectomy in cirrhotic patients: the role of subtotal cholecystectomy and its variants.

PubMed

Palanivelu, Chinnasamy; Rajan, Pidigu Seshiyer; Jani, Kalpesh; Shetty, Alangar Roshan; Sendhilkumar, Karuppasamy; Senthilnathan, Palanisamy; Parthasarthi, Ramakrishnan

2006-08-01

Open cholecystectomy is associated with considerable morbidity and mortality in cirrhotic patients. Laparoscopic cholecystectomy may offer a better option because of the magnification available and the availability of newer instruments like the ultrasonic shears. We present our experience of 265 laparoscopic cholecystectomies and attempt to identify the difficulties encountered in this group of patients. Between 1991 and 2005, 265 cirrhotic patients of Child-Pugh Classification A and B, with symptomatic gallstones, were subjected to laparoscopic cholecystectomy. We describe here our tailored approach and our techniques of subtotal cholecystectomy. Features of acute cholecystitis were present in 35.1% of the patients, and 64.9% presented with chronic cholecystitis. In 81.5% of the patients, the diagnosis of cirrhosis was established preoperatively. In 8.3% of the patients, a fundus first method was adopted when the hilum could not be approached despite additional ports. Modified subtotal cholecystectomy was performed in a total of 206 patients. Mean operative time in the subtotal cholecystectomy group was 72 minutes; in the standard group, it was 41 minutes. There was no mortality. In 15% of patients, postoperative deterioration in liver function occurred. Worsening of ascites, port site infection, port site bleeding, intraoperative hemorrhage, bilious drainage, and stone formation in the remnant were the other complications encountered. Laparoscopic cholecystectomy is a safe and effective treatment for calculous cholecystitis in cirrhotic patients. Appropriate modification of subtotal cholecystectomy should be practiced, depending on the risk factors present, to avoid complications.

The international normalized ratio does not reflect bleeding risk in esophageal variceal hemorrhage.

PubMed

Hshieh, Tammy T; Kaung, Aung; Hussain, Syed; Curry, Michael P; Sundaram, Vinay

2015-01-01

The international normalized ratio (INR) has not been validated as a predictor of bleeding risk in cirrhotics. The aim of this study was to determine whether elevation in the INR correlated with risk of esophageal variceal hemorrhage and whether correction of the INR prior to endoscopic therapy affects failure to control bleeding. Patient records were retrospectively reviewed from January 1, 2000 to December 31, 2010. Cases were cirrhotics admitted to the hospital due to bleeding esophageal varices. Controls were cirrhotics with a history of non-bleeding esophageal varices admitted with ascites or encephalopathy. All variceal bleeders were treated with octreotide, antibiotics, and band ligation. Failure to control bleeding was defined according to the Baveno V criteria. We analyzed 74 cases and 74 controls. The mean INR at presentation was lower in those with bleeding varices compared to non-bleeders (1.61 vs 1.74, P = 0.03). Those with bleeding varices had higher serum sodium (136.1 vs 133.8, P = 0.02), lower hemoglobin (9.59 vs 11.0, P < 0.001), and lower total bilirubin (2.47 vs 5.50, P < 0.001). Multivariable logistic regression showed total bilirubin to inversely correlate with bleeding (OR = 0.74). Bleeders received a mean of 1.14 units of fresh frozen plasma (FFP) prior to endoscopy (range 0-11 units). Of the 14 patients (20%) with failure to control bleeding, median INR (1.8 vs 1.5, P = 0.02) and median units of FFP transfused (2 vs 0, P = 0.01) were higher than those with hemostasis after the initial endoscopy. The INR reflects liver dysfunction, not bleeding risk. Correction of INR with FFP has little effect on hemostasis.

Prognostic scores in cirrhotic patients admitted to a gastroenterology intensive care unit.

PubMed

Freire, Paulo; Romãozinho, José M; Amaro, Pedro; Ferreira, Manuela; Sofia, Carlos

2011-04-01

prognostic scores have been validated in cirrhotic patients admitted to general Intensive Care Units. No assessment of these scores was performed in cirrhotics admitted to specialized Gastroenterology Intensive Care Units (GICUs). to assess the prognostic accuracy of Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA), Model for End-stage Liver Disease (MELD) and Child-Pugh-Turcotte (CPT) in predicting GICU mortality in cirrhotic patients. the study involved 124 consecutive cirrhotic admissions to a GICU. Clinical data, prognostic scores and mortality were recorded. Discrimination was evaluated with area under receiver operating characteristic curves (AUC). Calibration was assessed with Hosmer-Lemeshow goodness-of-fit test. GICU mortality was 9.7%. Mean APACHE II, SAPS II, SOFA, MELD and CPT scores for survivors (13.6, 25.4, 3.5,18.0 and 8.6, respectively) were found to be significantly lower than those of non-survivors (22.0, 47.5, 10.1, 30.7 and 12.5,respectively) (p < 0.001). All the prognostic systems showed good discrimination, with AUC = 0.860, 0.911, 0.868, 0.897 and 0.914 for APACHE II, SAPS II, SOFA, MELD and CPT, respectively. Similarly, APACHE II, SAPS II, SOFA, MELD and CPT scores achieved good calibration, with p = 0.146, 0.120, 0.686,0.267 and 0.120, respectively. The overall correctness of prediction was 81.9%, 86.1%, 93.3%, 90.7% and 87.7% for the APA-CHE II, SAPS II, SOFA, MELD and CPT scores, respectively. in cirrhotics admitted to a GICU, all the tested scores have good prognostic accuracy, with SOFA and MELD showing the greatest overall correctness of prediction.

Correlations between cerebral glucose metabolism and neuropsychological test performance in nonalcoholic cirrhotics.

PubMed

Lockwood, Alan H; Weissenborn, Karin; Bokemeyer, Martin; Tietge, U; Burchert, Wolfgang

2002-03-01

Many cirrhotics have abnormal neuropsychological test scores. To define the anatomical-physiological basis for encephalopathy in nonalcoholic cirrhotics, we performed resting-state fluorodeoxyglucose positron emission tomographic scans and administered a neuropsychological test battery to 18 patients and 10 controls. Statistical parametric mapping correlated changes in regional glucose metabolism with performance on the individual tests and a composite battery score. In patients without overt encephalopathy, poor performance correlated with reductions in metabolism in the anterior cingulate. In all patients, poor performance on the battery was positively correlated (p < 0.001) with glucose metabolism in bifrontal and biparietal regions of the cerebral cortex and negatively correlated with metabolism in hippocampal, lingual, and fusiform gyri and the posterior putamen. Similar patterns of abnormal metabolism were found when comparing the patients to 10 controls. Metabolic abnormalities in the anterior attention system and association cortices mediating executive and integrative function form the pathophysiological basis for mild hepatic encephalopathy.

Cost-effectiveness analysis of therapeutic options for chronic hepatitis C genotype 3 infected patients.

PubMed

Gimeno-Ballester, Vicente; Mar, Javier; O'Leary, Aisling; Adams, Róisín; San Miguel, Ramón

2017-01-01

This study provides a cost-effectiveness analysis of therapeutic strategies for chronic hepatitis C genotype 3 infected patients in Spain. A Markov model was designed to simulate the progression in a cohort of patients aged 50 years over a lifetime horizon. Sofosbuvir (SOF) plus peginterferon and ribavirin for 12 weeks was a cost-effective option when compared to standard of care (SoC) in the treatment of both 'moderate fibrosis' and 'cirrhotic' patients. Incremental cost-effectiveness ratios were €35,276/QALY and €18,374/QALY respectively. ICERs for SOF plus daclatasvir (DCV) regimens versus SoC were over the threshold limit considered, at €56,178/QALY and €77,378/QALY for 'moderate fibrosis' and 'cirrhotic' patients respectively. Addition of SOF to IFN-based regimens for genotype 3 was cost-effective for both 'moderate fibrosis' and 'cirrhotic' patients. IFN-free options including SOF and DCV association required price reductions lower than the list prices to be considered cost-effective.

Wine consumption is not associated with a decreased risk of alcoholic cirrhosis in heavy drinkers.

PubMed

Pelletier, Stéphanie; Vaucher, Emmanuel; Aider, Rachid; Martin, Sandrine; Perney, Pascal; Balmès, Jean Louis; Nalpas, Bertrand

2002-01-01

While it was thought that all alcoholic beverages share a similar liver toxicity when drunk at a high level, recent epidemiological surveys have suggested that wine drinking might decrease the risk of alcoholic cirrhosis in heavy drinkers. Therefore, we performed a study aiming to analyse the type and the intake levels of alcoholic beverages in heavy drinkers according to the severity of the liver disease. This is a case-control study enrolling 42 cirrhotic and 60 non-cirrhotic patients. Liver status was assessed using clinical, biological, histological and ultrasonographic procedures. Alcohol consumption was recorded using the Lifetime Drinking History method. We did not find any significant differences in total alcohol consumption between cases and controls and, moreover, in our series, the relative percentage of pure alcohol drunk in wine was significantly higher in cirrhotic, than in non-cirrhotic, patients. Our results confirm that the absence of a link between the type of alcoholic beverage and the occurrence of cirrhosis is still valid.

Examining the clinical course of genotype 1 chronic hepatitis C patients treated with the cosmos regimen: including patients with advanced liver disease and East Asian ancestry

PubMed Central

Roytman, Marina; Ramkissoon, Resham; Wu, Christina; Hong, Leena; Trujillo, Ruby; Huddleston, Leslie; Poerzgen, Peter; Seto, Todd; Wong, Linda; Tsai, Naoky

2017-01-01

Background/objectives The COSMOS study was a phase 2a clinical trial that showed high cure rates of genotype 1 chronic hepatitis C (CHC) and a favorable side effect profile using a 12-week regimen of simeprevir + sofosbuvir (SIM + SOF). Given the small number of patients treated with the SIM + SOF regimen in the COSMOS trial, there is uncertainty regarding the efficacy and safety of this combination therapy. We now report our experience with the COSMOS regimen in the multiethnic population of Hawaii, including patients of East Asian ancestry and with decompensated cirrhosis. Methods This study is a retrospective review of 138 patients treated with a fixed dose regimen of SIM 150 mg and SOF 400 mg daily at a single referral center. We collected data on demographics, side effects, laboratory studies and sustained virological response (SVR). Statistical analysis was performed with Stata v8.2 software. Results Baseline characteristics of the 138 patients initiated with SIM + SOF therapy were: 68.8 % cirrhotic (22.1 % of those Child-Pugh Class B), 37 % Asian, 11.6 % Pacific Islander, 63 % male, mean age 61.3 ± 7.8 years, mean BMI 27.8 ± 6.1 kg/m2, 26.8 % diabetic, 63.8 % genotype 1a, 44.9 % previously treatment experienced. A total of 100 % of patients that completed therapy (n = 137) had undetectable viral loads at end of treatment (EOT). Twelve patients relapsed post-treatment resulting in an overall 12 week SVR (SVR12) rate of 89.1 %. 95 % of decompensated cirrhotic patients achieved SVR12, compared to 85.3 % of compensated cirrhotic patients and 93 % of non-cirrhotic patients. 92 % of Asian patients achieved SVR12 compared to 87.5 % in non-Asian patients. There were no statistically significant differences in SVR12 between treatment naive and treatment experienced patients (86.8 vs 91.9 %). 87.5 % of post-transplant patients achieved SVR12. The main side effects were headache 16.2 %, fatigue 24.2 %, pruritis 14.1 %; none were >grade 2 in severity. There were no differences in side effect profiles of patients with decompensated cirrhosis. Pruritis only was statistically significant between Asians and non-Asians (22 vs 5.7 %). Trends toward improvement in platelet counts and total bilirubin were noted at 12-weeks post treatment, while improvement in albumin in cirrhotic patients reached statistical significance (3.77–4.01 mg/dL, p = 0.0108). Conclusions The 12-week fixed dose course of SIM + SOF was well tolerated in a multiethnic population of primarily cirrhotic patients, including those with decompensated disease. This real world trial achieved SVR12 rates comparable to the COSMOS data. Higher incidence of adverse side effects was not observed with an exception of higher rate of pruritis in Asians. The increase in albumin in cirrhotic patients was statistically significant and suggested early improvement in synthetic function following viral eradication. Higher BMI (≥30 kg/m2) was the only factor that correlated with post-treatment relapse by multivariate analysis. PMID:27026431

Sublingual microcirculatory alterations in cirrhotic patients.

PubMed

Gonzalez Ballerga, Esteban; Pozo, Mario O; Rubatto Birri, Paolo N; Kanoore Edul, Vanina Siham; Sorda, Juan A; Daruich, Jorge; Dubin, Arnaldo

2018-05-01

To assess sublingual microcirculation in cirrhotic patients and its relationship to spider angiomas, complications, and outcome. Thirty-one cirrhotic patients were prospectively compared to 31 matched controls. Sublingual microcirculation was evaluated by videomicroscopy. We specifically looked for capillaries with increased RBCV, which was defined as a velocity higher than the percentile 100th of controls. Compared to controls, cirrhotic patients showed decreased total and PVD (14.4 ± 2.2 vs 16.0 ± 1.3 and 14.1 ± 2.3 vs 15.9 ± 1.6 mm/mm 2 , respectively, P < .001 for both) and increased HFI (0.64 ± 0.39 vs 0.36 ± 0.21, P = .001). They also exhibited high RBCV in 2% of the microvessels (P < .0001). Patients with MELD score ≥10 had higher RBCV than patients with score <10 (1414 ± 290 vs 1206 ± 239 μm/s, P < .05). Patients with spider angiomas showed lower vascular densities. Microcirculation did not differ between survivors and nonsurvivors. Cirrhosis is associated with microcirculatory alterations that can be easily monitored in the sublingual mucosa. Alterations included decreased density and PPV and hyperdynamic microvessels. The most striking finding, however, was the microvascular heterogeneity. Patients with spider angiomas had more severe alterations. Larger studies should clarify the relationship between microcirculatory abnormalities and outcome. © 2018 John Wiley & Sons Ltd.

Emergence of rifampin-resistant staphylococci after rifaximin administration in cirrhotic patients.

PubMed

Chang, Ji Young; Kim, Seong-Eun; Kim, Tae Hun; Woo, So-Youn; Ryu, Min Sun; Joo, Yang-Hee; Lee, Ko Eun; Lee, Jihyun; Lee, Kang Hoon; Moon, Chang Mo; Jung, Hye-Kyung; Shim, Ki-Nam; Jung, Sung-Ae

2017-01-01

Rifaximin, a poorly absorbed antibiotics, has gut-specific therapeutic effects. Although frequently prescribed to manipulate intestinal luminal bacterial population in various diseases, the possible induction of antibacterial cross-resistance to a target pathogen is a major concern in long-term rifaximin administration. We aimed to evaluate whether rifampin-resistant staphylococci could evolve after rifaximin treatment in cirrhotic patients. A total of 25 cirrhotic patients who were administered rifaximin for the prevention of hepatic encephalopathy were enrolled. Swabs from both hands and the perianal skin were acquired on day 0 (before rifaximin treatment), period 1 (1-7 weeks after treatment), and period 2 (8-16 weeks after treatment) the staphylococcal strain identification and rifampin-resistance testing. A total of 198 staphylococcal isolates from 15 species were identified. Staphylococcus epidermidis was isolated most frequently, and Staphylococcus haemolyticus was the most common resistant species both from hands and perianal skin. Eleven patients (44.0%) developed rifampin-resistant staphylococcal isolates in period 1. Among these patients, only six (54.5%) were found to have rifampin-resistant isolates in period 2, with no significant infectious events. Rifampin-resistant staphylococcal isolates were more frequently found in perianal skin than from the hands. No patients acquired a newly resistant strain in period 2. About one-half of cirrhotic patients in this study developed rifampin-resistant staphylococcal isolates after rifaximin treatment. Although the resistant strains were no longer detected in about half of the patients in the short-term, the long-term influence of this drug treatment should be determined.

Transjugular portal vein recanalization with creation of intrahepatic portosystemic shunt (PVR-TIPS) in patients with chronic non-cirrhotic, non-malignant portal vein thrombosis.

PubMed

Klinger, Christoph; Riecken, Bettina; Schmidt, Arthur; De Gottardi, Andrea; Meier, Benjamin; Bosch, Jaime; Caca, Karel

2018-03-01

To determine safety and efficacy of transjugular portal vein recanalization with creation of intrahepatic portosystemic shunt (PVR-TIPS) in patients with chronic non-cirrhotic, non-malignant portal vein thrombosis (PVT). This retrospective study includes 17 consecutive patients with chronic non-cirrhotic PVT (cavernous transformation n = 15). PVR-TIPS was indicated because of variceal bleeding (n = 13), refractory ascites (n = 2), portal biliopathy with recurrent cholangitis (n = 1), or abdominal pain (n = 1). Treatment consisted of a combination of transjugular balloon angioplasty, mechanical thrombectomy, and-depending on extent of residual thrombosis-transjugular intrahepatic portosystemic shunt and additional stenting of the portal venous system. Recanalization was successful in 76.5 % of patients despite cavernous transformation in 88.2 %. Both 1- and 2-year secondary PV and TIPS patency rates were 69.5 %. Procedure-related bleeding complications occurred in 2 patients (intraperitoneal bleeding due to capsule perforation, n = 1; liver hematoma, n = 1) and resolved spontaneously. However, 1 patient died due to subsequent nosocomial pneumonia. During follow-up, 3 patients with TIPS occlusion and PVT recurrence experienced portal hypertensive complications. PVR-TIPS is safe and effective in selected patients with chronic non-cirrhotic PVT. Due to technical complexity and possible complications, it should be performed only in specialized centers with high experience in TIPS procedures. © Georg Thieme Verlag KG Stuttgart · New York.

Real time elastography - a non-invasive diagnostic method of small hepatocellular carcinoma in cirrhosis.

PubMed

Gheorghe, Liana; Iacob, Speranta; Iacob, Razvan; Dumbrava, Mona; Becheanu, Gabriel; Herlea, Vlad; Gheorghe, Cristian; Lupescu, Ioana; Popescu, Irinel

2009-12-01

Small nodules (under 3 cm) detected on ultrasound (US) in cirrhotics represent the most challenging category for noninvasive diagnosis of hepatocellular carcinoma (HCC). To evaluate real-time sonoelastography as a noninvasive tool for the diagnosis of small HCC nodules in cirrhotic patients. 42 cirrhotic patients with 58 nodules (1-3 cm) were evaluated with real-time elastography (Hitachi EUB-6500); the mean intensity of colors red, blue, green were measured using a semi-quantitative method. Analysis of histograms for each color of the sonoelastography images was performed for quantifying the elasticity of nodule tissue in comparison with the cirrhotic liver tissue. AUROC curves were constructed to define the best cut-off points to distinguish malignant features of the nodules. Univariate and multivariate logistic regression analysis was performed. 595 sonoelastography images from 42 patients (25 men; 17 women) were analyzed. The mean age was 56.4 +/- 0.7 years and 69% patients were in Child-Pugh class A, 19% class B, 11% class C. For the mean intensity of green color AUROC=0.81, a cut-off value under 108.7 being diagnostic for HCC with a Sp=91.1%, Se=50%, PPV=92.1%, NPV=47.1%. Mean intensity of blue color proved to be an excellent diagnostic tool for HCC (AUROC=0.94); for a cut-off value greater than 128.9, Sp=92.2%, Se=78.9%, PPV=95.4%, NPV=68%. Independent predictive factors of HCC for a small nodule in cirrhotic patients were: blue color over 128.9 at sonoelastography and hypervascular appearance at Doppler US. US elastography is a promising method for the non-invasive diagnosis of early HCC. Blue color at elastography and hypervascular aspects are independent predictors of HCC.

Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit.

PubMed

Cholongitas, E; Senzolo, M; Patch, D; Kwong, K; Nikolopoulou, V; Leandro, G; Shaw, S; Burroughs, A K

2006-04-01

Prognostic scores in an intensive care unit (ICU) evaluate outcomes, but derive from cohorts containing few cirrhotic patients. To evaluate 6-week mortality in cirrhotic patients admitted to an ICU, and to compare general and liver-specific prognostic scores. A total of 312 consecutive cirrhotic patients (65% alcoholic; mean age 49.6 years). Multivariable logistic regression to evaluate admission factors associated with survival. Child-Pugh, Model for End-stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were compared by receiver operating characteristic curves. Major indication for admission was respiratory failure (35.6%). Median (range) Child-Pugh, APACHE II, MELD and SOFA scores were 11 (5-15), 18 (0-44), 24 (6-40) and 11 (0-21), respectively; 65% (n = 203) died. Survival improved over time (P = 0.005). Multivariate model factors: more organs failing (FOS) (<3 = 49.5%, > or =3 = 90%), higher FiO(2), lactate, urea and bilirubin; resulting in good discrimination [area under receiver operating characteristic curve (AUC) = 0.83], similar to SOFA and MELD (AUC = 0.83 and 0.81, respectively) and superior to APACHE II and Child-Pugh (AUC = 0.78 and 0.72, respectively). Cirrhotics admitted to ICU with > or =3 failing organ systems have 90% mortality. The Royal Free model discriminated well and contained key variables of organ function. SOFA and MELD were better predictors than APACHE II or Child-Pugh scores.

Screening for Hepatopulmonary Syndrome in Cirrhotic Patients Using Technetium 99m-macroaggregated Albumin Perfusion Lung Scan (Tc-MAA): Diagnostic Approach and Clinical Correlations.

PubMed

Fragaki, Maria; Sifaki-Pistolla, Dimitra; Samonakis, Dimitrios N; Koulentaki, Mairi; Koukouraki, Sofia; Stathaki, Maria; Kouroumalis, Elias

2017-09-28

The aims of this study were to prospectively screen cirrhotic patients with arterial blood gas test and albumin perfusion scan, identify those fulfilling the classic hepatopulmonary syndrome (HPS) criteria, correlate with clinical parameters, and evaluate the survival of patients with HPS compared with those without HPS in a genetically homogenous Cretan cirrhotic population. Data on consecutive 102 patients within 1 year were collected and analyzed. All patients underwent a technetium 99m-macroaggregated albumin perfusion lung scan (Tc-MAA). Diagnosis of HPS was based on the presence of the quantitative index Tc-MAA≥6% and a [P(A-a)O2]≥15 mm Hg (≥20 mm Hg for patients over >64 y). In 94/102 patients, complete scintigraphic data were available. In total, 24 (26%) patients fulfilled the diagnostic criteria of HPS; 95.8% of them had mild-to-moderate HPS. In 8 patients the Tc-MAA scintigraphy could not be interpreted. There was no difference in HPS between decompensated (24.6%) and compensated cirrhosis (27.3%). In the multivariate analysis only the quantitative index was significant for the diagnosis of HPS (P=0.001, odds ratio; 95% confidence interval, 7.05; 2.27-21.87). Kaplan- Meier survival curves indicated a similar overall prognosis for patients diagnosed with HPS (P=0.105). HPS is a frequent complication of cirrhosis. Mild-to-moderate HPS has no significant effect on survival of cirrhotic patients. The quantitative Tc-MAA test is a reliable tool for diagnosis.

Portal Vein Thrombosis in Adult Omani Patients: A Retrospective Cohort Study.

PubMed

Al Hashmi, Khalid; Al Aamri, Lamya; Al Lamki, Sulayma; Pathare, Anil

2017-11-01

We sought to study the occurrence of portal vein thrombosis (PVT) in adult Omani patients. Methods: We conducted a retrospective cross-sectional study in patients diagnosed with PVT, which was confirmed by radiological imaging, from two tertiary hospitals over a 10-year period. Results: Amongst the 39 patients enrolled in the study, 15 (38.4%) had cirrhosis of the liver, and 24 (61.5%) were non-cirrhotic. In the non-cirrhotic PVT patients, 15 (62.5%) had acute PVT, whereas nine (37.5%) had chronic PVT. PVT was more common in males than females, (25 (64.1%) vs. 14 (35.8%), respectively, p = 0.020). The three most common clinical symptoms were abdominal pain (n = 25, 64.1%) followed by nausea (n = 12, 30.7%) and fever (n = 8, 20.5%) patients. Causative risk factors included prothrombotic states (17.9-28.2%) and local factors (20.5%) such as cholecystitis, cholangitis, and liver abscess. Complications were found in 23.0% of patients with PVT, namely variceal bleeding in seven patients (17.9%) patients and bowel ischemia in two patients (5.1%). Management with sclerotherapy was performed in all patients with variceal bleeding. Thrombectomy was done for one patient complicated with intestinal ischemia, but as it failed, he was treated with warfarin anticoagulation. This is the first study reflecting a real-life practice in PVT with possibly underlying inherited and acquired prothrombotic conditions as well as complications due to local and malignant conditions from Oman. We studied the prevalence, clinical presentation, underlying possible etiological factors, treatment, and outcomes. Since causative factors were found in 36 patients (92.3%), etiological screening seems worthwhile in every case with PVT, but thrombophilia screening may not be cost-effective.

[Effect of a serotonin S2 receptor antagonist on portal hypertension due to cirrhosis. Preliminary results of a heart and liver hemodynamic study].

PubMed

Deflandre, J; Pirotte, J; Etienne, M; Carlier, J

1988-01-01

In 10 cirrhotic patients, with two balloon catheters introduced in the right internal jugular vein, the following parameters were measured before and after injection of ketanserine (0.1 mg/kg): cardiac output using the thermo-dilution method, free supra-hepatic pressure, wedged supra-hepatic pressure at rest and during cough, right atrial pressure, pulmonary capillary and arterial pressures. After 30 minutes, the following modifications were recorded: the cardiac output goes from 8.0 +/- 2.4 l/min to 8.7 +/- 2.5 l/min (p less than 0.05); the mean arterial pressure goes from 107.0 +/- 18.8 mmHg to 94.7 +/- 25.9 mmHg (p less than 0.02); the wedged supra-hepatic pressure, during coughing goes from 85.2 +/- 36.1 mmHg to 64.6 +/- 23.1 mmHg (p less than 0.005). As in non-cirrhotic patients, ketanserine causes a drop in the mean arterial pressure and a transient elevation of the cardiac output. Ketanserine is able to lower portal pressure of cirrhotic patients at rest as well as during coughing. These results seem to indicate that the activation of serotonin S2 receptors may play a role in determining the portal hypertension in cirrhotic patients.

Changes in portal blood flow and liver functions in cirrhotics during Ramadan fasting in the summer; a pilot study

PubMed Central

Mohamed, Salem Y; Emara, Mohamed H; Hussien, Hala IM; Elsadek, Hany M

2016-01-01

Aim: Assessment of short term changes in portal blood flow and long term changes in liver functions in cirrhotic patients who chose to fast during the month of Ramadan in summer. Background: During Ramadan, healthy Muslims obligated to fast from predawn to sunset. Patients and methods: Forty cirrhotic patients intended to fast during the month of Ramadan in the year 2014, were examined by Congestion index (CI) as a non-invasive indicator of short term changes in the portal blood flow, while liver function tests were determined as an indicator of long term changes in liver functions. Results: A total of 38 patients completed the whole month fasting and two patients discontinued fasting due to variceal bleeding. The complicated patients were 7. CI showed a statistically significant increase from fasting to postprandial status (P<0.001), with statistically significant increases from fasting to postprandial status in Child class A (P<0.001), and B (P<0.001). We did not find a statistical significance between patients with complications and those without complications (P=0.6). There was a statistically significant rise in the serum bilirubin after Ramadan. Deterioration noticed as advanced Child classes, development of lower limb edema, increasing ascites, increasing jaundice and overt encephalopathy. Conclusion: Cirrhotic patients showed significant short-term changes in the portal blood flow. However, these changes are not linked to complications or deterioration of liver functions and accommodated especially in patients with Child class A and B. Child class C patients should not fast. PMID:27458510

Wall shear stress in portal vein of cirrhotic patients with portal hypertension.

PubMed

Wei, Wei; Pu, Yan-Song; Wang, Xin-Kai; Jiang, An; Zhou, Rui; Li, Yu; Zhang, Qiu-Juan; Wei, Ya-Juan; Chen, Bin; Li, Zong-Fang

2017-05-14

To investigate wall shear stress (WSS) magnitude and distribution in cirrhotic patients with portal hypertension using computational fluid dynamics. Idealized portal vein (PV) system models were reconstructed with different angles of the PV-splenic vein (SV) and superior mesenteric vein (SMV)-SV. Patient-specific models were created according to enhanced computed tomography images. WSS was simulated by using a finite-element analyzer, regarding the blood as a Newtonian fluid and the vessel as a rigid wall. Analysis was carried out to compare the WSS in the portal hypertension group with that in healthy controls. For the idealized models, WSS in the portal hypertension group (0-10 dyn/cm 2 ) was significantly lower than that in the healthy controls (10-20 dyn/cm 2 ), and low WSS area (0-1 dyn/cm 2 ) only occurred in the left wall of the PV in the portal hypertension group. Different angles of PV-SV and SMV-SV had different effects on the magnitude and distribution of WSS, and low WSS area often occurred in smaller PV-SV angle and larger SMV-SV angle. In the patient-specific models, WSS in the cirrhotic patients with portal hypertension (10.13 ± 1.34 dyn/cm 2 ) was also significantly lower than that in the healthy controls ( P < 0.05). Low WSS area often occurred in the junction area of SV and SMV into the PV, in the area of the division of PV into left and right PV, and in the outer wall of the curving SV in the control group. In the cirrhotic patients with portal hypertension, the low WSS area extended to wider levels and the magnitude of WSS reached lower levels, thereby being more prone to disturbed flow occurrence. Cirrhotic patients with portal hypertension show dramatic hemodynamic changes with lower WSS and greater potential for disturbed flow, representing a possible causative factor of PV thrombosis.

Wall shear stress in portal vein of cirrhotic patients with portal hypertension

PubMed Central

Wei, Wei; Pu, Yan-Song; Wang, Xin-Kai; Jiang, An; Zhou, Rui; Li, Yu; Zhang, Qiu-Juan; Wei, Ya-Juan; Chen, Bin; Li, Zong-Fang

2017-01-01

AIM To investigate wall shear stress (WSS) magnitude and distribution in cirrhotic patients with portal hypertension using computational fluid dynamics. METHODS Idealized portal vein (PV) system models were reconstructed with different angles of the PV-splenic vein (SV) and superior mesenteric vein (SMV)-SV. Patient-specific models were created according to enhanced computed tomography images. WSS was simulated by using a finite-element analyzer, regarding the blood as a Newtonian fluid and the vessel as a rigid wall. Analysis was carried out to compare the WSS in the portal hypertension group with that in healthy controls. RESULTS For the idealized models, WSS in the portal hypertension group (0-10 dyn/cm2) was significantly lower than that in the healthy controls (10-20 dyn/cm2), and low WSS area (0-1 dyn/cm2) only occurred in the left wall of the PV in the portal hypertension group. Different angles of PV-SV and SMV-SV had different effects on the magnitude and distribution of WSS, and low WSS area often occurred in smaller PV-SV angle and larger SMV-SV angle. In the patient-specific models, WSS in the cirrhotic patients with portal hypertension (10.13 ± 1.34 dyn/cm2) was also significantly lower than that in the healthy controls (P < 0.05). Low WSS area often occurred in the junction area of SV and SMV into the PV, in the area of the division of PV into left and right PV, and in the outer wall of the curving SV in the control group. In the cirrhotic patients with portal hypertension, the low WSS area extended to wider levels and the magnitude of WSS reached lower levels, thereby being more prone to disturbed flow occurrence. CONCLUSION Cirrhotic patients with portal hypertension show dramatic hemodynamic changes with lower WSS and greater potential for disturbed flow, representing a possible causative factor of PV thrombosis. PMID:28566887

Incarceration of umbilical hernia: a rare complication of large volume paracentesis.

PubMed

Khodarahmi, Iman; Shahid, Muhammad Usman; Contractor, Sohail

2015-09-01

We present two cases of umbilical hernia incarceration following large volume paracentesis (LVP) in patients with cirrhotic ascites. Both patients became symptomatic within 48 hours after the LVP. Although being rare, given the significantly higher mortality rate of cirrhotic patients undergoing emergent herniorrhaphy, this complication of LVP is potentially serious. Therefore, it is recommended that patients be examined closely for the presence of umbilical hernias before removal of ascitic fluid and an attempt should be made for external reduction of easily reducible hernias, if a hernia is present.

Incarceration of umbilical hernia: a rare complication of large volume paracentesis

PubMed Central

Khodarahmi, Iman; Shahid, Muhammad Usman; Contractor, Sohail

2015-01-01

We present two cases of umbilical hernia incarceration following large volume paracentesis (LVP) in patients with cirrhotic ascites. Both patients became symptomatic within 48 hours after the LVP. Although being rare, given the significantly higher mortality rate of cirrhotic patients undergoing emergent herniorrhaphy, this complication of LVP is potentially serious. Therefore, it is recommended that patients be examined closely for the presence of umbilical hernias before removal of ascitic fluid and an attempt should be made for external reduction of easily reducible hernias, if a hernia is present. PMID:26629305

Prevalence of hepatitis A and B markers and vaccine indication in cirrhotic patients evaluated for liver transplantation in Spain.

PubMed

Aoufi, S; Pascasio, J M; Sousa, J M; Sayago, M; Ferrer, M T; Gómez-Delgado, E; De la Cruz, M D; Alamo, J M; Gómez-Bravo, M A; Bernardos, A; Márquez, J L

2008-11-01

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is generally recommended for patients with chronic liver disease and those evaluated for liver transplantation in the absence of immunity. HAV and HBV infections after liver transplantation are frequent and associated with a worse prognosis. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV and HBV is substantial, and that new vaccination strategies are needed. The aim of this study was to determine the level of immunity from hepatitis A and B infections and the need for HBV and HAV vaccination among cirrhotic patients evaluated for liver transplantation. We studied HBV and HAV serological markers (HbsAg, anti-HBc, anti-HBs, IgG anti-HAV) in 451 cirrhotic patients evaluated for liver transplantation to investigate the association with gender, age, and etiology of cirrhosis. Negative HBV markers were observed in 57% of patients with 43% displaying one positive HBV marker: HBsAg (+), 9.5%; anti-HBc (+)/anti-HBs (-), 11.5%; anti-HBc (-)/anti-HBs(+), 4.2%; anti-HBc(+)/anti-HBs(+), 17.7%. HBV vaccine indication established in 68.5% of patients was greater among women and hepatitis C virus-negative patients. No differences were observed in age or cause of cirrhosis. HAV vaccination indicated in 6.7% of patients (IgG anti-HVA-negative) was greater among patients with negative HBV markers (9.3% vs 3.3%, P = .018) and younger patients (25.3% of patients

Additional BCAA-enriched nutrient mixture improves the nutritional condition in cirrhotic patients with hypoalbuminemia despite treatment with regular BCAA granules: A pilot study.

PubMed

Fukui, Aiko; Kawabe, Naoto; Hashimoto, Senju; Murao, Michihito; Nakano, Takuji; Shimazaki, Hiroaki; Kan, Toshiki; Nakaoka, Kazunori; Ohki, Masashi; Takagawa, Yuka; Kamei, Hiroyuki; Yoshioka, Kentaro

2015-07-01

To elucidate the effect of adding branched-chain amino acid (BCAA)-enriched nutrient mixtures in cirrhotic patients with hypoalbuminemia despite the use of BCAA granules. A BCAA-enriched nutrient mixture containing 5.6 g of BCAA and 210 kcal was additionally administered in 40 cirrhotic patients with hypoalbuminemia despite their treatment with BCAA granules containing 12 g of BCAA. Laboratory data were assessed at 6 months before beginning additional therapy, at baseline, and at 6 months after baseline. Serum albumin levels significantly decreased from 6 months before baseline (3.14±0.47 g/dL) to baseline (2.83±0.46 g/dL), despite the treatment with BCAA granules (p<0.001), and tended to increase from baseline to 6 months after baseline (2.95±0.42 g/dL) (p=0.084). In the subset of 23 patients without hepatocellular carcinoma treatments, upper gastrointestinal tract bleeding, or albumin infusion, serum albumin levels significantly increased from baseline (2.93±0.38 g/dL) to 6 months after baseline (3.15±0.34 g/dL) (p=0.014). Additional therapy with BCAA-enriched nutrient mixtures increased serum albumin levels of the cirrhotic patients with hypoalbuminemia despite the treatment with BCAA granules and without hepatocellular carcinoma treatment, upper gastrointestinal tract bleeding, or albumin infusion.

Cirrhosis could be associated with severe mutations of the cystic fibrosis gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lenaerts, C.; Piussan, C.; Soto, B.

1994-09-01

Previous studies failed to demonstrate a genetic predisposition to liver disease in cystic fibrosis. In order to characterize patients with cirrhosis defined on the basis of either hepatosplenomegaly, portal hypertension or liver biopsy, we analyzed a total number of 110 cirrhotic CF patients from different CF centers in France. Of them, 71 are males, which is not different from the overall CF french population. All but 2 are pancreatic insufficient. A history of meconium ileus {plus_minus} meconium ileus equivalent seems to be a risk factor for cirrhosis since these complications are present in 29% of the cirrhotic patients vs. 19%more » in the non-cirrhotic population (p = 0.03). This confirms our previous data in a postmortem study. Genotype analysis was performed in all the patients. {Delta}F508 represents 70% of the identified mutations with a higher proportion of {Delta}F508 +/+ in the cirrhotic than in the non-cirrhotic population (52% vs. 42%, p=0.003), 35% {Delta}F508 +/- vs. 42% and 13% {Delta}F508 -/- vs. 16%. Sixty percent of the other mutations associated with cirrhosis are identified, usually in {Delta}F508 +/- and include 1303 N-K, 542 G-X, 1078 del T, 1282 W-X, 1313 Q-X, 827 E-X, 1061 G-R, 1301 N-H, 14 K-X, 1717-1 G-A, 1918 delGC, 2183 A-G, 2184 delA, 405+1 G-A, 507 {Delta}l, 574 delA, 621+1 G-T, 85 G-E and 1303 N-K/other, 227 L-R/other. None of the cirrhotic patients bear one of the dominant missense mutations regarded as mild with respect to pancreatic function (117 R-H, 334 R-W, 347 R-P, 455 A-E, 574 P-H) or both the {Delta}F508 and the 5512 G-A mutations associated with a decreased risk of meconium ileus. Cirrhosis could thus be linked to the presence of 2 of the severe mutations of the CF gene associated with pancreatic insufficiency.« less

Is computed tomography volumetric assessment of the liver reliable in patients with cirrhosis?

PubMed Central

Goumard, Claire; Perdigao, Fabiano; Cazejust, Julien; Zalinski, Stéphane; Soubrane, Olivier; Scatton, Olivier

2014-01-01

Objectives: The estimation of liver volume (LV) has been widely studied in normal liver, the density of which is considered to be equivalent to 1 kg/l. In cirrhosis, volumetric evaluation and its correlation to liver mass remain unclear. The aim of this study was to evaluate the accuracy of computed tomography (CT) scanning to assess LV in patients with cirrhosis. Methods: Liver volume was evaluated by CT (CTLV) and correlated to the explanted liver weight (LW) in 49 patients. Liver density (LD) and its association with clinical features were analysed. Commonly used formulae for estimating LV were also evaluated. The real density of cirrhotic liver was prospectively measured in explant specimens. Results: Wide variations between CTLV (in ml) and LW (in g) were found (range: 3–748). Cirrhotic livers in patients with hepatitis B virus infection presented significantly increased LD (P = 0.001) with lower CTLV (P = 0.005). Liver volume as measured by CT was also decreased in patients with Model for End-stage Liver Disease scores of >15 (P = 0.023). Formulae estimating LV correlated poorly with CTLV and LW. The density of cirrhotic liver measured prospectively in 15 patients was 1.1 kg/l. Conclusions: In cirrhotic liver, LV assessed by CT did not correspond to real LW. Liver density changed according to the aetiology and severity of liver disease. Commonly used formulae did not accurately assess LV. PMID:23679861

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage

PubMed Central

Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

2014-01-01

AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). METHODS: This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. RESULTS: A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. CONCLUSION: Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT. PMID:25320538

Emergence of rifampin-resistant staphylococci after rifaximin administration in cirrhotic patients

PubMed Central

Chang, Ji Young; Woo, So-Youn; Ryu, Min Sun; Joo, Yang-Hee; Lee, Ko Eun; Lee, Jihyun; Lee, Kang Hoon; Moon, Chang Mo; Jung, Hye-Kyung; Shim, Ki-Nam; Jung, Sung-Ae

2017-01-01

Objectives Rifaximin, a poorly absorbed antibiotics, has gut-specific therapeutic effects. Although frequently prescribed to manipulate intestinal luminal bacterial population in various diseases, the possible induction of antibacterial cross-resistance to a target pathogen is a major concern in long-term rifaximin administration. We aimed to evaluate whether rifampin-resistant staphylococci could evolve after rifaximin treatment in cirrhotic patients. Method A total of 25 cirrhotic patients who were administered rifaximin for the prevention of hepatic encephalopathy were enrolled. Swabs from both hands and the perianal skin were acquired on day 0 (before rifaximin treatment), period 1 (1–7 weeks after treatment), and period 2 (8–16 weeks after treatment) the staphylococcal strain identification and rifampin-resistance testing. Results A total of 198 staphylococcal isolates from 15 species were identified. Staphylococcus epidermidis was isolated most frequently, and Staphylococcus haemolyticus was the most common resistant species both from hands and perianal skin. Eleven patients (44.0%) developed rifampin-resistant staphylococcal isolates in period 1. Among these patients, only six (54.5%) were found to have rifampin-resistant isolates in period 2, with no significant infectious events. Rifampin-resistant staphylococcal isolates were more frequently found in perianal skin than from the hands. No patients acquired a newly resistant strain in period 2. Conclusions About one-half of cirrhotic patients in this study developed rifampin-resistant staphylococcal isolates after rifaximin treatment. Although the resistant strains were no longer detected in about half of the patients in the short-term, the long-term influence of this drug treatment should be determined. PMID:28982166

Hepatic stellate cell and myofibroblast-like cell gene expression in the explanted cirrhotic livers of patients undergoing liver transplantation.

PubMed

Estep, J Michael; O'Reilly, Linda; Grant, Geraldine; Piper, James; Jonsson, Johann; Afendy, Arian; Chandhoke, Vikas; Younossi, Zobair M

2010-02-01

Hepatic stellate cells (HSC) are involved in hepatic fibrogenesis. Cell signaling associated with an insult to the liver affects an HSC transdifferentiation to fibrogenic myofibroblast-like cells. To investigate the transcriptional expression distinguishing HSC and myofibroblast-like cells between livers with and without cirrhosis. Tissue from ten cirrhotic livers (undergoing transplant) and four non-cirrhotic livers from the National Disease Research Interchange underwent cell separation to extract HSC and myofibroblast-like cell populations. Separated cell types as well as LI-90 cells were subjected to microarray analysis. Selected microarray results were verified by quantitative real-time PCR. Differential expression of some genes, such as IL-1beta, IL-1alpha, and IL-6, was associated with both transdifferentiation and disease. Other genes, such as fatty acid 2-hydroxylase only show differential expression in association with disease. Functional analysis supported these findings, indicating some signal transduction pathways (IL-6) are involved in disease and activation, whereas retinoid X receptor signaling in HSC from cirrhotic and non-cirrhotic livers varies in scope and quality. These findings indicate distinct phenotypes for HSC from cirrhotic and non-cirrhotic livers. Furthermore, coordinated differential expression between genes involved in the same signal transduction pathways provides some insight into the mechanisms that may control the balance between fibrogenesis and fibrolysis.

Examining the clinical course of genotype 1 chronic hepatitis C patients treated with the cosmos regimen: including patients with advanced liver disease and East Asian ancestry.

PubMed

Roytman, Marina; Ramkissoon, Resham; Wu, Christina; Hong, Leena; Trujillo, Ruby; Huddleston, Leslie; Poerzgen, Peter; Seto, Todd; Wong, Linda; Tsai, Naoky

2016-07-01

The COSMOS study was a phase 2a clinical trial that showed high cure rates of genotype 1 chronic hepatitis C (CHC) and a favorable side effect profile using a 12-week regimen of simeprevir + sofosbuvir (SIM + SOF). Given the small number of patients treated with the SIM + SOF regimen in the COSMOS trial, there is uncertainty regarding the efficacy and safety of this combination therapy. We now report our experience with the COSMOS regimen in the multiethnic population of Hawaii, including patients of East Asian ancestry and with decompensated cirrhosis. This study is a retrospective review of 138 patients treated with a fixed dose regimen of SIM 150 mg and SOF 400 mg daily at a single referral center. We collected data on demographics, side effects, laboratory studies and sustained virological response (SVR). Statistical analysis was performed with Stata v8.2 software. Baseline characteristics of the 138 patients initiated with SIM + SOF therapy were: 68.8 % cirrhotic (22.1 % of those Child-Pugh Class B), 37 % Asian, 11.6 % Pacific Islander, 63 % male, mean age 61.3 ± 7.8 years, mean BMI 27.8 ± 6.1 kg/m(2), 26.8 % diabetic, 63.8 % genotype 1a, 44.9 % previously treatment experienced. A total of 100 % of patients that completed therapy (n = 137) had undetectable viral loads at end of treatment (EOT). Twelve patients relapsed post-treatment resulting in an overall 12 week SVR (SVR12) rate of 89.1 %. 95 % of decompensated cirrhotic patients achieved SVR12, compared to 85.3 % of compensated cirrhotic patients and 93 % of non-cirrhotic patients. 92 % of Asian patients achieved SVR12 compared to 87.5 % in non-Asian patients. There were no statistically significant differences in SVR12 between treatment naive and treatment experienced patients (86.8 vs 91.9 %). 87.5 % of post-transplant patients achieved SVR12. The main side effects were headache 16.2 %, fatigue 24.2 %, pruritis 14.1 %; none were >grade 2 in severity. There were no differences in side effect profiles of patients with decompensated cirrhosis. Pruritis only was statistically significant between Asians and non-Asians (22 vs 5.7 %). Trends toward improvement in platelet counts and total bilirubin were noted at 12-weeks post treatment, while improvement in albumin in cirrhotic patients reached statistical significance (3.77-4.01 mg/dL, p = 0.0108). The 12-week fixed dose course of SIM + SOF was well tolerated in a multiethnic population of primarily cirrhotic patients, including those with decompensated disease. This real world trial achieved SVR12 rates comparable to the COSMOS data. Higher incidence of adverse side effects was not observed with an exception of higher rate of pruritis in Asians. The increase in albumin in cirrhotic patients was statistically significant and suggested early improvement in synthetic function following viral eradication. Higher BMI (≥30 kg/m(2)) was the only factor that correlated with post-treatment relapse by multivariate analysis.

Cognitive impairments of alcoholic cirrhotic patients: correlation with endogenous benzodiazepine receptor ligands and increased affinity of platelet receptors.

PubMed Central

Kapczinski, F; Curran, H V; Przemioslo, R; Williams, R; Fluck, E; Fernandes, C; File, S E

1996-01-01

OBJECTIVES--To determine whether differences in cognitive function between alcoholic and non-alcoholic cirrhotic patients relate to differences in endogenous ligands for the benzodiazepine receptor and/or benzodiazepine binding. METHODS--Seventeen grade-I hepatic encephalopathic patients (nine alcoholic, eight non-alcoholic) were compared with 10 matched controls on plasma concentrations of endogenous ligands for the neuronal benzodiazepine receptor, benzodiazepine binding in platelets, and performance on tests of cognitive function. RESULTS--Both groups of patients were impaired on verbal recall and on reaction time tasks compared with controls; alcoholic patients were also impaired on Reitan's trails test and digit cancellation. Four of the 17 patients had detectable concentrations of endogenous benzodiazepine ligands and they were more impaired than other patients on trails and cancellation tests. The groups did not differ in the density of benzodiazepine platelet receptors, but receptor affinity was higher in alcoholic patients than in controls; furthermore, receptor affinity correlated with the time to complete the cancellation task and with reaction time. CONCLUSION--Alcoholic cirrhotic patients may have enhanced concentrations of ligands for neuronal and peripheral benzodiazepine receptors and these may contribute to cognitive impairments in these patients. PMID:8648337

Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection

PubMed Central

Leggio, L.; Ferrulli, A.; Zambon, A.; Caputo, F.; Kenna, G.A.; Swift, R.M.; Addolorato, G.

2016-01-01

Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABAB receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some LFTs (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients. PMID:22244707

Obliterative portal venopathy without portal hypertension: an underestimated condition.

PubMed

Guido, Maria; Sarcognato, Samantha; Sonzogni, Aurelio; Lucà, Maria Grazia; Senzolo, Marco; Fagiuoli, Stefano; Ferrarese, Alberto; Pizzi, Marco; Giacomelli, Luciano; Colloredo, Guido

2016-03-01

Obliterative portal venopathy without portal hypertension has been described by a single study in a limited number of patients, thus very little is known about this clinical condition. This study aimed to investigate the prevalence of obliterative portal venopathy and its clinical-pathological correlations in patients with cryptogenic chronic liver test abnormalities without clinical signs of portal hypertension. We analysed 482 liver biopsies from adults with non-cirrhotic cryptogenic chronic liver disorders and without any clinical signs of portal hypertension, consecutively enrolled in a 5-year period. Twenty cases of idiopathic non-cirrhotic portal hypertension diagnosed in the same period, were included for comparison. Histological findings were matched with clinical and laboratory features. Obliterative portal venopathy was identified in 94 (19.5%) of 482 subjects and in all 20 cases of idiopathic non-cirrhotic portal hypertension: both groups shared the entire spectrum of histological changes described in the latter condition. The prevalence of incomplete fibrous septa and nodular regenerative hyperplasia was higher in the biopsies of idiopathic non-cirrhotic portal hypertension (P = 0.006 and P = 0.002), a possible hint of a more advanced stage of the disease. The two groups also shared several clinical laboratory features, including a similar liver function test profile, concomitant prothrombotic conditions and extrahepatic autoimmune disorders. Obliterative portal venopathy occurs in a substantial proportion of patients with unexplained chronic abnormal liver function tests without portal hypertension. The clinical-pathological profile of these subjects suggests that they may be in an early (non-symptomatic) stage of idiopathic non-cirrhotic portal hypertension. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantification of gluconeogenesis in cirrhosis: response to glucagon.

PubMed

Bugianesi, E; Kalhan, S; Burkett, E; Marchesini, G; McCullough, A

1998-12-01

Accelerated starvation and early recruitment of alternate fuels in cirrhosis have been attributed to reduced availability of hepatic glycogen. The aim of this study was to measure gluconeogenesis (as a marker of protein oxidation) in relation to total glucose production and glucagon-stimulated glycogenolysis. Glucose and urea production, gluconeogenesis, and glycogenolysis were calculated using stable isotope methods before and during glucagon infusion (3 ng. kg-1. min-1) in 5 cirrhotic patients and 5 matched controls before and after glycogen repletion. In the basal state, cirrhotic patients had a normal rate of glucose production, but the contribution of gluconeogenesis was increased (74.3% +/- 4.1% vs. 55. 6% +/- 12.1%; P < 0.005). Glycogen repletion normalized the rate of gluconeogenesis. The glycemic response to glucagon (3 ng. kg-1. min-1) was blunted in cirrhotic patients because of a lower rate of glycogenolysis (0.63 +/- 0.23 vs. 1.22 +/- 0.23 mg. kg-1. min-1; P < 0.01) and was not affected by glycogen repletion. Despite increased gluconeogenesis, the simultaneously measured rate of urea synthesis was lower in cirrhotic patients (3.11 +/- 1.02 vs. 5.0 +/- 1.0 mg/kg; P < 0.05). These data show that in cirrhosis, glucose production is sustained by an increased rate of gluconeogenesis. The hepatic resistance to glucagon action is not caused by reduced glycogen stores.

Hepatocellular Carcinoma is Associated with Gut Microbiota Profile and Inflammation in Non-Alcoholic Fatty Liver Disease.

PubMed

Ponziani, Francesca Romana; Bhoori, Sherrie; Castelli, Chiara; Putignani, Lorenza; Rivoltini, Licia; Del Chierico, Federica; Sanguinetti, Maurizio; Morelli, Daniele; Paroni Sterbini, Francesco; Petito, Valentina; Reddel, Sofia; Calvani, Riccardo; Camisaschi, Chiara; Picca, Anna; Tuccitto, Alessandra; Gasbarrini, Antonio; Pompili, Maurizio; Mazzaferro, Vincenzo

2018-04-17

The gut-liver axis plays a pivotal role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is the third cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study is to explore what features of the gut microbiota are associated with HCC in cirrhotic patients with NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1: 21 patients), NAFLD-related cirrhosis without HCC (group 2: 20 patients) and healthy controls (group 3: 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, whilst intestinal permeability was similar to cirrhotic patients without HCC. Plasma levels of interleukin (IL) 8, IL13, C-C motif chemokine ligand (CCL) 3, CCL4 and CCL5 were higher in the HCC group and were associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of cirrhotic patients showed higher abundance of Enterobacteriaceae and Streptococcus, and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides. Our results suggest that in cirrhotic patients with NAFLD gut microbiota profile and systemic inflammation are significantly correlated, and can concur in the process of hepatocarcinogenesis. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Retreatment with sofosbuvir/velpatasvir in cirrhotic patients with genotype 4 who failed a previous interferon-free regimen: a case series.

PubMed

Boglione, Lucio; Pinna, Simone Mornese; Lupia, Tommaso; Cariti, Giuseppe; Di Perri, Giovanni

2018-02-14

The novel available interferon (IFN)-free regimens significantly improved the sustained virological response (SVR) in patients with chronic hepatitis C (CHC), without important side-effects and with shorter duration of treatment. In a subset of patients, however, the treatment failure (TF) was due to the presence of resistance-associated substitutions (RAS) that lead to virological breakthrough (BT) or relapse. We analyzed in this case-series the role of RAS on the TF in cirrhotic patients with GT4, treated with a previous IFN-free regimen, and retreated with the combination of sofosbuvir (SOF)/velpatasvir (VEL) for 12 or 24 weeks, without ribavirin (RBV). We included in this analysis all patients with GT4 who failed a previous IFN-free treatment, with the presence of RAS at BT or relapse. All patients were retreated with a fixed combination of SOF/VEL for 12/24 weeks, without RBV. We evaluated the SVR and the MELD score change after the treatment. Seven patients were described. All were cirrhotic, Child-Pug A (n=5), B (n=2); baseline RAS were detected in 4/7 subjects; at post-treatment detection, NS5 RAS were: F28S (n=1), Q30K (n=2), S30G (n=1), NS3 were: S122R (n=1), S122G (n=2), D168V (n=3). All retreated patients gained the SVR. MELD score improved in all subjects with a median change of 3 points. No significant side-effects or adverse events were reported. The combination SOF/VEL could be considered for the retreatment of cirrhotic GT4 patients who failed a previous IFN-free treatment with the presence of RAS in NS3 or NS5 regions.

Retreatment with sofosbuvir/velpatasvir in cirrhotic patients with genotype-4 who failed a previous interferon-free regimen: a case series.

PubMed

Boglione, Lucio; Pinna, Simone Mornese; Lupia, Tommaso; Cariti, Giuseppe; Di Perri, Giovanni

2018-02-14

The novel available interferon (IFN)-free regimens significantly improved the sustained virological response (SVR) in patients with chronic hepatitis C (CHC), without important side effects and with shorter duration of treatment. In a subset of patients, however, the treatment failure (TF) was due to the presence of resistance-associated substitutions (RAS) that lead to virological breakthrough (BT) or relapse. We analysed in this case series the role of RAS on the TF in cirrhotic patients with genotype (GT)4, treated with a previous IFN-free regimen, and retreated with the combination of sofosbuvir (SOF)/velpatasvir (VEL) for 12 or 24 weeks, without ribavirin (RBV). We included in this analysis all patients with GT4 who failed a previous IFN-free treatment, with the presence of RAS at BT or relapse. All patients were retreated with a fixed combination of SOF/VEL for 12/24 weeks, without RBV. We evaluated the SVR and the MELD score change after the treatment. Seven patients were described. All were cirrhotic, Child-Pugh A (n=5), B (n=2); baseline RAS were detected in 4/7 subjects; at post-treatment detection, NS5 RAS were: F28S (n=1), Q30K (n=2), S30G (n=1), NS3 were: S122R (n=1), S122G (n=2), D168V (n=3). All retreated patients gained SVR. MELD score improved in all subjects with a median change of 3 points. No significant side effects or adverse events were reported. The combination SOF/VEL could be considered for the retreatment of cirrhotic GT4 patients who failed a previous IFN-free treatment with the presence of RAS in NS3 or NS5 regions.

Low incidence of spontaneous bacterial peritonitis in asymptomatic cirrhotic outpatients.

PubMed

Cadranel, Jean-François; Nousbaum, Jean-Baptiste; Bessaguet, Christophe; Nahon, Pierre; Nguyen-Khac, Eric; Moreau, Richard; Thévenot, Thierry; Silvain, Christine; Bureau, Christophe; Nouel, Olivier; Pilette, Christophe; Paupard, Thierry; Pauwels, Arnaud; Sapey, Thierry; Grangé, Jean-Didier; Tran, Albert

2013-03-27

To compare the incidence of spontaneous bacterial peritonitis in cirrhotic outpatients and inpatients undergoing therapeutic paracentesis From January 1 to May 31, 2004, 1041 patients from 70 different hospitals underwent 2123 therapeutic abdominal paracentesis (AP) performed as a outpatient procedure in 355 and as inpatient procedure in 686 cases respectively. The following parameters were compared prospectively between outpatients and inpatients: spontaneous bacterial peritonitis (SBP) prevalence, age, gender, cause of cirrhosis, symptoms, score and grade according to Child-Pugh classification, cirrhosis complications, antibiotics treatment, serum creatinine, platelet count and ascitic protein concentration. SBP was observed in 91 patients. In the whole population the SBP prevalence was 8.7% (95%CI: 7.2-10.6) it was 11.7% (95%CI: 9.5-14.3) in inpatients and 3.1% (95%CI: 1.7-5.5) in outpatients (P < 0.00001). SBP prevalence was 8.3% (95%CI: 4.3-15.6) in symptomatic outpatients vs 1.2% (95%CI: 0.4-3.4) in asymptomatic outpatients (P < 0.002). Patients undergoing outpatient AP were significantly different from those undergoing inpatient AP; they were older (61.1 ± 11.1 years vs 59.4 ± 11.7 years; P = 0.028), cause of cirrhosis was less often alcohol (83 .7 vs 88.2%; P < 0.001), Child-Pugh score was lower (8.9 vs 10.1; P < 0.001) and more often B than C (63.7% vs 38%; P < 0.001). In addition, in outpatients the platelet count was higher (161 ± 93 Giga/L vs 143 ± 89 Giga/L; P = 0.003), serum total bilirubin concentration was lower (38.2 ± 60.7 μmol/L vs 96.3 ± 143.3 μmol/L; P < 0.0001), and ascitic protein concentration higher (17.9 ± 10.7 g/L vs 14.5 ± 10.9 g/L; P < 0.001) than in inpatients. In asymptomatic cirrhotic outpatients, the incidence of spontaneous bacterial peritonitis is low thus exploratory paracentesis could be avoided in these patients without significant risk.

Effects of probiotic therapy on hepatic encephalopathy in patients with liver cirrhosis: an updated meta-analysis of six randomized controlled trials.

PubMed

Xu, Jun; Ma, Rui; Chen, Li-Feng; Zhao, Li-Jun; Chen, Kan; Zhang, Ren-Bing

2014-08-01

Liver cirrhotic patients with hepatic encephalopathy have poor prognosis. Probiotics alter the intestinal microbiota and reduce the production of ammonia. We conducted a meta-analysis about the role of probiotics on liver cirrhotic patients with hepatic encephalopathy. We collected the relevant literatures up to February 21, 2014 from databases of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. A statistical analysis was conducted by RevMan 5.2 and STATA 12.0 software. Six randomized controlled trials involving 496 liver cirrhotic patients were included. The results showed that probiotic therapy significantly reduced the development of overt hepatic encephalopathy (OR [95% CI]: 0.42 [0.26, 0.70], P=0.0007). However, probiotics did not affect mortality, levels of serum ammonia and constipation (mortality: OR [95% CI]: 0.73 [0.38, 1.41], P=0.35; serum ammonia: WMD [95% CI]: -3.67 [-15.71, 8.37], P=0.55; constipation: OR [95% CI]: 0.67 [0.29, 1.56], P=0.35). Probiotics decrease overt hepatic encephalopathy in patients with liver cirrhosis.

Chronic liver disease and 90-day mortality in 21,359 patients following peptic ulcer bleeding--a Nationwide Cohort Study.

PubMed

Holland-Bill, L; Christiansen, C F; Gammelager, H; Mortensen, R N; Pedersen, L; Sørensen, H T

2015-03-01

Bleeding is a serious and frequent complication of peptic ulcer disease. Hepatic dysfunction can cause coagulopathy and increases the risk of peptic ulcer bleeding. However, whether chronic liver disease increases mortality after peptic ulcer bleeding remains unclear. To examine the prognostic impact of chronic liver disease on mortality after peptic ulcer bleeding. We used population-based medical registries to conduct a cohort study of all Danish residents hospitalised with incident peptic ulcer bleeding from 2004 through 2011. We identified patients diagnosed with liver cirrhosis or non-cirrhotic chronic liver disease before their admission for peptic ulcer bleeding. We then computed 90-day mortality after peptic ulcer bleeding based on the Kaplan-Meier method (1 - survival function) and used a Cox regression model to estimate mortality rate ratios (MRRs), controlling for potential confounders. We identified 21,359 patients hospitalised with peptic ulcer bleeding. Among these, 653 (3.1%) had a previous diagnosis of liver cirrhosis and 474 (2.2%) had a history of non-cirrhotic chronic liver disease. Patients with liver cirrhosis and non-cirrhotic chronic liver disease had a cumulative 90-day mortality of 25.3% and 20.7%, respectively, compared to 18.3% among patients without chronic liver disease. Liver cirrhosis was associated with an adjusted 90-day MRR of 2.38 (95% CI: 2.02-2.80), compared to 1.49 (95% CI: 1.22-1.83) among patients with non-cirrhotic chronic liver disease. Patients with chronic liver disease, particularly liver cirrhosis, are at increased risk of death within 90 days after hospitalisation for peptic ulcer bleeding compared to patients without chronic liver disease. © 2015 John Wiley & Sons Ltd.

Umbilical hernia alloplastic dual-mesh treatment in cirrhotic patients.

PubMed

Guriță, R E; Popa, F; Bălălău, C; Scăunașu, R V

2013-03-15

Abdominal wall hernias represent a pathology with an impressive prevalence among the population of patients with cirrhosis complicated by ascites. The aggressive surgical approach of umbilical hernia for patients with cirrhotic background remains a controversial problem, accompanied by anesthetic and surgical risk. Its indication remains fully justified in case of severe symptoms or life threatening complications: strangulation, incarceration, evisceration. This article evaluates results obtained by using dual-mesh alloplastic materials for surgical treatment of umbilical hernias affecting cirrhotic patients with incipient liver injury. Our lot consists of twelve patients with ages between 45 and 65 years, diagnosed with hepatic cirrhosis, without other associated comorbidities. All patients were admitted for strangulated umbilical hernia. Among the analyzed lot, no decease was encountered, the morbidity being limited to two cases of parietal suppuration, solved conservatively, without the mesh removal. There were no ascitic fistulas. No recurrences were registered for a 12 months tracking period. The presence of cirrhosis implies a high anesthetic and surgical risk, the intervention being grafted by a substantial increase of mortality and morbidity in an emergency setting. The development of new alloplastic materials, together with the modern anesthetic techniques, allows superior results for patients with incipient hepatic injury.

Association between chronic hepatitis C infection and hepatocellular carcinoma in a Scottish population.

PubMed Central

Haydon, G H; Jarvis, L M; Simmonds, P; Harrison, D J; Garden, O J; Hayes, P C

1997-01-01

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The geographical prevalence varies considerably in different countries and Scotland is regarded as an area of low risk for the disease. AIMS: To assess the association between chronic hepatitis C infection (HCV) and HCC in a population of patients presenting to a single hospital. PATIENTS: One hundred and fourteen cases of histologically confirmed liver cancer presenting to the Royal Infirmary of Edinburgh between 1985 and 1994 were examined. METHODS: Of 114 cases of HCC, 80 samples of stored sera were available. Samples positive for HCV Ab were genotyped by restriction fragment length polymorphism analysis of HCV c-DNA. A population of 29 cirrhotic patients (diagnosed between 1985 and 1994) with chronic HCV infection was also genotyped. RESULTS: Chronic HCV infection was a major risk factor (30% of tested HCC patients) identified. HCV genotype 1b was predominant (16 of 20 patients). The time from HCV transmission to development of cancer ranged from 10 to 50 years (median 30). In the cirrhotic patient population, a broader distribution of genotypes was present (genotype 1a: 7; genotype 1b: 8; genotype 2b: 3; genotype 3a: 8 and genotype 4: 2). However, this population was significantly younger. (Mean (SD) 52 (14.5) years) (p = 0.0002) and demonstrated a significantly shorter duration of infection: range 10-40 years (median: 19). CONCLUSION: There is a strong association between chronic HCV infection, cirrhosis, and hepatocarcinogenesis in this Scottish population. The study was unable to distinguish whether the high prevalence of genotype 1b in the HCC population reflected increased oncogenicity in itself, or whether 1b was simply the most prevalent genotype in Scotland when these patients were infected. PMID:9155590

Non-cirrhotic portal fibrosis at a tertiary care centre in South India.

PubMed

Mukta, V; Panicker, Lakshmi C; Sivamani, Kalaimani; Goel, Amit; Basu, Debdutta; Dhanapathi, Halnayak

2017-01-01

Non-cirrhotic portal fibrosis (NCPF) is one of the important causes of upper gastrointestinal haemorrhage in patients in tropical countries. The aim of this study was to describe the clinical and laboratory profile of 68 patients with NCPF. NCPF is defined as liver disease with: (1) evidence of portal hypertension; (2) a liver biopsy showing no cirrhosis or a Tc-labelled sulphur colloid scan showing a pattern suggestive of NCPF; and (3) a patent splenoportal axis. The clinical, laboratory and demographic features of 68 patients with such criteria were studied and analysed. NCPF was common in women (73.5%) in the fourth decade of life. The median duration of illness was 24 months (range, 1 month-28 years). Patients presented to hospital with the sensation of a mass in the abdomen (50%) or with haematemesis (26.5%). They had splenomegaly (95.6%) and thrombocytopenia (88.2%). The majority of patients had normal liver function tests. Abdominal ultrasonography showed increased periportal and peri gallbladder echoes (72%), spontaneous collaterals (41.2%) and ascites (19.1%). Liver biopsy revealed portal venous sclerosis (76.3%) and periportal fibrosis (55.3%). Tc-labelled sulphur colloid scan was suggestive of NCPF in the remaining 30 cases. NCPF is common in South India. Transient ascites occurs due to decompensation of liver function after variceal bleeding and in long standing cases of NCPF. Our study used Tc-sulphur scan for diagnosing NCPF in patients where liver biopsy was contraindicated in view of severe thrombocytopenia; however, the diagnostic utility of Tc-sulphur nuclear scan to diagnose NCPF in patients with severe hypersplenism needs to be further evaluated in future studies. © The Author(s) 2016.

Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis

PubMed Central

Giannelli, Valerio; Di Gregorio, Vincenza; Iebba, Valerio; Giusto, Michela; Schippa, Serena; Merli, Manuela; Thalheimer, Ulrich

2014-01-01

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis. PMID:25492994

Modification in CSF specific gravity in acutely decompensated cirrhosis and acute on chronic liver failure independent of encephalopathy, evidences for an early blood-CSF barrier dysfunction in cirrhosis.

PubMed

Weiss, Nicolas; Rosselli, Matteo; Mouri, Sarah; Galanaud, Damien; Puybasset, Louis; Agarwal, Banwari; Thabut, Dominique; Jalan, Rajiv

2017-04-01

Although hepatic encephalopathy (HE) on the background of acute on chronic liver failure (ACLF) is associated with high mortality rates, it is unknown whether this is due to increased blood-brain barrier permeability. Specific gravity of cerebrospinal fluid measured by CT is able to estimate blood-cerebrospinal fluid-barrier permeability. This study aimed to assess cerebrospinal fluid specific gravity in acutely decompensated cirrhosis and to compare it in patients with or without ACLF and with or without hepatic encephalopathy. We identified all the patients admitted for acute decompensation of cirrhosis who underwent a brain CT-scan. Those patients could present acute decompensation with or without ACLF. The presence of hepatic encephalopathy was noted. They were compared to a group of stable cirrhotic patients and healthy controls. Quantitative brain CT analysis used the Brainview software that gives the weight, the volume and the specific gravity of each determined brain regions. Results are given as median and interquartile ranges and as relative variation compared to the control/baseline group. 36 patients presented an acute decompensation of cirrhosis. Among them, 25 presented with ACLF and 11 without ACLF; 20 presented with hepatic encephalopathy grade ≥ 2. They were compared to 31 stable cirrhosis patients and 61 healthy controls. Cirrhotic patients had increased cerebrospinal fluid specific gravity (CSF-SG) compared to healthy controls (+0.4 %, p < 0.0001). Cirrhotic patients with ACLF have decreased CSF-SG as compared to cirrhotic patients without ACLF (-0.2 %, p = 0.0030) that remained higher than in healthy controls. The presence of hepatic encephalopathy did not modify CSF-SG (-0.09 %, p = 0.1757). Specific gravity did not differ between different brain regions according to the presence or absence of either ACLF or HE. In patients with acute decompensation of cirrhosis, and those with ACLF, CSF specific gravity is modified compared to both stable cirrhotic patients and healthy controls. This pattern is observed even in the absence of hepatic encephalopathy suggesting that blood-CSF barrier impairment is manifest even in absence of overt hepatic encephalopathy.

Genetic polymorphisms of ADH1B, ADH1C and ALDH2 in Turkish alcoholics: lack of association with alcoholism and alcoholic cirrhosis.

PubMed

Vatansever, Sezgin; Tekin, Fatih; Salman, Esin; Altintoprak, Ender; Coskunol, Hakan; Akarca, Ulus Salih

2015-05-17

No data exists regarding the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) gene polymorphisms in Turkish alcoholic cirrhotics. We studied the polymorphisms of ADH1B, ADH1C and ALDH2 genes in alcoholic cirrhotics and compared the results with non-cirrhotic alcoholics and healthy volunteers. Overall, 237 subjects were included for the study: 156 alcoholic patients (78 cirrhotics, 78 non-cirrhotic alcoholics) and 81 healthy volunteers. Three different single-nucleotide-polymorphism genotyping methods were used. ADH1C genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism method. The identified ADH1C genotypes were named according to the presence or absence of the enzyme restriction sites. ADH1B (Arg47Hys) genotyping was performed using the allele specific primer extension method, and ALDH2 (Glu487Lys) genotyping was performed by a multiplex polymerase chain reaction using two allele-specific primer pairs. For ADH1B, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 97.4%, 94.9% and 99.4%, respectively. For ADH1C, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 47%, 36.3% and 45%, respectively. There was no statistical difference between the groups for ADH1B and ADH1C (p>0.05). All alcoholic and non-alcoholic subjects (100%) had the allele *1 for ALDH2. The obtained results for ADH1B, ADH1C, and ALDH gene polymorphisms in the present study are similar to the results of Caucasian studies. ADH1B and ADH1C genetic variations are not related to the development of alcoholism or susceptibility to alcoholic cirrhosis. ALDH2 gene has no genetic variation in the Turkish population.

A rare presentation of hepatocellular carcinoma in non-cirrhotic liver.

PubMed

Kabbage, Lamia; El Kouhen, Meryem; Taghy, Ahmed; Znati, Kaoutar; Kabbaj, Nawal

2017-01-01

Hepatocellular carcinoma is the most frequent type of liver malignancy. Most cases of hepatocellular carcinoma are secondary to either viral hepatitis (hepatitis B, C) or alcoholic cirrhosis. Liver cirrhosis due to any other causes is considered as a risk factor for development of hepatocellular carcinoma; however, hepatocellular carcinoma in non cirrhotic livers remains a rare condition. The present case report describes a 59-year-old woman patient admitted to explore right hypochondriac and epigastric pain, with no evidence of pre-existing liver disease and with a good general condition. The computed tomography was very suggestive of a gastro-intestinal stromal tumor. But, at laparotomy, a huge hepatic tumor was discovered. Histopathological study confirmed the presence of primary hepatocellular carcinoma. Hepatocellular carcinoma occurs more frequently on a cirrhotic liver. However, it can occur on a non cirrhotic liver and remains and extremely rare case.

Hepatic vein transit time of second-generation ultrasound contrast agent: new tool in the assessment of portal hypertension.

PubMed

Luisa, Siciliani; Vitale, Giovanna; Sorbo, Anna Rita; Maurizio, Pompili; Lodovico, Rapaccini Gian

2017-03-01

It has been demonstrated that Doppler waveform of the hepatic vein (normally triphasic) is transformed into a biphasic or monophasic waveform in cirrhotic patients. The compressive mechanism of liver tissue has been considered up till now the cause of this change. Moreover, cirrhotics show, after USCA injection, a much earlier HVTT due to intrahepatic shunts. Our aim was to prospectively evaluate the correlation between Doppler pattern of hepatic vein and HVTT of a second-generation USCA; we also correlated HVTT with the most common indexes of portal hypertension. We enrolled 38 participants: 33 cirrhotics and 5 healthy controls. Doppler shift signals were obtained from the right hepatic vein. To characterize the hepatic vein pattern, we used the hepatic vein waveform index (HVWI). This index becomes >1 with the appearance of the triphasic waveform. We recorded a clip from 20 s before to 2 min after a peripheral intravenous bolus injection of 2.4 ml of USCA (sulfur hexafluoride).The time employed by USCA to cross the liver from the hepatic artery and portal vein to the hepatic vein was defined as HA-HVTT and PV-HVTT, respectively. Cirrhotics with low HVWI showed an earlier transit time; participants with higher HVWI had a longer transit time ( p  < 0.001). HVTT was earlier as MELD, Child-Pugh score and spleen diameter increased. Patients with ascites and varices of large size had significantly shorter transit times. Abnormal hepatic vein Doppler waveform in cirrhotic patients could be due to intrahepatic shunts. HVTT could be useful in the non-invasive evaluation of portal hypertension.

The efficacy and the immunomodulatory effect of rifaximin in prophylaxis of spontaneous bacterial peritonitis in cirrhotic Egyptian patients.

PubMed

Mostafa, Tarek; Badra, Gamal; Abdallah, Mahmoud

2015-03-01

This study aimed to evaluate the efficacy and the immunomodulatory effect of rifaximin as another promising prophylactic therapy against spontaneous bacterial peritonitis (SBP) in cirrhotics. Seventy cirrhotic patients with ascites were included in the study. Patients were divided into two groups in a randomized single-blind fashion. Group one (n=40) received rifaximin and group two (n=30) received norfloxacin (control group). The treatment duration was 6 months. Serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 ( IL-6), and interleukin-10 (IL-10) were the primary inflammatory markers of the study to evaluate the effect of the medications used. Three months after treatment, five cases on norfloxacin therapy showed SBP, whereas all cases on rifaxmine therapy were free from SBP. In addition, there was no significant difference between patients on rifaximin and norfloxacin therapy with respect to TNF-α, IL-6, and IL-10 serum levels (p>0.05). Furthermore, patients on both rifaximin and norfloxacin therapies showed a statistically significant decrease in TNF-α and IL-6 serum levels compared with their baseline levels (p=0.000 and p=0.000, respectively). In contrast, serum IL-10 showed a statistically significant increase in both groups in comparison with its baseline level (p>0.00). Six-month after treatment, patients on rifaximin therapy showed more effective remission from SBP than those on norfloxacin therapy. In conclusion, the use of rifaximin not only prevents bacterial translocation but also modulates the immune response of the inflammatory and the anti-inflammatory cytokines in SBP patients. However, the efficacy and the immunomodulatory effect of rifaximin in the prophylaxis of SBP in cirrhotics needs further prospective large-scale, double-blind studies.

Treating hepatic encephalopathy in cirrhotic patients admitted to ICU with sodium phenylbutyrate: a preliminary study.

PubMed

Weiss, Nicolas; Tripon, Simona; Lodey, Marion; Guiller, Elsa; Junot, Helga; Monneret, Denis; Mayaux, Julien; Brisson, Hélène; Mallet, Maxime; Rudler, Marika; Imbert-Bismut, Françoise; Thabut, Dominique

2018-04-01

Hepatic encephalopathy (HE) influences short-term and long-term prognoses. Recently, glycerol phenylbutyrate (PB), that lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion, has shown that it was effective in preventing the occurrence of HE in RCT. The aim was to assess the benefits of sodium PB in cirrhotic patients admitted to ICU for overt HE, in terms of ammonia levels decrease, neurological improvement, and survival. Cirrhotic patients who presented with overt HE, ammonia levels >100 μmol/L, and did not display any contra-indication were included. Sodium PB was administered at 200 mg/kg/day. Control group included historical controls treated by standard therapy, matched for age, sex, MELD score, and severity of HE. Eighteen patients were included and treated with sodium PB (age: 59 [45-68], male gender: 15 [83%], Child-Pugh B: 8 [44%], Child-Pugh C: 10 [56%], and MELD score: 16 [13-23]). Ammonia levels significantly decreased in the PB as compared to the control group from inclusion to 12 h and from inclusion to 48 h (P = 0.0201 and P = 0.0230, respectively). The proportion of patients displaying neurological improvement was only higher in the PB-treated group as compared to controls at ICU discharge (15 [83%] vs. 9 [50%], P = 0.0339). ICU discharge survival was significantly higher in patients treated with PB (17 [94%] vs. 9 [50%], P = 0.0017). In cirrhotic patients with overt HE, sodium PB could be effective in reducing ammonia levels and might be effective in improving neurological status and ICU discharge survival. More extensive data, especially a RCT, are mandatory. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Severe bleeding from esophageal varices resistant to endoscopic treatment in a non cirrhotic patient with portal hypertension

PubMed Central

Caronna, Roberto; Bezzi, Mario; Schiratti, Monica; Cardi, Maurizio; Prezioso, Giampaolo; Benedetti, Michele; Papini, Federica; Mangioni, Simona; Martino, Gabriele; Chirletti, Piero

2008-01-01

A non cirrhotic patient with esophageal varices and portal vein thrombosis had recurrent variceal bleeding unsuccessfully controlled by endoscopy and esophageal transection. Emergency transhepatic portography confirmed the thrombosed right branch of the portal vein, while the left branch appeared angulated, shifted and stenotic. A stent was successfully implanted into the left branch and the collateral vessels along the epatoduodenal ligament disappeared. In patients with esophageal variceal hemorrhage and portal thrombosis if endoscopy fails, emergency esophageal transection or nonselective portocaval shunting are indicated. The rare patients with only partial portal thrombosis can be treated directly with stenting through an angioradiologic approach. PMID:18644135

One year of baclofen in 100 patients with or without cirrhosis: a French real-life experience.

PubMed

Barrault, Camille; Lison, Hortensia; Roudot-Thoraval, Françoise; Garioud, Armand; Costentin, Charlotte; Béhar, Véronique; Medmoun, Mourad; Pulwermacher, Georges; Hagège, Hervé; Cadranel, Jean-François

2017-10-01

Several studies have suggested the efficacy of baclofen in reducing alcohol consumption, leading to a temporary recommendation for use in France. Our aim was to report our experience in using baclofen in alcohol-dependant patients with or without liver cirrhosis. Consecutive patients from two liver and alcohol units were recruited over a 3-year period and received increasing doses of baclofen associated with social, psychological, and medical care. One hundred patients were treated, of whom 65 were cirrhotic. After 1 year, 86 patients were still being followed up. At a mean dosage of 40 mg/day (extremes: 30-210), the median daily alcohol consumption reduced from 80 to 0 g/day (P<0.001). Twenty patients drank a small amount of alcohol of up to 30 g/day and 44 patients were completely abstinent. These declarative results were associated with a significant improvement in alcohol-related biological markers in this 'low-consumption' group of 64 patients: the median γ-glutamyl transferase decreased from 3.9 to 2.0 UNL (P<0.001), the mean aspartate transaminase decreased from 2.6 to 1.2 UNL (P<0.001), and the mean corpuscular volume decreased from 101 to 93 µm (P<0.001). In cirrhotic patients, bilirubinemia decreased significantly from 22 to 11 µmol/l (P=0.026), prothrombin time increased from 68 to 77% (P<0.001), and albuminemia increased from 34.1 to 37.4 g/l (P<0.001). Twenty patients reported grades 1-2 adverse events. No liver or renal function deterioration occurred in cirrhotic patients. In our cohort, baclofen associated with a global care was very well tolerated even in cirrhotic patients. The marked reduction in alcohol consumption in 64 patients translated into a significant improvement in biological markers and in liver function tests. Baclofen could be very useful, especially in cases of severe alcoholic liver disease.

Correlation of transient elastography with hepatic venous pressure gradient in patients with cirrhotic portal hypertension: A study of 326 patients from India.

PubMed

Kumar, Ashish; Khan, Noor Muhammad; Anikhindi, Shrihari Anil; Sharma, Praveen; Bansal, Naresh; Singla, Vikas; Arora, Anil

2017-01-28

To study the diagnostic accuracy of transient elastography (TE) for detecting clinically significant portal hypertension (CSPH) in Indian patients with cirrhotic portal hypertension. This retrospective study was conducted at the Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, on consecutive patients with cirrhosis greater than 15 years of age who underwent hepatic venous pressure gradient (HVPG) and TE from July 2011 to May 2016. Correlation between HVPG and TE was analyzed using the Spearman's correlation test. Receiver operating characteristic (ROC) curves were prepared for determining the utility of TE in predicting various stages of portal hypertension. The best cut-off value of TE for the diagnosis of CSPH was obtained using the Youden index. The study included 326 patients [median age 52 (range 16-90) years; 81% males]. The most common etiology of cirrhosis was cryptogenic (45%) followed by alcohol (34%). The median HVPG was 16.0 (range 1.5 to 30.5) mmHg. Eighty-five percent of patients had CSPH. A significant positive correlation was noted between TE and HVPG (rho 0.361, P < 0.001). The area under ROC curve for TE in predicting CSPH was 0.740 (95%CI: 0.662-0.818) ( P < 0.01). A cut-off value of TE of 21.6 kPa best predicted CSPH with a positive predictive value (PPV) of 93%. TE has a fair positive correlation with HVPG; thus, TE can be used as a non-invasive modality to assess the degree of portal hypertension. A cut-off TE value of 21.6 kPa identifies CSPH with a PPV of 93%.

Correlation of transient elastography with hepatic venous pressure gradient in patients with cirrhotic portal hypertension: A study of 326 patients from India

PubMed Central

Kumar, Ashish; Khan, Noor Muhammad; Anikhindi, Shrihari Anil; Sharma, Praveen; Bansal, Naresh; Singla, Vikas; Arora, Anil

2017-01-01

AIM To study the diagnostic accuracy of transient elastography (TE) for detecting clinically significant portal hypertension (CSPH) in Indian patients with cirrhotic portal hypertension. METHODS This retrospective study was conducted at the Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, on consecutive patients with cirrhosis greater than 15 years of age who underwent hepatic venous pressure gradient (HVPG) and TE from July 2011 to May 2016. Correlation between HVPG and TE was analyzed using the Spearman’s correlation test. Receiver operating characteristic (ROC) curves were prepared for determining the utility of TE in predicting various stages of portal hypertension. The best cut-off value of TE for the diagnosis of CSPH was obtained using the Youden index. RESULTS The study included 326 patients [median age 52 (range 16-90) years; 81% males]. The most common etiology of cirrhosis was cryptogenic (45%) followed by alcohol (34%). The median HVPG was 16.0 (range 1.5 to 30.5) mmHg. Eighty-five percent of patients had CSPH. A significant positive correlation was noted between TE and HVPG (rho 0.361, P < 0.001). The area under ROC curve for TE in predicting CSPH was 0.740 (95%CI: 0.662-0.818) (P < 0.01). A cut-off value of TE of 21.6 kPa best predicted CSPH with a positive predictive value (PPV) of 93%. CONCLUSION TE has a fair positive correlation with HVPG; thus, TE can be used as a non-invasive modality to assess the degree of portal hypertension. A cut-off TE value of 21.6 kPa identifies CSPH with a PPV of 93%. PMID:28216976

Parallel transjugular intrahepatic portosystemic shunt for controlling portal hypertension complications in cirrhotic patients.

PubMed

He, Fu-Liang; Wang, Lei; Yue, Zhen-Dong; Zhao, Hong-Wei; Liu, Fu-Quan

2014-09-07

To evaluate the feasibility of a second parallel transjugular intrahepatic portosystemic shunt (TIPS) to reduce portal venous pressure and control complications of portal hypertension. From January 2011 to December 2012, 10 cirrhotic patients were treated for complications of portal hypertension. The demographic data, operative data, postoperative recovery data, hemodynamic data, and complications were analyzed. Ten patients underwent a primary and parallel TIPS. Technical success rate was 100% with no technical complications. The mean duration of the first operation was 89.20 ± 29.46 min and the second operation was 57.0 ± 12.99 min. The mean portal system pressure decreased from 54.80 ± 4.16 mmHg to 39.0 ± 3.20 mmHg after the primary TIPS and from 44.40 ± 3.95 mmHg to 26.10 ± 4.07 mmHg after the parallel TIPS creation. The mean portosystemic pressure gradient decreased from 43.80 ± 6.18 mmHg to 31.90 ± 2.85 mmHg after the primary TIPS and from 35.60 ± 2.72 mmHg to 15.30 ± 3.27 mmHg after the parallel TIPS creation. Clinical improvement was seen in all patients after the parallel TIPS creation. One patient suffered from transient grade I hepatic encephalopathy (HE) after the primary TIPS and four patients experienced transient grade I-II after the parallel TIPS procedure. Mean hospital stay after the first and second operations were 15.0 ± 3.71 d and 16.90 ± 5.11 d (P = 0.014), respectively. After a mean 14.0 ± 3.13 mo follow-up, ascites and bleeding were well controlled and no stenosis of the stents was found. Parallel TIPS is an effective approach for controlling portal hypertension complications.

Diagnostic Accuracy of Ascites Fluid Gross Appearance in Detection of Spontaneous Bacterial Peritonitis.

PubMed

Aminiahidashti, Hamed; Hosseininejad, Seyed Mohammad; Montazer, Hosein; Bozorgi, Farzad; Goli Khatir, Iraj; Jahanian, Fateme; Raee, Behnaz

2014-01-01

Spontaneous bacterial peritonitis (SBP) as a monomicrobial infection of ascites fluid is one of the most important causes of morbidity and mortality in cirrhotic patients. This study was aimed to determine the diagnostic accuracy of ascites fluid color in detection of SBP in cirrhotic cases referred to the emergency department. Cirrhotic patients referred to the ED for the paracentesis of ascites fluid were enrolled. For all studied patients, the results of laboratory analysis and gross appearance of ascites fluid registered and reviewed by two emergency medicine specialists. The sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ration of the ascites fluid gross appearance in detection of SBP were measured with 95% confidence interval. The present project was performed in 80 cirrhotic patients with ascites (52.5 female). The mean of the subjects' age was 56.25±12.21 years (35-81). Laboratory findings revealed SBP in 23 (29%) cases. Fifty nine (73%) cases had transparent ascites fluid appearance of whom 17 (29%) ones suffered from SBP. From 21 (26%) cases with opaque ascites appearance, 15 (71%) had SBP. The sensitivity and specificity of the ascites fluid appearance in detection of SBP were 46.88% (Cl: 30.87-63.55) and 87.50% (95% Cl: 75.3-94.14), respectively. It seems that the gross appearance of ascites fluid had poor diagnostic accuracy in detection of SBP and considering its low sensitivity, it could not be used as a good screening tool for this propose.

Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina.

PubMed

Piñero, Federico; Pages, Josefina; Marciano, Sebastián; Fernández, Nora; Silva, Jorge; Anders, Margarita; Zerega, Alina; Ridruejo, Ezequiel; Ameigeiras, Beatriz; D'Amico, Claudia; Gaite, Luis; Bermúdez, Carla; Cobos, Manuel; Rosales, Carlos; Romero, Gustavo; McCormack, Lucas; Reggiardo, Virginia; Colombato, Luis; Gadano, Adrián; Silva, Marcelo

2018-01-27

To investigate any changing trends in the etiologies of hepatocellular carcinoma (HCC) in Argentina during the last years. A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease (NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit. A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers ( n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC (37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLD-HCC was detected when the starting year, i.e ., 2009 was compared to the last one, i.e ., 2015 (4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3% ( P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups (6.6 ng/mL vs 26 ng/mL; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality. The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

Pro-Brain Natriuretic Peptide and Troponin T-Hypersensitivity Levels Correlate With the Severity of Liver Dysfunction in Liver Cirrhosis.

PubMed

Zhao, Jiancheng; Li, Sai; Ren, Linan; Guo, Xiaozhong; Qi, Xingshun

2017-08-01

Increased pro-brain natriuretic peptide (pro-BNP) or troponin T-hypersensitivity (TnT-HSST) levels are common in liver cirrhosis. We conducted a retrospective observational study aimed to evaluate the correlation of pro-BNP and TnT-HSST levels with the clinical characteristics, laboratory data and in-hospital outcomes of patients with liver cirrhosis. We selected cirrhotic patients admitted to our hospital between January 2011 and June 2014. All eligible patients had pro-BNP or TnT-HSST data, or both. The pro-BNP and TnT-HSST data were further divided according to the presence of cardiac diseases. The prevalence of pro-BNP level >900pg/mL was 41.72% (63 of 151 patients). The prevalence of TnT-HSST level >0.05ng/mL was 11.22% (45 of 401 patients). In the overall analysis, pro-BNP level significantly correlated with red blood cell (RBC), platelet, ascites, blood urea nitrogen (BUN), creatinine (Cr), Child-Pugh score, model for end-stage liver disease (MELD) score and in-hospital death; TnT-HSST level significantly correlated with white blood cell, ascites, albumin (ALB), BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients with cardiac diseases, pro-BNP level significantly correlated with RBC, ascites, BUN, Cr, Child-Pugh score and MELD score; TnT-HSST level significantly correlated with sex, ascites, white blood cell, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. In patients without cardiac diseases, pro-BNP level significantly correlated with ascites, RBC, platelet, BUN, Cr, MELD score and in-hospital death; TnT-HSST level significantly correlated with age, ascites, RBC, ALB, BUN, Cr, Child-Pugh score, MELD score and in-hospital death. Pro-BNP and TnT-HSST levels significantly correlated with the severity of liver dysfunction and in-hospital mortality in cirrhosis. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Alterations of Bacteroides sp., Neisseria sp., Actinomyces sp., and Streptococcus sp. populations in the oropharyngeal microbiome are associated with liver cirrhosis and pneumonia.

PubMed

Lu, Haifeng; Qian, Guirong; Ren, Zhigang; Zhang, Chunxia; Zhang, Hua; Xu, Wei; Ye, Ping; Yang, Yunmei; Li, Lanjuan

2015-06-23

The microbiomes of humans are associated with liver and lung inflammation. We identified and verified alterations of the oropharyngeal microbiome and assessed their association with cirrhosis and pneumonia. Study components were as follows: (1) determination of the temporal stability of the oropharyngeal microbiome; (2) identification of oropharyngeal microbial variation in 90 subjects; (3) quantitative identification of disease-associated bacteria. DNAs enriched in bacterial sequences were produced from low-biomass oropharyngeal swabs using whole genome amplification and were analyzed using denaturing gradient gel electrophoresis analysis. Whole genome amplification combined with denaturing gradient gel electrophoresis analysis monitored successfully oropharyngeal microbial variations and showed that the composition of each subject's oropharyngeal microbiome remained relatively stable during the follow-up. The microbial composition of cirrhotic patients with pneumonia differed from those of others and clustered together in subgroup analysis. Further, species richness and the value of Shannon's diversity and evenness index increased significantly in patients with cirrhosis and pneumonia versus others (p < 0.001, versus healthy controls; p < 0.01, versus cirrhotic patients without pneumonia). Moreover, we identified variants of Bacteroides, Eubacterium, Lachnospiraceae, Neisseria, Actinomyces, and Streptococcus through phylogenetic analysis. Quantitative polymerase chain reaction assays revealed that the populations of Bacteroides, Neisseria, and Actinomycetes increased, while that of Streptococcus decreased in cirrhotic patients with pneumonia versus others (p < 0.001, versus Healthy controls; p < 0.01, versus cirrhotic patients without pneumonia). Alterations of Bacteroides, Neisseria, Actinomyces, and Streptococcus populations in the oropharyngeal microbiome were associated with liver cirrhosis and pneumonia.

Circulating gamma-glutamyltransferase fractions in cirrhosis.

PubMed

Elawdi, Hassan A; Franzini, Maria; Paolicchi, Aldo; Emdin, Michele; Fornaciari, Irene; Fierabracci, Vanna; De Simone, Paolo; Carrai, Paola; Filipponi, Franco

2014-08-01

Four gamma-gultamyltransferases (GGT) fractions (b-, m-, s-, and f-GGT) have been identified in human plasma and their concentrations and ratios vary in different pathological conditions. To assess the behaviour of fractional GGT in cirrhotic patients evaluated for liver transplantation. This was a single-centre, cross-sectional study; GGT fractions were determined by gel-filtration chromatography. 264 cirrhotic patients (215 males; median age 54.5 years) were included and compared against a group of 200 healthy individuals (100 males; median age 41.5). Median (25th-75th percentile) total and fractional GGT were higher in cirrhotics, with s-GGT showing the greatest increase [36.6 U/L (21.0-81.4) vs. 5.6 U/L (3.2-10.2), P<0.0001], while the median b-GGT/s-GGT ratio was lower in cirrhotics than in healthy controls [0.06 (0.04-0.10)] vs. 0.28 (0.20-0.40), P<0.0001]. The ratio showed higher diagnostic accuracy (ROC-AUC, 95% CI: 0.951, 0.927-0.969) then either s-GGT (0.924, 0.897-0.947; P<0.05) or total GGT (0.900, 0.869-0.925; P<0.001). The diagnostic accuracy of the ratio was maintained (0.940, 0.907-0.963) in cirrhotic patients (n=113) with total GGT values within the reference range. The s-GGT fraction consisted of two components, with one (s2-GGT) showing a significant positive correlation with serum aspartate aminotransferases, alanine aminotransferase, lactate dehydrogenases (LDH), alkaline phosphatases and bilirubin, and negative with albumin. The b-GGT fraction showed a positive correlation with albumin, fibrinogen, and platelet counts, and negative with international normalized ratio, bilirubin and LDH. The ratio performs as a sensitive biomarker of the liver parenchymal rearrangement, irrespective of aetiology of cirrhosis and presence of hepatocellular carcinoma, even in patients with total GGT values within the reference range. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Learning and Memory Impairments in Patients with Minimal Hepatic Encephalopathy are Associated with Structural and Functional Connectivity Alterations in Hippocampus.

PubMed

García-García, Raquel; Cruz-Gómez, Álvaro Javier; Urios, Amparo; Mangas-Losada, Alba; Forn, Cristina; Escudero-García, Desamparados; Kosenko, Elena; Torregrosa, Isidro; Tosca, Joan; Giner-Durán, Remedios; Serra, Miguel Angel; Avila, César; Belloch, Vicente; Felipo, Vicente; Montoliu, Carmina

2018-06-25

Patients with minimal hepatic encephalopathy (MHE) show mild cognitive impairment associated with alterations in attentional and executive networks. There are no studies evaluating the relationship between memory in MHE and structural and functional connectivity (FC) changes in the hippocampal system. This study aimed to evaluate verbal learning and long-term memory in cirrhotic patients with (C-MHE) and without MHE (C-NMHE) and healthy controls. We assessed the relationship between alterations in memory and the structural integrity and FC of the hippocampal system. C-MHE patients showed impairments in learning, long-term memory, and recognition, compared to C-NMHE patients and controls. Cirrhotic patients showed reduced fimbria volume compared to controls. Larger volumes in hippocampus subfields were related to better memory performance in C-NMHE patients and controls. C-MHE patients presented lower FC between the L-presubiculum and L-precuneus than C-NMHE patients. Compared to controls, C-MHE patients had reduced FC between L-presubiculum and subiculum seeds and bilateral precuneus, which correlated with cognitive impairment and memory performance. Alterations in the FC of the hippocampal system could contribute to learning and long-term memory impairments in C-MHE patients. This study demonstrates the association between alterations in learning and long-term memory and structural and FC disturbances in hippocampal structures in cirrhotic patients.

Predictors of large esophageal varices in patients with cirrhosis.

PubMed

Chalasani, N; Imperiale, T F; Ismail, A; Sood, G; Carey, M; Wilcox, C M; Madichetty, H; Kwo, P Y; Boyer, T D

1999-11-01

Recent guidelines recommend that all cirrhotics undergo screening upper endoscopy to identify those patients at risk for bleeding from varices. However, this practice may not be cost effective as large esophageal varices are seen only in 9-36% of these patients. The aim of this study was to determine whether clinical variables were predictive of the presence of large esophageal varices. This is a retrospective analysis of cirrhotics who had a screening upper endoscopy during an evaluation for liver transplantation at three different centers and who had not previously bled from varices. A multivariate model was derived on the combined cohort using logistic regression. Three hundred forty-six patients were eligible for the study. The prevalence of large esophageal varices was 20%. On multivariate analysis, splenomegaly detected by computed tomographic scan (odds ratio: 4.3; 95% confidence interval: 1.6-11.5) or by physical examination (odds ratio: 2.0; 95% confidence interval: 1.1-3.8), and low platelet count were independent predictors of large esophageal varices. On the basis of these variables, cirrhotics were stratified into high- and low-risk groups for the presence of large esophageal varices. Patients with a platelet count of > or = 88,000/mm3 (median value) and no splenomegaly by physical examination had a risk of large esophageal varices of 7.2%. Those with splenomegaly or platelet count < 88,000/mm3 had a risk of large esophageal varices of 28% (p < 0.0001). Our data show that clinical predictors could be used to stratify cirrhotic patients for the risk of large esophageal varices and such stratification could be used to improve the cost effectiveness of screening endoscopy.

ALTERATION OF TASTE BUDS IN EXPERIMENTAL CIRRHOSIS. Is there correlation with human hypogeusia?

PubMed

Fernandes, Sabrina Alves; Bona, Silvia; Cerski, Carlos Thadeu Schmidt; Marroni, Norma Possa; Marroni, Claudio Augusto

2016-01-01

The inherent complications of cirrhosis include protein-calorie malnutrition and micronutrient deficiencies.Changes in taste are detrimental to the nutritional status, and the mechanism to explain these changes is not well documented in the cirrhotic patients. To evaluate the taste buds of cirrhotic rats. Fourteen male Wistar rats were evaluated. After 16 weeks, the liver was removed to histologically diagnose cirrhosis, and blood was collected to perform liver integrity tests. The tongue was removed for histological examination and immunohistochemistry using antibodies against protein gene product PGP 9.5 and the sweet taste receptors T1R2 and T1R3. Morphological changes were determined by scanning electron microscopy. Serum zinc levels were measured. The cirrhotic animals, but not the control animals, exhibited zinc deficiency. In both groups, there was positive immunoreactivity for type II and III cells and T1R2 receptors. The cirrhotic animals had no immunoreactivity for T1R3 receptors. Scanning electron microscopy analysis of the cirrhotic group revealed a uniform tapering of the gustatory papillae. In conclusion the experimental cirrhosis model mimicked the biochemical and histological parameters of human cirrhosis, therefore enabling a study of the gustatory papillae and taste buds.

EFFECT OF ANTIOXIDANT POTENTIAL ON SEVERITY OF CIRRHOSIS IN HUMANS.

PubMed

Colpo, Elisangela; Gomes Farias, Julia; Gomes Farias, Iria Luiza; Brenner Reetz, Luiz Gustavo; Oliveira, Liliane; Michelon de Carli, Diego; Irineu Müller, Edson; Marlon de Moraes Flores, Érico; Roth Dalcin, Saulo; Teixeira da Rocha, João Batista

2015-11-01

to examine the relationship between the antioxidant potential and severity parameters of cirrhosis in humans. fifteen patients with hepatic cirrhosis (nine subjects - Child group B, and six subjects - Child group C) and nine control subjects were enrolled in the study. The main criteria taken into account to characterize the diagnosis of cirrhosis and its complications were the AST: ALT ratio, AST to platelet ratio index, Bonacini score, Meld score and Child classification. Those parameters were determined based on laboratory results and patient's clinical records. Se, Zn, ascorbic acid (AA) levels and oxidative stress parameters were measured in blood samples of cirrhotic patients. the analysis of plasma levels of Se and AA showed low concentrations in cirrhotic patients compared with control subjects (P < 0.05). Though, there was a positive correlation between plasma of Se and severity parameters of cirrhosis in patients of Child group B and C. In the activity of the antioxidant enzymes only catalase was lower in patients of Child group C compared with control group. we found low plasma levels of Se and AA among cirrhotic patients. However, is not clear why selenium levels tend to increase with the severity of liver cirrhosis. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Umbilical hernia alloplastic dual-mesh treatment in cirrhotic patients

PubMed Central

Guriță, RE; Popa, F; Bălălău, C; Scăunașu, RV

2013-01-01

Rationale. Abdominal wall hernias represent a pathology with an impressive prevalence among the population of patients with cirrhosis complicated by ascites. The aggressive surgical approach of umbilical hernia for patients with cirrhotic background remains a controversial problem, accompanied by anesthetic and surgical risk. Its indication remains fully justified in case of severe symptoms or life threatening complications: strangulation, incarceration, evisceration. Objective. This article evaluates results obtained by using dual-mesh alloplastic materials for surgical treatment of umbilical hernias affecting cirrhotic patients with incipient liver injury. Methods and Results. Our lot consists of twelve patients with ages between 45 and 65 years, diagnosed with hepatic cirrhosis, without other associated comorbidities. All patients were admitted for strangulated umbilical hernia. Among the analyzed lot, no decease was encountered, the morbidity being limited to two cases of parietal suppuration, solved conservatively, without the mesh removal. There were no ascitic fistulas. No recurrences were registered for a 12 months tracking period. Discussion. The presence of cirrhosis implies a high anesthetic and surgical risk, the intervention being grafted by a substantial increase of mortality and morbidity in an emergency setting. The development of new alloplastic materials, together with the modern anesthetic techniques, allows superior results for patients with incipient hepatic injury. PMID:23599831

Morphometric and chronological behavior of 2.45 GHz microwave ablation zones for colorectal cancer metastases and hepatocellular carcinoma in the liver: preliminary report.

PubMed

Hickson, Guy; Patel, Nirav; King, Alexander; Breen, David

2016-08-01

Percutaneous microwave ablation (MWA) is increasingly utilized in the treatment of primary and secondary hepatic malignancy. As an in-situ treatment appreciation of any signs of recurrence is critical for improving long-term oncological outcomes. Volumetry has been recognized as having advantages over orthogonal measurements in the response assessment of malignant lesions. Our study set out to look at the normal involution of an ablation zone (AZ) both volumetrically and morphologically to see if this information might aid the detection of local tumor progression. Cases were identified retrospectively from our database of liver MWA. We identified 34 AZs in total, 18 AZs in 16 hepatocellular carcinoma (HCC) patients with cirrhosis on imaging grounds and 13 AZs in patients with metastatic colorectal cancer. How these AZs developed over time was analyzed both morphologically and quantitatively using Siemens Syngo Via post-processing software. We used the software to produce volume measurements and short axis orthogonal measurements. A baseline measurement was taken on the first <30 day post-ablation scan and the chronological changes were then plotted. We saw differences between the cirrhotic and non-cirrhotic patients both in terms of morphological and volumetric changes. 12/13 non-cirrhotic AZs had a volume of <50% of the baseline scan within the first year. The cirrhotic patients were less predictable, but 14/18 still shrunk to less than 50% of baseline volume in the first year. Orthogonal measurements were less useful in both groups. Qualitatively, there was initially a slightly less well-defined border to the AZ in the first 3 months, which became better defined over time and certainly over the first year of AZ involution. Volumetric analysis is a useful adjunct to conventional measurements and qualitative analysis of AZs. This can be reassuring when orthogonal measurements are static or difficult to interpret. Our preliminary data suggest that the normal pattern in a non-cirrhotic liver is that the AZ volume should drop below 50% of baseline at 1 year. Volumes in cirrhotic livers are less predictable, but the majority will still follow a similar pattern. Future studies could evaluate if failure to follow these patterns correlates with local tumor progression.

Diagnostic Accuracy of Ascites Fluid Gross Appearance in Detection of Spontaneous Bacterial Peritonitis

PubMed Central

Aminiahidashti, Hamed; Hosseininejad, Seyed Mohammad; Montazer, Hosein; Bozorgi, Farzad; Goli Khatir, Iraj; Jahanian, Fateme; Raee, Behnaz

2014-01-01

Introduction: Spontaneous bacterial peritonitis (SBP) as a monomicrobial infection of ascites fluid is one of the most important causes of morbidity and mortality in cirrhotic patients. This study was aimed to determine the diagnostic accuracy of ascites fluid color in detection of SBP in cirrhotic cases referred to the emergency department. Methods: Cirrhotic patients referred to the ED for the paracentesis of ascites fluid were enrolled. For all studied patients, the results of laboratory analysis and gross appearance of ascites fluid registered and reviewed by two emergency medicine specialists. The sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ration of the ascites fluid gross appearance in detection of SBP were measured with 95% confidence interval. Results: The present project was performed in 80 cirrhotic patients with ascites (52.5 female). The mean of the subjects’ age was 56.25±12.21 years (35-81). Laboratory findings revealed SBP in 23 (29%) cases. Fifty nine (73%) cases had transparent ascites fluid appearance of whom 17 (29%) ones suffered from SBP. From 21 (26%) cases with opaque ascites appearance, 15 (71%) had SBP. The sensitivity and specificity of the ascites fluid appearance in detection of SBP were 46.88% (Cl: 30.87-63.55) and 87.50% (95% Cl: 75.3-94.14), respectively. Conclusion: It seems that the gross appearance of ascites fluid had poor diagnostic accuracy in detection of SBP and considering its low sensitivity, it could not be used as a good screening tool for this propose. PMID:26495366

Role of D-dimer in the Development of Portal Vein Thrombosis in Liver Cirrhosis: A Meta-analysis

PubMed Central

Dai, Junna; Qi, Xingshun; Li, Hongyu; Guo, Xiaozhong

2015-01-01

Background and Aims: A meta-analysis was performed to explore the role of the D-dimer in the development of portal vein thrombosis (PVT) in liver cirrhosis. Methods: All papers were searched via PubMed, EMBASE, China National Knowledge Infrastructure, Wan Fang, and VIP databases. A standardized mean difference (SMD) with 95% confidence interval (CI) was pooled. Results: Overall, 284 studies were initially identified, of which 21 were included. Cirrhotic patients with PVT had a significantly higher D-dimer concentration than those without PVT (pooled SMD = 1.249, 95%CI = 0.740–1.758). After the portal hypertension-related surgery, cirrhotic patients with PVT had a similar preoperative D-dimer concentration to those without PVT (pooled SMD = 0.820, 95%CI = −0.122–0.286), but a higher postoperative value of D-dimer concentration than those without PVT (pooled SMD = 2.505, 95%CI = 0.975–4.036). Notably, the D-dimer concentration at the 1st postoperative day was similar between cirrhotic patients with and without PVT (pooled SMD = 0.137, 95%CI = −0.827–1.101), but that at the 7th post-operative day was higher in cirrhotic patients with PVT than in those without PVT (pooled SMD = 1.224, 95%CI = 0.277–2.171). Conclusion: D-dimer might be regarded as a diagnostic marker for PVT in liver cirrhosis. In addition, postoperative D-dimer testing is worthwhile for the diagnosis of PVT after portal hypertension-related surgery. PMID:26021776

[Dietetic assessment of patients with gastroenterologic diseases at the out-patient service of the Institute National of Sciences Medicine and Nutrition Salvador Zubiran].

PubMed

de la Cruz Góngora, Vanesa Vianey; Pando Aguilar, Nancy Esther; Milke García, Pilar; Vargas-Voráková, Florencia

2003-01-01

Assessment of dietetic management is necessary for detection/correction of faults and best care of patients. Our aim was to evaluate dietetic management and nutritional status of gastroenterologic patients. Anthropometric, clinical-nutritional, biochemical, and dietetic parameters were assessed in 110 patients (150 with liver cirrhosis [LC], 30 with inflammatory bowel disease [IBD], and 30 with chronic and skin. In CP, prescribed energy, g and % carbohydrates and lipids were less than ideal and proteins were greater; in cirrhotics, less proteins and a great % of carbohydrates were prescribed; in IBD fewer lipids and more proteins than ideal were prescribed. Cirrhotics usually consumed less fat (g) and more proteins than prescribed, and patients with CP and IBD a greater amount of carbohydrates than prescribed. Cirrhotics consumed more % carbohydrates and < % lipids than ideal; CP patients lipid intake was less and protein intake above ideal and in IBD, carbohydrate intake was greater and lipid intake lower than ideal. Anthropometric and biochemical parameters were not useful for assessment of these patients. Prescribed diet was too restricted regarding proteins in LC and was inadequate in energy/nutrients in patients with CP. Fewer lipids and more proteins were prescribed in IBD. The inadequacy of prescripted diet, lack of information regarding the person who prescribed it, and lack of constant supervision may cause non-adherence to diet and thus may affect nutritional status.

The importance of salivary cortisol in the diagnosis of adrenal insufficiency in cirrhosis.

PubMed

Araz, Filiz; Soydaş, Barış; Özer, Birol; Serin, Ender

2016-05-01

Reports on adrenal insufficiency (AI) are unexpectedly high in cirrhosis, and the diagnosis of this condition remains a challenge. We aimed to define the prevalence rate of AI in stable cirrhotic patients and determine the correlations of free cortisol and salivary cortisol with total cortisol. Between January 2011 and September 2011, 110 consecutive cirrhotic patients without any infection or hemodynamic instability were enrolled. Baseline total and salivary cortisol levels were measured. The free cortisol level was calculated according to the Coolens' formula. Post-stimulation total and salivary cortisol levels were measured, and the free cortisol level was recalculated. The mean age of the patients was 62.1±11.4 years. There were 54 males (49.1%). The mean Child-Turcotte-Pugh (CTP) score was 7.2±2.3. Twenty-two (20%) patients were at the CTP-C level. AI was present in 23 (20.9%) and 17 (15.5%) of all patients according to the total and free cortisol criteria, respectively. For basal and stimulated levels, salivary cortisol rather than total cortisol correlates well with free cortisol. The diagnosis of AI on the basis of total cortisol measurement overestimates the prevalence of AI in cirrhosis. Salivary cortisol, which correlates well with free cortisol, is a promising alternative for the diagnosis of AI in cirrhotic patients.

Ghrelin, leptin and insulin in cirrhotic children and adolescents: relationship with cirrhosis severity and nutritional status.

PubMed

Dornelles, Cristina T L; Goldani, Helena A S; Wilasco, Maria Inês A; Maurer, Rafael L; Kieling, Carlos O; Porowski, Marilene; Ferreira, Cristina T; Santos, Jorge L; Vieira, Sandra M G; Silveira, Themis R

2013-01-10

Ghrelin, leptin, and insulin concentrations are involved in the control of food intake and they seem to be associated with anorexia-cachexia in cirrhotic patients. The present study aimed to investigate the relationship between the nutritional status and fasting ghrelin, leptin and insulin concentrations in pediatric cirrhotic patients. Thirty-nine patients with cirrhosis and 39 healthy controls aged 0-15 years matched by sex and age were enrolled. Severity of liver disease was assessed by Child-Pugh classification, and Pediatric for End Stage Liver Disease (PELD) or Model for End-stage Liver Disease (MELD) scores. Blood samples were collected from patients and controls to assay total ghrelin, acyl ghrelin, leptin and insulin by using a commercial ELISA kit. Anthropometry parameters used were standard deviation score of height-for-age and triceps skinfold thickness-for-age ratio. A multiple linear regression analysis was used to determine the correlation between dependent and independent variables. Acyl ghrelin was significantly lower in cirrhotic patients than in controls [142 (93-278) pg/mL vs 275 (208-481) pg/mL, P=0.001]. After multiple linear regression analysis, total ghrelin and acyl ghrelin showed an inverse correlation with age; acyl ghrelin was associated with the severity of cirrhosis and des-acyl ghrelin with PELD or MELD scores ≥15. Leptin was positively correlated with gender and anthropometric parameters. Insulin was not associated with any variable. Low acyl ghrelin and high des-acyl ghrelin concentrations were associated with cirrhosis severity, whereas low leptin concentration was associated with undernourishment in children and adolescents with cirrhosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparison of non-invasive assessment to diagnose liver fibrosis in chronic hepatitis B and C patients.

PubMed

Stibbe, Krista J M; Verveer, Claudia; Francke, Jan; Hansen, Bettina E; Zondervan, Pieter E; Kuipers, Ernst J; de Knegt, Robert J; van Vuuren, Anneke J

2011-07-01

Chronic viral hepatitis B and C cause liver fibrosis, leading to cirrhosis. Fibrosis assessment is essential to establish prognosis and treatment indication. We compared seven non-invasive tests, separately and in combination, in chronic hepatitis patients to detect early stages of fibrosis according to the Metavir score in liver biopsy. Galactose and methacetin breath tests (GBT and MBT), biomarkers (hyaluronic acid (HA), aspartate aminotransferase platelet ratio index (APRI), FibroTest, and Fib-4) and transient elastography (TE) were evaluated in 89 patients. Additionally, 31 healthy controls were included for evaluation of breath tests and biomarkers. Serum markers (HA, APRI, FibroTest, and Fib-4) and elastography significantly distinguished non-cirrhotic (F0123) from cirrhotic (F4) patients (p < 0.001, p = 0.015, p < 0.001, p = 0.005, p = 0.006, respectively). GBT, HA, APRI, FibroTest, Fib-4, and TE detected F01 from F234 (p = 0.04, p = 0.011, p = 0.009, p < 0.001, p < 0.001, and p < 0.001, respectively). A combination of different tests (TE, HA, and FibroTest) improved the performance statistically, area under the curve (AUC) = 0.87 for F234, 0.92 for F34, and 0.90 for F4. HA, APRI, FibroTest, Fib-4, and TE reliably distinguish non-cirrhotic and cirrhotic patients. Except for MBT, all tests discriminate between mild and moderate fibrosis. As single tests: FibroTest, Fib-4, and TE were the most accurate for detecting early fibrosis; combining different non-invasive tests increased the accuracy for detection of liver fibrosis to such an extent and thus might be acceptable to replace liver biopsy.

Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis.

PubMed

Facciorusso, Antonio; Amoruso, Annabianca; Neve, Viviana; Antonino, Matteo; Prete, Valentina Del; Barone, Michele

2014-11-27

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.

The model for the end-stage liver disease and Child-Pugh score in predicting prognosis in patients with liver cirrhosis and esophageal variceal bleeding.

PubMed

Benedeto-Stojanov, Daniela; Nagorni, Aleksandar; Bjelaković, Goran; Stojanov, Dragan; Mladenović, Bojan; Djenić, Nebojsa

2009-09-01

Esophageal variceal bleeding is one of the most frequent and gravest complications of liver cirrhosis, directly life-threatening. By monitoring certain clinical and laboratory hepatocellular insufficiency parameters (Child-Pugh score), it is possible to determine prognosis in patients who are bleeding and evaluate further therapy. Recently, the Model for the End-Stage Liver Disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. The aim of the study was to evaluate survival prognosis of cirrhotic patients by the MELD and Child-Pugh scores and to analyze the MELD score prognostic value in patients with both liver cirrhosis and variceal bleeding. We retrospectively evaluated the survival rate of a group of 100 cirrhotic patients of a median age of 57 years. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. We also analysed clinical and laboratory hepatocellular insufficiency parameters in order to examine their connection with a 15-month survival. The MELD values were correlated with the Child-Pugh scores. The Student's t-test was used for statistical analysis. Twenty-two patients died within 15-months followup. Age and gender did not affect survival rate. The Child-Pugh and MELD scores, as well as ascites and encephalopathy significantly differed between the patients who survived and those who died (p < 0.0001). The International Normalized Ratio (INR) values, serum creatinine and bilirubin were significantly higher, and albumin significantly lower in the patients who died (p < 0.0001). The MELD score was significantly higher in the group of patients who died due to esophageal variceal bleeding (p < 0.0001). In cirrhotic patients the MELD score is an excellent survival predictor at least as well as the Child-Pugh score. Increase in the MELD score is associated with decrease in residual liver function. In the group of patients with liver cirrhosis and esophageal variceal bleeding, the MELD score identifies those with a higher intrahospital mortality risk.

The repair of umbilical hernia in cirrhotic patients: 18 consecutive case series in a single institute

PubMed Central

Yu, Byung Chul; Lee, Giljae

2015-01-01

Purpose Traditionally, the surgical repair of umbilical hernia in cirrhotic patients with ascites is avoided because of a significant recurrence rate and perioperative morbidity/mortality. However, recent reports recommend early elective surgery in these patients because surgery-related complications can be reduced with minimally invasive surgery and development of perioperative patient care. The current study was conducted to analyze safety and feasibility of umbilical hernia repairs performed in a single institute. Methods A single center retrospective analysis of patients' data was conducted. Eighteen patients with umbilical hernia accompanied by liver cirrhosis underwent hernia repair in the period between 2005 and 2012. The charts of these patients were reviewed and demographic data, postoperative complications, and recurrence were recorded. Results Eleven males and seven females with a mean age of 62.9 years were analyzed. Two of the patients were classified as Child's class A, 11 as Child's class B, and five as Child's class C. Four patients underwent emergency surgery because of perforations in the hernia sac in two cases and incarcerated hernias in the other two cases. Of the 18 patients who underwent surgery, four (22%) experienced a recurrence, three (17%) developed edema at the surgical sites, one (5%) experienced hepatic coma, and one (5%) showed postoperative variceal hemorrhage. All of these events occurred after emergency surgery. Conclusion In contrast to traditional concepts, early and elective repair of umbilical hernia can be performed easily and safely in cirrhotic patients. PMID:26236698

The repair of umbilical hernia in cirrhotic patients: 18 consecutive case series in a single institute.

PubMed

Yu, Byung Chul; Chung, Min; Lee, Giljae

2015-08-01

Traditionally, the surgical repair of umbilical hernia in cirrhotic patients with ascites is avoided because of a significant recurrence rate and perioperative morbidity/mortality. However, recent reports recommend early elective surgery in these patients because surgery-related complications can be reduced with minimally invasive surgery and development of perioperative patient care. The current study was conducted to analyze safety and feasibility of umbilical hernia repairs performed in a single institute. A single center retrospective analysis of patients' data was conducted. Eighteen patients with umbilical hernia accompanied by liver cirrhosis underwent hernia repair in the period between 2005 and 2012. The charts of these patients were reviewed and demographic data, postoperative complications, and recurrence were recorded. Eleven males and seven females with a mean age of 62.9 years were analyzed. Two of the patients were classified as Child's class A, 11 as Child's class B, and five as Child's class C. Four patients underwent emergency surgery because of perforations in the hernia sac in two cases and incarcerated hernias in the other two cases. Of the 18 patients who underwent surgery, four (22%) experienced a recurrence, three (17%) developed edema at the surgical sites, one (5%) experienced hepatic coma, and one (5%) showed postoperative variceal hemorrhage. All of these events occurred after emergency surgery. In contrast to traditional concepts, early and elective repair of umbilical hernia can be performed easily and safely in cirrhotic patients.

Jejunal permeability to water and electrolytes in patients with chronic intrahepatic hypertension: evidence for a role of aldosterone.

PubMed Central

Duclos, B; Bories, P; Mathieu-Daude, J C; Michel, H

1991-01-01

Acute prehepatic portal hypertension induces intestinal secretion in animal models. In the course of chronic liver disease, however, these changes are not observed, despite higher portal pressures than those found in experimental studies. Eight patients without diarrhoea and with chronic alcoholic liver disease were examined for evidence of increased jejunal secretion; their suprahepatic wedge pressure was raised from 21 to 45 mmHg (mean 34.6 mmHg). Jejunal perfusion with a triple lumen catheter and a proximal occluding balloon was used to study net flows of water and chloride as well as net and unidirectional flows of sodium and potassium. No statistical difference in intestinal flows of water and electrolytes was noted between cirrhotic patients and control subjects after infusion with a 30 mmol/l glucose solution. Infusion with a 30 mmol/l mannitol solution resulted in a lower absorption of water, Na, K, and Cl than with the glucose solution. A higher rate of Na secretion was observed in cirrhotic patients than control subjects after infusion with 30 mmol/l mannitol (p less than 0.01). In addition, the rate of Na secretion was higher in cirrhotic patients than in control subjects (p less than 0.05). There was no correlation between the net flow of Na and the suprahepatic wedge pressure. A second perfusion with a 30 mmol/l glucose solution was given 75 minutes after a bolus injection of spironolactone (400 mg). Net flows of Na and Cl were lower in cirrhotic patients than in control subjects (p less than 0.05) because of a lower absorption of Na. Patients with gradually developing portal hypertension have moderate jejunal secretions of H2O and electrolytes which we assume are partly masked by increased absorption resulting from hyperaldosteronism. In contrast to animal models, this mechanism may be part of the jejunal adaptation to permeability in acute portal hypertension. PMID:2060871

Gut microbiota in cirrhotic liver transplant candidates.

PubMed

Grąt, Michał; Hołówko, Wacław; Gałecka, Mirosława; Grąt, Karolina; Szachtaz, Patrycja; Lewandowsk, Zbigniew; Kosińska, Irena; Schmidts, Marcin; Olejnik-Schmidt, Agnieszka; Krawczyk, Marek

2014-09-01

The purpose of this study was to evaluate the gut microflora of liver transplant candidates. Fecal microflora of 20 cirrhotic liver transplant candidates was analyzed basing on prospectively collected stool samples. The results were compared with those of 20 non-cirrhotic patients with liver disease and/or abnormal liver function tests, 20 patients with Crohn’s disease, and 20 patients without any gastrointestinal disease. Moreover, correlations between particular counts of microbiota, as well as between microbial counts and stool pH were examined. The pattern of fecal microbiota of liver transplant candidates was characterized by increased counts of lactobacilli (p=0.001), including hydrogen peroxide producing strains (p=0.008). In these patients, lactobacilli were positively correlated to enterococci (p=0.006) and bifidobacteria (p=0.004). No correlations other than those observed for lactobacilli in general were observed between hydrogen peroxide producing lactobacilli and the remaining microbiota. Increased yeast and Escherichia coli counts were associated with a tendency towards lower (p=0.095) and higher (p=0.072) stool pH, respectively. Surprisingly, gut microflora of liver transplant candidates with cirrhosis is particularly enriched with lactobacilli, including hydrogen peroxide producing strains. Thus, the use of other potentially beneficial microorganisms, such as particular yeast strains, might be more appropriate for these patients.

The natural history of autoimmune hepatitis presenting with jaundice.

PubMed

Panayi, Vasilis; Froud, Oliver J; Vine, Louisa; Laurent, Paul; Woolson, Kathy L; Hunter, Jeremy G; Madden, Richard G; Miller, Catherine; Palmer, Jo; Harris, Nicola; Mathew, Joe; Stableforth, Bill; Murray, Iain A; Dalton, Harry R

2014-06-01

Forty percent of patients with autoimmune hepatitis (AIH) present with acute jaundice/hepatitis. Such patients, when treated promptly, are thought to have a good prognosis. The objective of this study was to describe the natural history of AIH in patients presenting with jaundice/hepatitis and to determine whether the diagnosis could have been made earlier, before presentation. This study is a retrospective review of 2249 consecutive patients who presented with jaundice to the Jaundice Hotline clinic, Truro, Cornwall, UK, over 15 years (1998-2013) and includes a review of the laboratory data over a 23-year period (1990-2013). Of the 955 patients with hepatocellular jaundice, 47 (5%) had criterion-referenced AIH: 35 female and 12 male, the median age was 65 years (range 15-91 years); the bilirubin concentration was 139 μmol/l (range 23-634 μmol/l) and the alanine transaminase level was 687 IU/l (range 22-2519 IU/l). Among the patients, 23/46 (50%) were cirrhotic on biopsy; 11/47 (23%) died: median time from diagnosis to death, 5 months (range 1-59); median age, 72 years (range 59-91 years). All 8/11 patients who died of liver-related causes were cirrhotic. Weight loss (P=0.04) and presence of cirrhosis (P=0.004) and varices (P=0.015) were more common among those who died. Among patients who died from liver-related causes, 6/8 (75%) died less than 6 months from diagnosis. Cirrhosis at presentation and oesophageal varices were associated with early liver-related deaths (P=0.011, 0.002 respectively). Liver function test results were available in 33/47 (70%) patients before presentation. Among these patients, 16 (49%) had abnormal alanine transaminase levels previously, and eight (50%) were cirrhotic at presentation. AIH presenting as jaundice/hepatitis was mainly observed in older women: 50% of the patients were cirrhotic, and liver-related mortality was high. Some of these deaths were potentially preventable by earlier diagnosis, as the patients had abnormal liver function test results previously, which had not been investigated.

[Role of splenectomy in the treatment of non-cirrhotic portal hypertension: about 3 cases].

PubMed

Belhamidi, Mohamed Said; Hammi, Salah Eddine; Bouzroud, Mohamed; Benmoussa, Mustapha; Ali, Abdelmounaim Ait; Bounaim, Ahmed

2017-01-01

Non-cirrhotic portal hypertension was first described by Guido BANTI in 1898 as a condition characterized by the association of portal hypertension with splenomegaly, anemia and healthy liver. The diagnosis was based on abdominal ultrasound, splenoportography and liver biopsy. Our study aimed to evaluate the role of splenectomy in non-cirrhotic portal hypertension. We conducted a retrospective study of 3 patients (2 women and 1 man) treated by our staff over the period January 2010 -September 2016. The diagnosis of idiopathic portal hypertension was based on the following criteria: portal hypertension, the presence of oesophageal varices associated with splenomegaly, the absence of cirrhosis or of other liver disorders responsible of portal hypertension. All patients underwent splenectomy. Outcome after splenectomy was marked by the standardization of clinical, radiological and biological signs of this disease associated with the absence of oesophageal varices recurrence. Splenectomy associated with ligation of oesophageal varices may be sufficient to treat this syndrome and especially its consequences without using splenorenal bypass.

Performance-based measures associate with frailty in patients with end-stage liver disease

PubMed Central

Lai, Jennifer C.; Volk, Michael L; Strasburg, Debra; Alexander, Neil

2016-01-01

Background Physical frailty, as measured by the Fried Frailty Index, is increasingly recognized as a critical determinant of outcomes in cirrhotics. However, its utility is limited by the inclusion of self-reported components. We aimed to identify performance-based measures associated with frailty in patients with cirrhosis. Methods Cirrhotics ≥50 years underwent: 6-minute walk test (6MWT, cardiopulmonary endurance), chair stands in 30 seconds (muscle endurance), isometric knee extension (lower extremity strength), unipedal stance time (static balance), and maximal step length (dynamic balance/coordination). Linear regression associated each physical performance test with frailty. Principal components exploratory factor analysis evaluated the inter-relatedness of frailty and the 5 physical performance tests. Results Of forty cirrhotics, with a median age of 64 years and Model for End-stage Liver Disease (MELD) MELD of 12,10 (25%) were frail by Fried Frailty Index ≥3. Frail cirrhotics had poorer performance in 6MWT distance (231 vs. 338 meters), 30 second chair stands (7 vs. 10), isometric knee extension (86 vs. 122 Newton meters), and maximal step length (22 vs. 27 inches) [p≤0.02 for each]. Each physical performance test was significantly associated with frailty (p<0.01), even after adjustment for MELD or hepatic encephalopathy. Principal component factor analysis demonstrated substantial, but unique, clustering of each physical performance test to a single factor – frailty. Conclusion Frailty in cirrhosis is a multi-dimensional construct that is distinct from liver dysfunction and incorporates endurance, strength, and balance. Our data provide specific targets for prehabilitation interventions aimed at reducing frailty in cirrhotics in preparation for liver transplantation. PMID:27495749

PIVKA-II is a useful tool for diagnostic characterization of ultrasound-detected liver nodules in cirrhotic patients

PubMed Central

Saitta, Carlo; Raffa, Giuseppina; Alibrandi, Angela; Brancatelli, Santa; Lombardo, Daniele; Tripodi, Gianluca; Raimondo, Giovanni; Pollicino, Teresa

2017-01-01

Abstract Protein induced by vitamin K absence-II (PIVKA-II) is a potential screening marker for hepatocellular carcinoma (HCC). Limited data are available about its utility in discriminating neoplastic from regenerative nodules at ultrasonography (US) evaluation in cirrhotic patients. Aim of this study was to investigate the diagnostic utility of PIVKA-II in cases showing liver nodules of uncertain diagnosis at US. Ninety cirrhotics with US evidence of liver nodule(s) were enrolled. All patients underwent blood sampling within 1 week of US and were thereafter followed up. HCC was confirmed in 40/90 cases, and in all cases it was in a very early/early stage. All sera were tested for PIVKA-II and alpha-fetoprotein (AFP) at the end of follow-up. PIVKA-II at a cut off of 60 mAU/mL was significantly associated with HCC at both univariate and multivariate analysis (P = .016 and P = .032, respectively). AFP at a cut off of 6.5 ng/mL was not associated with HCC at univariate analysis (P = .246). ROC curves showed that PIVKA-II had 60% sensitivity, 88% specificity, 80% positive predictive value (PPV), and 73% negative predictive value (NPV), whereas AFP had 67% sensitivity, 68% specificity, 63% PPV, and 72% NPV. AUROC curves showed that the combination of both biomarkers increased the diagnostic accuracy for HCC (AUC 0.76; sensitivity 70%, specificity 94%, PPV 91%, and NPV 79%). In conclusion, PIVKA-II is a useful tool for the diagnostic definition of US-detected liver nodules in cirrhotic patients, and it provides high diagnostic accuracy for HCC when combined with AFP. PMID:28658121

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement.

PubMed

Tag-Adeen, Mohammed; Sabra, Ahlam Mohamed; Akazawa, Yuko; Ohnita, Ken; Nakao, Kazuhiko

2017-01-01

Liver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 pre-dominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM) improvement after successful HCV eradication. The study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA) treatment and after achieving sustained virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified into F0-F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4), p -value <0.05 was statistically significant. Following DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%), mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m 2 . Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of -5.8 occurred in F4 versus -2.79, -1.28 and +0.08 in F3, F2 and F0-F1 respectively ( p <0.0001). At baseline, 41 patients were in the F4 group; only 16 (39%) regressed to non-cirrhotic range (<12.5 kPa), while 25 (61%) were still cirrhotic despite achieving SVR-24 ( p <0.0001). Patients who achieved LSM improvement (n=64) have had significantly higher baseline aspartate transferase (AST) and alanine transaminase (ALT). Also, those patients showed significant improvement in AST, AST/platelets ratio index (APRI) and fibrosis-4 index (Fib-4) after achieving SVR; 91% showed AST improvement ( p =0.01) and APRI improvement ( p =0.01) and 81% showed Fib-4 improvement ( p =0.04). Females, diabetics, patients with S3 steatosis and patients older than 50 years showed less LSM improvements than their counterparts. Baseline LSM ≥9 kPa, bilirubin ≥1 mg/dl, ALT ≥36 U/L and AST ≥31 U/L were significant predictors for LSM improvement. Successful HCV genotype-4 eradication results in significant LSM improvement; the best improvement occurs in F4 patients. But as the majority of cirrhotics are still at risk for liver decompensation and hepatocellular carcinoma development despite achieving SVR-24, early detection and treatment are highly recommended.

Retrospective Study to Compare Selective Decongestive Devascularization and Gastrosplenic Shunt versus Splenectomy with Pericardial Devascularization for the Treatment of Patients with Esophagogastric Varices Due to Cirrhotic Portal Hypertension.

PubMed

Bao, Haili; He, Qikuan; Dai, Ninggao; Ye, Ruifan; Zhang, Qiyu

2017-06-08

BACKGROUND For patients with esophagogastric varices secondary to portal hypertension due to liver cirrhosis, portosystemic shunts and devascularization have become the most commonly used treatment methods. We have developed a novel surgical approach for the treatment of patients with cirrhotic portal hypertension, selective decongestive devascularization, and shunt of the gastrosplenic region (SDDS-GSR). This aim of this study was to compare the efficacy and safety of SDDS-GSR with splenectomy with pericardial devascularization (SPD). MATERIAL AND METHODS A retrospective study was undertaken between 2006 and 2013 and included 110 patients with cirrhotic portal hypertension, 34 of whom underwent SDDS-GSR; 76 patients underwent SPD. Kaplan-Meier analysis was used to evaluate clinical outcomes, mortality, the incidence of re-bleeding, encephalopathy, and portal venous system thrombosis (PVST). RESULTS Postoperatively portal venous pressure decreased by 20% in both groups. The long-term incidence of re-bleeding and PVST was significantly lower in the SDDS-GSR group compared with the SPD group (P=0.018 and P=0.039, respectively). CONCLUSIONS This preliminary retrospective study has shown that SDDS-GSR was an effective treatment for patients with esophagogastric varices secondary to portal hypertension that may be used as a first-line treatment to prevent variceal bleeding and lower the incidence of PVST.

Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB–mediated mechanism

PubMed Central

Qiu, Jia; Thapaliya, Samjhana; Runkana, Ashok; Yang, Yu; Tsien, Cynthia; Mohan, Maradumane L.; Narayanan, Arvind; Eghtesad, Bijan; Mozdziak, Paul E.; McDonald, Christine; Stark, George R.; Welle, Stephen; Naga Prasad, Sathyamangla V.; Dasarathy, Srinivasan

2013-01-01

Loss of muscle mass, or sarcopenia, is nearly universal in cirrhosis and adversely affects patient outcome. The underlying cross-talk between the liver and skeletal muscle mediating sarcopenia is not well understood. Hyperammonemia is a consistent abnormality in cirrhosis due to impaired hepatic detoxification to urea. We observed elevated levels of ammonia in both plasma samples and skeletal muscle biopsies from cirrhotic patients compared with healthy controls. Furthermore, skeletal muscle from cirrhotics had increased expression of myostatin, a known inhibitor of skeletal muscle accretion and growth. In vivo studies in mice showed that hyperammonemia reduced muscle mass and strength and increased myostatin expression in wild-type compared with postdevelopmental myostatin knockout mice. We postulated that hyperammonemia is an underlying link between hepatic dysfunction in cirrhosis and skeletal muscle loss. Therefore, murine C2C12 myotubes were treated with ammonium acetate resulting in intracellular concentrations similar to those in cirrhotic muscle. In this system, we demonstrate that hyperammonemia stimulated myostatin expression in a NF-κB–dependent manner. This finding was also observed in primary murine muscle cell cultures. Hyperammonemia triggered activation of IκB kinase, NF-κB nuclear translocation, binding of the NF-κB p65 subunit to specific sites within the myostatin promoter, and stimulation of myostatin gene transcription. Pharmacologic inhibition or gene silencing of NF-κB abolished myostatin up-regulation under conditions of hyperammonemia. Our work provides unique insights into hyperammonemia-induced myostatin expression and suggests a mechanism by which sarcopenia develops in cirrhotic patients. PMID:24145431

Hepatocellular carcinoma Early Detection Strategy study — EDRN Public Portal

Cancer.gov

Part 1: The first part of this study is to conduct follow-up for patients that were enrolled in the EDRN Phase 2 Validation Study called DCP (13). For this part of the study, four groups are defined as follows: a) Vanguard Controls are cirrhotic controls, from the Phase 2 trial that have not developed HCC and sign a new consent form for HEDS participation. These patients will be followed for a minimum of an additional 24 months and have biospecimens collected every 6 months. b) Vanguard Interval Controls are cirrhotic controls, from the Phase 2 trial that have not developed HCC and do not sign a new consent form for HEDS participation. This group will have outcome data abstracted from their medical records. c) Vanguard Interval Cases are cirrhotic controls from the Phase 2 trial that developed HCC after completion of the Phase 2 trial but prior to the current study. This group will have outcome data abstracted from their medical records. d) Vanguard Cases are HCC cases from the Phase 2 trial. This group will have outcome data abstracted from their medical records. Part 2: New Controls - The second part of this study is the new accrual of cirrhotic controls at the seven participating sites. These patients will be followed for a minimum of 24 months and have biospecimens collected every 6 months. Data will be collected every 6 months: ultrasound, AFP, liver function tests, complete blood counts, MELD scores and any changes in medical history, personal cancer history and family cancer history.

Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB-mediated mechanism.

PubMed

Qiu, Jia; Thapaliya, Samjhana; Runkana, Ashok; Yang, Yu; Tsien, Cynthia; Mohan, Maradumane L; Narayanan, Arvind; Eghtesad, Bijan; Mozdziak, Paul E; McDonald, Christine; Stark, George R; Welle, Stephen; Naga Prasad, Sathyamangla V; Dasarathy, Srinivasan

2013-11-05

Loss of muscle mass, or sarcopenia, is nearly universal in cirrhosis and adversely affects patient outcome. The underlying cross-talk between the liver and skeletal muscle mediating sarcopenia is not well understood. Hyperammonemia is a consistent abnormality in cirrhosis due to impaired hepatic detoxification to urea. We observed elevated levels of ammonia in both plasma samples and skeletal muscle biopsies from cirrhotic patients compared with healthy controls. Furthermore, skeletal muscle from cirrhotics had increased expression of myostatin, a known inhibitor of skeletal muscle accretion and growth. In vivo studies in mice showed that hyperammonemia reduced muscle mass and strength and increased myostatin expression in wild-type compared with postdevelopmental myostatin knockout mice. We postulated that hyperammonemia is an underlying link between hepatic dysfunction in cirrhosis and skeletal muscle loss. Therefore, murine C2C12 myotubes were treated with ammonium acetate resulting in intracellular concentrations similar to those in cirrhotic muscle. In this system, we demonstrate that hyperammonemia stimulated myostatin expression in a NF-κB-dependent manner. This finding was also observed in primary murine muscle cell cultures. Hyperammonemia triggered activation of IκB kinase, NF-κB nuclear translocation, binding of the NF-κB p65 subunit to specific sites within the myostatin promoter, and stimulation of myostatin gene transcription. Pharmacologic inhibition or gene silencing of NF-κB abolished myostatin up-regulation under conditions of hyperammonemia. Our work provides unique insights into hyperammonemia-induced myostatin expression and suggests a mechanism by which sarcopenia develops in cirrhotic patients.

Management of Hepatic Encephalopathy Not Responsive to First-Line Treatments.

PubMed

Nardelli, Silvia; Ridola, Lorenzo; Gioia, Stefania; Riggio, Oliviero

2018-06-01

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that occurs in up to 30% of patients with cirrhosis. HE may be a consequence of pure liver failure, as in patients with fulminant hepatitis, or of the combination of liver failure and portal-systemic shunting, as in patients with liver cirrhosis. Episodes of HE are usually related to precipitating events, such as infections or gastrointestinal bleeding; a minority of cirrhotic patients experienced a chronic HE, refractory to standard medical treatment. The prevention of HE recurrence, after the first episode of HE, could be obtained by the administration of prophylactic therapy with lactulose, rifaximin or a combination of both. The aim of this review is to clarify some key points in the management of cirrhotic patients with HE, not responsive to first line treatment. Recent studies investigated the role of fecal microbiota transplantation in the treatment of HE with promising results, but further investigations are needed. In a cirrhotic patient with acute cognitive impairment, the correct diagnosis of HE, after excluding other causes of neurological diseases, is mandatory for the correct management of the precipitating factors and for the treatment. In patients not responsive to standard treatment, the probable precipitating factors have not been correctly identified, multiple precipitating events are coexisting or a new precipitating event is superimposed. In some patients with recurrent HE, characterized by persistent alterations in neurological symptoms, without specific precipitants events, the presence of spontaneous or iatrogenic shunts should be investigated.

Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis.

PubMed

Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

2015-11-07

Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.

Circulating levels of 3-hydroxymyristate, a direct quantification of endotoxemia in non-infected cirrhotic patients.

PubMed

Weil, Delphine; Pais de Barros, Jean-Paul; Mourey, Guillaume; Laheurte, Caroline; Cypriani, Benoit; Badet, Nicolas; Delabrousse, Eric; Grandclément, Emilie; Di Martino, Vincent; Saas, Philippe; Lagrost, Laurent; Thévenot, Thierry

2018-06-22

The quantification of lipopolysaccharide (LPS) in biological fluids is challenging. We aimed to measure plasma LPS concentration using a new method of direct quantification of 3-hydroxymyristate (3-HM), a lipid component of LPS, and to evaluate correlations between 3-HM and markers of liver function, endothelial activation, portal hypertension and enterocyte damage. Plasma from 90 non-infected cirrhotic patients (30 Child-Pugh [CP]-A, 30 CP-B, 30 CP-C) was prospectively collected. The concentration of 3-HM was determined by High Performance Liquid Chromatography coupled with Mass Spectrometry. 3-HM levels were higher in CP-C patients (CP-A/CP-B/CP-C: 68/70/103 ng/mL, p=0.005). Patients with severe acute alcoholic hepatitis (n=16; 113 vs 74 ng/mL,p=0.012), diabetic patients (n=22; 99 vs 70 ng/mL, p=0.028) and those not receiving beta-blockers (n=44; 98 vs 72 ng/mL, p=0.034) had higher levels of 3-HM. We observed a trend towards higher baseline levels of 3-HM in patients with hepatic encephalopathy (n=7; 144 vs 76 ng/mL, p=0.45) or SIRS (n=10; 106 vs 75 ng/mL, p=0.114). In multivariate analysis, high levels of 3-HM were associated with CP (OR=4.39; 95%CI=1.79-10.76) or MELD (OR=8.24; 95%CI=3.19-21.32) scores. Patients dying from liver insufficiency (n=6) during a 12-month follow-up had higher baseline levels of 3-HM (106 vs 75 ng/mL, p=0.089). In non-infected cirrhotic patients, 3-HM arises more frequently with impairment of liver function, heavy alcohol consumption, diabetic status, non-use of beta-blockers, and a trend towards poorer outcome is also observed. The direct mass-measurement of LPS using 3-HM appears reliable to detect transient endotoxemia and promising to manage the follow-up of cirrhotic patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis

PubMed Central

Facciorusso, Antonio; Amoruso, Annabianca; Neve, Viviana; Antonino, Matteo; Prete, Valentina Del; Barone, Michele

2014-01-01

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients. PMID:25429317

Sofosbuvir and ribavirin for genotype 2 HCV infected patients with cirrhosis: A real life experience.

PubMed

Mangia, Alessandra; Susser, Simone; Piazzolla, Valeria; Agostinacchio, Ernesto; De Stefano, Giulio; Palmieri, Vincenzo; Spinzi, Giancarlo; Carraturo, Immacolata; Potenza, Domenico; Losappio, Ruggero; Arleo, Andrea; Miscio, Maria; Santoro, Rosanna; Sarrazin, Christoph; Copetti, Massimiliano

2017-04-01

Sofosbuvir (SOF) and weight-based ribarivin (RBV) represented until recently the standard of care in hepatitis C virus (HCV) genotype (GT)2 patients. In registration studies 12-16weeks duration were associated with a 90% sustained virological response at 12weeks (SVR12). Real life cohorts showed lower SVR12 rates. SVR12 rates attained in an Italian real life cohort and possible benefits of a duration extended up to 20weeks was investigated in HCV GT2 patients with cirrhosis. The role of 2k/1b chimeras as potential predictor of treatment failure was also analysed. Overall, 291 HCV GT2 infected patients with bridging fibrosis or cirrhosis were evaluated. Median age was 68years (18-87); 163 were treatment naïve. Of 168 cirrhotic patients, 149 had Child-Pugh score A and 19 B, 50 platelets count <100,000/mm 3 and 62 albumin <3.5g/dl. SVR12 were 95.53% overall, with 99.15% in non-cirrhotic patients and 93.06% in cirrhotic patients. In patients who completed treatment, SVR rates for cirrhotic patients resulted in 94.51%, and 94.94% after 16 or 20weeks respectively. Predictors of SVR were low platelet count and esophageal varices (OR 7.2; 95% CI 1.67-31.25; p=0.0022 and OR 0.1; 95% CI 0.01-0.72; p=0.0079, respectively). Anemia was mild in 12.4%, moderate in 3.4%, and severe in 2.4% of cases. Anemia was slightly more frequent among longer duration but not associated with treatment discontinuations. No 2k/1b strains or genotypes different from those at baseline were identified at relapse. In GT2 cirrhotic patients, SOF/RBV for 16 or 20weeks is associated with real life SVR12 rates of 95%. A duration of treatment of 16-20weeks was recommended for treatment of HCV GT2 patients using the combination of sofosbuvir and ribavirin. Real life experiences, where patients received 12weeks of treatment regardless of the severity of liver disease, suggested that response rates are lower than expected, in particular in patients with liver cirrhosis. A misleading genotyping of a 2k/1b strain as GT2 was also hypothesized as a further explanation for less effectiveness. We demonstrated that using the recommended extended duration in patients with more severe disease 95% of patients with severe liver disease including cirrhosis can be cured and that 2k/1b strain plays only a secondary role in specific countries like Germany. Although this combination has been recently replaced by sofosbuvir and velpatasvir fixed dose combination as the standard of care for treating HCV GT2 patients, our findings may inform physicians from countries where the new regimen is not yet available. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[Survival in patients with liver cirrhosis at the Durango, IMSS Regional General Hospital].

PubMed

Rodríguez-Hernández, Heriberto; Jacobo-Karam, Janett S; Castañón-Santillán, María del Carmen; Arámbula-Chávez, Mayela; Martínez-Aguilar, Gerardo

2002-01-01

In Mexico, hepatic cirrhosis mortality exhibits important regional differences. To analyze global survival of cirrhotic patients, according to etiology and functional status. Between March 1990 to August 1998, newly diagnosed patients with hepatic cirrhosis were included in a follow-up study. Subjects were analyzed monthly. Information on clinical evolution, complications, and dates of events (death) and complications were registered. Survival was estimated using Kaplan-Meier method. Ninety nine subjects were included in the survival analysis, 66 with alcoholic and 33 with viral cirrhosis (HCV and HBV in 24 and nine patients, respectively). Ninety seven percent of patients were decompensated at diagnosis, and 81% had ascites. Probabilities for survival in the entire series were 69.7, 37.6 and 23.6% at 24, 48, and 60 months, respectively. There were no significant differences in the survival of patients grouped according to etiology. When survival was analyzed by Child-Pugh score, it was slightly higher in the alcoholic cirrhosis group. In this study survival probability of patients with viral cirrhosis was lower than in patients with alcohol cirrhosis.

Propranolol, isosorbide mononitrate and endoscopic band ligation - alone or in varying combinations for the prevention of esophageal variceal rebleeding.

PubMed

Ahmad, Irfan; Khan, Anwaar A; Alam, Altaf; Butt, Arshad Kamal; Shafqat, Farzana; Sarwar, Shahid

2009-05-01

To compare the efficacy of propranolol, propranolol with nitrate, band ligation, and band ligation with propranolol and nitrate for the prevention of esophageal variceal rebleeding. A prospective randomized trial. Department of Gastroenterology and Hepatology, Sheikh Zayed Hospital, Lahore, from November 2003 to July 2005. One hundred and sixty cirrhotic patients with esophageal variceal bleeding were randomized to four treatment groups (propranolol, propranolol plus isosorbide mononitrate, band ligation, band ligation plus propranolol and nitrate) with 40 patients in each group. Patients were followed for 6 months after the enrolment of last patient. Primary end points were recurrence of esophageal variceal bleeding and death. Treatment complications were noted. Four treatment groups were comparable regarding baseline characteristics. Esophageal variceal rebleeding occurred in 22% patients in band ligation plus drugs group, 26% patients in drug combination group, 31% patients in banding group and 38% patients in propranolol group (p=0.41). Difference in mortality rates was also not significant. There was no significant difference between treatment groups in prevention of esophageal variceal rebleeding.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma.

PubMed

Ponziani, Francesca Romana; Spinelli, Irene; Rinninella, Emanuele; Cerrito, Lucia; Saviano, Antonio; Avolio, Alfonso Wolfango; Basso, Michele; Miele, Luca; Riccardi, Laura; Zocco, Maria Assunta; Annicchiarico, Brigida Eleonora; Garcovich, Matteo; Biolato, Marco; Marrone, Giuseppe; De Gaetano, Anna Maria; Iezzi, Roberto; Giuliante, Felice; Vecchio, Fabio Maria; Agnes, Salvatore; Addolorato, Giovanni; Siciliano, Massimo; Rapaccini, Gian Lodovico; Grieco, Antonio; Gasbarrini, Antonio; Pompili, Maurizio

2017-12-28

To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) and to ascertain the factors predicting the achievement of disease control (DC). The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo (95%CI: 10.6-17.0). Only alphafetoprotein (AFP) serum level > 200 ng/mL and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up (HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year (HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC (OR = 0.263, 95%CI: 0.111-0.622, P = 0.002). The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

Nonselective Beta-Blockers Do Not Affect Survival in Cirrhotic Patients with Ascites.

PubMed

Facciorusso, Antonio; Roy, Sunil; Livadas, Sarantis; Fevrier-Paul, Adwalia; Wekesa, Clara; Kilic, Ismail Dogu; Chaurasia, Amit Kumar; Sadeq, Mina; Muscatiello, Nicola

2018-05-03

The role of nonselective beta-blockers in cirrhotic patients with ascites has been recently questioned; however, definitive evidence in this regard is still lacking. To analyze published data on the influence of nonselective beta-blockers as compared to control group on survival of cirrhotic patients with ascites. Computerized bibliographic search on the main databases was performed. Hazard ratios from Kaplan-Meier curves were extracted in order to perform an unbiased comparison of survival estimates. Secondary outcomes were mortality in patients with refractory ascites, pooled rate of nonselective beta-blockers interruption, spontaneous bacterial peritonitis and hepato-renal syndrome incidence. Three randomized controlled trials and 13 observational studies with 8279 patients were included. Overall survival was comparable between the two groups (hazard ratio = 0.86, 0.71-1.03, p = 0.11). Study design resulted as the main source of heterogeneity in sensitivity analysis and meta-regression. Mortality in refractory ascites patients was similar in the two groups (odds ratio = 0.90, 0.45-1.79; p = 0.76). No difference in spontaneous bacterial peritonitis (odds ratio = 0.78, 0.47-1.29, p = 0.33) and hepato-renal syndrome incidence (odds ratio = 1.22, 0.48-3.09; p = 0.67) was observed. Pooled rate of nonselective beta-blockers interruption was 18.6% (5.2-32.1%). Based on our findings, nonselective beta-blockers should not be routinely withheld in patients with cirrhosis and ascites, even if refractory.

Safety of laparoscopic resection for colorectal cancer in patients with liver cirrhosis: A retrospective cohort study.

PubMed

Zhou, Senjun; Zhu, Hepan; Li, Zhenjun; Ying, Xiaojiang; Xu, Miaojun

2018-05-26

Patients with liver cirrhosis represent a high risk group for colorectal surgery. The safety and effectiveness of laparoscopy in colorectal surgery for cirrhotic patients is not clear. The aim of this study was to compare the outcomes of laparoscopic colorectal surgery with those of open procedure for colorectal cancer in patients with liver cirrhosis. A total of 62 patients with cirrhosis who underwent radical resections for colorectal cancer from 2005 to 2014 were identified retrospectively from a prospective database according to the technique adopted (laparoscopic or open). Short- and long-term outcomes were compared between the two groups. Comparison of laparoscopic group and open group revealed no significant differences at baseline. In the laparoscopic group, the laparoscopic surgery was associated with reduced estimated blood loss (136 vs. 266 ml, p = 0.015), faster first flatus (3 vs. 4 days, p = 0.002) and shorter days to first oral intake (4 vs. 5 days, p = 0.033), but similar operative times (p = 0.856), number of retrieved lymph nodes (p = 0.400) or postoperative hospital stays (p = 0.170). Despite the similar incidence of overall complications between the two groups (50.0% vs. 68.8%, p = 0.133), we observed lower morbidities in laparoscopic group in terms of the rate of Grade II complication (20.0% vs. 50.0%, p = 0.014). Long-term of overall and Disease-free survival rates did not differ between the two groups. Laparoscopic colorectal surgery appears to be a safe and less invasive alternative to open surgery in some elective cirrhotic patients in terms of less blood loss or early recovery and does not result in additional harm in terms of the postoperative complications or long-term oncological outcomes. Copyright © 2018. Published by Elsevier Ltd.

Liver transplantation for hepatocellular carcinoma: a surgical perspective.

PubMed

Fortune, Brett E; Umman, Veysel; Gilliland, Thomas; Emre, Sukru

2013-07-01

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. Early detection and timely treatment of HCC is critical for better patient outcomes. Curative therapy consists of surgical hepatic resection or liver transplantation (LTx); however, both are restricted to explicit selective criteria. Liver resection is the gold standard of treatment for noncirrhotic patients but can be done in only a small fraction of cirrhotic patients depending on synthetic dysfunction, degree of portal hypertension, and number and location(s) of tumor(s). Therefore, the best treatment modality in cirrhotic patients with HCC is LTx as it will cure both HCC and the underlying cirrhosis. The limitation to offer transplant to all cirrhotic patients with HCC is the shortage of available donor organs. While these patients are waiting for transplant, their tumors may progress and develop distant metastases and may lead to patients losing their candidacy for LTx. Various ablation therapies can be used to treat HCC, prevent tumor progression, and thus, avoid patients losing the option of LTx. Future directions to improve HCC patient outcomes include advancement in tumor gene analysis and histopathology for better prediction of tumor behavior, improved immunosuppression regimens to reduce tumor recurrence in the posttransplant setting, and efficient use of an expanded donor pool that includes living donor organs. This paper will review the current methods of HCC diagnosis, selection for either hepatic resection or LTx, and will also summarize posttreatment outcomes. We will suggest future directions for the field as we strive to improve outcomes for our HCC patients.

Albumin-bilirubin score for predicting the in-hospital mortality of acute upper gastrointestinal bleeding in liver cirrhosis: A retrospective study.

PubMed

Zou, Deli; Qi, Xingshun; Zhu, Cuihong; Ning, Zheng; Hou, Feifei; Zhao, Jiancheng; Peng, Ying; Li, Jing; Deng, Han; Guo, Xiaozhong

2016-03-01

The albumin-bilirubin (ALBI) score is a new model for assessing the severity of liver dysfunction. In the present study, we aimed to retrospectively compare the performance of ALBI with Child-Pugh and the model for end-stage liver disease (MELD) scores for predicting the in-hospital mortality of acute gastrointestinal bleeding (AUGIB) in liver cirrhosis. All cirrhotic patients with AUGIB were eligible, provided they had the data needed to determine the ALBI score. Areas under the receiving-operator characteristics curve (AUC) are reported. Overall, 631 patients were included. In all the included patients, the AUC of the ALBI, Child-Pugh, and MELD scores were 0.808, 0.785 (p=0.5831), and 0.787 (p=0.7033), respectively. In patients with only hepatitis B virus-related liver cirrhosis, the AUC of the ALBI, Child-Pugh, and MELD scores were 0.865, 0.836 (p=0.6064), and 0.818 (p=0.6399), respectively. In patients with only alcohol-related liver cirrhosis, the AUC of the ALBI, Child-Pugh, and MELD scores were 0.869, 0.860 (p=0.9003), and 0.801 (p=0.5548), respectively. In patients treated with endoscopic therapy for AUGIB, the AUC of the ALBI, Child-Pugh, and MELD scores were 0.873, 0.884 (p=0.7898), and 0.834 (p=0.5531), respectively. The prognostic performance of the ALBI score was comparable with that of the Child-Pugh and MELD scores for predicting the in-hospital mortality of AUGIB in liver cirrhosis.

Functional restoration of cirrhotic liver after partial hepatectomy in the rat.

PubMed

Hashimoto, Masaji; Watanabe, Goro

2005-01-01

Although cirrhosis is the terminal stage of various liver diseases, thanks to recent advances one might eliminate some causes of liver damage. Liver has a potent regeneration capacity. It is important to evaluate the regenerating cirrhotic liver after partial hepatectomy, morphologically and functionally, in the long term. We evaluated the functional capacity of the rat liver rendered cirrhotic by orally administered thioacetamide, and examined the correlation between morphological and functional restoration after 2/3 hepatectomy in comparison with hepatectomized normal rats and sham-operated cirrhotic rats. Morphological restoration was evaluated by remnant liver weight, proliferating cell nuclear antigen labeling index, and fibrosis ratio. Functional restoration was evaluated by the indocyanine green disappearance rate and aminopyrine clearance. Cirrhotic rats were functionally deteriorated in comparison with the normal rats. Morphological restoration in cirrhotic rats was delayed in comparison with normal rats. Functional restoration after 2/3 hepatectomy was advanced in comparison with morphological restoration. In comparison with sham-operated cirrhotic rats, functional restoration of the cirrhotic liver was accelerated by partial hepatectomy. In cirrhotic rats, functional restoration of the liver after 2/3 hepatectomy was advanced in comparison with morphological restoration. Partial hepatectomy seemed to promote functional restoration of the cirrhotic liver.

Successful retreatment with sofosbuvir plus ledipasvir for cirrhotic patients with hepatitis C virus genotype 1b, who discontinued the prior treatment with asunaprevir plus daclatasvir: A case series and review of the literature

PubMed Central

Haga, Yuki; Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Ooka, Yoshihiko; Takahashi, Koji; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Chiba, Tetsuhiro; Maruyama, Hitoshi; Yokosuka, Osamu; Takada, Nobuo; Moriyama, Mitsuhiko; Imazeki, Fumio; Kato, Naoya

2018-01-01

Background Interferon-free treatment results in higher sustained virologic response (SVR) rates, with no serious adverse events in hepatitis C virus (HCV)-infected patients. However, in some patients with treatment-failure in HCV NS5A inhibitor-including interferon-free regimens, the treatment-emergent HCV NS5A resistance-associated variants (RAVs), which are resistant to interferon-free retreatment including HCV NS5A inhibitors, are observed. In HCV-infected Japanese patients with daclatasvir and asunaprevir treatment failure, retreatment with sofosbuvir and ledipasvir could lead to only ∼70% SVR rates. Case summary Three HCV genotype (GT)-1b-infected cirrhotic patients who discontinued the combination of daclatasvir and asunaprevir due to adverse drug reactions within 4 weeks; retreatment with sofosbuvir and ledipasvir combination could result in SVR in these patients without RAVs. One HCV GT-1b-infected cirrhotic patient who discontinued the combination of daclatasvir and asunaprevir due to viral breakthrough at week 10; retreatment with sofosbuvir and ledipasvir combination for this patient with the treatment-emergent HCV NS5A RAV-Y93H resulted in viral relapse at week 4 after the end of the treatment. Conclusion Retreatment with sofosbuvir and ledipasvir is effective for HCV GT-1b patients who discontinue the combination of daclatasvir and asunaprevir within 4 weeks. The treatment response should be related to the existence of treatment-emergent HCV NS5A RAVs, but may not be related to the short duration of treatment. PMID:29435197

Safe use of proton pump inhibitors in patients with cirrhosis.

PubMed

Weersink, Rianne A; Bouma, Margriet; Burger, David M; Drenth, Joost P H; Froukje Harkes-Idzinga, S; Hunfeld, Nicole G M; Metselaar, Herold J; Monster-Simons, Margje H; van Putten, Sandra A W; Taxis, Katja; Borgsteede, Sander D

2018-04-24

Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in cirrhosis. A systematic literature search identified studies about the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child-Turcotte-Pugh (CTP) classification. A total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having 'no additional risks known'. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole in a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe, because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered. We suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients. This article is protected by copyright. All rights reserved.

Elevated circulating endothelial cell-derived microparticle levels in patients with liver cirrhosis: a preliminary report

PubMed Central

Simon, Krzysztof Adam; Pazgan-Simon, Monika

2015-01-01

Aim of the study To determine plausible associations between liver cirrhosis and circulating endothelial cell-derived microparticles (EMPs), vascular endothelial growth factor (VEGF) levels and plasma nitric oxide (NO) metabolites. Material and methods Sixty patients with cirrhosis and 20 healthy control subjects were enrolled in the study. Circulating EMPs from platelet-poor plasma samples were examined by flow cytometry. These microparticles were categorized into endothelial cell-derived activated MPs (EMP-ac) (CD31+ CD42b– AN-V–) and endothelial cell-derived apoptotic MPs (EMP-ap) (CD31+ CD42b– AN-V+). Plasma VEGF levels were measured by enzyme-linked immunosorbent assay. Plasma NO metabolites (NOx–) levels were determined using a Greiss reaction method. Results Compared with the healthy control subjects, the patients with cirrhosis showed a significant increase in plasma levels of both phenotypes of EMPs. When the presence of ascites was considered, the plasma levels of EMP-ap were higher (p < 0.01), as well as NOx– (p < 0.05). EMP-ap positively correlated with VEGF level in all cirrhotic patients and this correlation was stronger in decompensated cirrhotic patients. In multivariate logistic regression analysis, the independent factors associated with the presence of ascites were high EMP-ap levels and elevated VEGF levels. Conclusions Elevated plasma levels of EMP-ap in addition to high levels of VEGF might be considered as valuable parameters for predicting the occurrence of ascites in cirrhotic patients. PMID:28856256

A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

PubMed

Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel

2017-11-01

Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P < 0.05). The decrease of EndMT in cirrhotic livers correlated with a significant decrease in liver fibrosis ( P < 0.05) and an improvement in the vascular disorganization rate ( P < 0.05). We demonstrated the acquisition of the EndMT phenotype by a subpopulation of endothelial cells from cirrhotic livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American Physiological Society.

Influence of insulin resistance on the development of hepatocellular carcinoma after antiviral treatment for non-cirrhotic patients with chronic hepatitis C.

PubMed

Hayashi, Takeo; Ogawa, Eiichi; Furusyo, Norihiro; Murata, Masayuki; Hayashi, Jun

2016-01-01

Insulin resistance is considered to be an important factor in the progression of fibrosis and the enhancement of the risk of hepatocellular carcinoma (HCC) for chronic hepatitis C patients. The aim of this study was to assess the effect of insulin resistance on the development of HCC by non-cirrhotic chronic hepatitis C patients treated with pegylated interferon alpha-2b (PEG-IFNα2b) and ribavirin. This retrospective study consisted of 474 Japanese non-cirrhotic patients with chronic hepatitis C. The cumulative incidence of HCC was estimated using the Kaplan-Meier method, according to insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) and treatment outcome. The overall sustained virological response (SVR) rate was 45.1 % (214/474, genotype 1: 35.4 % [129/364] and genotype 2: 77.3 % [85/110]). Twenty-one (4.4 %) patients developed HCC during the follow-up period. The 5-year cumulative incidence of HCC of the SVR group (2.6 %) was significantly lower than that of the non-SVR group (9.7 %) (log-rank test: P = 0.025). In multivariable logistic regression analysis, HOMA-IR (≥2.5) (hazard ratio [HR] 12.8, P = 0.0006), fibrosis status (F3) (HR 8.85, P < 0.0001), and post-treatment alanine aminotransferase (ALT) level (≥40 U/L) (HR 4.33, P = 0.036) were independently correlated to the development of HCC. Receiver operating characteristic analysis to determine the optimal threshold value of HOMA-IR for predicting the development of HCC in the non-SVR group showed that the areas under the curve was high (0.80, cutoff value: 3.0). Only three patients (1.4 %) who achieved SVR developed HCC. Two of them had severe insulin resistance and did not show improvement in HOMA-IR after achieving SVR. Insulin resistance has a strong impact on the development of HCC by non-cirrhotic patients who have PEG-IFNα2b and ribavirin treatment failure.

The rs2296651 (S267F) variant on NTCP (SLC10A1) is inversely associated with chronic hepatitis B and progression to cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B.

PubMed

Hu, Hui-Han; Liu, Jessica; Lin, Yu-Ling; Luo, Wun-Sheng; Chu, Yu-Ju; Chang, Chia-Lin; Jen, Chin-Lan; Lee, Mei-Hsuan; Lu, Sheng-Nan; Wang, Li-Yu; You, San-Lin; Yang, Hwai-I; Chen, Chien-Jen

2016-09-01

The sodium taurocholate co-transporting polypeptide (NTCP), encoded by SLC10A1, was recently identified as a receptor for HBV. We assessed the association of the p.Ser267Phe variant (rs2296651) with chronic hepatitis B (CHB) serostatus, cirrhosis and hepatocellular carcinoma (HCC) in patients with CHB. The variant was genotyped in 3801 patients with CHB and 3801 matched hepatitis B surface antigen (HBsAg) seronegative individuals. ORs with 95% CIs for the variant's association with CHB, cirrhosis and HCC were estimated using logistic regression. In patients with CHB, the S267F variant was observed in 515 (18.5%) controls, 40 (17.2%) cirrhosis only cases, 49 (13.2%) non-cirrhotic HCC cases, and 52 (12.7%) cirrhotic-HCC cases. After adjustment for known risk factors, S267F was significantly associated with decreased risk for cirrhosis (OR 0.65 (95% CI 0.49 to 0.86), p=0.002) and HCC (OR 0.55 (95% CI 0.42 to 0.72), p<0.001). This association persisted for non-cirrhotic and cirrhotic-HCC. Compared with patients with HBV DNA levels greater than 10(5) copies/mL who carried the GG genotype, patients who had undetectable HBV DNA and the GA or AA genotypes had a 25-fold decreased risk of developing HCC (OR 0.04 (95% CI 0.02 to 0.11), p<0.001). The AA genotype was also associated with HBsAg seronegativity (OR 0.13 (95% CI 0.05 to 0.34), p<0.001). The SLC10A1 (NTCP) S267F variant is independently associated with decreased risk of cirrhosis and HCC, and resistance to CHB infection. Together with serum HBV DNA levels, S267F may help to identify patients with CHB with very low risk of HCC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Soluble FGL2, a novel effector molecule of activated hepatic stellate cells, regulates T-cell function in cirrhotic patients with hepatocellular carcinoma.

PubMed

Sun, Ying; Xi, Dong; Ding, Wen; Wang, Faxi; Zhou, Haili; Ning, Qin

2014-10-01

To investigate the effects of soluble FGL2 (sFGL2) secreted by hepatic stellate cells (HSCs) on immune suppression in cirrhotic patients with hepatocellular carcinoma (HCC). Serum sFGL2 levels were examined by ELISA in 40 patients with HCC, liver cirrhosis (LC) or chronic HBV (CHB) infection. A double staining of the immunofluorescence analysis of α-SMA and FGL2 was performed in two cirrhotic liver specimens. The expression of FGL2 in the LX2 cell line was analyzed by immunofluorescence, Western blot and flow cytometry. T-cells purified from HCC patients using magnetic beads were cultured with LX2 cells at different ratios with anti-CD3-stimulating or FGL2-blocking antibodies. The proliferation index (PI) of CD8 + T cells was assessed by flow cytometry, and the secretion of IFN-γ was measured by ELISA. sFGL2 levels are significantly higher in patients with HCC or LC compared with those with CHB (p = 0.0039/p = 0.0020). Among HCC patients, those with cirrhosis exhibited significantly higher levels of sFGL2 compared with non-cirrhotic individuals (p = 0.0108). The expressions of FGL2 and α-SMA overlapped in HSCs in liver specimens. FGL2 protein secreted by LX2 cells inhibited T-cell proliferation of HCC patients in a dose-dependent manner in vitro. The PI of CD8 + T cells was significantly enhanced following addition of FGL2 antibody to the culture system (LX2/T-cell ratio of 1:10, p = 0.002). The level of IFN-γ in mixed cultures was inversely correlated with the number of HSCs and was reversed by incubation with FGL2 blocking antibody. sFGL2 protein is a novel effector molecule of activated HSCs, which suppresses CD8 + T cell proliferation and interferon-γ production, and it subsequently might contribute to immune suppression during fibrosis and tumorigenesis in the liver.

Risk factors for osteoporosis in liver cirrhosis patients measured by transient elastography.

PubMed

Zheng, Jian-Ping; Miao, Hai-Xiong; Zheng, Shao-Wei; Liu, Wei-le; Chen, Chu-Qun; Zhong, Hao-Bo; Li, Sheng-Fa; Fang, Yong-Ping; Sun, Chun-Han

2018-05-01

Osteoporosis or osteopenia is a common complication in patients with cirrhosis, but little is known about the risk factors for the occurrence of osteoporosis.Patients with liver cirrhosis due to chronic virus infection and alcoholic abuse were enrolled. Bone mineral density (BMD) was determined using dual-energy x-ray absorptiometry (DXA). Osteoporosis was diagnosed according to WHO criteria. The severity of liver stiffness was measured by Fibroscan. Demographic data, such as age, gender, weight, height, and body mass index (BMI), were collected. Logistic regression analysis was used to recognize the risk factors of osteoporosis in patients with cirrhosis.A total of 446 patients were included in this study: 217 had liver cirrhosis (male, 74.2%; mean age, 57.2 ± 10.27) and 229 were matched controls (male, 69%, mean age, 56.69 ± 9.37). Osteoporosis was found in 44 patients (44/217, 20.3%). The spine and hip BMD in cirrhotic patients were significantly lower than that in controls. When the cirrhotic and control subjects were stratified by age, gender, and BMI, the significant difference was also observed in women patients, patients older than 60, and patients with BMI < 18. Multivariate analysis showed that the older age [odds ratio (OR) = 1.78, P = .046], lower BMI (OR = 0.63, P = .049), greater fibroscan score (OR = 1.15, P = .009), and liver cirrhosis induced by alcohol liver disease (OR = 3.42, P < .001) were independently associated with osteoporosis in cirrhotic patients.Osteoporosis occurred in about one-fifth of patients with liver cirrhosis, which was associated with age, BMI, Fibroscan score, and alcohol liver disease related liver cirrhosis.

New advances in hepatocellular carcinoma

PubMed Central

Pascual, Sonia; Herrera, Iván; Irurzun, Javier

2016-01-01

Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

[Esophageal motor disorders in cirrhotic patients with esophageal varices non-submitted to endoscopic treatment].

PubMed

Flores, Priscila Pollo; Lemme, Eponina Maria de Oliveira; Coelho, Henrique Sérgio Moraes

2005-01-01

The hepatic cirrhosis has as one of the main morbid-mortality causes, the portal hypertension with the development of esophageal varices, the possibility of a digestive hemorrhage and worsening of hepatic insufficiency. It is important to identify causal predictive or aggravating factors and if possible to prevent them. In the last years, it has been observed the association of esophageal motor disorders and gastro-esophageal reflux in cirrhotic patients with esophageal varices. To study the prevalence of the esophageal motility disorders and among them, the ineffective esophageal motility, in patients with hepatic cirrhosis and esophageal varices, without previous endoscopic therapeutic and the predictive factors. Prospectively, it has been evaluate 74 patients suffering from liver cirrhosis and esophagic varices, without previous endoscopic treatment. All of them were submitted to a clinical protocol, esophageal manometry and 55 patients also held the ambulatory esophageal pHmetry. Esophageal motility disorders have been found in 44 patients (60%). The most prevalent was the ineffective esophageal motility, observed in 28%. The abnormal reflux disease was diagnosed through the pHmetry in 35% of the patients. There were no correlation between the manometrical abnormality in general and the ineffective esophageal motility in particular and the esophageal or gastroesophageal reflux disease symptoms, the abnormal reflux, the disease seriousness, the ascites presence and the gauge of the varices. The majority of cirrhotic patients with non-treated esophageal varices present esophageal motor disorders. No predictive factor was found. The clinical relevance of these findings need more researches in the scope to define the real meaning of theses abnormalities.

Two randomized controlled studies comparing the nutritional benefits of branched-chain amino acid (BCAA) granules and a BCAA-enriched nutrient mixture for patients with esophageal varices after endoscopic treatment.

PubMed

Sakai, Yoshiyuki; Iwata, Yoshinori; Enomoto, Hirayuki; Saito, Masaki; Yoh, Kazunori; Ishii, Akio; Takashima, Tomoyuki; Aizawa, Nobuhiro; Ikeda, Naoto; Tanaka, Hironori; Iijima, Hiroko; Nishiguchi, Shuhei

2015-01-01

The usefulness of branched-chain amino acid (BCAA) granules and BCAA-enriched nutrient mixtures for patients with liver cirrhosis is often reported. However, no randomized controlled studies have investigated the usefulness of these supplements in the nutritional intervention of cirrhotic patients receiving endoscopic treatment for esophageal varices. Patients without BCAA before endoscopic treatment were divided into study 1, and those who received BCAA were divided into study 2. In study 1, 44 eligible patients were divided into a control group (n = 13), a general liquid nutrient (snack) group (n = 15), and a BCAA-enriched nutrient mixture (BCAA-EN) group (n = 16). In study 2, 48 eligible patients were divided into a BCAA group (n = 24) and a BCAA-EN group (n = 24). The nutritional status including non-protein respiratory quotient (NPRQ) levels, weight gain, and albumin were evaluated on days 0, 7, and 50. In study 1, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 as compared with the snack group. In study 2, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 and in weight levels on day 50 relative to the BCAA group, while the BCAA group showed improved serum albumin levels on day 7 compared to the BCAA-EN group. The BCAA-enriched nutrient mixture maintained NPRQ and weight in cirrhotic patients. Our findings suggest that supplements including both BCAA and a nutritional energy supplement would be beneficial for cirrhotic patients undergoing endoscopic treatment for esophageal varices.

Randomised clinical trial: enteral nutrition does not improve the long-term outcome of alcoholic cirrhotic patients with jaundice.

PubMed

Dupont, B; Dao, T; Joubert, C; Dupont-Lucas, C; Gloro, R; Nguyen-Khac, E; Beaujard, E; Mathurin, P; Vastel, E; Musikas, M; Ollivier, I; Piquet, M-A

2012-05-01

Malnutrition and jaundice are independent prognostic factors in cirrhosis. To assess the impact of enteral nutrition on the survival of alcoholic cirrhotic patients with jaundice but without acute alcoholic hepatitis. The study was a multicentre prospective randomised controlled trial comparing effects of enteral nutrition vs. a symptomatic support in patients with alcoholic cirrhosis and jaundice (bilirubin ≥51 µmol/L) but without severe acute alcoholic hepatitis. A total of 99 patients were randomised to receive either the conventional symptomatic treatment (55 patients) or the symptomatic support associated with 35 kcal/Kg/day of enteral nutrition during 4 weeks followed by an oral nutritional support during 2 months (44 patients). Randomisation was stratified on nutritional status. One-year survival curves were compared using the Kaplan-Meier method and Logrank test. Populations in both arms were similar. One-year survival was similar in the overall population (27/44 patients (61.4%) in the enteral nutrition arm vs. 36/55 (65.5%) in the control arm; Logrank P = 0.60) and in the subgroup suffering from malnutrition [18/29 patients (62.1%) in the enteral nutrition arm vs. 20/32 (62.5%) in the control arm; Logrank P = 0.99]. There was no statistical difference for bilirubin, prothrombin rate, Child-Pugh score, albumin or nutritional assessment. Complications during treatment (bleeding, encephalopathy, infection) occurred in 23% of patients in the enteral nutrition group (10/44) vs. 16% (9/55) of the control patients (P = 0.59). Enteral nutrition does not improve the survival and hepatic or nutritional parameters of cirrhotic patients with jaundice. © 2012 Blackwell Publishing Ltd.

Predictive factors for long-term survival in patients with clinically significant portal hypertension following resection of hepatocellular carcinoma.

PubMed

Choi, Gi H; Park, Jun Y; Hwang, Ho K; Kim, Dong H; Kang, Chang M; Choi, Jin S; Park, Young N; Kim, Do Y; Ahn, Sang H; Han, Kwang-Hyub; Chon, Chae Y; Lee, Woo J

2011-04-01

Hepatic resection for hepatocellular carcinoma (HCC) is not currently recommended for patients with clinically significant portal hypertension (PHT); however, recent studies have shown similar post-operative outcomes between patients with and without clinically significant PHT. To clarify the post-operative prognostic relevance of clinically significant PHT in Child-Pugh A cirrhotic patients. A total of 100 Child-Pugh A cirrhotic patients who underwent curative resection of HCC were eligible for this analysis. Patients were divided into two groups: PHT group (n=47) and non-PHT group (n=53). Clinicopathological variables showed no significant differences except for prothrombine time. Liver-related complications were significantly higher in the PHT group (P=0.015), and the 5-year overall survival rate was significantly higher in the non-PHT group (78.7 vs. 37.9%, P<0.001). The proportion of patients who died because of complications of cirrhosis was significantly higher in the PHT group (P=0.001). Multivariate analysis indicated that the presence of clinically significant PHT was the most powerful adverse prognostic factor for overall survival. Multivariate analysis of the 47 patients with clinically significant PHT indicated that gross vascular invasion and non-single nodular type were poor prognostic factors. The 5-year survival rate of patients with single nodular type and without gross vascular invasion (n=17) was 78.4%. In Child-Pugh A cirrhotic patients, the presence of clinically significant PHT was significantly associated with post-operative hepatic decompensation and poor prognosis after resection of HCC. However, in patients with clinically significant PHT, those with single nodular tumours lacking gross vascular invasion may be good surgical candidates. © 2011 John Wiley & Sons A/S.

Detection of micronuclei formation and nuclear anomalies in regenerative nodules of human cirrhotic livers and relationship to hepatocellular carcinoma.

PubMed

de Almeida, Terezinha M B; Leitão, Regina C; Andrade, Joyce D; Beçak, Willy; Carrilho, Flair J; Sonohara, Shigueko

2004-04-01

Human cirrhosis is considered an important factor in hepatocarcinogenesis. The lack of substantial genetics and cytogenetics data in human cirrhosis led us to investigate spontaneous micronuclei formation, as an indicator of chromosomal damage. The analysis was performed in hepatocytes of regenerative, macroregenerative, and tumoral nodules from 30 cases of cirrhosis (paraffin-embedded archival material), retrospectively selected: cryptogenic, hepatitis C virus, and hepatitis C virus associated with hepatocellular carcinoma (HCC). Thirteen control liver samples of healthy organ donors were included. Micronucleated hepatocytes were analyzed with Feulgen-fast-green dyeing techniques. The spontaneous frequency of micronucleated hepatocytes in both regenerative and macroregenerative nodules of all cirrhotic patients was significantly higher than for the normal control group. There was no significant difference in frequency of micronucleated hepatocytes in regenerative nodules compared with macroregenerative nodules for all cases analyzed, whereas a significantly higher frequency of micronucleated hepatocytes was detected in tumoral nodules, compared with cirrhotic regenerative nodules and normal parenchyma. A higher frequency of the nuclear anomalies termed broken-eggs was observed in hepatitis C virus-related samples. Chromatinic losses and genotoxicity already existed in the cirrhotic regenerative nodules, which might predispose to development of HCC.

Depression, anxiety and alexithymia symptoms are major determinants of health related quality of life (HRQoL) in cirrhotic patients.

PubMed

Nardelli, Silvia; Pentassuglio, Ilaria; Pasquale, Chiara; Ridola, Lorenzo; Moscucci, Federica; Merli, Manuela; Mina, Concetta; Marianetti, Massimo; Fratino, Mariangela; Izzo, Chiara; Merkel, Carlo; Riggio, Oliviero

2013-06-01

HRQoL is impaired in cirrhosis. Establishing the relevance of depression, anxiety, alexithymia and cirrhosis stage on the patients' HRQoL. Sixty cirrhotics underwent a neuropsychological assessment, including ZUNG-SDS, STAI Y1-Y2 and TAS-20. Minimal hepatic encephalopathy (MHE) was detected by PHES, HRQoL by Short-Form-36 (SF-36). Depression was detected in 34 patients (57 %, 95%CI = 44-70 %), state-anxiety in 16 (27 %, 95%CI = 15-38 %), trait-anxiety in 17 (28 %, 95%CI = 17-40 %), alexithymia in 14 (31 % 95%CI = 16-46 %) and MHE in 22 (37 %, 95%CI = 24-49 %). Neuropsychological symptoms were unrelated to cirrhosis stage, hepatocellular carcinoma or MHE. A significant correlation was observed among psychological test scores and summary components of SF-36. At multiple linear regression analysis including Child-Pugh and MELD scores, previous-HE and the psychological test scores as possible covariates, alexithymia and depression as well as to the Child-Pugh score were significantly related to the SF-36 mental component; while trait-anxiety was the only variable significantly and independently related to the SF-36 physical component. Depression, state and trait-anxiety and alexithymia symptoms are frequent in cirrhotics and are among the major determinants of the altered HRQoL.

Breakfast improves cognitive function in cirrhotic patients with cognitive impairment.

PubMed

Vaisman, Nachum; Katzman, Helena; Carmiel-Haggai, Michal; Lusthaus, Michal; Niv, Eva

2010-07-01

Cognitive disturbances are relatively common in patients with liver disease. High protein load precipitates hepatic encephalopathy in cirrhotic patients. Minimal hepatic encephalopathy (MHE) is a prevalent neurocognitive complication of cirrhosis. Because the influence of nutritional factors on the progression of cognitive impairment has not been explored in depth, this study aimed to investigate the effect on cognition of acute metabolic changes induced by breakfast consumption. Twenty-one subjects (10 women) with Child A cirrhosis and 21 age- and sex-matched healthy controls were enrolled. Patients and controls were divided into 2 groups: those receiving a breakfast of 500 kcal and 21 g protein and those receiving no breakfast. Serum ammonia concentrations and cognitive functions were studied (Mindstreams; NeuroTrax, Fresh Meadows, NY) before and 2 h after breakfast. A mixed model was used to analyze the data. At baseline, cirrhotic patients had significantly lower total scores and significantly lower subscores (P < 0.015 global cognitive score) in 4 of 7 cognitive categories, which is indicative of MHE. Patients with hyperammonemia (>85 mug/dL) scored significantly lower for attention than did patients with normal serum ammonia concentrations (P < 0.003). After 2 h, MHE patients and controls responded differently to breakfast consumption with regard to attention and executive functions (P < 0.003 and P < 0.04, respectively). Although patients' scores improved after breakfast consumption, despite an increase in serum ammonia, healthy controls who continued to fast performed better. Chronic hyperammonemia may negatively affect attention. Eating breakfast improves attention and executive functions of patients with MHE. Prolonged periods of starvation may be partly responsible for these changes. This trial was registered at clinicaltrials.gov as NCT01083446.

Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function.

PubMed

Simpson, Kathleen E; Esmaeeli, Amir; Khanna, Geetika; White, Francis; Turnmelle, Yumirle; Eghtesady, Pirooz; Boston, Umar; Canter, Charles E

2014-02-01

Liver cirrhosis is recognized with long-term follow-up of patients after the Fontan procedure. The effect of liver cirrhosis on the use of heart transplant (HT) and on post-HT outcomes is unknown. We reviewed Fontan patients evaluated for HT from 2004 to 2012 with hepatic computed tomography (CT) imaging, classified as normal, non-cirrhotic changes, or cirrhosis. The primary outcome was 1-year all-cause mortality, and the secondary outcome was differences in serial post-HT liver evaluation. CT imaging in 32 Fontan patients evaluated for HT revealed 20 (63%) with evidence of liver disease, including 13 (41%) with cirrhosis. Twenty underwent HT, including 5 non-cirrhotic and 7 cirrhosis patients. Characteristics at listing between normal or non-cirrhotic (n = 13) and cirrhosis (n = 7) groups were similar, except cirrhosis patients were older (median 17.6 vs 9.6 years, p = 0.002) and further from Fontan (median 180 vs 50 months, p < 0.05). Serial liver evaluation was similar, including aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, and tacrolimus dose at 1, 3, 6, 9, and 12 months. Overall patient survival was 80% at 1 year, with no difference between cirrhosis and non-cirrhosis patients (86% vs 77%, p = 0.681). Liver biopsies were performed in 7 patients before HT, and all specimens showed architectural changes with bridging fibrosis. Most patients evaluated for HT had abnormal liver findings by CT, with cirrhosis in 41%. One-year mortality and serial liver evaluation were similar between groups after HT. Liver cirrhosis identified by CT imaging may not be an absolute contraindication to HT alone in this population. © 2014 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.

Rapid “Breath-Print” of Liver Cirrhosis by Proton Transfer Reaction Time-of-Flight Mass Spectrometry. A Pilot Study.

PubMed Central

Morisco, Filomena; Aprea, Eugenio; Lembo, Vincenzo; Fogliano, Vincenzo; Vitaglione, Paola; Mazzone, Giovanna; Cappellin, Luca; Gasperi, Flavia; Masone, Stefania; De Palma, Giovanni Domenico; Marmo, Riccardo; Caporaso, Nicola; Biasioli, Franco

2013-01-01

The aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42–80 years) with liver cirrhosis of different etiologies and at different severity of disease and 14 healthy subjects (M/F 5/9, mean age 52.3 years, min-max 35–77 years). Real time breath analysis was performed on fasting subjects using a buffered end-tidal on-line sampler directly coupled to a PTR-ToF-MS. Twelve volatile organic compounds (VOCs) resulted significantly differently in cirrhotic patients (CP) compared to healthy controls (CTRL): four ketones (2-butanone, 2- or 3- pentanone, C8-ketone, C9-ketone), two terpenes (monoterpene, monoterpene related), four sulphur or nitrogen compounds (sulfoxide-compound, S-compound, NS-compound, N-compound) and two alcohols (heptadienol, methanol). Seven VOCs (2-butanone, C8-ketone, a monoterpene, 2,4-heptadienol and three compounds containing N, S or NS) resulted significantly differently in compensate cirrhotic patients (Child-Pugh A; CP-A) and decompensated cirrhotic subjects (Child-Pugh B+C; CP-B+C). ROC (Receiver Operating Characteristic) analysis was performed considering three contrast groups: CP vs CTRL, CP-A vs CTRL and CP-A vs CP-B+C. In these comparisons monoterpene and N-compound showed the best diagnostic performance. Conclusions Breath analysis by PTR-ToF-MS was able to distinguish cirrhotic patients from healthy subjects and to discriminate those with well compensated liver disease from those at more advanced severity stage. A breath-print of liver cirrhosis was assessed for the first time. PMID:23573204

Correlation Between Severity Of Portal Hypertensive Gastropathy And Size Of Oesophageal Varices In Cirrhotic Hepatitis-C Patients.

PubMed

Saleem, Khurram; Baig, Faisal Amin; Nida, Mahwish; Javed, Munaza

2018-01-01

Portal hypertension can lead to oesophageal varices (EV) and portal hypertensive gastropathy (PHG). The aim of this study is to determine the relationship between severity of Portal hypertensive gastropathy and size of oesophageal varices. One hundred and ninety-five patients of hepatitis C positive chronic liver disease having oesophageal varices were assessed for severity of portal hypertensive gastropathy. Mild Portal Hypertensive Gastropathy was observed in 16 (8.2 %), moderate in 54 (27.7 %) and severe in 120 (61.6 %) patients. Grade 1 Oesophageal Varices were present in 79 (40.5%) patients, grade 2 in 44 (21.9%) patients, grade 3 in 62 (31.8%) and grade 4 in 10 (5.2%) patients. No significant correlation was observed between grades of gastropathy and size of varices. The frequency of portal hypertensive gastropathy was 97.5% in Hepatitis C positive cirrhotic patients having oesophageal varices. Severity of gastropathy is not related to the grade or size of oesophageal varices.

Phytoestrogens and liver disease.

PubMed

Lei, Barbara; Roncaglia, Vera; Viganò, Raffaella; Cremonini, Claudia; De Maria, Nicola; Del Buono, Maria Grazia; Manenti, Federico; Villa, Erica

2002-07-31

Phytoestrogens are plant substances that are similar to 17-beta-estradiol and produce estrogenic effects. A protective role in the development of breast and prostate cancer has been hypothesized. Estrogen receptors and their variant forms play a significant role in the pathogenesis of hepatocellular carcinoma (HCC); therefore weak estrogenic substances in the diet may play a role in its development. To investigate the role of phytoestrogens in HCC an investigation of dietary intake of these substances has been performed. Cases, patients at first diagnosis of cirrhosis or HCC were chosen. Questionnaire was built up using indications from previously published papers, extending the registration of details of the diet to reconstruct intake of nutrients for the last year. Interviews were always performed by the same dietician. Quantities determined with the help of photos of servings. Data were analyzed with Winfood database completed with data regarding content in phytoestrogens of food, beverages and seasonings. So far 92 cirrhotic patients and 32 HCCs have been interviewed. No significant difference was registered among the two groups regarding total caloric intake or single nutrients (lipids, carbohydrates, proteins). A significant lower intake of genistein was evidenced in patients at first diagnosis of HCC in comparison with cirrhotics; no significant difference was found in daidzein intake. Lignans intake was strictly related with wine intake; intake was significantly lower in cases only when wine was taken into account otherwise it was similar. Results can be summarized as follows: (1) there are no clear-cut differences (both qualitative or quantitative) between cirrhotics and HCC patients in the overall daily caloric intake while; (2) definite differences exist in the intake of some of the phytoestrogens (genistein, SEC, MAT); (3) differences between cases and controls in SEC and MAT are mainly attributable to lower alcohol intake in cases while; (4) significantly lower genistein intake in HCC only seems due to personal preferences of patients. In conclusion, these differences that we have evidenced in the diet in regard to estrogen-like substances may be relevant in modulating the risk of developing HCC in cirrhotic patients. Copyright 2002 Elsevier Science Ireland Ltd.

Systemic thrombolysis of portal vein thrombosis in cirrhotic patients: a pilot study.

PubMed

De Santis, Adriano; Moscatelli, Rosanna; Catalano, Carlo; Iannetti, Antonio; Gigliotti, Francesca; Cristofari, Francesca; Trapani, Silvia; Attili, Adolfo F

2010-06-01

Portal vein thrombosis is a frequent complication in liver cirrhosis. Encouraging reports of systemic thrombolysis in non-cirrhotic patients suffering from acute portal vein thrombosis led us to start a pilot study on the efficacy and safety of systemic low dose recombinant tissue plasminogen activator (Actilyse, Boheringer Ingelheim, Florence, Italy). Nine cirrhotic patients (6 males and 3 females) with recent portal vein thrombosis were enrolled. Exclusion criteria were portal cavernomatosis, recent (30 days) surgery, active bleeding, hepatocellular carcinoma and cancer in other sites. All cases were treated for a maximum of 7 days by continuous i.v. infusion of 0.25mg/kg/die of r-tPA plus subcutaneous low molecular weight heparin. Efficacy was evaluated by colour doppler sonography monitoring and confirmed by contrast enhanced computerized tomography. The combined r-tPA/LMWH treatment was well tolerated without clinically significant side effects. Complete resolution of thrombosis occurred in 4 cases, partial regression in 4 and none in 1. Retreatment of a complete recurrence in 1 patient was successful. Variceal pressure dropped from 30.7+/-4.5 mmHg to 21.2+/-6.6 mmHg (p=0.012). Our preliminary data demonstrate that thrombolytic treatment of recent portal vein thrombosis with i.v. r-tPA and LMWH in patients with cirrhosis appears to be safe and effective and can significantly reduce pressure in oesophageal varices. Copyright 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Vitamin K status in cystic fibrosis patients with liver cirrhosis.

PubMed

Krzyżanowska, Patrycja; Drzymała-Czyż, Sławomira; Pogorzelski, Andrzej; Duś-Żuchowska, Monika; Skorupa, Wojciech; Bober, Lyudmyla; Sapiejka, Ewa; Oralewska, Beata; Rohovyk, Nataliya; Moczko, Jerzy; Nowak, Jan; Wenska-Chyży, Ewa; Rachel, Marta; Lisowska, Aleksandra; Walkowiak, Jarosław

2017-06-01

The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Evaluation of Lung Function in Liver Transplant Candidates.

PubMed

Roque, L; Sankarankutty, A K; Silva, O C; Mente, E D

2018-04-01

A wide variety of pulmonary conditions are found in cirrhotic patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary vasculature, influencing the results of liver transplantation. To evaluate the pulmonary function (lung capacities, volumes, and gasometric study) of patients with liver cirrhosis awaiting liver transplantation. Cirrhotic patients, subdivided into 3 groups stratified by liver disease severity using the Child-Pugh-Turcotte score, were compared with a control group of healthy volunteers. In spirometry, the parameters evaluated were total lung capacity, forced volume in the first second, and the relationship between forced volume in the first minute and forced vital capacity. Blood gas analysis was performed. In the control group, arterial oxygenation was evaluated by peripheral oxygen saturation by pulse oximetry. Of the 55 patients (75% men, 51 ± 12.77 years), 11 were Child A (73% men, 52 ± 14.01 years), 23 were Child B (75% men, 51 ± 12.77 years), and 21 were Child C (95% men, 50 ± 12.09 years). The control group had 20 individuals (50% men, 47 ± 8.15 years). Pulmonary capacities and volumes by the parameters evaluated were within the normal range. Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial gas pressure was noted. In this population of cirrhotic patients the parameters of spirometry were normal in relation to the lung capacities and volumes in the different groups. No hypoxemia was detected, but a tendency to hypocapnia in the blood gas was noted. Copyright © 2018. Published by Elsevier Inc.

Relationship of red-cell 2,3-diphosphoglycerate with anaemia, hypoxaemia and acid-base status in patients with cirrhosis of the liver.

PubMed

Espinós, D; Alvarez-Sala, J L; Villegas, A

1982-12-01

The red-cell 2,3-diphosphoglycerate (DPG) concentration is determined in 60 patients with hepatic cirrhosis, in 33 with iron deficiency anaemia and in 86 healthy subjects. In all cases, the erythrocyte volume fraction and the haemoglobin concentration are simultaneously measured, while the cirrhotic patients undergo, at the same time, analyses of the arterial pH, pO2 and pCO2 and of the levels of inorganic phosphate, bicarbonate and lactate in their venous blood. In the 60 cirrhotic patients the red-cell DPG concentration (7.40 +/- 1.23 mmol/l) is significantly higher (P less than 0.001) than in the 86 control subjects (4.58 +/- 0.59 mmol/l) and the 33 patients with iron deficiency anaemia (5.86 +/- 1.06 mmol/l), although the level of anaemia in the latter is greater (P less than 0.001) than in the patients with liver cirrhosis. The DPG concentration found in the cirrhotic patients was far higher (P less than 0.001) than the theoretical value attributable to them by virtue of their grade of anaemia (5.21 +/- 0.95 mmol/l), which value is deduced mathematically from the equation of the regression line between haemoglobin and DPG normal in patients with iron deficiency anaemia. Anaemia, hypoxaemia and acid-base disturbances are disorders frequently associated with cirrhosis of the liver. In the present study we deduce that alkalosis, and therefore the plasma pH level, is the most important factor causing the increased DPG concentration in patients with liver cirrhosis for any level of haemoglobin, with respect to other subjects with anaemia.

Enzymatic liver function capacity correlates with disease severity of patients with liver cirrhosis: a study with the LiMAx test.

PubMed

Malinowski, Maciej; Jara, Maximilian; Lüttgert, Katja; Orr, James; Lock, Johan Friso; Schott, Eckart; Stockmann, Martin

2014-12-01

Assessment and quantification of actual liver function is crucial in patients with chronic liver disease to monitor disease progression and predict individual prognosis. Mathematical models, such as model for end-stage liver disease, are used for risk stratification of patients with chronic liver disease but do not include parameters that reflect the actual functional state of the liver. We aimed to evaluate the potential of a (13)C-based liver function test as a stratification tool by comparison with other liver function tests and clinical parameters in a large sample of healthy controls and cirrhotic patients. We applied maximum liver function capacity (LiMAx) to evaluate actual liver function in 347 patients with cirrhosis and in 86 controls. LiMAx showed strong negative correlation with Child-Pugh Score (r = -0.707; p < 0.001), MELD (r = -0.686; p < 0.001) and liver function tests. LiMAx was lower in patients with liver cirrhosis compared to healthy controls [99 (57-160) µg/kg/h vs. 412 (365-479) µg/kg/h, p < 0.001] and differed among Child-Pugh classes [a: 181 (144-227) µg/kg/h, b: 96 (62-132) µg/kg/h and c: 52 (37-81) µg/kg/h; p < 0.001]. When stratified patients according to disease severity, LiMAx results were not different between cirrhotic patients and cirrhotic patients with transjugular intrahepatic portosystemic shunt. LiMAx appears to provide reliable information on remnant enzymatic liver function in chronic liver disease and allows graduation of disease severity.

1H nuclear magnetic resonance spectroscopy-based metabonomic study in patients with cirrhosis and hepatic encephalopathy

PubMed Central

Dabos, Konstantinos John; Parkinson, John Andrew; Sadler, Ian Howard; Plevris, John Nicholas; Hayes, Peter Clive

2015-01-01

AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and encephalopathics. METHODS: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using 1H - nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients (FID’s) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three groups. RESULTS: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate (0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate (0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine (0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine (0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine (0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate (1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate (1.53 ± 0.11 vs 0.42 ± 0.05, P < 0.01), pyruvate (0.11 ± 0.02 vs 0.03 ± 0.00, P < 0.01) threonine (0.39 ± 0.02 vs 0.08 ± 0.01, P < 0.01) and aspartate (0.37 ± 0.03 vs 0.03 ± 0.01). A five metabolite signature by stepwise discriminant analysis could separate between controls and cirrhotic patients with an accuracy of 98%. In patients with encephalopathy we observed further derangement of ketone body metabolism, impaired production of glycerol and myoinositol, reversal of Fischer’s ratio and impaired glutamine production as demonstrated by lower b-hydroxybutyrate (0.58 ± 0.14 vs 0.16 ± 0.02, P < 0.0002), higher acetoacetate (0.23 ± 0.02 vs 0.41 ± 0.16, P < 0.05), leucine (0.33 ± 0.02 vs 0.49 ± 0.05, P < 0.005) and isoleucine (0.12 ± 0.02 vs 0.27 ± 0.02, P < 0.0004) and lower glutamine (0.44 ± 0.08 vs 0.36 ± 0.04, P < 0.013), glycerol (0.53 ± 0.03 vs 0.19 ± 0.02, P < 0.000) and myoinositol (0.36 ± 0.04 vs 0.18 ± 0.02, P < 0.010) concentrations. A four metabolite signature by stepwise discriminant analysis could separate between encephalopathic and cirrhotic patients with an accuracy of 87%. CONCLUSION: Patients with cirrhosis and patients with hepatic encephalopathy exhibit distinct metabolic abnormalities and the use of metabonomics can select biomarkers for these diseases. PMID:26140090

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

PubMed Central

Ponziani, Francesca Romana; Spinelli, Irene; Rinninella, Emanuele; Cerrito, Lucia; Saviano, Antonio; Avolio, Alfonso Wolfango; Basso, Michele; Miele, Luca; Riccardi, Laura; Zocco, Maria Assunta; Annicchiarico, Brigida Eleonora; Garcovich, Matteo; Biolato, Marco; Marrone, Giuseppe; De Gaetano, Anna Maria; Iezzi, Roberto; Giuliante, Felice; Vecchio, Fabio Maria; Agnes, Salvatore; Addolorato, Giovanni; Siciliano, Massimo; Rapaccini, Gian Lodovico; Grieco, Antonio; Gasbarrini, Antonio; Pompili, Maurizio

2017-01-01

AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) and to ascertain the factors predicting the achievement of disease control (DC). METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo (95%CI: 10.6-17.0). Only alphafetoprotein (AFP) serum level > 200 ng/mL and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up (HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year (HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC (OR = 0.263, 95%CI: 0.111-0.622, P = 0.002). CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients’ survival confers them as useful predictive tools for treatment management and clinical decisions. PMID:29359015

Serum creatinine and bilirubin predict renal failure and mortality in patients with spontaneous bacterial peritonitis: a retrospective study.

PubMed

Terg, Rubén; Gadano, Adrian; Cartier, Mariano; Casciato, Paola; Lucero, Romina; Muñoz, Alberto; Romero, Gustavo; Levi, Diana; Terg, Gonzalo; Miguez, Carlos; Abecasis, Raquel

2009-03-01

Patients with spontaneous bacterial peritonitis (SBP) are at a high risk for renal failure and death despite successful treatment of infection. Intravenous (IV) albumin administration combined with antibiotic treatment has been shown to significantly decrease these risks. Clinical evidence is lacking on which patients are appropriate candidates for albumin treatment. To retrospectively analyse the usefulness of serum creatinine and bilirubin levels in predicting renal failure and mortality of patients hospitalized for SBP. Between March 1995 and September 1998, 127 cirrhotic patients with SBP who had not received plasma expansion were evaluated. Eighty-one patients (64%) were classified as having a high risk for renal failure and mortality (serum bilirubin >4 mg/dl or serum creatinine >1 mg/dl) and 46 (36%) as having a low risk. At admission, 36.3% of all patients presented renal failure. Mortality during their hospitalization was 23% among those with a high risk and 6.5% among those with a low risk (P=0.01). Renal failure occurred in 23% of the high-risk patients, compared with 2.6% of the low-risk patients (P=0.006). The presence of hyponatraemia was significantly associated with higher mortality and renal failure in the high-risk group. Our retrospective review of patients with SBP suggests that serum bilirubin levels >4 mg and serum creatinine levels >1 mg/dl at the time of diagnosis represent significant risk factors for the clinical outcomes of patients with SBP. Patients without these risk factors may have a very low likelihood of death or renal failure.

Diminished viral replication and compartmentalization of hepatitis C virus in hepatocellular carcinoma tissue.

PubMed

Harouaka, Djamila; Engle, Ronald E; Wollenberg, Kurt; Diaz, Giacomo; Tice, Ashley B; Zamboni, Fausto; Govindarajan, Sugantha; Alter, Harvey; Kleiner, David E; Farci, Patrizia

2016-02-02

Analysis of hepatitis C virus (HCV) replication and quasispecies distribution within the tumor of patients with HCV-associated hepatocellular carcinoma (HCC) can provide insight into the role of HCV in hepatocarcinogenesis and, conversely, the effect of HCC on the HCV lifecycle. In a comprehensive study of serum and multiple liver specimens from patients with HCC who underwent liver transplantation, we found a sharp and significant decrease in HCV RNA in the tumor compared with surrounding nontumorous tissues, but found no differences in multiple areas of control non-HCC cirrhotic livers. Diminished HCV replication was not associated with changes in miR-122 expression. HCV genetic diversity was significantly higher in livers containing HCC compared with control non-HCC cirrhotic livers. Tracking of individual variants demonstrated changes in the viral population between tumorous and nontumorous areas, the extent of which correlated with the decline in HCV RNA, suggesting HCV compartmentalization within the tumor. In contrast, compartmentalization was not observed between nontumorous areas and serum, or in controls between different areas of the cirrhotic liver or between liver and serum. Our findings indicate that HCV replication within the tumor is restricted and compartmentalized, suggesting segregation of specific viral variants in malignant hepatocytes.

Hepatocellular Carcinoma Surveillance Among Cirrhotic Patients With Commercial Health Insurance.

PubMed

Goldberg, David S; Valderrama, Adriana; Kamalakar, Rajesh; Sansgiry, Sujit S; Babajanyan, Svetlana; Lewis, James D

2016-03-01

To evaluate hepatocellular carcinoma (HCC) surveillance rates among commercially insured patients, and evaluate factors associated with compliance with surveillance recommendations. Most HCC occurs in patients with cirrhosis. American Association for the Study of Liver Diseases and European Association for the Study of the Liver guidelines each recommend biannual HCC surveillance for cirrhotic patients to diagnose HCC at an early, curable stage. However, compliance with these guidelines in commercially insured patients is unknown. We used the Truven Health Analytics databases from 2006 to 2010, using January 1, 2006 as the anchor date for evaluating outcomes. The primary outcome was continuous surveillance measure, defined as the proportion of time "up-to-date" with surveillance (PTUDS), with the 6-month interval immediately following each ultrasound categorized as "up-to-date." During a median follow-up of 22.9 (interquartile range, 16.3 to 33.9) months among 8916 cirrhotic patients, the mean PTUDS was 0.34 (SD, 0.29), and the median was 0.31 (interquartile range, 0.03 to 0.52). These values increased only modestly with inclusion of serum alpha-fetoprotein testing, contrast-enhanced abdominal computed tomographic scans or magnetic resonance imagings, and/or extension of up-to-date time to 12 months. Being diagnosed by a nongastroenterology provider and increasing age were significantly associated with decreased HCC surveillance (P<0.05), whereas a history of a hepatic decompensation event, presence of any component of the metabolic syndrome, and diagnosis of hepatitis B or hepatitis C were significantly associated with increased surveillance (P<0.05). However, even among patients with the most favorable characteristics, surveillance rates remained low. HCC surveillance rates in commercially insured at-risk patients remain poor despite formalized guidelines, highlighting the need to develop interventions to improve surveillance rates.

Real-World Study on Sofosbuvir-based Therapies in Asian Americans With Chronic Hepatitis C.

PubMed

Pan, Calvin Q; Tiongson, Benjamin C; Hu, Ke-Qin; Han, Steven-Huy B; Tong, Myron; Chu, Danny; Park, James; Lee, Tai Ping; Bhamidimarri, Kalyan Ram; Ma, Xiaoli; Xiao, Pei Ying; Mohanty, Smruti R; Wang, Dan

2018-06-16

Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans. Eligible Asian Americans patients with CHC who had posttreatment follow-up of 24 weeks for SOF -based therapies from December 2013 to June 2017 were enrolled from 11 sites across the United States. The primary endpoint was sustained virologic response (SVR) rates at posttreatment weeks 12 and 24. Secondary endpoints were to evaluate safety by tolerability and adverse events (AEs). Among 231 patients screened, 186 were enrolled. At baseline, 31% (57/186) patients were cirrhotic, 34% (63/186) were treatment experienced. Most of the subjects (42%, 79/186) received ledispavir/SOF therapy. The overall SVR12 was 95%, ranging from 86% in genotype (GT) 1b on SOF+ribavirin to 100% in GT 1b patients on ledipasvir/SOF at subgroup analyses. SVR12 was significantly lower in cirrhotic than in noncirrhotic patients [88% (50/57) vs. 98% (126/129), P<0.01]. Stratified by GT, SVR12 were: 96% (43/45) in GT 1a; 93% (67/72) in GT 1b; 100% (23/23) in GT 2; 90% (19/21) in GT 3; 100% (1/1) in GT 4; 83% (5/6) in GT 5; and 100% (16/16) in GT 6. Cirrhotic patients with treatment failure were primarily GT 1, (GT 1a, n=2; GT 1b, n=4) with 1 GT 5 (n=1). Patients tolerated the treatment without serious AEs. Late relapse occurred in 1 patient after achieving SVR12. In Asian Americans with CHC, SOF-based regimens were well tolerated without serious AEs and could achieve high SVR12 regardless of hepatitis C viral infection GT.

Change in hepatic function, hemodynamics, and morphology after liver transplant. Physiological effect of therapy.

PubMed

Millikan, W J; Henderson, J M; Stewart, M T; Warren, W D; Marsh, J W; Galloway, J R; Jennings, H; Kawasaki, S; Dodson, T F; Perlino, C A

1989-05-01

Orthotopic liver transplantation (OLT) has become standard therapy for patients with acute hepatic necrosis and end-stage liver disease. This study measured change in hepatic function (galactose elimination capacity [GEC]), liver blood flow (low dose galactose clearance: flow), hepatic volume (CT scan; volume) and morphology after OLT. The aim was to measure the physiologic response after OLT and compare this response with that after selective shunt (SS) and sclerotherapy (ES) to determine which patients should receive specific therapy. Between January 1987 and November 1988, 37 patients underwent OLT. Operative mortality was 18%, which was similar to that of SS in Child's C cirrhotics. GEC and volume were less in transplant patients than in cirrhotics treated with SS or ES. GEC, flow, and volume normalized after OLT; GEC was preserved after ES and SS, but volume decreased. Three preoperative patterns were observed that can aid in selection of OLT candidates. Patients with chronic cirrhosis (chronic active hepatitis; cryptogenic) need OLT when GEC is less than or equal to 225 mg/min and volume is less than or equal to 50% normal. Patients with Budd-Chiari Syndrome require OLT if cirrhosis has evolved. Patients with sclerosing cholangitis and primary biliary cirrhosis qualify for transplants when complications of the portal hypertensive syndrome develop. The studies can also direct therapy for ES failures. Selective shunt is indicated in those patients with stable disease whose GEC is greater than or equal to 300 mg/min and liver volume is greater than 75% normal; OLT is indicated for cirrhotics with GEC that is less than 225 mg/min and liver volume that is less than 50% predicted normal.

Does the cost of care differ for patients with fee-for-service vs. capitation of payment? A case-control study in gastroenterology.

PubMed

Slattery, E; Clancy, K X; Harewood, G C; Murray, F E; Patchett, S

2013-12-01

There is growing evidence to demonstrate overuse of medical resources in fee for service (FFS) payment models (in which physicians are reimbursed according to volume of care provided) compared to capitation payment models (in which physicians receive a fixed salary regardless of level of care provided). In this medical centre, patients with and without insurance are admitted through the same access point (emergency room) and cared for by the same physicians. Therefore, apart from insurance status, all other variables influencing delivery of care are similar for both patient groups. However, physician reimbursement differs for both groups: FFS for patients with private insurance (i.e. the admitting physician's reimbursement escalates progressively with each day that the patient spends in hospital) and base salary irrespective of care provided for patients with universal insurance (capitation payment model). All admitting physicians are aware of the patient's insurance status and the duration of hospitalization is at the discretion of the admitting physician. This study aimed to compare cost of care of patients with and without insurance admitted to a teaching hospital with a primary gastroenterology or hepatology (GIH) diagnosis. All hospital inpatients admitted between January 2008 and December 2009 with a primary GI-related diagnosis related group (DRG) were identified. Patients were classified as uninsured (state-funded) or privately insured. Only DRGs with at least five patients in both the insured and uninsured patient groups were analyzed to ensure a precise estimate of inpatient costs. Patient level costing (PLC) was used to express the total cost of hospital care for each patient; PLC comprised a weighted daily bed cost plus cost of all medical services provided (e.g. radiology, pathology tests) calculated according to an activity-based costing approach, cost of medications were excluded. An overall mean cost of care per patient was calculated for both groups. All costs were discounted to 2009 values. In total, 630 patients were admitted with one of 11 GIH DRGs, 181 (29 %) with private insurance. Pooled mean cost of care was higher for uninsured (6,781 euros/patient) compared to insured patients (6,128 euros/patient). Apart from patients with 'non-cirrhotic non-alcoholic liver disease (non-complex)' in whom mean cost was higher for insured patients, there were no significant differences in mean cost of care nor mean patient age for insured and uninsured groups for any other diagnoses. Inpatient hospital costs were equivalent for patients with and without private health insurance when care was provided in a single hospital. Provision of care for all patients in a common hospital setting regardless of health insurance status may reduce disparities in healthcare utilization.

A prospective study on elective umbilical hernia repair in patients with liver cirrhosis and ascites.

PubMed

Eker, Hasan H; van Ramshorst, G H; de Goede, B; Tilanus, H W; Metselaar, H J; de Man, R A; Lange, J F; Kazemier, G

2011-09-01

Patients with both cirrhosis and ascites have a 20% risk of developing umbilical hernia. A retrospective study from our center comparing conservative management of umbilical hernia with elective repair in these patients showed a significant risk of mortality as a result of hernia incarceration in conservatively treated patients. The goal of this study was to assess the safety and efficacy of elective umbilical hernia repair in these patients prospectively. Patients with liver cirrhosis and ascites presenting with an umbilical hernia were included in this study. For all patients, the expected time to liver transplantation was more than 3 months, and they did not have a patent umbilical vein in the hernia sac. The following data were collected prospectively for all patients: Child-Pugh-Turcotte (CPT) classification, model for end-stage liver disease (MELD) score, kidney failure, cardiovascular comorbidity, operation-related complications, and duration of hospital stay. Mortality rates were registered in hospital records and verified in government records during follow-up. Mortality rates were registered in hospital records and verified in government records during follow-up. On completion of the study, a retrospective survey was performed to search for any patients who met the study inclusion criteria but were left out of the study cohort. In total, 30 patients (25 males) underwent operation at a mean age of 58 years (standard deviation [SD] ± 9 years). Of these 30 patients, 6 were classified as CPT grade A (20%), 19 (63%) as grade B, and 5 (17%) as grade C. The patients' median MELD score was 12 (interquartile range [IQR], 8-16). In 10 (33%) of the 30 patients hernia repair was performed with mesh. The median duration of hospital stay was 3 days (IQR, 2-4). None of the patients were admitted to the intensive care unit. Postoperative complications included pneumonia and decompensation of cirrhosis (1 case each,) resulting in prolonged hospital stay for those 2 patients. After a median follow-up period of 25 months (IQR, 14-34), 2 (7%) of the 30 patients died; neither of the deaths were attributable to the umbilical hernia repair. A total of 2 patients suffered recurrence. Elective umbilical hernia repair is safe and the preferred approach in cirrhotic patients with ascites. Copyright © 2011 Mosby, Inc. All rights reserved.

Visceral Artery Aneurysms in Liver Transplant Candidates and in Patients after Liver Transplantation

PubMed Central

Maggi, Umberto; Dondossola, Daniele; Consonni, Dario; Gatti, Stefano; Arnoldi, Rossella; Bossi, Manuela; Rossi, Giorgio

2011-01-01

There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of papers on visceral aneurysms in liver transplant patients. The present paper investigates this condition in both groups of patients in a 10-year-retrospective study. PMID:22216310

Closing the Gap: The Challenges of Treating Hepatitis C Virus Genotype 3 Infection.

PubMed

Martin, Michelle T; Deming, Paulina

2017-06-01

The efficacy of hepatitis C virus (HCV) treatment has increased over the last 5 years to nearly 100% for many patient groups. Patients with genotype (GT) 3 HCV infection, however, and specifically cirrhotic or treatment-experienced patients, have lower sustained virologic response (SVR) rates than patients with other GTs. Because GT 3 presents more clinical challenges than other GTs, this review focuses on the evolution and efficacy of direct-acting antiviral (DAA) treatment options for HCV GT 3 infection after the historical standard of care with pegylated interferon and ribavirin. Our objective was to review the SVR rates with available and late-pipeline DAAs for HCV GT 3 infection and discuss challenges with successful GT 3 treatment. Authors performed a literature search of the PubMed/MEDLINE database (inception to March 27, 2017) and narrowed the field to clinical trials published in English. Trials that evaluated alternative treatments, non-DAA historical treatment, and DAAs not currently indicated for HCV were excluded. Trials only involving patients with human immunodeficiency virus/HCV coinfection were also excluded. Additional trials were identified from a review of the ClinicalTrials.gov database. Authors further identified references from a review of literature citations and reviewed annual meeting abstracts from the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver for pipeline and real-world GT 3 data. Phase III trial data were not available to support all GT 3 treatment recommendations found in the guidelines. The SVR rates were lower in treatment-experienced and cirrhotic patients with GT 3 than other HCV populations. Treatment failure was associated with resistance to current treatment regimens. Clinical studies included patients with various levels of advanced liver disease, but few patients with decompensated cirrhosis were represented. Recent advances in pharmacologic treatment with DAAs have greatly increased SVR rates in patients with all HCV GTs, but SVR rates for treatment-experienced cirrhotic patients with GT 3 are lower than for other GTs. Given the limited data and observed SVR rates in this patient population, the optimal therapy for patients with decompensated cirrhotic GT 3 HCV infection is not yet established. Newer agents and recommendations regarding baseline resistance are likely to evolve treatment strategies in the near future. © 2017 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals, Inc. on behalf of Pharmacotherapy Publications, Inc.

Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

PubMed

Romero-Gómez, Manuel; Montagnese, Sara; Jalan, Rajiv

2015-02-01

Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Bone marrow cells obtained from cirrhotic rats do not improve function or reduce fibrosis in a chronic liver disease model.

PubMed

Mannheimer, Elida Gripp; Quintanilha, Luiz Fernando; Carvalho, Adriana Bastos; Paredes, Bruno Diaz; Gonçalves de Carvalho, Felipe; Takyia, Cristina Maeda; Resende, Célia Maria Coelho; Ferreira da Motta Rezende, Guilherme; Campos de Carvalho, Antonio Carlos; Schanaider, Alberto; dos Santos Goldenberg, Regina Coeli

2011-01-01

The objective of this study was to evaluate the therapeutic potential of bone marrow cells (BMCs) obtained from cirrhotic donors in a model of chronic liver disease. Chronic liver injury was induced in female Wistar rats by the association of an alcoholic diet with intraperitoneal injections of carbon tetrachloride. BMCs obtained from cirrhotic donors or placebo were injected through the portal vein. Blood analysis of alanine aminotransferase (ALT) and albumin levels, ultrasound assessment including the measurement of the portal vein diameter (PVD) and liver echogenicity, histologic evaluation with hematoxylin and eosin and Sirius red staining, and quantification of collagen deposition were performed. ALT and albumin blood levels showed no significant differences between the experimental groups two months after injection. Additionally, no significant variation in PVD and liver echogenicity was found. Histological analysis also showed no significant variation in collagen deposition two months after placebo or BMC injection. This study suggests that, even though BMC therapy using cells from healthy donors has previously shown to be effective, this is not the case when BMCs are obtained from cirrhotic animals. This result has major clinical implications when considering the use of autologous BMCs from patients with chronic liver diseases. © 2009 John Wiley & Sons A/S.

Bacterial pneumonia in patients with liver cirrhosis, with or without HIV co-infection: a possible definition of antibiotic prophylaxis associated pneumonia (APAP).

PubMed

Cuomo, Gianluca; Brancaccio, Giuseppina; Stornaiuolo, Gianfranca; Manno, Daniela; Gaeta, Giuseppe L; Mussini, Cristina; Puoti, Massimo; Gaeta, Giovanni B

2018-02-01

Introducion: Bacterial infections frequently complicate liver cirrhosis. The aim of this study was to identify risk factors and clinical impact of bacterial pneumonia in patients with cirrhosis. Bacterial infection prevalence study: consecutive patients with cirrhosis were enroled over a six-month period in 13 Italian centres. Pneumonia and other infections were diagnosed by standard methods. Pneumonia study: cirrhotic patients with pneumonia were enroled for an additional six-month period and HIV-positive patients were included. Pneumonia was the fourth most frequent infection. In the two parts of the study, 79 cases of pneumonia were recorded and 441 patients with cirrhosis without infections served as controls. Seventy-eight patients had extra-pulmonary infections. There were no clinical differences between HIV-negative and -positive cases with pneumonia. Previous gastro-intestinal bleeding (p = .02) and long-term prophylactic antibiotic use (p < .0001) were associated with pneumonia. Hospital stay was longer and renal failure more frequent than in patients without infections. Pneumonia was hospital acquired (HAP) in 6 cases, healthcare associated (HCAP) in 24 and community acquired (CAP) in 28. A new category of antibiotic prophylaxis associated pneumonia (APAP) was proposed for 21 cases. Cultures were positive in 21/79 patients (26.6%) with Gram-positive isolates in 57%. Unfavourable outcomes were recorded in 11.4% of the cases (3.6% of CAP, 33% of HAP, 12.5% of HCAP and 14.3% of APAP). Receiving antibiotic prophylaxis was associated with pneumonia and the study identified a new sub-group of patients, who require broad spectrum initial antibiotic therapy.

13C-methacetin and 13C-galactose breath tests can assess restricted liver function even in early stages of primary biliary cirrhosis.

PubMed

Holtmeier, Julia; Leuschner, Maria; Schneider, Arne; Leuschner, Ulrich; Caspary, Wolfgang F; Braden, Barbara

2006-11-01

The 13C-methacetin breath test quantitatively evaluates cytochrome P450-dependent liver function. The 13C-galactose breath test non-invasively measures the galactose oxidation capacity of the liver. The aim of this study was to find out whether these breath tests are sensitive parameters also in non-cirrhotic patients with primary biliary cirrhosis. Nineteen patients with early-stage primary biliary cirrhosis (no cirrhotic alterations in the liver biopsy, Ludwig stage I-III) and 20 healthy controls underwent the 13C-methacetin and 13C-galactose breath tests. Patients with primary biliary cirrhosis metabolized less 13C-methacetin than controls (cumulative recovery within 30 min 7.5+/-2.4% versus 14.0+/-2.6%; p < 0.001). When a cut-off > 9.8% was used for the cumulative recovery after 30 min, the methacetin breath test reached 84.2% sensitivity and 95.0 specificity. In the 13C-galactose breath test, the percentage recovery at 60 min in patients was 3.1+/-1.3%/h, and 6.3+/-1.1%/h in controls (p < 0.001). Using a cut-off > 4.7%/h, the galactose breath test reached 89.5% sensitivity and 95.0 specificity. In non-cirrhotic, early-stage, primary biliary cirrhosis the 13C-methacetin breath test and the 13C-galactose breath test reliably indicate decreased liver function. The 13C-galactose breath test can also predict the histological score.

Elevated serum tumor necrosis factor-alpha and soluble tumor necrosis factor receptors correlate with aberrant energy metabolism in liver cirrhosis.

PubMed

Shiraki, Makoto; Terakura, Yoichi; Iwasa, Junpei; Shimizu, Masahito; Miwa, Yoshiyuki; Murakami, Nobuo; Nagaki, Masahito; Moriwaki, Hisataka

2010-03-01

Protein-energy malnutrition is frequently observed in patients with liver cirrhosis and is associated with their poor prognosis. Tumor necrosis factor-alpha (TNF-alpha) is elevated in those patients and may contribute to the alterations of energy metabolism. Our aim was to characterize the aberrant energy metabolism in cirrhotic patients with regard to TNF-alpha. Twenty-four patients (mean age 65 +/- 6 y) with viral liver cirrhosis who did not have hepatocellular carcinoma or acute infections were studied. Twelve healthy volunteers were recruited after matching for age, gender, and body mass index with the patients and served as controls (59 +/- 8 y). Serum levels of TNF-alpha, soluble 55-kDa TNF receptor (sTNF-R55), soluble 75-kDa TNF receptor (sTNF-R75), and leptin were determined by immunoassay. Substrate oxidation rates of carbohydrate and fat were estimated by indirect calorimetry after overnight bedrest and fasting. In cirrhotic patients, serum levels of TNF-alpha, sTNF-R55, and sTNF-R75 were significantly higher than those in the controls and correlated with the increasing grade of disease severity as defined by Child-Pugh classification. Serum leptin concentration was not different between cirrhotics and controls but correlated with their body mass index. The decrease in substrate oxidation rate of carbohydrate and the increase in substrate oxidation rate of fat significantly correlated with serum TNF-alpha, sTNF-R55, and sTNF-R75 concentrations. Tumor necrosis factor-alpha might be associated with the aberrant energy metabolism in patients with liver cirrhosis. Copyright (c) 2010 Elsevier Inc. All rights reserved.

The effect of cirrhosis on the risk for failure of nonoperative management of blunt liver injuries.

PubMed

Barmparas, Galinos; Cooper, Zara; Ley, Eric J; Askari, Reza; Salim, Ali

2015-12-01

The purpose of this study was to delineate the association between cirrhosis and failure of nonoperative management (F-NOM) after blunt liver trauma. We carried out a review of the National Trauma Databank from 2007 to 2011 including patients ≥ 16 years old admitted after a blunt injury. Propensity score was used to match each cirrhotic to 3 noncirrhotic patients. Primary outcome was F-NOM (liver procedure >2 hours after admission and/or operative intervention directed at the liver after angiography). A total of 57 cirrhotic patients who met inclusion criteria were matched with 171 noncirrhotic patients. Splenic injury was present in 41% (35% vs 43%; P = .31) and 28% had a high-grade liver injury III/VI/V (26% vs 29%; P = .73). The majority of patients in both groups were selected for a trial of NOM (77% vs 85%; P = .15). There was no difference in the rate of F-NOM between the 2 groups (14% vs 14%; P = 1.00), even for high-grade injuries (13% vs 20%; P = .72). Cirrhotic patients had a greater overall mortality (28% vs 7%; P < .01), especially if they required a laparotomy (58% vs 17%; P < .01) or if they failed NOM (50% vs 4%; P < .01). Cirrhosis has no effect on the selection of patients with blunt liver injuries for a trial of nonoperative management and does not seem to be associated with a greater risk for failure of nonoperative management within the constraints of our study. Nonoperative management in this population is highly successful and failure is rarely related directly to the liver injury itself. Failure of non-operative management increases the already high mortality risk in this population. Copyright © 2015 Elsevier Inc. All rights reserved.

Emergency endoscopic variceal ligation in cirrhotic patients with blood clots in the stomach but no active bleeding or stigmata increases the risk of rebleeding.

PubMed

Kim, Su Jin; Choi, Cheol Woong; Kang, Dae Hwan; Kim, Hyung Wook; Park, Su Bum; Hong, Young Mi; Yoon, Ki Tae; Cho, Mong; Nam, Hyung Seok; Islam, Sm Bakhtiar Ui

2016-12-01

This study aimed to evaluate the efficacy and safety of emergency variceal ligation for the prevention of rebleeding in cirrhotic patients who are found on initial endoscopy to have blood clots in the stomach but no actively bleeding esophageal and gastric varices or stigmata. This study included 28 cirrhotic patients who underwent emergency prophylactic EVL and 41 who underwent an elective intervention between January 2009 and June 2014. Clinical outcomes were analyzed, including the rebleeding, 6-week mortality, and rebleeding-free survival rates. The rebleeding rate was higher in the emergency than in the elective group (28.6% vs. 7.3%, P =0.041). Multivariate analysis showed that emergency prophylactic EVL (odds ratio [OR] = 7.4, 95% confidence interval [CI]=1.634.8, P =0.012) and Child-Pugh score C (OR=10.6, 95% CI=1.4-80.8, P =0.022) were associated with rebleeding. In the emergency group, the gastric varices were associated with rebleeding (OR=12.0, 95% CI=1.7-83.5, P =0.012). Emergency EVL may be associated with variceal rebleeding when blood clots are present in the stomach without active esophageal and gastric variceal bleeding or stigmata. Elective intervention should be considered as a safer strategy for preventing variceal rebleeding in this situation.

Plasma Levels of Matrix Metalloproteinase (MMP)-2, MMP-9 and Tumor Necrosis Factor-α in Chronic Hepatitis C Virus Patients.

PubMed

Abdel-Latif, Mohamed S

2015-01-01

In chronic HCV infection, pathological accumulation of the extracellular matrix is the main feature of liver fibrosis; that indicates the imbalanced rate of increased matrix synthesis to decreased breakdown of connective tissue proteins. Matrix metalloproteinases (MMPs) play a crucial role in remodeling of extracellular matrix. It is known that expression of MMPs is regulated by Tumor necrosis factor (TNF)-α. Also, levels of TNF-α in liver and serum are increased in chronic HCV patient. Accordingly, this study aimed to correlate the plasma levels of MMP-2, MMP-9 and TNF-α in chronic HCV patients with the pathogenesis of the liver. The current study was conducted on 15 fibrotic liver cases with detectable HCV RNA, 10 HCV cirrhotic liver cases, and 15 control subjects of matched age and sex. Plasma MMP-2, MMP-9 and TNF-α were measured by ELISA. Data revealed that the MMP2, MMP9 and TNF-α levels showed a significant elevation in chronic HCV patients compared to control group (p= 0.001). But, no significant correlation was observed in levels of MMP-2, MMP-9, and TNF-α between fibrotic and cirrhotic cases. MMP-2, MMP-9 and TNF-α showed high reproducibility to differentiate chronic HCV patients from control group. On the contrary, MMP-2, MMP-9 and TNF-α were not able to differentiate fibrotic from cirrhotic liver cases. Thus, MMP-2, MMP-9 and TNF-α could not be correlated with the progression of liver disease. Rather they could be used as prognostic markers of liver fibrosis.

The use of human albumin for the treatment of ascites in patients with liver cirrhosis: item of safety, facts, controversies and perspectives.

PubMed

Facciorusso, Antonio; Nacchiero, Maurizio Cosimo; Rosania, Rosa; Laonigro, Giulio; Longo, Nunzio; Panella, Carmine; Ierardi, Enzo

2011-09-01

Albumin constitutes approximately one half of the proteins in the plasma and plays a pivotal role in modulating the distribution of fluid between body compartments. Hence it is commonly employed in cirrhotic patients in association with diuretics for the treatment of ascites. Nevertheless, its usefulness is controversial in this condition and well-stated only in some circumstances. The item of safety of the drug appears to be convincing due to the accurate cautions in the course of its preparation. Side effects are described in literature only as sporadic events. Indeed, albumin administration is effective to prevent the circulatory dysfunctions after large-volume paracentesis and renal failure and after Spontaneous Bacterial Peritonitis (SBP). Finally albumin represents, associated with vasoconstrictors, the therapeutic gold standard for the hepatorenal-syndrome (HRS). Physiopathological bases of the therapeutic use of albumin in hepatic cirrhosis consist in both hypoalbuminemia and portal hypertension consequences. In fact, cirrhotic patient with ascites, in spite of hydrosaline retention, shows an effective hypovolemia with peripheral arterial vasodilatation and increase in heart rate. Therefore the effectiveness of albumin administration in the treatment of ascites is due to its plasma volume expander property as well as its efficacy in restoring plasmatic oncotic pressure. Trials are in progress in order to define the effectiveness of the prolonged home-administration of human albumin in the treatment and prevention of ascites. Finally, it has been recently demonstrated that the binding, transport and detoxification capacities of human albumin are severely reduced in cirrhotics and this impairment correlates with the degree of liver failure. Therefore, the next challenge will be to determine whether the alterations of non-oncotic properties of albumin are able to forecast mortality in cirrhotics with ascites and exogenous albumin chronic administration will be effective in predicting and preventing such alterations.

Portal hypertension and liver cirrhosis in rats: effect of the β3-adrenoceptor agonist SR58611A

PubMed Central

Vasina, Valentina; Giannone, Ferdinando; Domenicali, Marco; Latorre, Rocco; Berzigotti, Annalisa; Caraceni, Paolo; Zoli, Marco; De Ponti, Fabrizio; Bernardi, Mauro

2012-01-01

BACKGROUND AND PURPOSE β3-Adrenoceptors participate in the regulation of vascular tone in physiological and pathological conditions. We aimed to assess the effect of pharmacological modulation of β3-adrenoceptors on portal pressure (PP) and systemic haemodynamics and their expression in the liver and mesenteric vessels of cirrhotic rats. EXPERIMENTAL APPROACH PP, central venous pressure (CVP) and systemic haemodynamics were invasively assessed in control and CCl4-treated cirrhotic rats before and during infusion of the selective β3-adrenoceptor agonist, SR58611A. Tissue samples were also collected from liver, heart, portal vein and mesenteric artery for immunohistochemistry and molecular biology analysis. The effect of SR58611A on isolated portal vein was assessed. KEY RESULTS At baseline, cirrhotic rats showed portal hypertension, reduced CVP and hyperdynamic circulation. SR58611A induced a significant, dose-dependent decrease in PP in cirrhotic rats, but not in controls. Although both groups manifested a dose-dependent reduction in mean arterial pressure, this effect was associated with decreased cardiac index (CI) and unchanged indicized peripheral vascular resistance (PVRI) in cirrhotic rats and increased CI and decreased PVRI in control animals. Pretreatment with the selective β3-adrenoceptor antagonist SR59230 prevented all SR58611A-induced changes in cirrhotic rats. SR58611A concentration-dependently relaxed portal vein in cirrhotic rats to a significantly greater extent than in healthy rats; pretreatment with SR59230A completely prevented SR58611A-induced cirrhotic portal vein relaxation. Finally, β3-adrenoceptors were identified in the liver, heart and portal vein of cirrhotic and control animals; their expression was increased in cirrhotic rats. CONCLUSIONS AND IMPLICATIONS β3-Adrenoceptors are altered in portal hypertension of experimental cirrhosis and may represent a novel therapeutic target. PMID:22708587

Predictors of Mortality in the Critically Ill Cirrhotic Patient: Is the Model for End-Stage Liver Disease Enough?

PubMed

Annamalai, Alagappan; Harada, Megan Y; Chen, Melissa; Tran, Tram; Ko, Ara; Ley, Eric J; Nuno, Miriam; Klein, Andrew; Nissen, Nicholas; Noureddin, Mazen

2017-03-01

Critically ill cirrhotics require liver transplantation urgently, but are at high risk for perioperative mortality. The Model for End-stage Liver Disease (MELD) score, recently updated to incorporate serum sodium, estimates survival probability in patients with cirrhosis, but needs additional evaluation in the critically ill. The purpose of this study was to evaluate the predictive power of ICU admission MELD scores and identify clinical risk factors associated with increased mortality. This was a retrospective review of cirrhotic patients admitted to the ICU between January 2011 and December 2014. Patients who were discharged or underwent transplantation (survivors) were compared with those who died (nonsurvivors). Demographic characteristics, admission MELD scores, and clinical risk factors were recorded. Multivariate regression was used to identify independent predictors of mortality, and measures of model performance were assessed to determine predictive accuracy. Of 276 patients who met inclusion criteria, 153 were considered survivors and 123 were nonsurvivors. Survivor and nonsurvivor cohorts had similar demographic characteristics. Nonsurvivors had increased MELD, gastrointestinal bleeding, infection, mechanical ventilation, encephalopathy, vasopressors, dialysis, renal replacement therapy, requirement of blood products, and ICU length of stay. The MELD demonstrated low predictive power (c-statistic 0.73). Multivariate analysis identified MELD score (adjusted odds ratio [AOR] = 1.05), mechanical ventilation (AOR = 4.55), vasopressors (AOR = 3.87), and continuous renal replacement therapy (AOR = 2.43) as independent predictors of mortality, with stronger predictive accuracy (c-statistic 0.87). The MELD demonstrated relatively poor predictive accuracy in critically ill patients with cirrhosis and might not be the best indicator for prognosis in the ICU population. Prognostic accuracy is significantly improved when variables indicating organ support (mechanical ventilation, vasopressors, and continuous renal replacement therapy) are included in the model. Copyright © 2016. Published by Elsevier Inc.

Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

PubMed Central

Hernández-Bartolomé, Ángel; López-Rodríguez, Rosario; Borque, María Jesús; González-Moreno, Leticia; Real-Martínez, Yolanda; García-Buey, Luisa; Moreno-Otero, Ricardo; Sanz-Cameno, Paloma

2016-01-01

AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins (Ang) as cirrhosis biomarkers of chronic hepatitis C (CHC). METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays (ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR system. Groups were compared by non-parametric Mann-Whitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics (AUC-ROC). RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic (P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease (P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis (P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values (above 0.7, both), but the Ang2/Ang1 ratio was much better (AUC-ROC = 0.810) and displayed outstanding values of sensitivity (71%), specificity (84%) and accuracy (82.1%) at the optimal cut-off (10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in CHC. CONCLUSION Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target. PMID:27956798

The renal effects of droxidopa are maintained in propranolol treated cirrhotic rats.

PubMed

Rodríguez, Sarai; Raurell, Imma; Ezkurdia, Nahia; Augustin, Salvador; Esteban, Rafael; Genescà, Joan; Martell, María

2015-02-01

Droxidopa improves hemodynamic and renal alterations of cirrhotic rats without changing portal pressure. We aimed to evaluate the effects of a combined treatment with droxidopa and non-selective beta-blockers or statins in order to decrease portal pressure, while maintaining droxidopa beneficial effects. Acute studies combining droxidopa with carvedilol, propranolol or atorvastatin in four-week bile-duct ligated (BDL) rats and a chronic study combining propranolol and droxidopa for 5 days in CCl4 -cirrhotic rats were performed. Hemodynamic values were registered and biochemical parameters from blood and urine samples analyzed. Bile-duct ligated rats treated with carvedilol + droxidopa showed no changes in mean arterial pressure (MAP) and portal pressure (PP) compared to vehicles. Atorvastatin + droxidopa combination also failed to reduce PP, but maintained the beneficial increase in MAP and superior mesenteric artery resistance (SMAR) and decrease in blood flow (SMABF) caused by droxidopa. In contrast, the acute administration of propranolol + droxidopa significantly reduced PP maintaining a mild increase in MAP and improving, in an additive way, the decrease in SMABF and increase in SMAR caused by droxidopa. This combination also preserved droxidopa diuretic effect. When chronically administered to CCl4 -cirrhotic rats, propranolol + droxidopa caused a decrease in PP, a significant reduction in SMABF and an increase in SMAR. The combination did not alter liver function and droxidopa diuretic and natriuretic effect, and even improved free water clearance. Droxidopa could be effective for the renal alterations of cirrhotic patients on propranolol therapy and the combination of both drugs may balance the adverse effects of each treatment. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The efficacy and safety of epsilon-aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis.

PubMed

Gunawan, B; Runyon, B

2006-01-01

Patients with decompensated cirrhosis are at risk for hyperfibrinolysis; this is potentially fatal. epsilon-aminocaproic acid has been used to treat patients with hyperfibrinolysis; however, the data about its benefit in the setting of cirrhosis are minimal. To analyse the efficacy of epsilon-aminocaproic acid and its safety in cirrhotic patients with hyperfibrinolysis. All patients with an abnormal euglobin lysis time who were admitted to Rancho Los Amigos Medical Center from 1 January 2001 to 31 December 2002 were included in the study. Their medical records were reviewed and analysed. There were 60 cirrhotic patients with shortened euglobin lysis time. Fifty-two patients received epsilon-aminocaproic acid. Of the 52 patients, seven had one or more bleeding episodes with the subcutaneous or soft tissue bleeding as the most common indication for epsilon-aminocaproic acid use. Of the 37 patients, 34 (92%) had improvement or resolution of their bleeding. Only two (3%) patients had epsilon-aminocaproic acid treatment discontinued because of minor side effects, rash and lightheadedness. There were no thromboembolic complications of treatment. epsilon-aminocaproic acid was found to be effective and safe for treatment of hyperfibrinolysis in patients with cirrhosis.

Direct-Acting Antiviral Therapy Outcomes in Canadian Chronic Hepatitis C Telemedicine Patients.

PubMed

Cooper, Curtis L; Hatashita, Holly; Corsi, Daniel J; Parmar, Parmvir; Corrin, Raymond; Garber, Gary

Many of the 300,000 HCV-infected Canadians live in under-served and remote areas without access to HCV healthcare specialists. Telemedicine (TM) and advances in HCV management can facilitate linkage of these marginalized patients to healthcare. A cohort database analysis was performed on patients followed at The Ottawa Hospital and Regional Viral Hepatitis Program between January 2012 and August 2016. We compared patient characteristics, fibrosis work-up and antiviral treatment outcomes in TM (n = 157) and non-TM (n = 1,130) patients (The Ottawa Hospital Viral Hepatitis Outpatient Clinic) residing in Eastern Ontario. TM patients were more often infected with genotype 3 (25.9% vs. 16.4%), were more commonly Indigenous (7.0% vs. 2.2%) had a history of injection drug use (70.1% vs. 54.9%) and incarceration (46.5% vs 35.5%). Groups were comparable in age (48.9 years), gender (63.7% male) and cirrhotic stage (24.0%). 59.2% of TM patients underwent transient elastography during regional outreach blitzes compared to 61.8% of non-TM patients (p = 0.54). Overall, half as many TM patients initiated antiviral therapy as non-TM patients (27.4% vs. 53.8%, p < 0.001). The introduction of DAA regimens is bridging this gap (22.2% of TM patients vs. 34.3% of non-TM patients). SVR rates with interferon-free, DAA regimens were 94.7% and 94.8% in TM and non-TM groups (p = 0.99). Our TM program engages and retains a population that faces many barriers to effective HCV treatment. TM patients initiated HCV therapy and achieved High SVR rates comparable to those obtained using traditional models of care.

Alpha Klotho and Fibroblast Growth Factor-23 Among Alcoholics.

PubMed

Quintero-Platt, Geraldine; González-Reimers, Emilio; Rodríguez-Gaspar, Melchor; Martín-González, Candelaria; Pérez-Hernández, Onán; Romero-Acevedo, Lucía; Espelosín-Ortega, Elisa; Vega-Prieto, María José de la; Santolaria-Fernández, Francisco

2017-09-01

Alcoholism may be a cardiovascular risk factor. Osteocyte derived molecules such as fibroblast growth factor 23 (FGF-23) and soluble α Klotho have recently been associated with cardiovascular disease, but their role in alcoholics is unknown. We here analyze the behavior of FGF23 and α Klotho in alcoholics. Ninety-seven alcoholic patients were assessed for liver function, presence of hypertension, diabetes, atrial fibrillation, left ventricular hypertrophy (LVH), vascular calcifications (assessed by chest X-ray) and nutritional status (lean and fat mass measured by densitometry). We measured plasma levels of FGF-23 and serum soluble α Klotho, using ELISA in 97 patients and 20 age- and sex-matched controls. FGF-23 levels were higher in patients than in controls (Z = 3.50; P < 0.001). FGF-23 (Z = 5.03; P < 0.001) and soluble α Klotho (Z = 5.61; P < 0.001) were higher in cirrhotics, and both were related to liver function, independently of serum creatinine FGF-23 levels were higher among alcoholics with diabetes (Z = 2.55; P = 0.011) or hypertension (Z = 2.56; P = 0.01), and increased body fat (ρ = 0.28; P = 0.022 for trunk fat), whereas α Klotho levels were higher in patients with LVH (Z = 2.17; P = 0.03) or atrial fibrillation (Z = 2.34; P = 0.019). FGF-23 was higher in alcoholics than in controls, especially among cirrhotics, and soluble α Klotho levels were also higher among cirrhotics. Both were related to liver function impairment, independently of serum creatinine levels, and also showed significant associations with vascular risk factors, such as hypertension, diabetes or trunk fat amount in the case of FGF-23, or LVH or atrial fibrillation in the case of α Klotho. We report increased values of fibroblast growth factor 23 (FGF-23) and soluble α Klotho in cirrhotic alcoholics. Both molecules are associated with liver function impairment, and with some cardiovascular risk factors such as diabetes, hypertension, increased body fat, left ventricular hypertrophy and atrial fibrillation independently of serum creatinine. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Are different cut-off values of liver stiffness assessed by transient elastography according to the etiology of liver cirrhosis for predicting significant esophageal varices?

PubMed

Sporea, Ioan; Raţiu, Iulia; Bota, Simona; Şirli, Roxana; Jurchiş, Ana

2013-06-01

To determine if liver stiffness (LS) measurements by means of Transient Elastography (TE) vary according to the etiology of the underlying liver cirrhosis and to find if there are different TE cut-off values able to predict the presence of significant EV in alcoholic vs. viral etiology of cirrhosis. This retrospective study included patients diagnosed with liver cirrhosis of viral or alcoholic etiology. All patients were evaluated by means of TE (FibroScan) and upper gastrointestinal endoscopy. We performed 10 LS measurements in each patient and a median value expressed in kiloPascals (kPa) was calculated. Only those with a SR >/= 60% and an IQR<30% were considered as reliable MS measurements. According to the presence of EV the patients were divided in two categories: without significant EV and patients with significant EV (at least grade 2). The study included 697 cirrhotic patients with reliable LS measurements. The median LS values assessed by TE were significantly higher in cirrhotic patients with alcoholic etiology as compared with those with viral etiology of liver disease: 41 kPa vs. 21.1 kPa, p<0.0001. In the entire cohort of cirrhotic patients, LS assessed by means of TE for a cut-off value >29.5 kPa, had 77.5% sensitivity and 86.9% specificity for predicting the presence of significant EV (AUROC=0.871). The best LS cut-off value for predicting the presence of significant EV was higher in alcoholic cirrhosis as compared with those with viral etiology of liver cirrhosis: 32.5 kPa (AUROC=0.836) vs. 24.8 kPa (AUROC=0.867). LS cut-off values assessed by TE for predicting significant EV are significantly higher in patients with alcoholic cirrhosis as compared with patients with liver cirrhosis of viral etiology.

Ultrasound-based elastography for the diagnosis of portal hypertension in cirrhotics

PubMed Central

Şirli, Roxana; Sporea, Ioan; Popescu, Alina; Dănilă, Mirela

2015-01-01

Progressive fibrosis is encountered in almost all chronic liver diseases. Its clinical signs are diagnostic in advanced cirrhosis, but compensated liver cirrhosis is harder to diagnose. Liver biopsy is still considered the reference method for staging the severity of fibrosis, but due to its drawbacks (inter and intra-observer variability, sampling errors, unequal distribution of fibrosis in the liver, and risk of complications and even death), non-invasive methods were developed to assess fibrosis (serologic and elastographic). Elastographic methods can be ultrasound-based or magnetic resonance imaging-based. All ultrasound-based elastographic methods are valuable for the early diagnosis of cirrhosis, especially transient elastography (TE) and acoustic radiation force impulse (ARFI) elastography, which have similar sensitivities and specificities, although ARFI has better feasibility. TE is a promising method for predicting portal hypertension in cirrhotic patients, but it cannot replace upper digestive endoscopy. The diagnostic accuracy of using ARFI in the liver to predict portal hypertension in cirrhotic patients is debatable, with controversial results in published studies. The accuracy of ARFI elastography may be significantly increased if spleen stiffness is assessed, either alone or in combination with liver stiffness and other parameters. Two-dimensional shear-wave elastography, the ElastPQ technique and strain elastography all need to be evaluated as predictors of portal hypertension. PMID:26556985

Automatic seed selection for segmentation of liver cirrhosis in laparoscopic sequences

NASA Astrophysics Data System (ADS)

Sinha, Rahul; Marcinczak, Jan Marek; Grigat, Rolf-Rainer

2014-03-01

For computer aided diagnosis based on laparoscopic sequences, image segmentation is one of the basic steps which define the success of all further processing. However, many image segmentation algorithms require prior knowledge which is given by interaction with the clinician. We propose an automatic seed selection algorithm for segmentation of liver cirrhosis in laparoscopic sequences which assigns each pixel a probability of being cirrhotic liver tissue or background tissue. Our approach is based on a trained classifier using SIFT and RGB features with PCA. Due to the unique illumination conditions in laparoscopic sequences of the liver, a very low dimensional feature space can be used for classification via logistic regression. The methodology is evaluated on 718 cirrhotic liver and background patches that are taken from laparoscopic sequences of 7 patients. Using a linear classifier we achieve a precision of 91% in a leave-one-patient-out cross-validation. Furthermore, we demonstrate that with logistic probability estimates, seeds with high certainty of being cirrhotic liver tissue can be obtained. For example, our precision of liver seeds increases to 98.5% if only seeds with more than 95% probability of being liver are used. Finally, these automatically selected seeds can be used as priors in Graph Cuts which is demonstrated in this paper.

Cirrhotic cardiomyopathy: Implications for the perioperative management of liver transplant patients

PubMed Central

Rahman, Suehana; Mallett, Susan V

2015-01-01

Cirrhotic cardiomyopathy is a disease that has only recently been recognised as a definitive clinical entity. In the setting of liver cirrhosis, it is characterized by a blunted inotropic and chronotropic response to stress, impaired diastolic relaxation of the myocardium and prolongation of the QT interval in the absence of other known cardiac disease. A key pathological feature is the persistent over-activation of the sympathetic nervous system in cirrhosis, which leads to down-regulation and dysfunction of the β-adrenergic receptor. Diagnosis can be made using a combination of echocardiography (resting and stress), tissue Doppler imaging, cardiac magnetic resonance imaging, 12-lead electrocardiogram and measurement of biomarkers. There are significant implications of cirrhotic cardiomyopathy in a number of clinical situations in which there is an increased physiological demand, which can lead to acute cardiac decompensation and heart failure. Prior to transplantation there is an increased risk of hepatorenal syndrome, cardiac failure following transjugular intrahepatic portosystemic shunt insertion and increased risk of arrhythmias during acute gastrointestinal bleeding. Liver transplantation presents the greatest physiological challenge with a further risk of acute cardiac decompensation. Peri-operative management should involve appropriate choice of graft and minimization of large fluctuations in preload and afterload. The avoidance of cardiac failure during this period has important prognostic implications, as there is evidence to suggest a long-term resolution of the abnormalities in cirrhotic cardiomyopathy. PMID:25848474

Aberrant topological organization of the functional brain network associated with prior overt hepatic encephalopathy in cirrhotic patients.

PubMed

Chen, Hua-Jun; Chen, Qiu-Feng; Yang, Zhe-Ting; Shi, Hai-Bin

2018-05-30

A higher risk of cognitive impairments has been found after an overt hepatic encephalopathy (OHE) episode in cirrhotic patients. We investigated the effect of prior OHE episodes on the topological organization of the functional brain network and its association with the relevant cognitive impairments. Resting-state functional MRI data were acquired from 41 cirrhotic patients (19 with prior OHE (Prior-OHE) and 22 without (Non-Prior-OHE)) and 21 healthy controls (HC). A Psychometric Hepatic Encephalopathy Score (PHES) assessed cognition. The whole-brain functional network was constructed by thresholding functional correlation matrices of 90 brain regions (derived from the Automated Anatomic Labeling atlas). The topological properties of the brain network, including small-worldness, network efficiency, and nodal efficiency, were examined using graph theory-based analysis. Globally, the Prior-OHE group had a significantly decreased clustering coefficient and local efficiency, compared with the controls. Locally, the nodal efficiency in the bilateral medial superior frontal gyrus and the right postcentral gyrus decreased in the Prior-OHE group, while the nodal efficiency in the bilateral anterior cingulate/paracingulate gyri and right superior parietal gyrus increased in the Prior-OHE group. The alterations of global and regional network parameters progressed from Non-Prior-OHE to Prior-OHE and the clustering coefficient and local efficiency values were significantly correlated with PHES results. In conclusion, cirrhosis leads to the reduction of brain functional network efficiency, which could be aggravated by a prior OHE episode. Aberrant topological organization of the functional brain network may contribute to a higher risk of cognitive impairments in Prior-OHE patients.

Cost-Effectiveness of New Direct-Acting Antivirals to Prevent Post-Liver Transplant Recurrent Hepatitis.

PubMed

Cortesi, P A; Mantovani, L G; Ciaccio, A; Rota, M; Mazzarelli, C; Cesana, G; Strazzabosco, M; Belli, L S

2015-07-01

Preliminary studies on HCV-cirrhotics listed for transplant suggest that sofosbuvir in combination with ribavirin is very effective in promoting viral clearance and preventing disease recurrence. Unfortunately, the high cost of such treatment (€46 500 per 12 weeks of treatment) makes its cost-effectiveness questionable. A semi-Markov model was developed to assess the cost-effectiveness of sofosbuvir/ribavirin treatment in cirrhotic patients without HCC (HCV-CIRRH) and with HCC (HCV-HCC) listed for transplant. In the base-case analysis, the incremental cost-effectiveness ratio for 24 weeks of sofosbuvir/ribavirin was €44 875 per quality-adjusted life-year gained in HCV-CIRRH and €60 380 in HCV-HCC patients. Both results were above the willingness to pay threshold of €37 000 per quality-adjusted life-year. Our data also show that in order to remain cost-effective (with a 24-week treatment), any novel interferon-free treatment endowed with ideal efficacy should cost less than €67 224 or €95 712 in HCV-cirrhotics with and without HCC, respectively. The results shows that sofosbuvir/ribavirin therapy, given to patients listed for transplant, is not cost-effective at current prices despite being very effective, and new, more effective treatments will have little economic margins to remain cost-effective. New interferon-free combinations have the potential to revolutionize the treatment and prognosis of HCV-positive patients listed for transplant; however, without sustainable prices, this revolution is unlikely to happen. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Hepatocellular carcinoma in cirrhotic patients at multidetector CT: hepatic venous phase versus delayed phase for the detection of tumour washout

PubMed Central

Furlan, A; Marin, D; Vanzulli, A; Patera, G Palermo; Ronzoni, A; Midiri, M; Bazzocchi, M; Lagalla, R; Brancatelli, G

2011-01-01

Objectives Our aim was to compare retrospectively hepatic venous and delayed phase images for the detection of tumour washout during multiphasic multidetector row CT (MDCT) of the liver in patients with hepatocellular carcinoma (HCC). Methods 30 cirrhotic patients underwent multiphasic MDCT in the 90 days before liver transplantation. MDCT was performed before contrast medium administration and during hepatic arterial hepatic venous and delayed phases, images were obtained at 12, 55 and 120 s after trigger threshold. Two radiologists qualitatively evaluated images for lesion attenuation. Tumour washout was evaluated subjectively and objectively. Tumour-to-liver contrast (TLC) was measured for all pathologically proven HCCs. Results 48 HCCs were detected at MDCT. 46 of the 48 tumours (96%) appeared as either hyper- or isoattenuating during the hepatic arterial phase subjective washout was present in 15 HCCs (33%) during the hepatic venous phase and in 35 (76%) during the delayed phase (p<0.001, McNemar’s test). Objective washout was present in 30 of the 46 HCCs (65%) during the hepatic venous phase and in 42 of the HCCs (91%) during the delayed phase (p=0.001). The delayed phase yielded significantly higher mean TLC absolute values compared with the hepatic venous phase (−16.1±10.8 HU vs −10.5±10.2 HU; p<0.001). Conclusions The delayed phase is superior to the hepatic venous phase for detection of tumour washout of pathologically proven HCC in cirrhotic patients. PMID:21081569

Trans-jugular intrahepatic porto-systemic shunt placement for refractory ascites: a ‘real-world’ UK health economic evaluation

PubMed Central

Parker, Matthew J; Guha, Neil; Stedman, Brian; Hacking, Nigel; Wright, Mark

2013-01-01

Objective To assess the benefit of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement for refractory ascites. Design A retrospective observational study of all patients undergoing TIPS for refractory ascites in our hospital between 2003 and 2012. Setting Secondary care. Patients Cirrhotic patients with refractory ascites. Main outcome measures We examined direct real-world (National Health Service) health related costs in the year before and after the TIPS procedure took place. Data were collected relating to the need for reintervention and hepatic encephalopathy. Results Data were available for 24 patients who underwent TIPS for refractory ascites (86% of eligible patients). TIPS was technically successful in all cases. Mean number of bed days in the year prior to TIPS was 30.3 and 14.3 in the year following (p=0.005). No patient had ascites at the end of the year after the TIPS with less requirement for paracentesis over the course of the year (p<0.001). Mean reduction in cost was £2759 per patient. TIPS was especially cost-effective in patients requiring between 6 and 12 drains per year with a mean saving of £9204 per patient. Conclusions TIPS is both a clinically effective and economically advantageous therapeutic option for selected patients with refractory ascites. PMID:28839725

Cirrhosis and Rapid Virological Response to Peginterferon Plus Ribavirin Determine Treatment Outcome in HCV-1 IL28B rs12979860 CC Patients

PubMed Central

Aghemo, Alessio; Degasperi, Elisabetta; Rumi, Maria Grazia; Galmozzi, Enrico; Valenti, Luca; De Francesco, Raffaele; De Nicola, Stella; Cheroni, Cristina; Grassi, Eleonora; Colombo, Massimo

2013-01-01

Background. The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphism is associated with high rates of sustained virological response (SVR) to peginterferon (PegIFN) and ribavirin (Rbv) in hepatitis C virus genotype-1 (HCV-1) patients. The impact of baseline predictors of treatment outcome and their interplay with viral kinetics in HCV-1 CC patients has not been fully evaluated. Aim. To identify baseline and on-therapy predictors of treatment failure in HCV-1 IL28B CC patients. Methods. Treatment-naïve HCV-1 patients, compliant to PegIFN and Rbv who did not discontinue treatment for nonvirological reasons, were analyzed. Results. 109 HCV-1 IL28B CC were studied. Sixty were males, 39 with BMI >25, 69 with >600,000 IU/mL HCV RNA, 15 with HCV1a, and 30 with cirrhosis. Overall, 75 (69%) achieved an SVR; cirrhosis was the only baseline predictor of treatment failure (OR: 2.58, 95% CI: 1.07–6.21) as SVR rates were 53% in cirrhotics versus 75% in noncirrhotics (P = 0.03). HCV RNA undetectability (<50 IU/mL) at week 4 (RVR) was achieved by 58 patients (53%). The SVR rates were independent of RVR in noncirrhotics, 76% (34/45) RVR (+) and 74% (25/34) RVR (−) (P = 0.9). In cirrhotic patients, SVR rates were significantly higher in RVR (+) compared to RVR (−) (10/13 (77%) versus 6/17 (35%) P = 0.03). Conclusions. In HCV-1 IL28B CC patients, cirrhosis is the only clinical baseline predictor of PegIFN and Rbv treatment failure. However, in IL28B CC cirrhotics, the achievement of RVR identifies those patients who still have high rates of SVR to Peg-IFN/Rbv therapy. PMID:23936821

MINIMAL HEPATIC ENCEPHALOPATHY IS ASSOCIATED WITH MOTOR VEHICLE CRASHES: THE REALITY BEYOND THE DRIVING TEST

PubMed Central

Bajaj, Jasmohan S; Saeian, Kia; Schubert, Christine M; Hafeezullah, Muhammad; Franco, Jose; Varma, Rajiv R; Gibson, Douglas P; Hoffmann, Raymond G; Stravitz, R Todd; Heuman, Douglas M; Sterling, Richard K; Shiffman, Mitchell; Topaz, Allyne; Boyett, Sherry; Bell, Debulon; Sanyal, Arun J

2009-01-01

Patients with minimal hepatic encephalopathy (MHE) have impaired driving skills, but association of MHE with motor vehicle crashes is unclear. Standard psychometric tests (SPT) or inhibitory control test (ICT) can be used to diagnose MHE. The aim was to determine the association of MHE with crashes and traffic violations over the preceding year and on 1-year follow-up. Cirrhotics were diagnosed with MHE by ICT (MHEICT) and SPT (MHESPT). Self and department-of-transportation (DOT)-reports were used to determine crashes and violations over the preceding year. Agreement between self and DOT-reports was analyzed. Patients then underwent 1 year follow-up for crash/violation occurrence. Crashes in those with/without MHEICT and MHESPT were compared. 167 cirrhotics had DOT-reports, of which 120 also had self-reports. A significantly higher proportion of MHEICT cirrhotics experienced crashes in the preceding year compared to those without MHE by self-report (17% vs. 0%, p=0.0004) and DOT-reports (17% vs. 3%, p=0.004, relative risk:5.77). SPT did not differentiate between those with/without crashes. A significantly higher proportion of patients with crashes had MHEICT compared to MHESPT, both self-reported (100% vs. 50%, p=0.03) and DOT-reported (89% vs. 44%, p=0.01). There was excellent agreement between self and DOT-reports for crashes and violations (Kappa 0.90 and 0.80). 109 patients were followed prospectively. MHEICT patients had a significantly higher future crashes/violations compared to those without (22% vs. 7%, p=0.03) but MHESPT did not. MHEICT (Odds ratio:4.51) and prior year crash/violation (Odds ratio:2.96) were significantly associated with future crash/violation occurrence. PMID:19670416

Stemness-Related Transcriptional Factors and Homing Gene Expression Profiles in Hepatic Differentiation and Cancer

PubMed Central

Toraih, Eman A; Fawzy, Manal S; El-Falouji, Abdullah I; Hamed, Elham O; Nemr, Nader A; Hussein, Mohammad H; Fadeal, Noha M Abd El

2016-01-01

Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profiles of three pluripotency-associated genes, OCT4, NANOG and SOX2, G-protein-coupled chemokine receptor 4 (CXCR4) and the ligand CXCL2, and alpha-fetoprotein (AFP) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed for relative quantification of the six target genes using the Livak method. In silico network analysis was also executed to explore the pluripotency and tumorigenetic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG, CXCR4 and AFP were significantly upregulated in late clinical stage HCC patients. In contrast, SOX2 and CXCL2 were markedly overexpressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of the SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high expression with late HCC could contribute to the acquisition of stem cell–like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have potential application in HCC prognosis and treatment. PMID:27623812

Factors associated with health-related quality of life among patients with liver cirrhosis in Egypt.

PubMed

Youssef, Naglaa F A; Shepherd, Ashley; Evans, Josie M M

2015-03-01

Although the disease burden of liver cirrhosis in Egypt is high and there are few resources for its management, there is limited research on the health-related quality of life (HRQOL) of Egyptian patients with liver cirrhosis. To describe the HRQOL of liver cirrhotic patients in Egypt and to analyse factors associated with this construct. A cross-sectional study with a convenience sample of 401 patients from three hospitals in Cairo, Egypt, was carried out in June-August 2011. Patients were interviewed to complete a background data form, Short Form-36, the Liver Disease Symptom Index-2.0 and the Multidimensional Scale of Perceived Social Support. Patients had low HRQOL, with mental health perceived to be poorer than physical health. In regression analyses, severity of symptoms, disease stage, comorbidities and employment status were associated significantly with physical health, accounting for 19% of the variance. For mental health, 31.7% of the variation was explained by severity of symptoms, employment status and perceived spouse and family support. These findings highlight the needs of patients with liver cirrhosis in Egypt. Engaging the patients' family in care planning may decrease patients' burden and improve their HRQOL. This study also provides a rationale to develop future research in symptom management to enhance HRQOL.

Trans-jugular intrahepatic porto-systemic shunt placement for refractory ascites: a 'real-world' UK health economic evaluation.

PubMed

Parker, Matthew J; Guha, Neil; Stedman, Brian; Hacking, Nigel; Wright, Mark

2013-07-01

To assess the benefit of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement for refractory ascites. A retrospective observational study of all patients undergoing TIPS for refractory ascites in our hospital between 2003 and 2012. Secondary care. Cirrhotic patients with refractory ascites. We examined direct real-world (National Health Service) health related costs in the year before and after the TIPS procedure took place. Data were collected relating to the need for reintervention and hepatic encephalopathy. Data were available for 24 patients who underwent TIPS for refractory ascites (86% of eligible patients). TIPS was technically successful in all cases. Mean number of bed days in the year prior to TIPS was 30.3 and 14.3 in the year following (p=0.005). No patient had ascites at the end of the year after the TIPS with less requirement for paracentesis over the course of the year (p<0.001). Mean reduction in cost was £2759 per patient. TIPS was especially cost-effective in patients requiring between 6 and 12 drains per year with a mean saving of £9204 per patient. TIPS is both a clinically effective and economically advantageous therapeutic option for selected patients with refractory ascites.

Classification of cirrhotic liver in Gadolinium-enhanced MR images

NASA Astrophysics Data System (ADS)

Lee, Gobert; Uchiyama, Yoshikazu; Zhang, Xuejun; Kanematsu, Masayuki; Zhou, Xiangrong; Hara, Takeshi; Kato, Hiroki; Kondo, Hiroshi; Fujita, Hiroshi; Hoshi, Hiroaki

2007-03-01

Cirrhosis of the liver is characterized by the presence of widespread nodules and fibrosis in the liver. The fibrosis and nodules formation causes distortion of the normal liver architecture, resulting in characteristic texture patterns. Texture patterns are commonly analyzed with the use of co-occurrence matrix based features measured on regions-of-interest (ROIs). A classifier is subsequently used for the classification of cirrhotic or non-cirrhotic livers. Problem arises if the classifier employed falls into the category of supervised classifier which is a popular choice. This is because the 'true disease states' of the ROIs are required for the training of the classifier but is, generally, not available. A common approach is to adopt the 'true disease state' of the liver as the 'true disease state' of all ROIs in that liver. This paper investigates the use of a nonsupervised classifier, the k-means clustering method in classifying livers as cirrhotic or non-cirrhotic using unlabelled ROI data. A preliminary result with a sensitivity and specificity of 72% and 60%, respectively, demonstrates the feasibility of using the k-means non-supervised clustering method in generating a characteristic cluster structure that could facilitate the classification of cirrhotic and non-cirrhotic livers.

Plasma Prothrombin Time and Esophageal Varices in Patients with Cirrhosis of Liver.

PubMed

Islam, Md Nasirul; Khan, Mobin; Ahmad, Nooruddin; Mamun-Al-Mahtab; Karim, Md Fazal

2016-01-01

Cirrhosis of the liver is a common complication of chronic liver disease and is associated with portal hypertension and esophageal varices. In this study, we checked the implication of prothrombin time, if any, in the genesis of esophageal varices. Sixty patients with cirrhosis of the liver were randomly assigned into two groups: Group I - 30 cirrhotic patients with esophageal varices, and group II - 30 cirrhotic patients without esophageal varices. The prothrombin time was checked for both groups. A positive correlation was found between the prolonged plasma prothrombin time (> 4 seconds) and esophageal varices with a sensitivity of 56.67% and specificity of 73.33%. The Child-Pugh score showed a correlation; however, the size of varices did not exhibit any such relation. Prothrombin time may be cautiously used to assess portal hypertension in a field level and rural setting where endoscopy is not available or feasible. Islam MN, Khan M, Ahmad N, Al-Mahtab M, Karim MF. Plasma Prothrombin Time and Esophageal Varices in Patients with Cirrhosis of Liver. Euroasian J Hepato-Gastroenterol 2016;6(1):10-12.

Sarcopenia in patients with advanced liver disease.

PubMed

Ponziani, Francesca Romana; Gasbarrini, Antonio

2017-04-28

Sarcopenia is the loss of muscle mass and function, affecting up to 70% of patients with advanced liver disease. Liver cirrhosis is characterized by an altered glucose metabolism, lipid oxidation, ketogenesis and protein catabolism, leading to the loss of adipose and muscle tissue. The gastrointestinal dysfunction of cirrhotic patients results in inadequate nutrients intake and is responsible for muscle weakness thus limiting physical exercise and perpetuating the reduction of muscle mass. Recently, alterations of hormonal pathways involved in muscle growth, increased intestinal permeability and changes in the gut microbiota composition have been reported in cirrhotic patients. Interestingly, a role of intestinal bacteria in maintaining muscle health has been hypothesized through the translocation of bacteria and bacterial products into the bloodstream triggering the production of muscle wasting-associated cytokines. Sarcopenia is associated with severe outcomes in patients with liver cirrhosis, mostly due to the incidence of disease complications. Furthermore, sarcopenia may represent an important prognostic factor for patients with hepatocellular carcinoma and for those undergoing liver transplantation and can be considered a useful additional tool in the global assessment of patients with advanced liver disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report

PubMed Central

Clavien, Pierre-Alain; Lesurtel, Mickael; Bossuyt, Patrick M M; Gores, Gregory J; Langer, Bernard; Perrier, Arnaud

2012-01-01

Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2–4, 2010, in Zurich, Switzerland, with the aim of reviewing current practice regarding liver transplantation in patients with HCC and to develop internationally accepted statements and guidelines. The format of the conference was based on the Danish model. 19 working groups of experts prepared evidence-based reviews according to the Oxford classification, and drafted recommendations answering 19 specific questions. An independent jury of nine members was appointed to review these submissions and make final recommendations, after debates with the experts and audience at the conference. This report presents the final 37 statements and recommendations, covering assessment of candidates for liver transplantation, criteria for listing in cirrhotic and non-cirrhotic patients, role of tumour downstaging, management of patients on the waiting list, role of living donation, and post-transplant management. PMID:22047762

Liver stiffness predicts the response to direct-acting antiviral-based therapy against chronic hepatitis C in cirrhotic patients.

PubMed

Neukam, K; Morano-Amado, L E; Rivero-Juárez, A; Macías, J; Granados, R; Romero-Palacios, A; Márquez, M; Merino, D; Ortega, E; Alados-Arboledas, J C; Cucurull, J; Omar, M; Ryan-Murua, P; Pineda, J A

2017-05-01

The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group (p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group (p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344-13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse.

Generic ledipasvir-sofosbuvir for patients with chronic hepatitis C: A real-life observational study.

PubMed

Zeng, Qing-Lei; Xu, Guang-Hua; Zhang, Ji-Yuan; Li, Wei; Zhang, Da-Wei; Li, Zhi-Qin; Liang, Hong-Xia; Li, Chun-Xia; Yu, Zu-Jiang

2017-06-01

Few patients from developing countries can afford brand name direct-acting antiviral agents for treating hepatitis C virus (HCV) infection, and controversy regarding the bioequivalence of generics exists. This study aimed to observe the safety and efficacy of 8 or 12weeks of generic ledipasvir-sofosbuvir with or without ribavirin for Chinese genotype 1b HCV-infected patients. In this open-labelled observational study, 63 cirrhotic (group 1) and 65 non-cirrhotic (group 2) patients were administered generic ledipasvir-sofosbuvir plus 1000-1200mg of ribavirin daily for 12 and 8weeks, respectively; and 64 non-cirrhotic patients (group 3) received ledipasvir-sofosbuvir for 8weeks. The primary efficacy endpoint was undetectable HCV RNA at week 12 (SVR12) after cessation of therapy. Safety and pharmacokinetic data were collected. One hundred and eighty-seven patients completed treatment, and the latest undetectable HCV RNA was observed in three patients with cirrhosis at week 5 during treatment. Intention-to-treat analysis revealed 96.8% (61/63), 96.9% (63/65), and 96.9% (62/64) of SVR12 rates in groups 1, 2, and 3, respectively. One patient in group 3 relapsed at post-treatment week 4. The regimens were generally well-tolerated. The most common adverse events were fatigue (17.8%), diarrhea (10.9%), and headache (9.9%). Four patients discontinued therapy due to diarrhea and vomiting. One patient from group 2 discontinued treatment on day 29 because of drug-unaffordability; fortunately, she achieved SVR12. This study demonstrated that 8 or 12weeks of generic ledipasvir-sofosbuvir with or without ribavirin are safe and effective for patients with genotype 1b HCV infection. The price of Harvoni® has led to restrictions and access limitations in many developing and even developed countries with limited healthcare budgets. Gilead approved generic ledipasvir-sofosbuvir costs far less than Harvoni® and presents a similar cure rate for patients with chronic hepatitis C. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Thallium-201 per rectum for the diagnosis of cirrhosis in patients with asymptomatic chronic hepatitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'Arienzo, A.; Celentano, L.; Scuotto, A.

1988-07-01

In normal subjects, thallium-201, administered per rectum, is taken up mainly by the liver (heart/liver ratio in normal subjects: 0.04 to 0.12). It has been claimed that an increased heart/liver ratio is suggestive of portal-caval shunting and portal hypertension. To evaluate the possibility of using thallium-201 as a test to diagnose cirrhosis, we administered this substance per rectum to 33 patients with biochemical evidence, but no clinical symptoms, of liver disease. Laparoscopy and liver biopsy revealed chronic active hepatitis without cirrhosis in 18 patients, and chronic active hepatitis with cirrhosis in the others. The results of conventional liver function testsmore » were similar in both groups. A significant difference, however, was found between the means of fasting serum bile acid concentrations (9.8 +/- 3.2 and 18.3 +/- 4.2 microM per liter) in chronic active hepatitis without cirrhosis and cirrhotic patients, and between the means of the heart/liver ratios 20 min after thallium-201 administration (heart/liver: 0.09 +/- 0.03 and 0.54 +/- 0.13, respectively). Unlike the serum bile acid concentration which gave some overlapping values, the thallium-201 test clearly distinguished the chronic active hepatitis without cirrhosis group from the cirrhotics. In the cirrhotic group, there was a significant correlation between the heart/liver ratio and signs of portal hypertension such as esophageal varices, increased diameter of the vena porta and hypersplenism. The thallium-201 test is therefore useful in discriminating between chronic active hepatitis with and without cirrhosis in clinically asymptomatic subjects with biochemical evidence of moderate liver function impairment. A heart/liver uptake ratio much higher than normal (above 0.30) strongly suggests the development of hepatic cirrhosis.« less

Evaluation of the Value of d-Dimer, P-Selectin, and Platelet Count for Prediction of Portal Vein Thrombosis After Devascularization.

PubMed

Fei, Yang; Zong, Guang-Quan; Chen, Jian; Liu, Ren-Min

2016-07-01

To evaluate the value of d-dimer, P-selectin, and platelet count in patients with cirrhotic portal hypertension (PHT) for prediction of portal vein thrombosis (PVT) after devascularization. A total of 137 patients with cirrhotic PHT who undergone devascularization from January 2012 to April 2014 were retrospectively reviewed, all of them were divided into 2 groups (PVT group and non-PVT group) by Doppler ultrasonography (DU) examination. The level of d-dimer, P-selectin, and platelet count was tested during the perioperative period. In all, 38 (27.7%) patients were found to have PVT by DU examination postoperatively. In contrast to the non-PVT group, the level of d-dimer, P-selectin, and platelet count in the PVT group was much higher significantly at 1, 3, and 7 days after devascularization. (P < .05). However, in the 15 days after surgery, the difference in P-selectin between the 2 groups was not significant (P = .260). It was shown that the highest sensitivity of the 3 markers for PVT was d-dimer, the highest specificity belonged to P-selectin. The area under receiver-operating characteristic (ROC) curve of P-selectin was the biggest of the 3 markers. When the 3 markers were combined to be used to diagnose PVT, the sensitivity was increased to 0.907, with a slight drop of specificity to 0.693, the area under the ROC curve was 0.927. The level of d-dimer, P-selectin, and platelet count might be good candidate predictive markers for PVT in patients with cirrhotic PHT after devascularization. The combined test of the 3 markers can increase the value of prediction. © The Author(s) 2015.

Label-free bimodal waveguide immunosensor for rapid diagnosis of bacterial infections in cirrhotic patients.

PubMed

Maldonado, Jesús; González-Guerrero, Ana Belén; Domínguez, Carlos; Lechuga, Laura M

2016-11-15

Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid; it has a high incidence in cirrhotic patients and it is associated with high mortality. In such a situation, early diagnosis and treatment is crucial for the survival of the patient. However, bacterial analysis in ascitic fluid is currently based on culture methods, which are time-consuming and laborious. We report here the application of a photonic interferometer biosensor based on a bimodal waveguide (BiMW) for the rapid and label-free detection of bacteria directly in ascitic fluid. The device consists of a straight waveguide in which two modes of the same polarization interfere while interacting with the external medium through their evanescent fields. A bimolecular event occurring on the sensor area of the device (e.g. capturing bacteria) will differently affect each light mode, inducing a variation in the phase of the light exiting at the output of the waveguide. In this work, we demonstrate the quantitative detection of Bacillus cereus in buffer medium and Escherichia coli in undiluted ascitic fluid from cirrhotic patients. In the case of Bacillus cereus detection, the device was able to specifically detect bacteria at relevant concentrations in 12.5min and in the case of Escherichia coli detection, the analysis time was 25min. Extrapolation of the data demonstrated that the detection limits of the biosensor could reach few bacteria per milliliter. Based on the results obtained, we consider that the BiMW biosensor is positioned as a promising new clinical tool for user-friendly, cost-effective and real-time microbiological analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding.

PubMed

Sempere, L; Palazón, J M; Sánchez-Payá, J; Pascual, S; de Madaria, E; Poveda, M J; Carnicer, F; Zapater, P; Pérez-Mateo, M

2009-04-01

to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age >= 65 years, presence of HCC, CTP score >=10, and MELD score >= 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding.

Clinical study on the therapeutic role of midodrine in non azotemic cirrhotic patients with tense ascites: a double-blind, placebo-controlled, randomized trial.

PubMed

Ali, Ahmed; Farid, Samar; Amin, Mona; Kassem, Mohamed; Al-Garem, Nouman

2014-10-01

Midodrine is an α-agonist prodrug of desglymidodrine used for the management of hypotension. Midodrine has demonstrated usefulness in hepatorenal syndrome. The objective of the present work was to study the role of midodrine in patients with non-azotemic cirrhosis with tense ascites. This prospective randomized double blind placebo-controlled study was conducted on 67 non azotemic inpatients with liver cirrhosis and tense ascites (52 men and 15 women; age range, 45-72). One patient declined to participate in the study, 33 patients were randomly assigned to take midodrine hydrochloride, and 33 patients were randomly assigned to take placebo. Out of 67 enrolled patients, 60 patients (30: in midodrine group; 30: in placebo group) completed the study and 6 patients lost to follow up. Patients were assessed for patients’ characteristics, history of tapping their ascetic fluid, laboratory values, and Doppler parameters before and after the study. Average 24-h urine volume was assessed before and after the start of the study. significant reduction in body weight and abdominal girth was observed after 2 weeks of midodrine therapy. Midodrine appeared to be effective in lowering body weights and abdominal girths of non azotemic cirrhotic patients with tense ascites.

Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis.

PubMed

Mohamad, Bashar; Shah, Vaishal; Onyshchenko, Mykola; Elshamy, Mohammed; Aucejo, Federico; Lopez, Rocio; Hanouneh, Ibrahim A; Alhaddad, Razan; Alkhouri, Naim

2016-07-01

The incidence of hepatocellular carcinoma (HCC) has increased significantly in United States over the last few decades in parallel with the epidemic of nonalcoholic fatty liver disease (NAFLD). Limited data suggests that HCC could arise in steatotic liver without the presence of cirrhosis. The present study was conducted to characterize patients with NAFLD presenting with HCC in non-cirrhotic liver (NCL) compared to the NAFLD- HCC patients in association with cirrhotic liver (CL). A retrospective analysis of all patients diagnosed with HCC and NAFLD diagnosis seen at our institution between 2003 and 2012 was done. The patients were characterized based on demographic and clinical variables as well as histological and tumor features. Comparisons between the NCL and CL groups were done using analysis of variance (ANOVA) or the non-parametric Kruskal-Wallis tests and Pearson's chi-square tests or Fisher's Exact tests as appropriate. P value of <0.05 was considered statistically significant. Thirty-six patients with NAFLD and HCC in NCL (HCC-NCL group) were identified and compared to 47 patients with NAFLD-HCC and Liver Cirrhosis (HCC-LC group). Liver fibrosis was not present in 55.9 % of patients in the HCC-NCL group (F0), stage 1 was present in 17.6 %, stage 2 in 8.8 % and stage 3 in 17.6 %. Lobular inflammation was present in 63.6 % of non-cirrhotic patients. Patients in the HCC-NCL were older (67.5 ± 12.3 vs. 62.7 ± 8.1 years), and less likely to be obese (52 % vs. 83 %) or have type 2 diabetes (38 % vs. 83 %), with p value <0.05 for all. More importantly, compared with the HCC-CL group, those in the HCC-NCL group were more likely to present with a single nodule (80.6 % vs. 52.2 %), larger nodule size (>5 cm) (77.8 % vs. 10.6 %), and receive hepatic resection as the modality of HCC treatment (66.7 % vs. 17 %); and were less likely to receive loco-regional therapy (22.3 % vs. 61.7 %) or orthotopic liver transplantation (OLT) (0 % vs. 72.3 %), with p value <0.001 for all. Furthermore, 86 % of patients without cirrhosis had HCC recurrence compared to only 14 % in patients with cirrhosis (p < 0.001). Unadjusted analysis indicates that non-cirrhotics had worse survival with mortality rate of 47 % vs. 28 % in CL group (p = 0.03); however this difference in survival between two groups was not significant after adjusting for age or OLT (p > 0.05). Patients with HCC in the absence of liver cirrhosis are more likely to present at an older age with larger tumor and have higher rates of tumor recurrence. Studies to assess the cost-effectiveness of HCC surveillance in this group should be conducted.

Successful surgical management of ruptured umbilical hernias in cirrhotic patients

PubMed Central

Chatzizacharias, Nikolaos A; Bradley, J Andrew; Harper, Simon; Butler, Andrew; Jah, Asif; Huguet, Emmanuel; Praseedom, Raaj K; Allison, Michael; Gibbs, Paul

2015-01-01

Acute umbilical hernia rupture in patients with hepatic cirrhosis and ascites is an unusual, but potentially life-threatening complication, with postoperative morbidity about 70% and mortality between 60%-80% after supportive care and 6%-20% after urgent surgical repair. Management options include primary surgical repair with or without concomitant portal venous system decompression for the control of the ascites. We present a retrospective analysis of our centre’s experience over the last 6 years. Our cohort consisted of 11 consecutive patients (median age: 53 years, range: 36-63 years) with advanced hepatic cirrhosis and refractory ascites. Appropriate patient resuscitation and optimisation with intravenous fluids, prophylactic antibiotics and local measures was instituted. One failed attempt for conservative management was followed by a successful primary repair. In all cases, with one exception, a primary repair with non-absorbable Nylon, interrupted sutures, without mesh, was performed. The perioperative complication rate was 25% and the recurrence rate 8.3%. No mortality was recorded. Median length of hospital stay was 14 d (range: 4-31 d). Based on our experience, the management of ruptured umbilical hernias in patients with advanced hepatic cirrhosis and refractory ascites is feasible without the use of transjugular intrahepatic portosystemic shunt routinely in the preoperative period, provided that meticulous patient optimisation is performed. PMID:25780312

Inverse relationship between cirrhosis and massive tumours in hepatocellular carcinoma.

PubMed

Sarpel, Umut; Ayo, Diego; Lobach, Iryna; Xu, Ruliang; Newman, Elliot

2012-11-01

A subset of patients with hepatocellular carcinoma (HCC) present with massive tumours. It is unknown why certain patients develop these massive tumours, and whether this presentation is specific to the underlying viral aetiology or patient demographics such as gender, race and age. All patients with HCC at Bellevue Hospital Center, New York from 1998 to 2012 were identified and relevant demographic and clinical information was collected. Computed tomography/magnetic resonance imaging (CT/MRI) images were reviewed and the maximal tumour diameter on axial sections was recorded. Cirrhosis was defined histologically or by radiographical criteria. The two cohorts of massive and non-massive HCC were compared. A total of 361 patients with HCC were identified, of which 58 were categorized as having a massive HCC using a 13 cm size cut-off. Univariate and multivariate analysis demonstrated a significant association of massive HCC with age <40 years; hepatitis B or Asian ethnicity; and a lack of cirrhosis or platelet count >100. Massive HCC represents a tumour subtype that is associated with young, chronic hepatitis B carriers with non-cirrhotic livers. The clinical implications of this finding are that patients with massive HCC are typically excellent resection candidates barring the presence of gross vascular invasion or distant metastases. © 2012 International Hepato-Pancreato-Biliary Association.

Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule

PubMed Central

Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A.; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

2016-01-01

Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity. PMID:27782157

Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule.

PubMed

Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

2016-10-26

Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity.

Prospective evaluation of the impact of covert hepatic encephalopathy on quality of life and sleep in cirrhotic patients.

PubMed

Labenz, C; Baron, J S; Toenges, G; Schattenberg, J M; Nagel, M; Sprinzl, M F; Nguyen-Tat, M; Zimmermann, T; Huber, Y; Marquardt, J U; Galle, P R; Wörns, M-A

2018-06-04

Minimal hepatic encephalopathy (HE) and HE grade 1 (HE1) according to the West Haven criteria have recently been grouped as one entity named-covert HE- (CHE). Data regarding the impact of CHE on health-related quality of life (HRQoL) and sleep quality are controversial. First, to determine whether CHE affects HRQoL and sleep quality of cirrhotic patients and second, whether minimal HE (MHE) and HE1 affect HRQoL and sleep quality to a comparable extent. A total of 145 consecutive cirrhotic patients were enrolled. HE1 was diagnosed clinically according to the West Haven criteria. Critical flicker frequency and the Psychometric Hepatic Encephalopathy Score were used to detect MHE. Chronic Liver Disease Questionnaire (CLDQ) was used to assess HRQoL and Pittsburgh Sleep Quality Index (PSQI) was applied to assess sleep quality. Covert HE was detected in 59 (40.7%) patients (MHE: n = 40; HE1: n = 19). Multivariate analysis identified CHE (P < 0.001) and female gender (P = 0.006) as independent predictors of reduced HRQoL (CLDQ total score). CHE (P = 0.021), low haemoglobin (P = 0.024) and female gender (P = 0.003) were identified as independent predictors of poor sleep quality (PSQI total score). Results of CLDQ and PSQI were comparable in patients with HE1 and MHE (CLDQ: 4.6 ± 0.9 vs 4.5 ± 1.2, P = 0.907; PSQI: 11.3 ± 3.8 vs 9.9 ± 5.0, P = 0.3). Covert HE was associated with impaired HRQoL and sleep quality. MHE and HE1 affected both outcomes to a comparable extent supporting the use of CHE as a clinically useful term for patients with both entities of HE in clinical practice. © 2018 John Wiley & Sons Ltd.

Discrimination between neoplastic and non-neoplastic lesions in cirrhotic liver using contrast-enhanced ultrasound

PubMed Central

Xu, H-X; Lu, M-D; Liu, L-N; Zhang, Y-F; Guo, L-H; Xu, J-M; Liu, C

2012-01-01

Objectives To assess the value of contrast-enhanced ultrasound (CEUS) in differentiating hepatocellular carcinoma (HCC) from non-neoplastic lesion in cirrhotic liver in comparison with baseline ultrasound. Methods A total of 147 nodules (diameter ≤5.0 cm) in 133 cirrhotic patients (mean age±standard deviation: 52±13 years, range 20–82 years; gender: 111 males and 22 females) were examined with CEUS. There were 116 HCCs, 26 macroregenerative nodules and 5 high-grade dysplastic nodules. CEUS was performed with a real-time contrast-specific mode and a sulphur hexafluoride-filled microbubble contrast agent. Results Hypervascularity was observed in 94.8% (110/116) HCCs, 3.8% (1/26) macroregenerative nodules and 60.0% (3/5) high-grade dysplastic nodules during arterial phase on CEUS. Detection rates of typical vascular pattern (i.e. hypervascularity during arterial phase and subsequent washout) in HCCs with a diameter of ≤2.0 cm, 2.1–3.0 cm and 3.1–5.0 cm were 69.2% (27/39), 97.1% (33/34) and 100.0% (43/43), respectively. CEUS significantly improved the sensitivity [88.8% (103/116) vs 37.1% (43/116), p<0.001], negative predictive value [70.5% (31/44) vs 31.5% (29/92), p<0.001], and accuracy [91.2% (134/147) vs 49.0% (72/147), p<0.001] in differentiating HCCs from non-neoplastic lesions when compared with baseline ultrasound. However, the sensitivity and accuracy of CEUS for HCCs ≤2.0 cm in diameter were significantly lower than those for HCCs of 2.1–3.0 cm and 3.1–5.0 cm in diameter. Conclusions CEUS improves diagnostic performance in differentiating HCCs from non-neoplastic nodules in cirrhotic patients compared with baseline ultrasound. Diagnosis of HCCs ≤2.0 cm diameter by CEUS is still a clinical concern, and thus needs further investigation. PMID:22553290

Facing the enigma of the vascular network in hepatocellular carcinomas in cirrhotic and non-cirrhotic livers.

PubMed

Vasuri, Francesco; Fittipaldi, Silvia; Giunchi, Francesca; Monica, Melissa; Ravaioli, Matteo; Degiovanni, Alessio; Bonora, Sonia; Golfieri, Rita; Bolondi, Luigi; Grigioni, Walter F; Pasquinelli, Gianandrea; D'Errico-Grigioni, Antonia

2016-02-01

In this paper we aimed to analyse the typology and the phenotype of the different vascular modifications in human hepatocellular carcinomas (HCCs) with a new immunomorphological and gene expression approach. We also attempted to correlate these modifications with the histological parameters of tumour aggressiveness and the surrounding liver parenchyma. Ninety-six HCCs (from 80 patients) were retrospectively enrolled, 46 occurring in non-cirrhotic livers, and 50 in livers transplanted for cirrhosis. Histopathological analysis, immunohistochemistry for CD34, Nestin and WT1 and RT-PCR for Nestin, transforming growth factor-β1 (TGFβ1) and insulin-like growth factor 1 (IGF1R) mRNA were performed in all nodules. By correlating the CD34 and Nestin immunoreactivity in HCC vasculature with the tumorous architecture, we identified four vascular patterns (named from 'a' to 'd'). Each of them was characterised by different expressions of TGFβ1 and IGF1R mRNA. Pattern a showed CD34-positive/Nestin-negative sinusoids, and was prevalent in microtrabecular lesions. Pattern b showed similar morphology and architecture as pattern a, but with Nestin-positive sinusoids and a significant 'boost' in IGF1R and TGFβ1 mRNAs. In patterns c and d a progressive sinusoid loss and a gain of newly formed arterioles were seen. Notably, HCCs with pattern a arose more frequently in cirrhosis (p=0.024), and showed lower incidence of microvascular invasion (p=0.002) and infiltration (p=0.005) compared with HCCs with other patterns. Although future studies are surely required, the identification of different vascular profiles in HCCs from cirrhotic and non-cirrhotic livers may help clarify the relationship between HCC progression and aggressiveness. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis.

PubMed

Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, Hochong; Heuman, Douglas M; Bajaj, Jasmohan S

2013-09-01

Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality of life (HRQOL) and cognition in cirrhosis. We aimed at studying the effect of hyponatremia on cognition, HRQOL, and brain MR spectroscopy (MRS) independent of HE. Four cirrhotic groups (no HE/HN, HE alone, HN alone (sodium <130 mEq/L), HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psychosocial and physical sub-scores) and brain MRS (myoinositol (mI) and glutamate+glutamine (Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN, and 10 HN, MELD 12, 63% hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN: 3, HN: 3.5, HE: 6.5, HE+HN: 7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP (p<0.0001, all comparisons). Brain MRS showed the lowest Glx in HN and the highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE, HE+HN, and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psychosocial SIP scores. Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Decreased vasopressin-mediated renal water reabsorption in rats with compensated liver cirrhosis.

PubMed

Jonassen, T E; Nielsen, S; Christensen, S; Petersen, J S

1998-08-01

Experiments were performed to investigate vasopressin type 2 receptor (V2)-mediated renal water reabsorption and the renal expression of the vasopressin-regulated water channel aquaporin-2 (AQP-2) in cirrhotic rats with sodium retention but without ascites. In addition, the expression of the furosemide-sensitive type 1 Na-K-2Cl cotransporter (BSC-1) and the natriuretic response to an intravenous test dose furosemide (7.5 mg/kg) during acute V2-receptor blockade was measured. Acute V2-receptor blockade with the selective nonpeptide antagonist OPC-31260 (800 microg . kg-1 . h-1) was performed during conditions in which volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 150 mM glucose. OPC-31260 produced a significantly smaller increase in urine flow rate (-26%) and free water clearance (-18%) in cirrhotic rats than in control rats. The natriuretic response to an intravenous test dose furosemide (7.5 mg/kg) was significantly increased in cirrhotic rats (+52%), but pretreatment with OPC-31260 did not affect the natriuretic response to furosemide in neither cirrhotic nor in control rats. Semiquantitative immunoblotting showed a significant downregulation of AQP-2 in the renal cortex (-72%) and in the outer medulla (-44%). The relative expression of BSC-1 in the outer medulla was unchanged in cirrhotic rats. The corticopapillary gradient of Na was significantly increased in cirrhotic rats. Since daily urine flow rate was similar in cirrhotic and sham-operated rats, we suggest that non-vasopressin-mediated water reabsorption is increased in cirrhotic rats probably as a result of an increased corticomedullary gradient due to exaggerated NaCl reabsorption in the thick ascending limb of Henle's loop.

[The influence of hepatoprotector 2-ethylthiobenzimidazole hydrobromide (bemithyl) on the content of glycogen in cirrhotic rat liver hepatocytes located in various microenvironments].

PubMed

Kudriavtseva, M V; Bezborodkina, N N; Okovityĭ, S V; Kudriavtsev, B N

2004-01-01

Using absorption and fluorescent cytophotometry methods, glycogen contents were studied in hepatocytes located in liver lobules and in hepatocytes, which make the general population of these cells in normal and cirrhotic rat liver. In cirrhosis, the content of glycogen in hepatocytes located in lobules obviously rises in comparison with the norm, but to a lesser degree, than in hepatocytes making the general population of these cells in cirrhotic liver. The content of glycogen in hepatocytes, located in lobules of pathologically changed liver in bemithyl treated rats, did not differ from the norm. At the same time, the glycogen content in hepatocytes, representing the general population of these cells in cirrhotically altered bemithyl injected rat liver, remained higher than in the norm. The data obtained indicate that distinctions in particular cell microinvironment, obviously present in cirrhotic liver, render essential influence on hepatocyte functional activity.

[Effect of bemythyl on carbohydrate metabolism in cirrhotic rat liver].

PubMed

Kudriavtseva, M V; Bezborodkina, N N; Okovityĭ, S V; Nilova, V K; Ivanikova, N V; Kudriavtsev, B N

2002-01-01

Effect of actoprotector bemitil (2-ethylthiobenzimidazole hydrobromide) on glycogen content and activities of glycogen synthase, glycogen phosphorylase, and glucose-6-phosphatase was studied in cirrhotically altered rat liver. The contents of glycogen and its fraction were determined a cytofluorimetrically (Kudryavtseva et al., 1974). In cirrhosis, the total glycogen content in hepatocytes increases by nearly 3 times, while the amount of a stable fraction of glycogen rises by 7.5 times. Glucose-6-phosphatase activity fell to the level of 25% compare to the norm. Activities of glycogen synthase and glycogen phosphorylase in the cirrhotic liver did not differ from the norm. In cirrhotically altered liver, bemitil produced a decrease in the total glycogen content due to a decrease in glycogen synthase activity in an increase in glucose-6-phosphatase and glycogen phosphorylase activities. The above results suggest a favorable effect of bemitil on cirrhotic liver.

Streptococcus sanguinis meningitis following endoscopic ligation for oesophageal variceal haemorrhage.

PubMed

Liu, Yu-Ting; Lin, Chin-Fu; Lee, Ya-Ling

2013-05-01

We report a case of acute purulent meningitis caused by Streptococcus sanguinis after endoscopic ligation for oesophageal variceal haemorrhage in a cirrhotic patient without preceding symptoms of meningitis. Initial treatment with flomoxef failed. The patient was cured after 20 days of intravenous penicillin G. This uncommon infection due to S. sanguinis adds to the long list of infectious complications among patients with oesophageal variceal haemorrhage.

Role of N-acetylcysteine on fibrosis and oxidative stress in cirrhotic rats.

PubMed

Pereira-Filho, Gustavo; Ferreira, Clarissa; Schwengber, Alex; Marroni, Cláudio; Zettler, Cláudio; Marroni, Norma

2008-01-01

Hepatic cirrhosis is the final stage of liver dysfunction, characterized by diffuse fibrosis which is the main response to the liver injury. The inhalatory carbon tetrachloride is an effective experimental model that triggers cirrhosis and allows to obtain histological and physiological modifications similar to the one seen in humans. To investigate the effects of N-acetylcysteine (NAC) on the fibrosis and oxidative stress in the liver of cirrhotic rats, analyzing liver function tests, lipoperoxidation, activity of glutathione peroxidase enzyme, collagen quantification, histopathology, as well as the nitric oxide role. The animals were randomly in three experimental groups: control (CO); cirrhotic (CCl4) and CCl4 + NAC. Evaluate the lipid peroxidation, the glutathione peroxidase enzyme, the collagen and the expression of inducible nitric oxide synthase (iNOS). The cirrhotic group treated with N-acetylcysteine showed trough the histological analysis and collagen quantification lower degrees of fibrosis. This group has also shown less damage to the cellular membranes, less decrease on the glutathione peroxidase levels and less expression of inducible nitric oxide synthase when matched with the cirrhotic group without treatment. N-acetylcysteine seams to offer protection against hepatic fibrosis and oxidative stress in cirrhotic rat livers.

Big spleens and hypersplenism: fix it or forget it?

PubMed

Boyer, Thomas D; Habib, Shahid

2015-05-01

Hypersplenism is a common manifestation of portal hypertension in the cirrhotic. More than half of cirrhotics will have low platelet counts, but neutropenia is much less common. Despite being common in the cirrhotic population, the presence of hypersplenism is of little clinical consequence. The presence of hypersplenism suggests more advanced liver disease and an increase in risk of complications, but there is no data showing that correcting the hypersplenism improves patient survival. In most series, the most common indications for treating the hypersplenism is to increase platelet and white blood cell counts to allow for use of drugs that suppress the bone marrow such as interferon alpha and chemotherapeutic agents. There are several approaches used to treat hypersplenism. Portosystemic shunts are of questionable benefit. Splenectomy, either open or laparoscopically, is the most effective but is associated with a significant risk of portal vein thrombosis. Partial splenic artery embolization and radiofrequency ablation are effective methods for treating hypersplenism, but counts tend to fall back to baseline long-term. Pharmacological agents are also effective in increasing platelet counts. Development of direct acting antivirals against hepatitis C will eliminate the most common indication for treatment. We lack controlled trials designed to determine if treating the hypersplenism has benefits other than raising the platelet and white blood cell counts. In the absence of such studies, hypersplenism in most patients should be considered a laboratory abnormality and not treated, in other words forget it. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Systematic review: The model for end-stage liver disease--should it replace Child-Pugh's classification for assessing prognosis in cirrhosis?

PubMed

Cholongitas, E; Papatheodoridis, G V; Vangeli, M; Terreni, N; Patch, D; Burroughs, A K

2005-12-01

Prognosis in cirrhotic patients has had a resurgence of interest because of liver transplantation and new therapies for complications of end-stage cirrhosis. The model for end-stage liver disease score is now used for allocation in liver transplantation waiting lists, replacing Child-Turcotte-Pugh score. However, there is debate as whether it is better in other settings of cirrhosis. To review studies comparing the accuracy of model for end-stage liver disease score vs. Child-Turcotte-Pugh score in non-transplant settings. Transjugular intrahepatic portosystemic shunt studies (with 1360 cirrhotics) only one of five, showed model for end-stage liver disease to be superior to Child-Turcotte-Pugh to predict 3-month mortality, but not for 12-month mortality. Prognosis of cirrhosis studies (with 2569 patients) none of four showed significant differences between the two scores for either short- or long-term prognosis whereas no differences for variceal bleeding studies (with 411 cirrhotics). Modified Child-Turcotte-Pugh score, by adding creatinine, performed similarly to model for end-stage liver disease score. Hepatic encephalopathy and hyponatraemia (as an index of ascites), both components of Child-Turcotte-Pugh score, add to the prognostic performance of model for end-stage liver disease score. Based on current literature, model for end-stage liver disease score does not perform better than Child-Turcotte-Pugh score in non-transplant settings. Modified Child-Turcotte-Pugh and model for end-stage liver disease scores need further evaluation.

Rates of cirrhosis and hepatocellular carcinoma in chronic hepatitis B and the role of surveillance: a 10-year follow-up of 673 patients

PubMed Central

Poh, Zhongxian; Goh, Boon-Bee George; Chang, Pik-Eu Jason

2015-01-01

Background and objectives Development of cirrhosis and hepatocellular carcinoma (HCC) are critical milestones in the natural history of chronic hepatitis B virus (HBV) infection. There are no prospective data on the risk of these critical milestones in HBV patients in Singapore. The efficacy and justification of HCC surveillance is determined by the rate of HCC development. Our study aims to determine the rates of cirrhosis and HCC in HBV patients in Singapore and hence the appropriateness of HCC surveillance. Materials and methods A total of 673 HBV patients were enrolled between March 2003 and March 2004 and followed up for 10 years with regular surveillance for HCC using α-fetoprotein and abdominal ultrasound. Results Overall, 62.6% of the patients were men, mean age 56.4 years. In all, 31% were hepatitis B e antigen-positive and 14.9% had cirrhosis at baseline. Seventy-four patients developed cirrhosis and 42 patients developed HCC after 10 years. The overall 10-year incidence of cirrhosis and HCC was 16.2% (1.6%/year) and 7.8% (0.8%/year), respectively. The overall incidence of HCC in cirrhotics was 29.7% (3.0%/year), highest within a year of diagnosis of cirrhosis (7.9%). The rate of cirrhosis was significantly higher in those aged more than 55 years (P=0.001). Sex and hepatitis B e antigen status did not affect the rate of cirrhosis. Factors with significantly higher overall rates of HCC were age 55 years or more (P=0.001), male sex (P=0.001), and baseline α-fetoprotein of 4.1 µg/l or more (P<0.0001). However, age more than 55 years was not significant in the development of HCC in cirrhotics. Conclusion The rate of cirrhosis in HBV patients in Singapore is about 1.6% per year. The rate of HCC is about 0.8% per year overall and 3.0% per year in cirrhotics, which justifies HCC surveillance. PMID:25831135

Gut Microbiome-based Therapeutics in Liver Cirrhosis: Basic Consideration for the Next Step.

PubMed

Fukui, Hiroshi

2017-09-28

Infections account for significant morbidity and mortality in liver cirrhosis and most are related to the gut microbiome. Fecal dysbiosis, characterized by an overgrowth of potentially pathogenic bacteria and a decrease in autochthonous non-pathogenic bacteria, becomes prominent with the progression of liver cirrhosis. In cirrhotic patients, disruption of the intestinal barrier causes intestinal hyperpermeability (i.e. leaky gut), which is closely related to gut dysmotility, dysbiosis and small intestinal bacterial overgrowth and may induce pathological bacterial translocation. Although the involved microbial taxa are somewhat different between the cirrhotic patients from the East and the West, the common manifestation of a shortage of bacteria that contribute to the production of short-chain fatty acids and secondary bile acids may facilitate intestinal inflammation, leaky gut and gut dysbiosis. Translocated endotoxin and bacterial DNA are capable of provoking potent inflammation and affecting the metabolic and hemodynamic systems, which may ultimately enhance the progression of liver cirrhosis and its various complications, such as hepatic encephalopathy (HE), variceal bleeding, infection and renal disturbances. Among studies on the microbiome-based therapeutics, findings of probiotic effects on HE have been contradictory in spite of several supportive results. However, the effects of synbiotics and prebiotics are substantially documented. The background of their effectiveness should be evaluated again in relation to the cirrhosis-related changes in gut microbiome and their metabolic effects. Strict indications for the antibiotic rifaximin remain unestablished, although its effect is promising, improving HE and other complications with little influence on microbial populations. The final goal of microbiome-based therapeutics is to adjust the gut-liver axis to the maximal benefit of cirrhotic patients, with the aid of evolving metagenomic and metabolomic analyses.

Gut Microbiome-based Therapeutics in Liver Cirrhosis: Basic Consideration for the Next Step

PubMed Central

Fukui, Hiroshi

2017-01-01

Abstract Infections account for significant morbidity and mortality in liver cirrhosis and most are related to the gut microbiome. Fecal dysbiosis, characterized by an overgrowth of potentially pathogenic bacteria and a decrease in autochthonous non-pathogenic bacteria, becomes prominent with the progression of liver cirrhosis. In cirrhotic patients, disruption of the intestinal barrier causes intestinal hyperpermeability (i.e. leaky gut), which is closely related to gut dysmotility, dysbiosis and small intestinal bacterial overgrowth and may induce pathological bacterial translocation. Although the involved microbial taxa are somewhat different between the cirrhotic patients from the East and the West, the common manifestation of a shortage of bacteria that contribute to the production of short-chain fatty acids and secondary bile acids may facilitate intestinal inflammation, leaky gut and gut dysbiosis. Translocated endotoxin and bacterial DNA are capable of provoking potent inflammation and affecting the metabolic and hemodynamic systems, which may ultimately enhance the progression of liver cirrhosis and its various complications, such as hepatic encephalopathy (HE), variceal bleeding, infection and renal disturbances. Among studies on the microbiome-based therapeutics, findings of probiotic effects on HE have been contradictory in spite of several supportive results. However, the effects of synbiotics and prebiotics are substantially documented. The background of their effectiveness should be evaluated again in relation to the cirrhosis-related changes in gut microbiome and their metabolic effects. Strict indications for the antibiotic rifaximin remain unestablished, although its effect is promising, improving HE and other complications with little influence on microbial populations. The final goal of microbiome-based therapeutics is to adjust the gut-liver axis to the maximal benefit of cirrhotic patients, with the aid of evolving metagenomic and metabolomic analyses. PMID:28936406

Baveno VI Recommendation on Avoidance of Screening Endoscopy in Cirrhotic Patients: Are We There Yet?

PubMed Central

Silva, Mário Jorge; Bernardes, Carlos; Pinto, João; Loureiro, Rafaela; Duarte, Pedro; Mendes, Milena; Calinas, Filipe

2017-01-01

Introduction Recent studies assessed the predictive value of liver transient elastography, combined or not with platelet count, for the presence of esophageal varices in patients with liver cirrhosis, and multiple cutoffs have been proposed. The Baveno VI consensus states that patients with compensated advanced chronic liver disease, liver stiffness <20 kPa, and a platelet count >150,000 have a very low risk of having varices requiring treatment and can avoid screening endoscopy. We aimed to validate this recommendation in a cohort of cirrhotic patients. Methods Retrospective analysis of all patients evaluated at the Gastroenterology Department (Centro Hospitalar de Lisboa Central) between September 2009 and October 2015 with a liver stiffness (FibroScan®) compatible with liver cirrhosis as well as upper endoscopy and blood tests within 12 months from elastography. Patients on propranolol ≥80 mg/day or carvedilol ≥12.5 mg/day, as well as those with previous variceal bleeding, variceal endoscopic treatments, or cirrhosis decompensations were excluded. We validated the new Baveno VI recommendation and explored alternative cutoffs. Results Ninety-seven patients were analyzed, 76.3% (74/97) male, mean age 54.3 ± 11.2 years. Most patients (55.7%) had no varices and 14.4% had varices requiring treatment. Most patients (78.4%) had cirrhosis related to chronic hepatitis C. If the new Baveno VI recommendation had been applied to this cohort, upper endoscopy would have been avoided in 11.3% (11/97) of patients, none of them with esophageal varices requiring treatment: specificity 100%, sensitivity 13.3%, positive predictive value 100%, and negative predictive value 16.3% for absence of varices requiring treatment. If screening endoscopy had been avoided in those patients with liver stiffness <30 kPa and platelet count ≥120,000, endoscopy would have been avoided in 27.8% (27/97) of patients, none of whom with esophageal varices requiring treatment: specificity 100%, sensitivity 32.5%, positive predictive value 100%, and negative predictive value 20% for absence of varices requiring treatment. Conclusions The new Baveno VI criteria identified compensated cirrhotic patients without varices requiring treatment in whom screening endoscopy could have been avoided safely. Further studies are needed to confirm these findings and potentially explore more ambitious but still safe cutoffs for those criteria. PMID:28848787

Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: A randomized controlled trial.

PubMed

Pollo-Flores, Priscila; Soldan, Mônica; Santos, Ubiratan Cassano; Kunz, Danielle Gobbi; Mattos, Denise Espindola; da Silva, Alexandre Cerqueira; Marchiori, Roberta Cabral; Rezende, Guilherme Ferreira da Motta

2015-11-01

Pleiotropic effects of statins decrease intrahepatic resistance and portal hypertension. We evaluated the effects of simvastatin on hepatic venous pressure gradient (HVPG) and azygos vein blood flow in cirrhotic patients. A 3-month prospective, randomized, triple-blind trial with simvastatin (40 mg/day) vs. placebo was conducted in patients with cirrhotic portal hypertension. HVPG and azygos blood flow, measured by colour Doppler endoscopic ultrasound, were assessed before and after treatment. The primary endpoint was a decrease in the HVPG of at least 20% from baseline or to ≤12 mmHg after the treatment. 34 patients were prospectively enrolled, and 24 completed the protocol. In the simvastatin group 6/11 patients (55%) presented a clinically relevant decrease in the HVPG; no decrease was observed in the placebo group (p=0.036). Patients with medium/large oesophageal varices and previous variceal bleeding had a higher response rate to simvastatin. HVPG and azygos blood flow values were not correlated. No significant adverse events occurred. Simvastatin lowers portal pressure and may even improve liver function. The haemodynamic effect appears to be more evident in patients with severe portal hypertension. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

UK guidelines on the management of variceal haemorrhage in cirrhotic patients

PubMed Central

Tripathi, Dhiraj; Stanley, Adrian J; Hayes, Peter C; Patch, David; Millson, Charles; Mehrzad, Homoyon; Austin, Andrew; Ferguson, James W; Olliff, Simon P; Hudson, Mark; Christie, John M

2015-01-01

These updated guidelines on the management of variceal haemorrhage have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines which this document supersedes were written in 2000 and have undergone extensive revision by 13 members of the Guidelines Development Group (GDG). The GDG comprises elected members of the BSG liver section, representation from British Association for the Study of the Liver (BASL) and Liver QuEST, a nursing representative and a patient representative. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. The nature of variceal haemorrhage in cirrhotic patients with its complex range of complications makes rigid guidelines inappropriate. These guidelines deal specifically with the management of varices in patients with cirrhosis under the following subheadings: (1) primary prophylaxis; (2) acute variceal haemorrhage; (3) secondary prophylaxis of variceal haemorrhage; and (4) gastric varices. They are not designed to deal with (1) the management of the underlying liver disease; (2) the management of variceal haemorrhage in children; or (3) variceal haemorrhage from other aetiological conditions. PMID:25887380

Neurosurgical procedures in patients with liver cirrhosis: A review.

PubMed

Chen, Ching-Chang; Huang, Yin-Cheng; Yeh, Chun-Nan

2015-09-28

Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review possible comorbid results in neurosurgical procedures in cirrhotic patients. In the reviewed literature, Child-Pugh and model for end-stage liver disease scores are commonly used in the assessment of surgical risks for cirrhotic patients undergoing abdominal, cardiovascular or neurosurgical procedures. The major categories of neurosurgery are traumatic brain injury (TBI), spontaneous intracranial hemorrhage (SICH), brain tumors, and spinal instrumentation procedures. TBI was reported with surgical mortality as high as 34.5% and a complication rate of 87.2%. For SICH, mortality ranged from 22.7% to 47.0%, while complications were reported to be 43.2%. Less is discussed in brain tumor patients; still the postoperative hemorrhage rate approached 26.7%. In spinal fusion instrumentation procedures, the complication rate was as high as 41.0%. Preoperative assessment and correction could possibly decrease complications such as hemorrhage, wound infection and other cirrhosis-related complications (renal, pulmonary, ascites and encephalopathy). In this study, we reviewed the neurosurgical-related literature with regard to liver cirrhosis as a prognostic factor influencing neurosurgical outcomes.

Neurosurgical procedures in patients with liver cirrhosis: A review

PubMed Central

Chen, Ching-Chang; Huang, Yin-Cheng; Yeh, Chun-Nan

2015-01-01

Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review possible comorbid results in neurosurgical procedures in cirrhotic patients. In the reviewed literature, Child-Pugh and model for end-stage liver disease scores are commonly used in the assessment of surgical risks for cirrhotic patients undergoing abdominal, cardiovascular or neurosurgical procedures. The major categories of neurosurgery are traumatic brain injury (TBI), spontaneous intracranial hemorrhage (SICH), brain tumors, and spinal instrumentation procedures. TBI was reported with surgical mortality as high as 34.5% and a complication rate of 87.2%. For SICH, mortality ranged from 22.7% to 47.0%, while complications were reported to be 43.2%. Less is discussed in brain tumor patients; still the postoperative hemorrhage rate approached 26.7%. In spinal fusion instrumentation procedures, the complication rate was as high as 41.0%. Preoperative assessment and correction could possibly decrease complications such as hemorrhage, wound infection and other cirrhosis-related complications (renal, pulmonary, ascites and encephalopathy). In this study, we reviewed the neurosurgical-related literature with regard to liver cirrhosis as a prognostic factor influencing neurosurgical outcomes. PMID:26413225

Electrolyte and Acid-Base Disturbances in End-Stage Liver Disease: A Physiopathological Approach.

PubMed

Jiménez, José Víctor; Carrillo-Pérez, Diego Luis; Rosado-Canto, Rodrigo; García-Juárez, Ignacio; Torre, Aldo; Kershenobich, David; Carrillo-Maravilla, Eduardo

2017-08-01

Electrolyte and acid-base disturbances are frequent in patients with end-stage liver disease; the underlying physiopathological mechanisms are often complex and represent a diagnostic and therapeutic challenge to the physician. Usually, these disorders do not develop in compensated cirrhotic patients, but with the onset of the classic complications of cirrhosis such as ascites, renal failure, spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte, and acid-base disturbances emerge. Hyponatremia parallels ascites formation and is a well-known trigger of hepatic encephalopathy; its management in this particular population poses a risky challenge due to the high susceptibility of cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease and resulting from its management make these patients particularly susceptible to potassium depletion even in the setting of normokalemia. Acid-base disturbances range from classical respiratory alkalosis to high anion gap metabolic acidosis, almost comprising the full acid-base spectrum. Because most electrolyte and acid-base disturbances are managed in terms of their underlying trigger factors, a systematic physiopathological approach to their diagnosis and treatment is required.

Evaluation of CD44 and CD133 as markers of liver cancer stem cells in Egyptian patients with HCV-induced chronic liver diseases versus hepatocellular carcinoma

PubMed Central

Rozeik, Mohammed Saeed; Hammam, Olfat Ali; Ali, Ali Ibrahim; Magdy, Mona; Khalil, Heba; Anas, Amgad; Abo el Hassan, Ahmed Abdelaleem; Rahim, Ali Abdel; El-Shabasy, Ahmed Ibrahim

2017-01-01

Background Cancer stem cells (CSCs) play a critical role in tumor development, progression, metastasis and recurrence. Aim To evaluate hepatic expression of CD44 and CD133 in Egyptian patients with HCV-induced chronic liver diseases and hepatocellular carcinomas (HCCs), and to assess its correlation with inflammatory activity scores, stages of fibrosis (in chronic hepatitis with or without cirrhosis) and grades of HCC. Methods This prospective case-control study was conducted on eighty subjects who attended the Tropical Diseases Department, Al-Azhar University Hospital, and in collaboration with Theodor Bilharz Research Institute (2014–2016). They were divided as follows: A) Control healthy group: Ten individuals with serologically negative HCV-Ab and HBsAg, and histopathologically normal liver, B) Seventy patients subdivided into 3 groups; Twenty subjects each, as: HCV-Ab+ non-cirrhotic, HCV-Ab+ cirrhotic and HCC. Necroinflammatory activity and fibrosis in non-neoplastic liver biopsies were scored according to the METAVIR scoring system. CD44 and CD133 immunostaining was evaluated in all groups semi-quantitatively using H score. Statistical analysis was performed by SPSS version 22, using independent-samples t-test. Results Our study showed a significant increase of mean CD44 & CD133 expression values with disease progression among the groups (p<0.05). Their expressions increased significantly with the inflammatory activity scores and stages of fibrosis, reaching the highest values in A3F4 score compared to A1F1 (p<0.05). Moreover, there was a significant increase of their expressions across HCC grades (p<0.05), however with no significant correlation with focal lesions size. Conclusion CSCs clusters exhibiting CD133+ and/or CD44+ profiles were identified in chronic hepatitis, liver cirrhosis and HCC. CD133 and CD44 expressions significantly corresponded to the increased inflammatory activity, fibrosis stages and higher tumor grades. Therefore, evaluation of CD44 and CD133 expression profiles as CSCs markers in non-neoplastic liver and HCCs can help in development of novel therapeutic agents for HCC targeting and prevention. PMID:28894525

Effects of the 2-ethylthiobenzimidazole hydrobromide (bemithyl) on carbohydrate metabolism in cirrhotic rat liver.

PubMed

Kudryavtseva, Margarita V; Bezborodkina, Natalia N; Okovity, Sergey V; Kudryavtsey, Boris N

2003-03-01

The effect of the actoprotector bemithyl (2-ethylthiobenzimidazole hydrobromide) on the content of glycogen and activities of glycogen synthase, glycogen phosphorylase, and glucose-6-phosphatase was studied in the cirrhotic rat liver. The content of glycogen and its fraction was determined by a cytofluorimetric method (Kudryavtseva et al. 1974). It has been shown that in cirrhosis the content of total glycogen in hepatocytes increases about 3 times and the content of its stable fraction increases 7.5 times. The activity of glucose-6-phosphatase fell to a level as low as 25% of normal. Activities of glycogen synthase and glycogen phosphorylase in the cirrhotic liver did not differ from normal. In the cirrhotic liver, bemithyl produced a decrease of the total glycogen content which was associated with a decrease of the glycogen synthase activity and an increase of the glucose-6-phosphatase and glycogen phosphorylase activities. Thus, the results of our studies indicate a favorable effect of bemithyl on the cirrhotic liver.

[Clinical dilemma: an unusual case of ascites].

PubMed

Romi, Hila; Hausman, Michael; Kachko, Leonid; Emanuel, Sikuler

2012-12-01

Cirrhotic portal hypertension is the major cause of ascites. Ascites is the most common expression of decompensated liver disease. However, other etiologies may occur and may pose a diagnostic and therapeutic challenge. A patient with chronic hepatitis C and an unusual cause of ascites is presented.

ALCOHOLIC VERSUS NONALCOHOLIC CIRRHOSIS IN A RANDOMIZED CONTROLLED TRIAL OF EMERGENCY THERAPY OF BLEEDING VARICES

PubMed Central

Orloff, Marshall J.; Isenberg, Jon I.; Wheeler, Henry O.; Haynes, Kevin S.; Jinich-Brook, Horacio; Rapier, Roderick; Vaida, Florin; Hye, Robert J.; Orloff, Susan L.

2010-01-01

Background It has been proposed that portal-systemic shunts be avoided in alcoholic cirrhotics because survival rate is allegedly lower in alcoholics than in nonalcoholics. We examined this issue in a randomized controlled trial. Methods 211 unselected, consecutive patients with cirrhosis and bleeding esophageal varices were randomized to endoscopic sclerotherapy (EST) (n=106) or emergency portacaval shunt (EPCS) (105). Treatment was initiated within 8 hours. EST failure was treated by rescue PCS. 10-yr follow-up was 96%. Results Results strongly favored EPCS over EST (p<0.001). Among EPCS patients, 83% were alcoholic and 17% nonalcoholic. Outcomes were (1) permanent control of bleeding 100% vs. 100%; (2) 5-yr survival 71% vs.78%; (3) encephalopathy 14% vs. 19%; (4) yearly charges $38,300 vs. $43,000. Conclusions EPCS results were similar in alcoholic and nonalcoholic cirrhotics. EPCS is an effective first line emergency treatment in all forms of cirrhosis, including alcoholic. PMID:21195430

A Mechanistic Pharmacokinetic Model for Liver Transporter Substrates Under Liver Cirrhosis Conditions

PubMed Central

Li, R; Barton, HA; Maurer, TS

2015-01-01

Liver cirrhosis is a disease characterized by the loss of functional liver mass. Physiologically based pharmacokinetic (PBPK) modeling was applied to interpret and predict how the interplay among physiological changes in cirrhosis affects pharmacokinetics. However, previous PBPK models under cirrhotic conditions were developed for permeable cytochrome P450 substrates and do not directly apply to substrates of liver transporters. This study characterizes a PBPK model for liver transporter substrates in relation to the severity of liver cirrhosis. A published PBPK model structure for liver transporter substrates under healthy conditions and the physiological changes for cirrhosis are combined to simulate pharmacokinetics of liver transporter substrates in patients with mild and moderate cirrhosis. The simulated pharmacokinetics under liver cirrhosis reasonably approximate observations. This analysis includes meta-analysis to obtain system-dependent parameters in cirrhosis patients and a top-down approach to improve understanding of the effect of cirrhosis on transporter-mediated drug disposition under cirrhotic conditions. PMID:26225262

Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats

PubMed Central

Lim, Tong-Hye; Nor-Amdan, Nur-Asyura

2017-01-01

Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08) were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA). These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM) proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x) and level of GGT (more than 2x) in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver. PMID:28280515

A Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease.

PubMed

Tovoli, Francesco; Napoli, Lucia; Negrini, Giulia; D'Addato, Sergio; Tozzi, Giulia; D'Amico, Jessica; Piscaglia, Fabio; Bolondi, Luigi

2017-05-25

Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.

Volatile Biomarkers in Breath Associated With Liver Cirrhosis — Comparisons of Pre- and Post-liver Transplant Breath Samples

PubMed Central

Fernández del Río, R.; O'Hara, M.E.; Holt, A.; Pemberton, P.; Shah, T.; Whitehouse, T.; Mayhew, C.A.

2015-01-01

Background The burden of liver disease in the UK has risen dramatically and there is a need for improved diagnostics. Aims To determine which breath volatiles are associated with the cirrhotic liver and hence diagnostically useful. Methods A two-stage biomarker discovery procedure was used. Alveolar breath samples of 31 patients with cirrhosis and 30 healthy controls were mass spectrometrically analysed and compared (stage 1). 12 of these patients had their breath analysed after liver transplant (stage 2). Five patients were followed longitudinally as in-patients in the post-transplant period. Results Seven volatiles were elevated in the breath of patients versus controls. Of these, five showed statistically significant decrease post-transplant: limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide. On an individual basis limonene has the best diagnostic capability (the area under a receiver operating characteristic curve (AUROC) is 0.91), but this is improved by combining methanol, 2-pentanone and limonene (AUROC curve 0.95). Following transplant, limonene shows wash-out characteristics. Conclusions Limonene, methanol and 2-pentanone are breath markers for a cirrhotic liver. This study raises the potential to investigate these volatiles as markers for early-stage liver disease. By monitoring the wash-out of limonene following transplant, graft liver function can be non-invasively assessed. PMID:26501124

Improved assessment of body cell mass by segmental bioimpedance analysis in malnourished subjects and acromegaly.

PubMed

Pirlich, M; Schütz, T; Ockenga, J; Biering, H; Gerl, H; Schmidt, B; Ertl, S; Plauth, M; Lochs, H

2003-04-01

Estimation of body cell mass (BCM) has been regarded valuable for the assessment of malnutrition. To investigate the value of segmental bioelectrical impedance analysis (BIA) for BCM estimation in malnourished subjects and acromegaly. Nineteen controls and 63 patients with either reduced (liver cirrhosis without and with ascites, Cushing's disease) or increased BCM (acromegaly) were included. Whole-body and segmental BIA (separately measuring arm, trunk, leg) at 50 kHz was compared with BCM measured by total-body potassium. Multiple regression analysis was used to develop specific equations for BCM in each subgroup. Compared to whole-body BIA equations, the inclusion of arm resistance improved the specific equation in cirrhotic patients without ascites and in Cushing's disease resulting in excellent prediction of BCM (R(2) = 0.93 and 0.92, respectively; both P<0.001). In acromegaly, inclusion of resistance and reactance of the trunk best described BCM (R(2) = 0.94, P<0.001). In controls and in cirrhotic patients with ascites, segmental impedance parameters did not improve BCM prediction (best values obtained by whole-body measurements: R(2)=0.88 and 0.60; P<0.001 and <0.003, respectively). Segmental BIA improves the assessment of BCM in malnourished patients and acromegaly, but not in patients with severe fluid overload. Copyright 2003 Elsevier Science Ltd.

Gallstones in patients with liver cirrhosis: Incidence, etiology, clinical and therapeutical aspects

PubMed Central

Acalovschi, Monica

2014-01-01

Gallstones occur in about one third of the patients having liver cirrhosis. Pigment gallstones are the most frequent type, while cholesterol stones represent about 15% of all stones in cirrhotics. Increased secretion of unconjugated bilirubin, increased hydrolysis of conjugated bilirubin in the bile, reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics. Gallbladder hypomotility also contributes to lithogenesis. The most recent data regarding risk factors for gallstones are presented. Gallstone prevalence increases with age, with a ratio male/female higher than in the general population. Chronic alcoholism, viral C cirrhosis, and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones. Gallstones are often asymptomatic, and discovered incidentally. If asymptomatic, expectant management is recommended, as for asymptomatic gallstones in the general population. However, a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications. For symptomatic stones, laparoscopic cholecystectomy has become the therapy of choice. Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy. Patients with severe liver disease are at highest surgical risk, therefore gallstone complications should be treated using noninvasive or minimally invasive procedures, until stabilization of the patient condition. PMID:24966598

Thromboelastometry versus standard coagulation tests versus restrictive protocol to guide blood transfusion prior to central venous catheterization in cirrhosis: study protocol for a randomized controlled trial.

PubMed

Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Neto, Ary Serpa; do Prado, Rogerio Ruscitto; Silva, Eliezer; de Almeida, Marcio Dias; Correa, Thiago Domingos

2017-02-27

Liver failure patients have traditionally been empirically transfused prior to invasive procedures. Blood transfusion is associated with immunologic and nonimmunologic reactions, increased risk of adverse outcomes and high costs. Scientific evidence supporting empirical transfusion is lacking, and the best approach for blood transfusion prior to invasive procedures in cirrhotic patients has not been established so far. The aim of this study is to compare three transfusion strategies (routine coagulation test-guided - ordinary or restrictive, or thromboelastometry-guided) prior to central venous catheterization in critically ill patients with cirrhosis. Design and setting: a double-blinded, parallel-group, single-center, randomized controlled clinical trial in a tertiary private hospital in São Paulo, Brazil. adults (aged 18 years or older) admitted to the intensive care unit with cirrhosis and an indication for central venous line insertion. Patients will be randomly assigned to three groups for blood transfusion strategy prior to central venous catheterization: standard coagulation tests-based, thromboelastometry-based, or restrictive. The primary efficacy endpoint will be the proportion of patients transfused with any blood product prior to central venous catheterization. The primary safety endpoint will be the incidence of major bleeding. Secondary endpoints will be the proportion of transfusion of fresh frozen plasma, platelets and cryoprecipitate; infused volume of blood products; hemoglobin and hematocrit before and after the procedure; intensive care unit and hospital length of stay; 28-day and hospital mortality; incidence of minor bleeding; transfusion-related adverse reactions; and cost analysis. This study will evaluate three strategies to guide blood transfusion prior to central venous line placement in severely ill patients with cirrhosis. We hypothesized that thromboelastometry-based and/or restrictive protocols are safe and would significantly reduce transfusion of blood products in this population, leading to a reduction in costs and transfusion-related adverse reactions. In this manner, this trial will add evidence in favor of reducing empirical transfusion in severely ill patients with coagulopathy. ClinicalTrials.gov, identifier: NCT02311985 . Retrospectively registered on 3 December 2014.

Ledipasvir/sofosbuvir for treatment of hepatitis C virus in sofosbuvir-experienced, NS5A treatment-naïve patients: Findings from two randomized trials.

PubMed

Tam, Edward; Luetkemeyer, Anne F; Mantry, Parvez S; Satapathy, Sanjaya K; Ghali, Peter; Kang, Minhee; Haubrich, Richard; Shen, Xianlin; Ni, Liyun; Camus, Gregory; Copans, Amanda; Rossaro, Lorenzo; Guyer, Bill; Brown, Robert S

2018-06-01

We report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF) ± ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virological response (SVR) with prior SOF-based, non-NS5A inhibitor-containing regimens. The RESCUE study enrolled HCV mono-infected adults with genotype (GT) 1 or 4. Non-cirrhotic participants were randomized to 12 weeks of LDV/SOF or LDV/SOF + RBV. Compensated cirrhotic participants were randomized to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). The AIDS Clinical Trials Group A5348 study randomized genotype 1 adults with HCV/HIV co-infection to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). Both studies used SVR at 12 weeks post-treatment (SVR12) as the primary endpoint. In the RESCUE study, 82 participants were randomized and treated, and all completed treatment. Overall, SVR12 was 88% (72/82); 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOF + RBV for 12 weeks and 80-92% in cirrhotic participants treated with LDV/SOF + RBV for 12 weeks or LDV/SOF for 24 weeks. Adverse events (AEs), mostly mild-to-moderate in severity, were experienced by 78% of participants, with headache and fatigue most frequently reported. One serious AE, not related to treatment, was observed. No premature discontinuations of study drug, or deaths occurred. In the A5348 study, seven participants were randomized (cirrhotic n = 1; GT1a n = 5) and all attained SVR12, with no serious AEs or premature discontinuations. In this SOF-experienced, NS5A inhibitor-naïve population, which included participants with cirrhosis or HCV/HIV co-infection, high SVR12 rates were achieved. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bone Mineral Density, Bone Turnover, and Systemic Inflammation in Non-cirrhotics with Chronic Hepatitis C.

PubMed

Lai, Jennifer C; Shoback, Dolores M; Zipperstein, Jacob; Lizaola, Blanca; Tseng, Samuel; Terrault, Norah A

2015-06-01

Whether chronic HCV, a disease characterized by systemic inflammation, impacts bone mineral density (BMD) independent of cirrhosis is unknown. We aimed to evaluate the association between BMD, systemic inflammation, and markers of bone turnover in chronic HCV without cirrhosis. Non-cirrhotics, 40-60 years old, with chronic HCV underwent measurement of: (1) BMD by dual-energy X-ray absorptiometry scan and (2) serum markers of systemic inflammation and bone turnover. By Chi-squared or t test, we compared those with normal versus low BMD. Of the 60 non-cirrhotics, 53 % were female and 53 % Caucasian. Mean (SD) age was 53.3 years (5.7), total bilirubin 0.7 mg/dL (0.3), creatinine 0.8 mg/dL (0.2), and body mass index 28.4 kg/m(2) (6.5). Low BMD was observed in 42 %: 30 % had osteopenia, 12 % had osteoporosis. Elevated tumor necrosis factor α, interleukin-6, and C-reactive protein levels were found in 26, 32, and 5 %, respectively, but did not differ by BMD group (p > 0.05). Patients with low BMD had higher serum phosphorus (4.1 vs. 3.5 mg/dL) and pro-peptide of type 1 collagen (P1NP; 73.1 vs. 47.5 ng/mL) [p < 0.05], but similar bone-specific alkaline phosphatase, serum C-telopeptide, and parathyroid hormone levels. Low BMD is prevalent in 40- to 60-year-old non-cirrhotics with chronic HCV, but not associated with systemic inflammatory markers. Elevated P1NP levels may help to identify those at increased risk of bone complications in this population. Chronic HCV should be considered a risk factor for bone loss, prompting earlier BMD assessments in both men and women.

[Ascitic peritonitis due to Candida albicans].

PubMed

Suárez, A; Otero, L; Navascués, C A; Menéndez, M T; Román, F J; García, R; Saro, C; Rodríguez, A

1994-09-01

We report a case of spontaneous peritonitis due to Candida albicans, in a diabetic patient with alcoholic liver cirrhosis, ascites, gastrointestinal bleeding from esophageal varices, sepsis, renal failure and encephalopathy. These factors, added to prolonged antibiotic therapy and instrumental manipulations, could have resulted in the colonization by Candida, usually described in secondary peritonitis, but perhaps underdiagnosed in cirrhotic patients with spontaneous peritonitis and severe multiorgan failure.

Acute Abdomen Secondary to Incarcerated Umbilical Hernia after Treatment of Massive Cirrhotic Ascites

PubMed Central

Tan, Hiang Keat; Chang, Pik Eu

2013-01-01

Umbilical herniation is common in patients with liver cirrhosis and ascites. Rarely, they suffer from incarceration and strangulation of the umbilical hernia after treatment of ascites. We report 3 cases of umbilical hernia incarceration following removal of massive ascites with different treatment modalities. Physicians managing this group of patients should be aware of this rare and potentially fatal complication. PMID:25374722

Unsupervised classification of cirrhotic livers using MRI data

NASA Astrophysics Data System (ADS)

Lee, Gobert; Kanematsu, Masayuki; Kato, Hiroki; Kondo, Hiroshi; Zhou, Xiangrong; Hara, Takeshi; Fujita, Hiroshi; Hoshi, Hiroaki

2008-03-01

Cirrhosis of the liver is a chronic disease. It is characterized by the presence of widespread nodules and fibrosis in the liver which results in characteristic texture patterns. Computerized analysis of hepatic texture patterns is usually based on regions-of-interest (ROIs). However, not all ROIs are typical representatives of the disease stage of the liver from which the ROIs originated. This leads to uncertainties in the ROI labels (diseased or non-diseased). On the other hand, supervised classifiers are commonly used in determining the assignment rule. This presents a problem as the training of a supervised classifier requires the correct labels of the ROIs. The main purpose of this paper is to investigate the use of an unsupervised classifier, the k-means clustering, in classifying ROI based data. In addition, a procedure for generating a receiver operating characteristic (ROC) curve depicting the classification performance of k-means clustering is also reported. Hepatic MRI images of 44 patients (16 cirrhotic; 28 non-cirrhotic) are used in this study. The MRI data are derived from gadolinium-enhanced equilibrium phase images. For each patient, 10 ROIs selected by an experienced radiologist and 7 texture features measured on each ROI are included in the MRI data. Results of the k-means classifier are depicted using an ROC curve. The area under the curve (AUC) has a value of 0.704. This is slightly lower than but comparable to that of LDA and ANN classifiers which have values 0.781 and 0.801, respectively. Methods in constructing ROC curve in relation to k-means clustering have not been previously reported in the literature.

Fractal and Fourier analysis of the hepatic sinusoidal network in normal and cirrhotic rat liver

PubMed Central

Gaudio, Eugenio; Chaberek, Slawomir; Montella, Andrea; Pannarale, Luigi; Morini, Sergio; Novelli, Gilnardo; Borghese, Federica; Conte, Davide; Ostrowski, Kazimierz

2005-01-01

The organization of the hepatic microvascular network has been widely studied in recent years, especially with regard to cirrhosis. This research has enabled us to recognize the distinctive vascular patterns in the cirrhotic liver, compared with the normal liver, which may explain the cause of liver dysfunction and failure. The aim of this study was to compare normal and cirrhotic rat livers by means of a quantitative mathematical approach based on fractal and Fourier analyses performed on photomicrographs and therefore on discriminant analysis. Vascular corrosion casts of livers belonging to the following three experimental groups were studied by scanning electron microscopy: normal rats, CCl4-induced cirrhotic rats and cirrhotic rats after ligation of the bile duct. Photomicrographs were taken at a standard magnification; these images were used for the mathematical analysis. Our experimental design found that use of these different analyses reaches an efficiency of over 94%. Our analyses demonstrated a higher complexity of the normal hepatic sinusoidal network in comparison with the cirrhotic network. In particular, the morphological changes were more marked in the animals with bile duct-ligation cirrhosis compared with animals with CCl4-induced cirrhosis. The present findings based on fractal and Fourier analysis could increase our understanding of the pathophysiological alterations of the liver, and may have a diagnostic value in future clinical research. PMID:16050897

Expression of vasoactive proteins in gastric antral mucosa reflects vascular dysfunction in patients with cirrhosis and portal hypertension.

PubMed

Trebicka, Jonel; Wix, Cyrus; von Heydebrand, Matthias; Hittatiya, Kanishka; Reiberger, Thomas; Klein, Sabine; Schierwagen, Robert; Kristiansen, Glen; Peck-Radosavljevic, Markus; Fischer, Hans-Peter; Møller, Søren; Bendtsen, Flemming; Krag, Aleksander; Sauerbruch, Tilman

2015-04-01

Patients with cirrhosis display hypocontractility of splanchnic vessels because of dysregulation of vasoactive proteins, such as decreased effect of RhoA/ROCK and increased activity of β-Arrestin-2 and eNOS. However, it is unknown whether the dysregulation of vasoactive proteins is displayed in other vessels. We investigated whether expression of vasoactive proteins can be evaluated in gastric mucosa vessels. Biopsies from the gastric mucosa of 111 patients with cirrhosis were collected at three different centres and from 13 controls. Forty-nine patients had received TIPS. Portal pressure gradient was measured in 49 patients with TIPS and in 16 patients without TIPS. Biopsies from the antrum were conserved in formaldehyde for immunohistochemistry or shock-frozen for PCR and Western blot. The mucosal transcription of vascular markers (αSMA, CD31) was higher in cirrhotic patients than controls, which was confirmed by immunohistochemistry. On average, relative mucosal levels of RhoA and ROCK were lower, while β-Arrestin-2 levels were higher in cirrhotic patients compared to controls. Transcriptional levels of eNOS increased with presence of ascites and grade of oesophageal varices. Patients with TIPS showed less pronounced markers of vascular dysfunction in gastric mucosa. This is the first evidence that the expression of vasoactive proteins in mucosa from the gastric antrum of patients with cirrhosis reflects their vascular dysfunction and possibly changes after therapeutic interventions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between road accidents and low-grade hepatic encephalopathy among Sri Lankan drivers with cirrhosis: a prospective case control study.

PubMed

Subasinghe, S K C E; Nandamuni, Y; Ranasinghe, S; Niriella, M A; Miththinda, J K N D; Dassanayake, A; de Silva, A P; de Silva, H J

2016-06-13

Low-grade hepatic encephalopathy (LGHE) comprises minimal hepatic encephalopathy (MHE) and grade 1 hepatic encephalopathy. LGHE has no or minimal recognizable symptoms but has mild cognitive and psychomotor deficits. Studies in Western countries have demonstrated increased road accidents (RA) among patients with MHE. Our objective was to investigate the association between Sri Lankan LGHE phenotype and RA. A prospective, case-control study was conducted in the University Medical Unit, North Colombo Teaching Hospital, Ragama Sri Lanka. Patients with cirrhosis of any aetiology, without OHE, who had been driving during previous 1 month were included. A similar number of age matched, healthy control drivers were also enrolled. Both groups were subjected to five pencil-paper based psychometric tests used to detect LGHE in cirrhotics. Self-reported RA during the previous 1 month were recorded: categorized as 'major' when resulted in hospitalization of the involved, 'minor' when there were injuries, but not serious enough for hospitalization of the involved and 'other' when limited to damages to vehicle or environment without injuries. Among 55 drivers with cirrhosis and LGHE [males, median age 53 years (range 30-60)], 7 (12.7 %) reported RA compared to 6 (10.9 %) among 55 controls [males; median age 51 years (range 30-60)]. There were no 'major' accidents in either group. 2/55 (3.6 %) cases and 2/55 (3.6 %) controls reported 'minor' accidents. There was no increased frequency of RA among Sri Lankan drivers with LGHE compared to healthy controls. This is with the limitation of the study based only on self reported RA.

Spontaneous evisceration of bowel through an umbilical hernia in a patient with refractory ascites

PubMed Central

Ogu, Uchechukwu Stanley; Valko, Janice; Wilhelm, Jakub; Dy, Victor

2013-01-01

Umbilical hernia in the cirrhotic patient is frequently seen in the setting of refractory ascites. This article reports a rare case of spontaneous rupture of a recurrent umbilical hernia in a patient with persistent ascites, following an acute increase in intra-abdominal pressure, leading to bowel evisceration. This case highlights a potentially fatal complication of umbilical hernia in the setting of chronic ascites, which was successfully managed with prompt surgical intervention. PMID:24964319

Idiopathic Non-Cirrhotic Intrahepatic Portal Hypertension (NCIPH)—Newer Insights into Pathogenesis and Emerging Newer Treatment Options

PubMed Central

Goel, Ashish; Elias, Joshua E.; Eapen, Chundamannil E.; Ramakrishna, Banumathi; Elias, Elwyn

2014-01-01

Chronic microangiopathy of portal venules results in idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH). Recent data suggest a role for vasoactive factors of portal venous origin in the pathogenesis of this ‘pure’ vasculopathy of the liver. Enteropathies (often silent), are an important ‘driver’ of this disease. NCIPH is under-recognized and often mis-labeled as cryptogenic cirrhosis. Liver biopsy is needed to prove the diagnosis of NCIPH. In these patients, with advancing disease and increased porto-systemic shunting, the portal venous vasoactive factors bypass the liver filter and contribute to the development of pulmonary vascular endothelial disorders—porto-pulmonary hypertension and hepato-pulmonary syndrome as well as mesangiocapillary glomerulonephritis. Prognosis in NCIPH patients is determined by presence, recognition and management of associated disorders. With better understanding of the pathogenesis of NCIPH, newer treatment options are being explored. Imbalance in ADAMTS 13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13): vWF (von-Willebrand factor) ratio is documented in NCIPH patients and may have a pathogenic role. Therapeutic interventions to correct this imbalance may prove to be important in the management of NCIPH. PMID:25755567

Cost-Utility of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Genotype 1 Infection.

PubMed

Corman, Shelby; Elbasha, Elamin H; Michalopoulos, Steven N; Nwankwo, Chizoba

2017-09-01

To evaluate the cost-utility of treatment with elbasvir/grazoprevir (EBR/GZR) regimens compared with ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± RBV), and sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C genotype (GT) 1 infection. A Markov cohort state-transition model was constructed to evaluate the cost-utility of EBR/GZR ± RBV over a lifetime time horizon from the payer perspective. The target population was patients infected with chronic hepatitis C GT1 subtypes a or b (GT1a or GT1b), stratified by treatment history (treatment-naive [TN] or treatment-experienced), presence of cirrhosis, baseline hepatitis C virus RNA (< or ≥6 million IU/mL), and presence of NS5A resistance-associated variants. The primary outcome was incremental cost-utility ratio for EBR/GZR ± RBV versus available oral direct-acting antiviral agents. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model. EBR/GZR ± RBV was economically dominant versus LDV/SOF in all patient populations. EBR/GZR ± RBV was also less costly than SOF/VEL and 3D ± RBV, but produced fewer quality-adjusted life-years in select populations. In the remaining populations, EBR/GZR ± RBV was economically dominant. One-way sensitivity analyses showed varying sustained virologic response rates across EBR/GZR ± RBV regimens, commonly impacted model conclusions when lower bound values were inserted, and at the upper bound resulted in dominance over SOF/VEL in GT1a cirrhotic and GT1b TN noncirrhotic patients. Results of the probabilistic sensitivity analysis showed that EBR/GZR ± RBV was cost-effective in more than 99% of iterations in GT1a and GT1b noncirrhotic patients and more than 69% of iterations in GT1b cirrhotic patients. Compared with other oral direct-acting antiviral agents, EBR/GZR ± RBV was the economically dominant regimen for treating GT1a noncirrhotic and GT1b TN cirrhotic patients, and was cost saving in all other populations. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Circadian occurrence of variceal bleeding in patients with liver cirrhosis.

PubMed

Siringo, S; Bolondi, L; Sofia, S; Hermida, R C; Gramantieri, L; Gaiani, S; Piscaglia, F; Carbone, C; Misitano, B; Corinaldesi, R

1996-12-01

Several clinical events have a rhythmicity over the 24 h period. We assessed the presence of periodic rhythm in the occurrence of haematemesis in patients with liver cirrhosis under different daylight regimens, namely during standard time and during daylight savings. Over a 48 month period there were 212 consecutive admissions of 118 cirrhotics with variceal bleeding. Complete data were available for 181 episodes of bleeding: 121 (66.9%) started with haematemesis and 60 (33.1%) started with melaena. One hundred and two (56%) episodes occurred during daylight savings and 79 (44%) occurred during standard time. The cosinor test showed a 24 h biphasic peak for the occurrence of haematemesis (09.45 and 21.45 h). Moreover, a biphasic diurnal asymmetric frequency was also found by multiple component rhythmometry. The time peaks of onset of variceal haemorrhage did not change significantly during standard time and daylight savings. Patients with more than one haematemesis episode significantly bled over the same time interval. The present study confirms that over the 24 h period variceal bleeding in cirrhotic patients occurs with a predictable rhythmicity that does not seem to be under the control of the light-dark cycle. The finding of a chronorisk for variceal haemorrhage addresses specific questions for pathophysiological studies as well as for new treatment strategies.

Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross-over comparison.

PubMed

Bianchi, G P; Marchesini, G; Fabbri, A; Rondelli, A; Bugianesi, E; Zoli, M; Pisi, E

1993-05-01

In a randomized cross-over comparison, the effects of a mainly vegetable protein diet were compared with an animal protein diet in eight patients with cirrhosis and chronic permanent encephalopathy, under optimum lactulose therapy. After a run-in period, patients were fed two equi-caloric, equi-nitrogenous diets for 7 days (71 g total proteins), containing either 50 g protein of animal origin or 50 g vegetable proteins. In the last 3 days of each period, nitrogen balance was significantly better during the vegetable protein diet (+0.2 (SD 1.4) g vs. -1.7 (2.4); P < 0.01), the difference being entirely due to a reduced urinary nitrogen excretion. Average daytime integrated blood glucose was slightly higher during vegetable proteins, whereas insulin, plasma amino acids and ammonia were lower. The clinical grading of encephalopathy improved slightly on vegetable proteins, and psychometric tests improved significantly, but remained grossly abnormal. Compliance to dietary manipulation was good. The data prove that a mainly vegetable protein diet is worthwhile in cirrhotic patients with chronic encephalopathy under optimum lactulose therapy. Improved nitrogen balance may be related to more effective nitrogen use for protein synthesis, probably due to blunted hormonal response, and largely outweighs the effects on encephalopathy.

Robotic liver surgery is the optimal approach as bridge to transplantation.

PubMed

Magistri, Paolo; Tarantino, Giuseppe; Ballarin, Roberto; Coratti, Andrea; Di Benedetto, Fabrizio

2017-02-08

The role of minimally invasive liver surgery as a bridge to transplantation is very promising but still underestimated. However, it should be noted that surgical approach for hepatocellular carcinomas (HCC) is not merely a technical or technological issue. Nowadays, the epidemiology of HCC is evolving due to the increasing role of non-alcoholic fatty-liver-disease, and the emerging concerns on direct-acting antivirals against hepatitis C virus in terms of HCC incidence. Therefore, a fully multidisciplinary study of the cirrhotic patient is currently more important than ever before, and the management of those patients should be reserved to tertiary referral hepatobiliary centers. In particular, minimally invasive approach to the liver showed several advantages compared to the classical open procedure, in terms of: (1) the small impact on abdominal wall; (2) the gentle manipulation on the liver; (3) the limited surgical trauma; and (4) the respect of venous shunts. Therefore, more direct indications should be outlined also in the Barcelona Clinic Liver Cancer model. We believe that treatment of HCC in cirrhotic patients should be reserved to tertiary referral hepatobiliary centers, that should offer patient-tailored approaches to the liver disease, in order to provide the best care for each case, according to the individual comorbidities, risk factors, and personal quality of life expectations.

Mosapride Stabilizes Intestinal Microbiota to Reduce Bacterial Translocation and Endotoxemia in CCl4-Induced Cirrhotic Rats.

PubMed

Xu, Hong; Xiong, Jingfang; Xu, Jianjun; Li, Shuiming; Zhou, Yang; Chen, Dongya; Cai, Xinjun; Ping, Jian; Deng, Min; Chen, Jianyong

2017-10-01

Impaired intestinal motility may lead to the disruption of gut microbiota equilibrium, which in turn facilitates bacterial translocation (BT) and endotoxemia in cirrhosis. We evaluated the influence of mosapride, a prokinetic agent, on BT and DNA fingerprints of gut microbiota in cirrhotic rats. A rat model of cirrhosis was set up via subcutaneous injection of carbon tetrachloride (CCl 4 ). The portal pressure, liver and intestinal damage, plasma endotoxin, BT, and intestinal transit rate (ITR) of cirrhotic rats were determined. Fecal DNA fingerprints were obtained by ERIC-PCR. The expressions of tight junction proteins were evaluated by western blotting. Mosapride treatment to cirrhotic rats significantly reduced the plasma endotoxin level and incidence of BT, accompanied by increased ITR. Cirrhotic rats (including those treated with mosapride) suffered from BT exhibited significantly lower ITR than those who are free of BT. Pearson coefficient indicated a significant and negative correlation between the plasma endotoxin level and ITR. The genomic fingerprints of intestinal microbiota from the three groups fell into three distinctive clusters. In the mosapride-treated group, Shannon's index was remarkably increased compared to the model group. Significantly positive correlation was detected between Shannon's index and ITR. Mosapride did not improve hepatic and intestinal damages and ileal expressions of occludin and ZO-1. Mosapride significantly increases intestinal motility in cirrhotic rats, thus to recover the disordered intestinal microbiota, finally resulting in decreased plasma endotoxin and BT.

Pathology of idiopathic non-cirrhotic portal hypertension.

PubMed

Guido, Maria; Sarcognato, Samantha; Sacchi, Diana; Colloredo, Guido

2018-04-12

Idiopathic non-cirrhotic portal hypertension is an under-recognized vascular liver disease of unknown etiology, characterized by clinical signs of portal hypertension in the absence of cirrhosis. By definition, any disorder known to cause portal hypertension in the absence of cirrhosis and any cause of chronic liver disease must be excluded to make a diagnosis of idiopathic non-cirrhotic portal hypertension. However, the diagnosis is often difficult because the disease resembles cirrhosis and there is no gold standard test. Liver biopsy is an essential tool: it is able to exclude cirrhosis and other causes of portal hypertension and it allows the identification of the characteristic lesions. Nonetheless, the histological diagnosis of idiopathic non-cirrhotic portal hypertension is not always straightforward, in particular by needle biopsy samples, because there is no pathognomonic lesion, but rather a variety of vascular changes which are unevenly distributed, very subtle, and not all necessarily identified in a single specimen. Pathologists should be able to recognize several patterns of injury, involving portal/periportal areas as well as parenchymal structures.The histological features of idiopathic non-cirrhotic portal hypertension are described in this review, focusing on their interpretation in needle biopsy specimens.

Evaluation of liver functional reserve by combining D-sorbitol clearance rate and CT measured liver volume

PubMed Central

Li, Yi-Ming; Lv, Fan; Xu, Xin; Ji, Hong; Gao, Wen-Tao; Lei, Tuan-Jie; Ren, Gui-Bing; Bai, Zhi-Lan; Li, Qiang

2003-01-01

AIM: Our research attempted to evaluate the overall functional reserve of cirrhotic liver by combination of hepatic functional blood flow, liver volume, and Child-Pugh’s classification, and to discuss its value of clinical application. METHODS: Ninety two patients with portal hypertension due to hepatic cirrhosis were investigated. All had a history of haematemesis and hematochezia, esophageal and gastric fundus varices, splenomegaly and hypersplenia. A 2-year follow-up was routinely performed and no one was lost. Twenty two healthy volunteers were used as control group. Blood and urine samples were collected 4 times before and after intravenous D-sorbitol infusion. The hepatic clearance (CLH) of D-sorbitol was then calculated according to enzymatic spectrophotometric method while the total blood flow (QTOTAL) and intrahepatic shunt (RINS) were detected by multicolor Doppler ultrasound, and the liver volume was measured by spiral CT. Data were estimated by t-test, variance calculation and chi-squared test. The relationships between all these parameters and different groups were investigated according to Child-Pugh classification and postoperative complications respectively. RESULTS: Steady blood concentration was achieved 120 mins after D-sorbitol intravenous infusion, which was (0.358 ± 0.064) mmol·L-1 in cirrhotic group and (0.189 ± 0.05) mmol·L-1 in control group (P < 0.01). CLH = (812.7 ± 112.4) mL·min-1, QTOTAL = (1280.6 ± 131.4) mL·min-1, and RINS = (36.54 ± 10.65)% in cirrhotic group and CLH = (1248.3 ± 210.5) mL·min-1, QTOTAL = (1362.4 ± 126.9) mL·min-1, and RINS = (8.37 ± 3.32)% in control group (P < 0.01). The liver volume of cirrhotic group was 1057 ± 249 cm3, 851 ± 148 cm3 and 663 ± 77 cm3 in Child A, B and C group respectively with significant difference (P < 0.001). The average volume of cirrhotic liver in Child B, C group was significantly reduced in comparison with that in control group (P < 0.001). The patient, whose liver volume decreased by 40% with the CLH below 600 mL·min-1, would have a higher incidence of postoperative complications. There was no strict correspondent relationship between CLH, liver volume and Child-Pugh’s classification. CONCLUSION: The hepatic clearance of D-sorbitol, CT measured liver volume can be reliably used for the evaluation of hepatic functional blood flow and liver metabolic volume. Combined with the Child-Pugh’s classification, it could be very useful for further understanding the liver functional reserve, therefore help determine reasonable therapeutic plan, choose surgical procedures and operating time. PMID:12970913

Esophagectomy in patients with liver cirrhosis: a systematic review and Bayesian meta-analysis.

PubMed

Asti, E; Sozzi, M; Bonitta, G; Bernardi, D; Bonavina, L

2018-04-10

Patients with esophageal carcinoma and concomitant liver cirrhosis carry a high operative risk and may be denied esophagectomy. We performed a systematic review of the literature and meta-analysis to investigate postoperative outcomes in these patients. Studies reporting outcomes after esophagectomy in patients with liver cirrhosis were searched in Medline, Embase, Cochrane Library, ISI Web of Science, and Scopus until June 2017, matching the terms "liver cirrhosis", "esophageal neoplasm" and/or "esophageal surgery". Extracted data included study characteristics, demographic and clinical patient characteristics, type of surgical procedure, and postoperative outcomes. A systematic review and Bayesian meta-analysis were performed. Five observational, retrospective and single-arm studies with a total of 157 patients were included. The main cause of death was liver failure followed by pneumonia/sepsis and anastomotic leak. Ascites and pleural effusion were the most frequent postoperative complications (pooled rates 36% and 34%, respectively). The pooled morbidity rate was 74% (95% HPD=46-81%) while the pooled mortality was 18% (95% HPD=17-27%). Study heterogeneity (τ2) was low, ranging from 0.046 to 0.080. An incidental diagnosis of liver cirrhosis was reported in 15.6% of patients in one series. Five-year survival was similar between cirrhotic and non-cirrhotic patients but was statistically significantly higher in patients with MELD score<10. Sound scientific evidence with regard to efficacy and outcomes of esophagectomy in patients with concomitant liver cirrhosis is lacking. There is a need to properly select these frail patients to reduce postoperative morbidity and mortality rates. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Bacterial infections and hepatic encephalopathy in liver cirrhosis-prophylaxis and treatment.

PubMed

Piotrowski, Damian; Boroń-Kaczmarska, Anna

2017-09-01

Infections are common among patients with liver cirrhosis. They occur more often in cirrhotic patient groups than in the general population and result in higher mortality. One reason for this phenomenon is bacterial translocation from the intestinal lumen that occurs as a consequence of intestinal bacterial overgrowth, increased permeability and decreased motility. The most common infections in cirrhotic patients are spontaneous bacterial peritonitis and urinary tract infections, followed by pneumonia, skin and soft tissue infections. Intestinal bacterial overgrowth is also responsible for hyperammonemia, which leads to hepatic encephalopathy. All of these complications make this group of patients at high risk for mortality. The role of antibiotics in liver cirrhosis is to treat and in some cases to prevent the development of infectious complications. Based on our current knowledge, antibiotic prophylaxis should be administered to patients with gastrointestinal hemorrhage, low ascitic fluid protein concentration combined with liver or renal failure, and spontaneous bacterial peritonitis as a secondary prophylaxis, as well as after hepatic encephalopathy episodes (also as a secondary prophylaxis). In some cases, the use of non-antibiotic prophylaxis can also be considered. Current knowledge of the treatment of infections allows the choice of a preferred antibiotic for empiric therapy depending on the infection location and whether the source of the disease is nosocomial or community-acquired. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Diagnosis and treatment of hepatocellular carcinoma: An update

PubMed Central

Tejeda-Maldonado, Javier; García-Juárez, Ignacio; Aguirre-Valadez, Jonathan; González-Aguirre, Adrián; Vilatobá-Chapa, Mario; Armengol-Alonso, Alejandra; Escobar-Penagos, Francisco; Torre, Aldo; Sánchez-Ávila, Juan Francisco; Carrillo-Pérez, Diego Luis

2015-01-01

Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium “washout” in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and loco-regional therapies (alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion’s stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib. PMID:25848464

Clinical utility of breath ammonia for evaluation of ammonia physiology in healthy and cirrhotic adults

PubMed Central

Spacek, Lisa A; Mudalel, Matthew; Tittel, Frank; Risby, Terence H; Solga, Steven F

2016-01-01

Blood ammonia is routinely used in clinical settings to assess systemic ammonia in hepatic encephalopathy and urea cycle disorders. Despite its drawbacks, blood measurement is often used as a comparator in breath studies because it is a standard clinical test. We sought to evaluate sources of measurement error and potential clinical utility of breath ammonia compared to blood ammonia. We measured breath ammonia in real time by quartz enhanced photoacoustic spectrometry and blood ammonia in 10 healthy and 10 cirrhotic participants. Each participant contributed 5 breath samples and blood for ammonia measurement within 1 h. We calculated the coefficient of variation (CV) for 5 breath ammonia values, reported medians of healthy and cirrhotic participants, and used scatterplots to display breath and blood ammonia. For healthy participants, mean age was 22 years (±4), 70% were men, and body mass index (BMI) was 27 (±5). For cirrhotic participants, mean age was 61 years (±8), 60% were men, and BMI was 31 (±7). Median blood ammonia for healthy participants was within normal range, 10 μmol L−1 (interquartile range (IQR), 3–18) versus 46 μmol L−1 (IQR, 23–66) for cirrhotic participants. Median breath ammonia was 379 pmol mL−1 CO2 (IQR, 265–765) for healthy versus 350 pmol mL−1 CO2 (IQR, 180–1013) for cirrhotic participants. CV was 17 ± 6%. There remains an important unmet need in the evaluation of systemic ammonia, and breath measurement continues to demonstrate promise to fulfill this need. Given the many differences between breath and blood ammonia measurement, we examined biological explanations for our findings in healthy and cirrhotic participants. We conclude that based upon these preliminary data breath may offer clinically important information this is not provided by blood ammonia. PMID:26658550

Contribution of mammalian target of rapamycin in the pathophysiology of cirrhotic cardiomyopathy.

PubMed

Saeedi Saravi, Seyed Soheil; Ghazi-Khansari, Mahmoud; Ejtemaei Mehr, Shahram; Nobakht, Maliheh; Mousavi, Seyyedeh Elaheh; Dehpour, Ahmad Reza

2016-05-21

To explore the role of mammalian target of rapamycin (mTOR) in the pathogenesis of cirrhotic cardiomyopathy and the potential of rapamycin to improve this pathologic condition. Male albino Wistar rats weighing 100-120 g were treated with tetrachloride carbon (CCl4) for 8 wk to induce cirrhosis. Subsequently, animals were administered rapamycin (2 mg/kg per day). The QTc intervals were calculated in a 5-min electrocardiogram. Then, the left ventricular papillary muscles were isolated to examine inotropic responsiveness to β-adrenergic stimulation using a standard organ bath equipped by Powerlab system. Phosphorylated-mTOR localization in left ventricles was immunohistochemically assessed, and ventricular tumor necrosis factor (TNF)-α was measured. Western blot was used to measure levels of ventricular phosphorylated-mTOR protein. Cirrhosis was confirmed by hematoxylin and eosin staining of liver tissues, visual observation of lethargy, weight loss, jaundice, brown urine, ascites, liver stiffness, and a significant increase of spleen weight (P < 0.001). A significant prolongation in QTc intervals occurred in cirrhotic rats exposed to CCl4 (P < 0.001), while this prolongation was decreased with rapamycin treatment (P < 0.01). CCl4-induced cirrhosis caused a significant decrease of contractile responsiveness to isoproterenol stimulation and a significant increase in cardiac TNF-α. These findings were correlated with data from western blot and immunohistochemical studies on phosphorylated-mTOR expression in left ventricles. Phosphorylated-mTOR was significantly enhanced in cirrhotic rats, especially in the endothelium, compared to controls. Rapamycin treatment significantly increased contractile force and myocardial localization of phosphorylated-mTOR and decreased cardiac TNF-α concentration compared to cirrhotic rats with no treatment. In this study, we demonstrated a potential role for cardiac mTOR in the pathophysiology of cirrhotic cardiomyopathy. Rapamycin normalized the inotropic effect and altered phosphorylated-mTOR expression and myocardial localization in cirrhotic rats.

Whole-body protein turnover in malnourished patients with child class B and C cirrhosis on diets low to high in protein energy.

PubMed

Dichi, J B; Dichi, I; Maio, R; Correa, C R; Angeleli, A Y; Bicudo, M H; Rezende, T A; Burini, R C

2001-03-01

The purpose of this study was to determine the rate of whole-body protein turnover in moderately and severely alcoholic, malnourished, cirrhotic patients fed with different amounts of protein or energy. Six male patients (Child classes B and C) and four age- and sex-matched healthy control subjects were studied for 18 d in fasting and feeding states; a single oral dose of [(15)N]glycine was used as a tracer and urinary ammonia was the end product. The kinetic study showed that patients had higher protein catabolism while fasting (patients: 3.14 +/- 1.2 g of lean body mass/9 h; controls: 1.8 +/- 0.3 g of lean body mass/9 h; P < 0.02). Although not statistically significant, protein catabolism (grams of lean body mass/9 h) was lower with the hyperproteic/hyperenergetic diet when compared with fasting. Nitrogen retention was consistent with the lower protein-catabolism rate; a statistically significant increase in nitrogen balance was observed when patients were fed with the hyperproteic/hyperenergetic diet compared with fasting (4.3 +/- 3.2 g of nitrogen/d and -2.2 +/- 1.9 g of nitrogen/d, respectively; P < 0.01). These data indicate that Child class B and C cirrhotic patients are hypercatabolic and that long-term nutritional intervention with a hyperproteic/hyperenergetic diet is likely needed to improve their clinical and nutritional status.

Efficacy and safety of alternating norfloxacin and rifaximin as primary prophylaxis for spontaneous bacterial peritonitis in cirrhotic ascites: a prospective randomized open-label comparative multicenter study.

PubMed

Assem, M; Elsabaawy, M; Abdelrashed, M; Elemam, S; Khodeer, S; Hamed, W; Abdelaziz, A; El-Azab, G

2016-03-01

Primary prevention of spontaneous bacterial peritonitis (SBP) is an important strategy to reduce morbidity and mortality in cirrhotic patients with ascites. Efficacy and safety of alternating rifaximin and norfloxacin as primary prophylaxis is questionable. Three hundred thirty-four cirrhotic patients with high SAAG (≥1.1) ascites, protein level in ascitic fluid less than 1.5 g/dL with advanced liver disease (Child-Pugh score >9 points with serum bilirubin level >3 mg/dL) or renal impairment (serum creatinine level >1.2 mg/dL, blood urea nitrogen level >25 mg/dL, or serum sodium level <130 mEq/L) were included in an open-label, randomized study aimed at comparing alternating use of norfloxacin and rifaximin vs. norfloxacin or rifaximin alone as primary prophylaxis for SBP. Both intention-to-treat and per-protocol efficacy analyses were done after 6 months of treatment by assessment of ascitic fluid neutrophil count. Safety analysis was done for all intention-to-treat populations. Alternating norfloxacin and rifaximin showed superior prophylaxis by intention-to-treat (74.7 vs. 56.4% vs. 68.3%, p < 0.048). Pairwise analysis showed that alternating regimen had lower probability to develop SBP when compared to a norfloxacin-based regimen in intention-to-treat (p = 0.016) and per protocol analysis (p = 0.039). There was no difference among the studied groups regarding the incidence and severity of adverse events reported. Alternating norfloxacin- and rifaximin-based primary prophylaxis for SBP showed higher efficacy with the same safety profile when compared with monotherapy of norfloxacin.

Expression and function of the atypical cadherin FAT1 in chronic liver disease.

PubMed

Valletta, Daniela; Czech, Barbara; Thasler, Wolfgang E; Müller, Martina; Bosserhoff, Anja-Katrin; Hellerbrand, Claus

2012-09-28

Hepatic fibrosis can be considered as wound healing process in response to hepatocellular injury. Activation of hepatic stellate cells (HSCs) is a key event of hepatic fibrosis since activated HSCs are the cellular source of enhanced extracellular matrix deposition, and reversion of liver fibrosis is accompanied by clearance of activated HSCs by apoptosis. The atypical cadherin FAT1 has been shown to regulate diverse biological functions as cell proliferation and planar cell polarity, and also to affect wound healing. Here, we found increased FAT1 expression in different murine models of chronic liver injury and in cirrhotic livers of patients with different liver disease. Also in hepatic tissue of patients with non-alcoholic steatohepatitis FAT1 expression was significantly enhanced and correlated with collagen alpha I(1) expression. Immunohistochemistry revealed no significant differences in staining intensity between hepatocytes in normal and cirrhotic liver tissue but myofibroblast like cells in fibrotic septa of cirrhotic livers showed a prominent immunosignal. Furthermore, FAT1 mRNA and protein expression markedly increased during in vitro activation of primary human and murine HSCs. Together, these data indicated activated HSCs as cellular source of enhanced FAT1 expression in diseased livers. To gain insight into the functional role of FAT1 in activated HSCs we suppressed FAT1 in these cells by siRNA. We newly found that FAT1 suppression in activated HSCs caused a downregulation of NFκB activity. This transcription factor is critical for apoptosis resistance of HSCs, and consequently, we detected a higher apoptosis rate in FAT1 suppressed HSCs compared to control cells. Our findings suggest FAT1 as new therapeutic target for the prevention and treatment of hepatic fibrosis in chronic liver disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy.

PubMed

Gjeorgjievski, Mihajlo; Cappell, Mitchell S

2016-02-08

To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.

Combinatorial gene therapy renders increased survival in cirrhotic rats

PubMed Central

2010-01-01

Background Liver fibrosis ranks as the second cause of death in México's productive-age population. This pathology is characterized by acummulation of fibrillar proteins in hepatic parenchyma causing synthetic and metabolic disfunction. Remotion of excessive fibrous proteins might result in benefit for subjects increasing survival index. The goal of this work was to find whether the already known therapeutical effect of human urokinase Plasminogen Activator and human Matrix Metalloprotease 8 extends survival index in cirrhotic animals. Methods Wistar rats (80 g) underwent chronic intoxication with CCl4: mineral oil for 8 weeks. Cirrhotic animals were injected with a combined dose of Ad-delta-huPA plus Ad-MMP8 (3 × 1011 and 1.5 × 1011 vp/Kg, respectively) or with Ad-beta-Gal (4.5 × 1011) and were killed after 2, 4, 6, 8 and 10 days. Then, liver and serum were collected. An additional set of cirrhotic animals injected with combined gene therapy was also monitored for their probability of survival. Results Only the cirrhotic animals treated with therapeutical genes (Ad-delta-huPA+Ad-MMP-8) showed improvement in liver fibrosis. These results correlated with hydroxyproline determinations. A significant decrement in alpha-SMA and TGF-beta1 gene expression was also observed. Cirrhotic rats treated with Ad-delta-huPA plus Ad-MMP8 had a higher probability of survival at 60 days with respect to Ad-beta-Gal-injected animals. Conclusion A single administration of Ad-delta-huPA plus Ad-MMP-8 is efficient to induce fibrosis regression and increase survival in experimental liver fibrosis. PMID:20509929

Role of the heme oxygenases in abnormalities of the mesenteric circulation in cirrhotic rats.

PubMed

Sacerdoti, David; Abraham, Nader G; Oyekan, Adebayo O; Yang, Liming; Gatta, Angelo; McGiff, John C

2004-02-01

Carbon monoxide (CO), a product of heme metabolism by heme-oxygenase (HO), has biological actions similar to those of nitric oxide (NO). The role of CO in decreasing vascular responses to constrictor agents produced by experimental cirrhosis induced by carbon tetrachloride was evaluated before and after inhibition of HO with tin-mesoporphyrin (SnMP) in the perfused superior mesenteric vasculature (SMV) of cirrhotic and normal rats and in normal rats transfected with the human HO-1 (HHO-1) gene. Perfusion pressure and vasoconstrictor responses of the SMV to KCl, phenylephrine (PE), and endothelin-1 (ET-1) were decreased in cirrhotic rats. SnMP increased SMV perfusion pressure and restored the constrictor responses of the SMV to KCl, PE, and ET-1 in cirrhotic rats. The relative roles of NO and CO in producing hyporeactivity of the SMV to PE in cirrhotic rats were examined. Vasoconstrictor responses to PE were successively augmented by stepwise inhibition of CO and NO production, suggesting a complementary role for these gases in the regulation of reactivity of the SMV. Expression of constitutive but not of inducible HO (HO-1) was increased in the SMV of cirrhotic rats as was HO activity. Administration of adenovirus containing HHO-1 gene produced detection of HHO-1 RNA and increased HO activity in the SMV within 7 days. Rats transfected with HO-1 demonstrated reduction in both perfusion pressure and vasoconstrictor responses to PE in the SMV. We propose that HO is an essential component in mechanisms that modulate reactivity of the mesenteric circulation in experimental hepatic cirrhosis in rats.

Feasibility of transnasal endoscopy in screening for esophageal and gastric varices in patients with chronic liver disease

PubMed Central

de Faria, Anderson Antônio; Dias, Carlos Alberto Freitas; Dias Moetzsohn, Luciana; de Castro Carvalho, Silas; Ferrari, Tereza Abreu; Nunes Arantes, Vitor

2017-01-01

Background and study aims  Screening for esophageal and gastric varices is indicated for patients with portal hypertension or cirrhosis. Typically, conventional endoscopy is used; however, the need for sedation increases the costs and risks, especially in cirrhotic patients. Use of transnasal endoscopy with an ultrathin endoscope enables study of the upper gastrointestinal tract without the need for sedation. The objective of this study is to evaluate the feasibility of transnasal endoscopy in screening for esophageal and gastric varices in patients with chronic liver disease. Patients and methods  This was a prospective study in which transnasal endoscopy was carried out in patients with cirrhosis or portal hypertension who had indications for screening of esophageal and gastric varices. The following variables were evaluated: demographical data, duration of procedure, patient tolerance and acceptance, adverse events (AEs), endoscopic findings and interobserver agreement related to portal hypertension alterations ( kappa index). Results  A total of 50 patients entered the study. The most common cause of liver disease was chronic viral hepatitis (66 %). Among the cirrhotic patients, most of the patients were Child-Pugh A (74 %). In 5 patients (10 %), nasal intubation was not possible. Two patients (4 %) experienced minor epistaxis. Tolerance was excellent or good in 92 % according with a visual analogic scale. In 16 patients (32 %), esophageal varices were detected and in 2 patients (4 %) gastric varices were detected. The mean duration of the procedure was 7 minutes. Conclusions  Transnasal endoscopy is feasible, effective and well tolerated for screening of esophageal and gastric varices in patients with chronic liver disease. It can be performed in outpatient clinics safely and without the use of sedation. PMID:28691048

IMPACT OF MICROBIOLOGICAL CHANGES ON SPONTANEOUS BACTERIAL PERITONITIS IN THREE DIFFERENT PERIODS OVER 17 YEARS.

PubMed

Almeida, Paulo Roberto Lerias de; Leão, Gabriel Stefani; Gonçalves, Charlles David Gonçalves; Picon, Rafael Veiga; Tovo, Cristiane Valle

2018-01-01

Spontaneous bacterial peritonitis is a serious complication in cirrhotic patients, and changes in the microbiological characteristics reported in the last years are impacting the choice of antibiotic used for treatment. The aim of the present study is to evaluate the changes in the epidemiology and bacterial resistance of the germs causing spontaneous bacterial peritonitis over three different periods over 17 years. All cirrhotic patients with spontaneous bacterial peritonitis and positive culture of ascites fluid were retrospectively studied in a reference Hospital in Southern Brazil. Three periods were ramdomly evaluated: 1997-1998, 2002-2003 and 2014-2015. The most frequent infecting organisms and the sensitivity in vitro to antibiotics were registered. In the first period (1997-1998) there were 33 cases, the most common were: E. coli in 13 (36.11%), Staphylococcus coagulase-negative in 6 (16.66%), K. pneumoniae in 5 (13.88%), S. aureus in 4 (11.11%) and S. faecalis in 3 (8.33%). In the second period (2002-2003), there were 43 cases, the most frequent were: Staphylococus coagulase-negative in 16 (35.55%), S. aureus in 8 (17.77%), E. coli in 7 (15.55%) and K. pneumoniae in 3 (6.66%). In the third period (2014-2015) there were 58 cases (seven with two bacteria), the most frequent were: E. coli in 15 (23.1%), S. viridans in 12 (18.5%), K. pneumoniae in 10 (15.4%) and E. faecium 5 (7.7%). No one was using antibiotic prophylaxis. Considering all staphylococci, the prevalence increased to rates of the order of 50% in the second period, with a reduction in the third period evaluated. Likewise, the prevalence of resistant E. coli increased, reaching 14%. There was a modification of the bacterial population causing spontaneous bacterial peritonitis, with high frequency of gram-positive organisms, as well as an increase in the resistance to the traditionally recommended antibiotics. This study suggests a probable imminent inclusion of a drug against gram-positive organisms in the empiric treatment of spontaneous bacterial peritonitis.

Adherence to Barcelona Clinic Liver Cancer guidelines in field practice: Results of Progetto Epatocarcinoma Campania.

PubMed

Guarino, Maria; Tortora, Raffaella; de Stefano, Giorgio; Coppola, Carmine; Morisco, Filomena; Salomone Megna, Angelo; Izzo, Francesco; Nardone, Gerardo; Piai, Guido; Adinolfi, Luigi Elio; D'Adamo, Giuseppe; Gaeta, Giovanni Battista; Messina, Vincenzo; Francica, Giampiero; De Girolamo, Vincenzo; Coppola, Nicola; Persico, Marcello; Di Costanzo, Giovan Giuseppe

2018-05-01

The Barcelona Clinic Liver Cancer (BCLC) algorithm is the standard system for clinical management of hepatocellular carcinoma (HCC). Data on adherence to this therapeutic paradigm are scarce. This field practice study aimed to provide a description of HCC cirrhotic patients in Southern Italy, to evaluate the adherence to BCLC guidelines and its impact on patients' survival. We analyzed the region-wide Italian database of Progetto Epatocarcinoma Campania, which includes data of HCC cirrhotic patients, prospectively collected from January 2013 to December 2015 in 16 regional centers. Overall, 1008 HCC patients were enrolled: 70.6% patients received therapies recommended by BCLC algorithm, while 29.4% underwent different treatments. Among patients who were treated in adherence to guidelines, a higher rate of diagnosis on surveillance programs, better liver function, lower rate of alpha-fetoprotein > 200 ng/mL, more early-stage and monofocal HCC, lower frequency of nodules > 5 cm, portal vein thrombosis and metastases were observed. The overall survival was evaluated according to HCC stage and no differences between groups and patients managed differently were found. The multivariate analysis showed that non-adherence to treatment guidelines was independently associated to the BCLC stage B, Child-Pugh classes B and C, and the presence of neoplastic thrombosis and metastases. Adherence to BCLC algorithm in field practice was high in early and end-stage HCC patients, but it was poor in intermediate and advanced patients. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Hepatitis C Cure Is Associated with Decreased Healthcare Costs in Cirrhotics in Retrospective Veterans Affairs Cohort.

PubMed

Maier, Marissa M; Zhou, Xiao-Hua; Chapko, Michael; Leipertz, Steven L; Wang, Xuan; Beste, Lauren A

2018-06-01

Approximately 233,898 individuals in the Veterans Affairs healthcare network are hepatitis C virus (HCV)-infected, making the Veterans Affairs the single largest provider of HCV care in the USA. Direct-acting antiviral treatment regimens for HCV offer high cure rates. However, these medications pose an enormous financial burden, and whether HCV cure is associated with decreased healthcare costs is poorly defined. To measure downstream healthcare costs in a national population of HCV-infected patients up to 9 years post-HCV antiviral treatment, to compare downstream healthcare costs between cured and uncured patients, and to assess impact of cirrhosis status on cost differences. This is a retrospective cohort study (2004-2014) of hepatitis C-infected patients who initiated antiviral treatment within the United States Veterans Affairs healthcare system October 2004-September 2013. We measured inpatient, outpatient, and pharmacy costs after HCV treatment. For the entire cohort, cure was associated with mean cumulative cost savings in post-treatment years three-six, but no cost savings by post-treatment year nine. By post-treatment year nine, cure in cirrhosis patients was associated with a mean cumulative cost savings of $9474 (- 32,666 to 51,614) per patient, while cure in non-cirrhotic patients was associated with a mean cumulative cost excess of $2526 (- 12,211 to 7159) per patient. Among patients with cirrhosis at baseline, cure is associated with absolute cost savings up to 9 years post-treatment compared to those without cure. Among patients without cirrhosis, early post-treatment cost savings are counterbalanced by higher costs in later years.

Improved survival of patients with hepatocellular carcinoma and compensated hepatitis C virus-related cirrhosis who attained sustained virological response.

PubMed

Bruno, Savino; Di Marco, Vito; Iavarone, Massimo; Roffi, Luigi; Boccaccio, Vincenzo; Crosignani, Andrea; Cabibbo, Giuseppe; Rossi, Sonia; Calvaruso, Vincenza; Aghemo, Alessio; Giacomelli, Luca; Craxì, Antonio; Colombo, Massimo; Maisonneuve, Patrick

2017-10-01

Few studies examined the outcome of patients with hepatitis C virus (HCV)-related cirrhosis who developed hepatocellular carcinoma (HCC). The relative weight as determinant of death for cancer vs end-stage liver disease (ESLD) and the benefit of HCV eradication remain undefined. This multicentre, retrospective analysis evaluates overall survival (OS), rate of decompensation and tumour recurrence in compensated HCC patients treated with interferon (IFN) according to HCV status since HCC diagnosis. Two groups of patients with HCV-related cirrhosis and HCC were followed since HCC diagnosis: (i) compensated cirrhotics with prior sustained virological response (SVR) on IFN-based regimens (N=19); (ii) compensated cirrhotics without SVR (viraemic) (N=156). Over a median follow-up of 3.0 years since the onset of HCC, OS was longer for HCC patients with SVR than for viraemic patients (log-rank P=.004). The 5-year OS rate was 65.9% in patients with SVR vs 31.9% in viraemic patients. Similar trends were reported for hepatic decompensation (log-rank P=.01) and tumour recurrence (log-rank P=.01). These findings were confirmed at multivariable and propensity score analysis. At propensity analysis, 0/19 compensated patients with SVR died for ESLD vs 7/19 (37%) viraemic patients (P=.004). HCC mortality was similar in the two groups. Hepatocellular carcinoma patients with prior SVR and compensated cirrhosis at the time of tumour diagnosis have prolonged OS than viraemic patients. Given the lack of cirrhosis progression, no SVR patient ultimately died for ESLD while this condition appears the main cause of death among viraemic patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Current Concepts in Diabetes Mellitus and Chronic Liver Disease: Clinical Outcomes, Hepatitis C Virus Association, and Therapy.

PubMed

García-Compeán, Diego; González-González, José Alberto; Lavalle-González, Fernando Javier; González-Moreno, Emmanuel Irineo; Villarreal-Pérez, Jesús Zacarías; Maldonado-Garza, Héctor J

2016-02-01

Hereditary type 2 diabetes mellitus is a risk factor for chronic liver disease, and ~30 % of patients with liver cirrhosis develop diabetes. Diabetes mellitus has been associated with cirrhotic and non-cirrhotic hepatitis C virus liver infection, can aggravate the course the liver infection, and can induce a lower sustained response to antiviral treatment. Evidences that HCV may induce metabolic and autoimmune disturbances leading to hypobetalipoproteinemia, steatosis, insulin resistance, impaired glucose tolerance, thyroid disease, and gonadal dysfunction have been found. Prospective studies have demonstrated that diabetes increases the risk of liver complications and death in patients with cirrhosis. However, treatment of diabetes in these patients is complex, as antidiabetic drugs can promote hypoglycemia and lactic acidosis. There have been few therapeutic studies evaluating antidiabetic treatments in patients with liver cirrhosis published to date; thus, the optimal treatment for diabetes and the impact of treatment on morbidity and mortality are not clearly known. As numbers of patients with chronic liver disease and diabetes mellitus are increasing, largely because of the global epidemics of obesity and nonalcoholic fatty liver disease, evaluation of treatment options is becoming more important. This review discusses new concepts on hepatogenous diabetes, the diabetes mellitus–hepatitis C virus association, and clinical implications of diabetes mellitus in patients with chronic liver disease. In addition, the effectiveness and safety of old and new antidiabetic drugs, including incretin-based therapies, will be described.

The effect of Saccharomyces boulardii in patients eligible for liver transplantation.

PubMed

Liboredo, Juliana Costa; Ferrari, Maria de Lourdes Abreu; Vilela, Eduardo Garcia; Lima, Agnaldo Soares; Correia, Maria Isabel Toulson Davisson

2014-09-12

The aim of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability, laboratory parameters and MELD and Child-Pugh severity scores in cirrhotic patients eligible for liver transplantation. Eighteen patients followed in a Transplant Outpatient Clinic were evaluated immediately before the beginning of treatment, after a 30-day period of treatment period with probiotics and at the end of the second study month (after a thirty-day period without probiotics). Fifteen healthy controls also underwent the intestinal permeability test (lactulose/mannitol). Before the probiotic, the median lactulose/ mannitol ratio was greater in the cirrhotic patients (0.0209, range 0.0012-0.1984) compared to the healthy controls (0.0030, range 0.0020-0.0013) (p < 0.05). Eight of fifteen patients, half of whom had ascites, showed increased intestinal permeability above the higher value observed in the controls. No significant association was found between the severity scores for liver disease, age, presence of ascites and intestinal permeability immediately before the beginning of study. After treatment with S. boulardii, there was no improvement in intestinal permeability or significant differences in the laboratory parameters for the three evaluations. Patients eligible for liver transplants presented with increased intestinal permeability compared to healthy controls. A thirty-day treatment with S. boulardii did not improve this intestinal permeability or the severity scores, nor did it impact the laboratory parameters. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Mitochondrial protection by low doses of insulin-like growth factor- I in experimental cirrhosis.

PubMed

Pérez, Raquel; García-Fernández, María; Díaz-Sánchez, Matías; Puche, Juan E; Delgado, Gloria; Conchillo, Marian; Muntané, Jordi; Castilla-Cortázar, Inma

2008-05-07

To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-I (IGF- I) therapy (4 wk) is able to induce beneficial effects on damaged mitochondria leading to cellular protection. Wistar rats were divided into three groups: Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF- I treatment (2 microg/100 g bw/d). Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three experimental groups. Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3); an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity. IGF- I therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes I and III was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- I therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. These results show that IGF- I exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.

Mitochondrial protection by low doses of insulin-like growth factor-Iin experimental cirrhosis

PubMed Central

Pérez, Raquel; García-Fernández, María; Díaz-Sánchez, Matías; Puche, Juan E; Delgado, Gloria; Conchillo, Marian; Muntané, Jordi; Castilla-Cortázar, Inma

2008-01-01

AIM: To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-I(IGF-I) therapy (4 wk) is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHODS: Wistar rats were divided into three groups: Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Itreatment (2 μg/100 g bw/d). Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three experimental groups. RESULTS: Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3); an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity. IGF-Itherapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Iand III was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF-Itherapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. CONCLUSION: These results show that IGF-Iexerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production. PMID:18461658

ENDOSCOPIC FINDINGS OF UPPER GASTROINTESTINAL BLEEDING IN PATIENTS WITH LIVER CIRROSIS.

PubMed

Hadayat, Rania; Jehangiri, Attique-ur-Rehman; Gul, Rahid; Khan, Adil Naseer; Said, Khalid; Gandapur, Asadullah

2015-01-01

Acute upper gastrointestinal (GI) bleeding is a common medical emergency. A common risk factor of upper GI bleeding is cirrhosis of liver, which can lead to variceal haemorrhage. 30-40% of cirrhotic patients who bleed may have non-variceal upper GI bleeding and it is frequently caused by peptic ulcers, portal gastropathy, Mallory-Weiss tear, and gastroduodenal erosions. The objective of this study was to determine the frequency of upper gastrointestinal endoscopic findings among patients presenting with upper gastrointestinal bleeding with liver cirrhosis. This descriptive cross-sectional study was carried out in Gastroenterology & Hepatology Department of Ayub Teaching Hospital, Abbottabad from February 2012 to June 2013. 252 patients diagnosed with cirrhosis, presenting with upper GI bleed, age 50 years of either gender, and were included in the study. Non-probability consecutive sampling was used, Endoscopy was performed on each patient and the findings documented. The mean age was 57.84 +/- 6.29 years. There were 158 (62.7%) males and 94 (37.3%) females. The most common endoscopic finding was oesophageal varices (92.9%, n=234) followed by portal hypertensive gastropathy (38.9%, n=98) with almost equal distribution among males and females. Gastric varices were found in 33.3% of patients (n=84). Among other non-variceal lesions, peptic ulcer disease was seen in 26 patients (10.3%) while gastric erosions were found in 8 patients (3.2%). In patients with acute upper GI bleeding and liver cirrhosis, the most common endoscopic finding is oesophageal varices, with a substantially higher value in our part of the country, apart from other non-variceal causes.

A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects: validation by GC-MS and LC-MS[S

PubMed Central

Kakiyama, Genta; Muto, Akina; Takei, Hajime; Nittono, Hiroshi; Murai, Tsuyoshi; Kurosawa, Takao; Hofmann, Alan F.; Pandak, William M.; Bajaj, Jasmohan S.

2014-01-01

We have developed a simple and accurate HPLC method for measurement of fecal bile acids using phenacyl derivatives of unconjugated bile acids, and applied it to the measurement of fecal bile acids in cirrhotic patients. The HPLC method has the following steps: 1) lyophilization of the stool sample; 2) reconstitution in buffer and enzymatic deconjugation using cholylglycine hydrolase/sulfatase; 3) incubation with 0.1 N NaOH in 50% isopropanol at 60°C to hydrolyze esterified bile acids; 4) extraction of bile acids from particulate material using 0.1 N NaOH; 5) isolation of deconjugated bile acids by solid phase extraction; 6) formation of phenacyl esters by derivatization using phenacyl bromide; and 7) HPLC separation measuring eluted peaks at 254 nm. The method was validated by showing that results obtained by HPLC agreed with those obtained by LC-MS/MS and GC-MS. We then applied the method to measuring total fecal bile acid (concentration) and bile acid profile in samples from 38 patients with cirrhosis (17 early, 21 advanced) and 10 healthy subjects. Bile acid concentrations were significantly lower in patients with advanced cirrhosis, suggesting impaired bile acid synthesis. PMID:24627129

Gastrointestinal dysfunction in liver cirrhosis

PubMed Central

Kalaitzakis, Evangelos

2014-01-01

Patients with liver cirrhosis exhibit several features of gut dysfunction which may contribute to the development of cirrhosis complications as well as have an impact on nutritional status and health-related quality of life. Gastrointestinal symptoms are common in cirrhosis and their pathophysiology probably involves factors related to liver disease severity, psychological distress, and gut dysfunction (e.g., increased gastric sensitivity to distension and delayed gut transit). They may lead to reduced food intake and, thus, may contribute to the nutritional status deterioration in cirrhotic patients. Although tense ascites appears to have a negative impact on meal-induced accommodation of the stomach, published data on gastric accommodation in cirrhotics without significant ascites are not unanimous. Gastric emptying and small bowel transit have generally been shown to be prolonged. This may be related to disturbances in postprandial glucose, insulin, and ghrelin levels, which, in turn, appear to be associated to insulin resistance, a common finding in cirrhosis. Furthermore, small bowel manometry disturbances and delayed gut transit may be associated with the development of small bowel bacterial overgrowth. Finally, several studies have reported intestinal barrier dysfunction in patients with cirrhosis (especially those with portal hypertension), which is related to bacterial translocation and permeation of intestinal bacterial products, e.g., endotoxin and bacterial DNA, thus potentially being involved in the pathogenesis of complications of liver cirrhosis. PMID:25356031

Reprint of: Nutrition in the Management of Cirrhosis and its Neurological Complications☆

PubMed Central

Bémeur, Chantal; Butterworth, Roger F.

2015-01-01

Malnutrition is a common feature of chronic liver diseases that is often associated with a poor prognosis including worsening of clinical outcome, neuropsychiatric complications as well as outcome following liver transplantation. Nutritional assessment in patients with cirrhosis is challenging owing to confounding factors related to liver failure. The objectives of nutritional intervention in cirrhotic patients are the support of liver regeneration, the prevention or correction of specific nutritional deficiencies and the prevention and/or treatment of the complications of liver disease per se and of liver transplantation. Nutritional recommendations target the optimal supply of adequate substrates related to requirements linked to energy, protein, carbohydrates, lipids, vitamins and minerals. Some issues relating to malnutrition in chronic liver disease remain to be addressed including the development of an appropriate well-validated nutritional assessment tool, the identification of mechanistic targets or therapy for sarcopenia, the development of nutritional recommendations for obese cirrhotic patients and liver-transplant recipients and the elucidation of the roles of vitamin A hepatotoxicity, as well as the impact of deficiencies in riboflavin and zinc on clinical outcomes. Early identification and treatment of malnutrition in chronic liver disease has the potential to lead to better disease outcome as well as prevention of the complications of chronic liver disease and improved transplant outcomes. PMID:26041952

A Proposed Physiopathological Pathway to Hyperammonemic Encephalopathy in a Non-Cirrhotic Patient with Fibrolamellar Hepatocellular Carcinoma without Ornithine Transcarbamylase (OTC) Mutation.

PubMed

Surjan, Rodrigo C; Dos Santos, Elizabeth S; Basseres, Tiago; Makdissi, Fabio F; Machado, Marcel A

2017-03-08

BACKGROUND Hyperammonemic encephalopathy is a potentially fatal condition that may progress to irreversible neuronal damage and is usually associated with liver failure or portosystemic shunting. However, other less common conditions can lead to hyperammonemia in adults, such as fibrolamellar hepatocellular carcinoma. Clinical awareness of hyperammonemic encephalopathy in patients with normal liver function is paramount to timely diagnosis, but understanding the underlying physiopathology is decisive to initiate adequate treatment for complete recovery. CASE REPORT A 31-year-old male with fibrolamellar carcinoma and peritoneal carcinomatosis presented with rapid onset hyperammonemic encephalopathy. Despite usual treatment for hepatic encephalopathy, his hyperammonemia was aggravated. A physiopathological pathway to encephalopathy resulting from hepatocellular dysfunction or portosystemic shunting was suspected and proper treatment was initiated, which resulted in complete remission of encephalopathy. Thus, we propose there is a physiopathology path to hyperammonemic encephalopathy in non-cirrhotic patients with fibrolamellar carcinoma independent of ornithine transcarbamylase (OTC) mutation. An ornithine metabolism imbalance resulting from overexpression of Aurora Kinase A as a result of a single, recurrent heterozygous deletion on chromosome 19, common to all fibrolamellar carcinomas, can lead to a c-Myc and ornithine decarboxylase overexpression that results in ornithine transcarboxylase dysfunction with urea cycle disorder and subsequent hyperammonemia. CONCLUSIONS The identification of a physiopathological pathway allowed adequate medical treatment and full patient recovery from severe hyperammonemic encephalopathy.

Declining mortality in critically ill patients with cirrhosis in Australia and New Zealand between 2000 and 2015.

PubMed

Majumdar, Avik; Bailey, Michael; Kemp, William M; Bellomo, Rinaldo; Roberts, Stuart K; Pilcher, David

2017-12-01

Few studies have described the outcomes of patients with cirrhosis receiving intensive care unit (ICU) admission at a population level. We aimed to describe trends in the mortality of such patients in Australia and New Zealand (ANZ), and to investigate the relationship with associated organ failures. We studied patients admitted to 172 ICUs on a non-elective basis, with and without cirrhosis between January 1st 2000 and December 31st 2015, as recorded by the ANZ Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. We assessed severity of illness on admission using organ failure models and acute physiology scores. The primary outcome was hospital mortality. Patients with cirrhosis accounted for 17,044 of 776,873 non-elective ICU admissions (2.2%). Cirrhosis hospital mortality was 32.4% compared to 16.9% in the non-cirrhotic group (p<0.0001). After adjustment for key confounders, cirrhosis had an independent effect on mortality with an odds ratio (OR) of 1.10 (1.06-1.15). There was no difference in the adjusted annual decline in mortality between patients with or without cirrhosis (OR 0.96 [0.95-0.97] vs. 0.96 [0.96-0.96], p=0.67). No difference was seen in the adjusted decline in mortality of patients with cirrhosis when stratified by mechanical ventilation (p=0.92), liver transplant centre status (p=0.27) or presence of sepsis (p=0.09). Mortality increased with number of organ failures, however, the presence of cirrhosis was not found to affect this relationship (p=0.33). The mortality of patients with cirrhosis admitted to ICU on a non-elective basis has declined significantly over time, comparable to patients without cirrhosis, and is predominantly governed by the number of organ failures. Outcomes are similar between non-liver transplant ICUs and liver transplant centres. The outcomes of patients with liver cirrhosis admitted to intensive care units (ICUs) have been previously regarded as poor. We have demonstrated that in Australia and New Zealand, annual in-hospital death rates following ICU admission in this patient group are lower than previously reported, have improved over 16years to 29% and are at a rate similar to patients without cirrhosis. Our data justify recommendations that advocate better access to intensive care for patients with cirrhosis. Copyright © 2017 European Association for the Study of the Liver. All rights reserved.

Therapeutic efficacy of the non-peptide AVP antagonist OPC-31260 in cirrhotic rats.

PubMed

Tsuboi, Y; Ishikawa, S; Fujisawa, G; Okada, K; Saito, T

1994-07-01

The present study was undertaken to determine whether a non-peptide arginine vasopressin (AVP) antagonist [5-dimethylamino-1-(4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetra hydro-1H- benzazepine] (OPC-31260) improves the impaired water excretion in rats with experimental liver cirrhosis. Male Wistar rats weighing 200 to 250 g were injected in an equal volume (4 ml/kg) of carbon tetrachloride and olive oil at an interval of seven days for three months, causing liver cirrhosis with ascites. Control rats were injected with only olive oil. Body weight (body wt) and hematocrit (Hct) were lower in the cirrhotic rats than the control rats (body wt 360.7 vs. 238.5 g, P < 0.01; Hct 46.3 vs. 39.2%, P < 0.01). A water loading test (30 ml/kg) was carried out and 20-minute urine collections were made for three hours. The percent of water load excreted was 62.5% in the cirrhotic rats, a value significantly less than that of 102.1% in the control rats. However, its percent increased to 215.1% after the oral administration of 5 mg/kg OPC-31260 (P < 0.01). Minimal urinary osmolality (UOsm) was 185.5 mOsm/kg H2O in the cirrhotic rats receiving the vehicle, a value greater than the control rats of 125.5 mOsm/kg H2O (P < 0.01). The oral administration of 5 mg/kg OPC-31260 reduced minimal UOsm to 85.2 mOsm/kg H2O in the cirrhotic rats (P < 0.01). Urinary excretion of sodium was lower in the cirrhotic rats than the control rats (87.1 vs. 312.4 microEq/3 hr, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

PubMed

Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

2017-07-01

In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of Cirrhosis on Resource Use and Inpatient Complications in Patients Undergoing Total Knee and Hip Arthroplasty.

PubMed

Newman, Jared M; Schiltz, Nicholas K; Mudd, Christopher D; Szubski, Caleb R; Klika, Alison K; Barsoum, Wael K

2016-11-01

Cirrhosis is a major cause of morbidity and mortality and is an important risk factor for complications in surgical patients. The purpose of this study was to investigate the association of cirrhosis with postoperative complications, length of stay (LOS), and costs among patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA). Using the Nationwide Inpatient Sample between 2000 and 2011, we identified patients who had a primary TKA or primary THA. TKA patients were divided into 2 groups: (1) cirrhosis (n = 41,464) and (2) no cirrhosis (n = 5,721,297) and THA patients were divided into 2 groups: (1) cirrhosis (n = 27,401) and (2) no cirrhosis (n = 2,622,539). Patient demographics, comorbidities, perioperative complications, LOS, and incremental costs were analyzed. An additional subgroup analysis by cirrhosis etiology was performed. Multivariable analysis revealed cirrhosis was associated with 1.55 (95% confidence interval: 1.47-1.63) times higher odds of any complication after TKA and 1.59 (1.50-1.69) higher odds after THA. Adjusted outcomes showed cirrhotic TKA patients had $1857 higher costs and 0.30 days longer LOS and THA cirrhotic patients had $1497 higher costs and 0.48 longer LOS. We found similar results for each cirrhosis subtype but alcohol-related had the highest resource use and complication rate. Patients with cirrhosis who are undergoing TKA or THA are at a significantly increased risk for perioperative complications, increased LOS, and higher costs. The perioperative complications and costs were highest among patients with alcohol-related cirrhosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Raltegravir Pharmacokinetics in Patients on Asunaprevir-Daclatasvir

PubMed Central

Vincent, Corine; Furlan, Valérie; Rosa, Isabelle; Rosenthal, Eric; Cheret, Antoine; Molina, Jean-Michel; Taburet, Anne-Marie; Piroth, Lionel

2015-01-01

Raltegravir pharmacokinetics was studied in 20 patients included in the ANRS HC30 QUADRIH Study before and after addition of anti-hepatitis C virus (anti-HCV) quadritherapy, including pegylated-interferon–ribavirin and asunaprevir plus daclatasvir. Raltegravir pharmacokinetic parameters remained unchanged whether administered on or off anti-HCV therapy. In addition, concentrations of raltegravir, asunaprevir, and daclatasvir were not affected by liver cirrhosis. These data suggest that in human immunodeficiency virus (HIV)-HCV-coinfected patients, whether cirrhotic or not, asunaprevir and daclatasvir could be administered safely with raltegravir. PMID:26438504

A hot, swollen joint in a cirrhotic patient

PubMed Central

Omakobia, E; Hossain, J; Nash, J; Uhuegbu, C

2010-01-01

Septic arthritis in the elderly carries a high mortality. Underlying risk factors, such as diabetes, malignancy, chronic renal failure, rheumatoid arthritis, hepatobiliary disease and AIDS, should be assessed. Rare causative organisms are occasionally encountered. Here, we describe a case of an 80-year-old diabetic patient with liver cirrhosis who developed Klebsiella pneumoniae septic arthritis, which is a rare cause of joint infection. We postulate that this case supports the notion that the patient's knee effusion seeded during a primary K pneumoniae bacteraemia of intestinal origin and related to liver cirrhosis. PMID:22798443

Liver mobilization and liver hanging for totally laparoscopic right hepatectomy: an easy way to do it.

PubMed

Rotellar, Fernando; Pardo, Fernando; Martí-Cruchaga, Pablo; Zozaya, Gabriel; Valentí, Victor; Bellver, Manuel; Lopez-Olaondo, Luis; Hidalgo, Francisco

2017-02-01

The purpose of this study is to describe a technical modification that facilitates right liver mobilization in laparoscopic right hepatectomy (LRH). In the supine position, an inflatable device is placed under the patient's right chest. For right hemiliver mobilization, the table is placed in 30° anti-Trendelenburg and full-left tilt. Balloon inflation offers an additional 30° left inclination that places the patient in an almost left lateral position. Foot and lateral supports are placed to prevent patient slippage during changes in the patient positioning. From December 2013 to October 2015, this technique has been used in 10 consecutive LRH. The indications for these procedures were as follows: four donor hepatectomies for living donor liver transplant, three hepatocellular carcinomas and one peripheral cholangiocarcinoma in cirrhotic patients, one hepatocellular carcinoma in a non-cirrhotic patient, and one case of colorectal cancer metastases. In this period, it has also been used to facilitate mobilization and resection in the posterior segments of the liver in seven patients. In every case, right hemiliver mobilization was easily performed in a maximum time of 15 min and placement of a tape or plastic tube for liver hanging was prepared. We have not observed any complication directly attributable to the technique herein described (i.e. right brachialgia; arms, back or left flank pain) in the early or late postoperative follow-up. The additional left inclination obtained with the inflation of a balloon under the right chest facilitates right hemiliver mobilization. Its use may help in the performance and adoption of LRH.

Effectiveness and safety of ledipasvir/sofosbuvir±ribavirin in the treatment of HCV infection: The real-world HARVEST study.

PubMed

Flisiak, Robert; Łucejko, Mariusz; Mazur, Włodzimierz; Janczewska, Ewa; Berak, Hanna; Tomasiewicz, Krzysztof; Mozer-Lisewska, Iwona; Kozielewicz, Dorota; Gietka, Andrzej; Sikorska, Katarzyna; Wawrzynowicz-Syczewska, Marta; Nowak, Krzysztof; Zarębska-Michaluk, Dorota; Musialik, Joanna; Simon, Krzysztof; Garlicki, Aleksander; Pleśniak, Robert; Baka-Ćwierz, Barbara; Olszok, Iwona; Augustyniak, Krystyna; Stolarz, Wojciech; Białkowska, Jolanta; Badurek, Anna; Piekarska, Anna

2017-09-01

To evaluate the effectiveness and safety of ledipasvir/sofosbuvir (LDV/SOF)±ribavirin (RBV) regimen in a real-world setting. Patients received a fixed-dose combination tablet containing LDV and SOF with or without RBV, for 8, 12 or 24 weeks. Patients were assessed at baseline, end of treatment, and 12 weeks after the end of treatment. The primary effectiveness endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Of the 86 patients, aged 20-80 years, 82.6% were HCV genotype 1b-infected and 50.0% were cirrhotic. More than half (52.3%) had previously followed pegylated interferon-containing (PEG-IFN) treatment regimens, and 38.5% were null-responders. SVR12 was achieved by 94.2% of patients. All non-responders were cirrhotic: two demonstrated virologic breakthrough and the remaining three relapsed. All patients treated with an 8-week regimen achieved SVR12 despite having high viral load at baseline (HCV RNA of >1 million IU/mL in 8/10 patients, including one with a viral load of >6 million IU/mL). Adverse events were generally mild and transient. Most frequently, fatigue (22.1%), headache (15.1%), and arthralgia (7.0%) were observed. Laboratory abnormalities included anemia and hyperbilirubinemia. Treatment with LDV/SOF±RBV is an effective and safe option for patients with HCV, including those with advanced liver disease or a history of non-response to PEG-IFN-based therapy. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canini, Laetitia; DebRoy, Swati; Mariño, Zoe

HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to ε max) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001).more » A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, ε max, was significantly (p≤0.032) associated with increasing severity of liver disease (ε max[s.e.]=0.86[0.05], ε max=0.69[0.06] and ε max=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log 10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

Classical and emerging roles of vitamin D in hepatitis C virus (HCV) infection

PubMed Central

Gutierrez, Julio A.; Parikh, Neil; Branch, Andrea D.

2014-01-01

The risk of clinically-significant vitamin D deficiency increases at 25-hydroxyvitamin D levels below 20 ng/mL, according to the Institute of Medicine. By this standard, most cirrhotic hepatitis C virus (HCV)-positive patients and many non-cirrhotic patients are vitamin D deficient. The high prevalence of vitamin D deficiency among HCV patients is a cause for concern for several specific reasons. Classic studies established the importance of vitamin D and calcium in maintaining bone. Vitamin D's beneficial effects on bone are likely to be vital for HCV-infected patients because these individuals have a high prevalence of low bone mineral density. Many pharmaceutical agents reduce bone density and exposure to these drugs may increase bone disease in HCV-positive patients. Bone loss occurs following liver transplantation and bone density is often low in patients with HIV/HCV co-infection who are on combination antiretroviral therapy. Some evidence suggests that ribavirin reduces bone density, underscoring the special need to monitor vitamin D in patients receiving HCV treatment and to prescribe supplements, as appropriate. In addition to its role in calcium metabolism, vitamin D is also an immune modulator that reduces inflammation while enhancing protective immune responses. Higher vitamin D levels are associated with less liver fibrosis and less inflammation in HCV patients. Recent studies show that low vitamin D levels are associated with treatment failure among HCV-infected patients receiving pegylated-interferon and ribavirin. If confirmed, these findings will provide an additional reason to ensure adequate levels of vitamin D. The article concludes with information about how to monitor vitamin D status and how to use vitamin D supplements most effectively in HCV-infected patients. PMID:22189978

In vitro efficacy of pro- and anticoagulant strategies in compensated and acutely ill patients with cirrhosis.

PubMed

Lisman, Ton; Kleiss, Simone; Patel, Vishal C; Fisher, Caleb; Adelmeijer, Jelle; Bos, Sarah; Singanayagam, Arjuna; Stoy, Sidsel Hyldgaard; Shawcross, Debbie L; Bernal, William

2018-05-16

A simultaneous decline in pro- and anticoagulant drivers in patients with liver diseases results in a 'rebalanced' hemostatic system, even in acutely ill patients. Nevertheless, both bleeding and thrombotic events are common. Here, we explored efficacy of pro- and antihemostatic strategies in compensated and acutely ill cirrhotics which may be unpredictable given the profound hemostatic changes. We tested the effects in vitro of the addition of clinically relevant doses of commonly used pro- and antihemostatic strategies in plasma from healthy individuals (n=30) and patients with compensated (n=18) and acutely decompensated cirrhosis (n=18), and acute-on-chronic liver failure (n=10). We used thrombin generation tests and fibrin clot permeability assays to assess potency of various approaches. Fresh frozen plasma and recombinant factor VIIa modestly increased thrombin generation (10-20%). Prothrombin complex concentrate increased thrombin generation 2-fold in controls and 2-4-fold in patients. Clot permeability decreased after addition of fibrinogen concentrate by 51% in controls and by 50-60% in patients. Low molecular weight heparin decreased thrombin generation by 18% in controls and by 23-54% in patients. Similarly, dabigatran decreased thrombin generation by 33% in controls and by 47-100% in patients. In contrast, rivaroxaban decreased thrombin generation by 55% in controls, but only by 11-38% in patients. These in vitro data suggest little prohemostatic effect of fresh frozen plasma and recombinant factor VIIa in acutely ill cirrhotics, whereas prothrombin complex concentrate and fibrinogen concentrate clearly improved hemostasis. Furthermore, our data suggest the requirement for dose-adjustments of commonly used anticoagulants in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C.

PubMed

Virlogeux, Victor; Pradat, Pierre; Hartig-Lavie, Kerstin; Bailly, François; Maynard, Marianne; Ouziel, Guillaume; Poinsot, Domitille; Lebossé, Fanny; Ecochard, Marie; Radenne, Sylvie; Benmakhlouf, Samir; Koffi, Joseph; Lack, Philippe; Scholtes, Caroline; Uhres, Anne-Claire; Ducerf, Christian; Mabrut, Jean-Yves; Rode, Agnès; Levrero, Massimo; Combet, Christophe; Merle, Philippe; Zoulim, Fabien

2017-08-01

Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; P<.001). Hepatocellular carcinoma recurrence rate was significantly lower among patients treated with direct-acting antivirals compared with untreated patients. Given the potential impact of our observation, large-scale prospective cohort studies are needed to confirm these results. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Outcomes and predictors of treatment response with sofosbuvir plus daclatasvir with or without ribavirin in Egyptian patients with genotype 4 hepatitis C virus infection

PubMed Central

Ahmed, Ossama A; Elsebaey, Mohamed A; Fouad, Mohamed Hassan A; Elashry, Heba; Elshafie, Ahmed I; Elhadidy, Ahmed A; Esheba, Noha E; Elnaggar, Mohammed H; Soliman, Shaimaa; Abd-Elsalam, Sherief

2018-01-01

Background and aims Treatment of hepatitis C virus (HCV) changed dramatically with the introduction of oral direct-acting antiviral drugs due to their high antiviral potency and safety profile. Sofosbuvir plus daclatasvir combination therapy was extensively investigated in HCV genotypes 1, 2, and 3, while published data regarding its real-life application in the treatment of genotype 4 is lacking. Therefore, we conducted this study to assess the outcomes and predictors of treatment response with sofosbuvir plus daclatasvir with or without ribavirin in Egyptian patients with genotype 4 hepatitis C virus infection. Patients and methods This prospective study included 300 Egyptian patients with chronic genotype 4 HCV, treated with sofosbuvir plus daclatasvir with or without ribavirin for 12–24 weeks. Primary outcome was the number of patients who achieved sustained virologic response (SVR12), and secondary outcome was the occurrence of adverse events. Results A total of 92.67% of all patients achieved SVR12. SVR12 rates of 96.55% and 84.54% were reported in non-cirrhotic and cirrhotic patients, respectively. SVR12 in treatment-naïve and treatment-experienced patients were 94.12% and 87.01%, respectively. A total of 19.7% of patients experienced mild adverse events. Older age, cirrhosis, and low platelet count were the predictors of treatment non-response. Conclusion Based on this multi-center prospective study, sofosbuvir plus daclatasvir with or without ribavirin for 12–24 weeks appears to have favorable outcomes in the treatment of genotype 4 HCV-infected Egyptian patients. Older age, cirrhosis, especially Child–Pugh class B, and low platelet count are independent risk factors of treatment non-response. PMID:29628768

Interferon-free therapy of chronic hepatitis C with direct-acting antivirals does not change the short-term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis.

PubMed

Mettke, F; Schlevogt, B; Deterding, K; Wranke, A; Smith, A; Port, K; Manns, M P; Vogel, A; Cornberg, M; Wedemeyer, H

2018-02-01

Hepatitis C virus (HCV) clearance with IFN-based therapies reduces the incidence of hepatocellular carcinoma (HCC). There has been some debate if IFN-free therapy with direct-acting antivirals alters the risk for HCC. To investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with direct-acting antivirals vs untreated controls. We prospectively monitored 373 patients with chronic hepatitis C who received IFN-free therapies with direct-acting antiviral after January 2014. A retrospective control cohort of untreated cirrhotic patients was recruited out of 3715 HCV patients who were followed at our centre between 2007 and 2013, with similar HCC screening protocols. 158 direct-acting antiviral-treated and 184 control patients with liver cirrhosis were included in this analysis. The groups did not differ in gender and genotype distribution, severity of liver disease and prevalence of diabetes mellitus. Patients were followed up for a median of 440 (range 91-908) and 592 (range 90-1000) days. HCCs developed in 6 and 14 patients during follow-up, resulting in an incidence of 2.90 vs 4.48 HCCs per 100 person-years. In the direct-acting antiviral-treated group, there was no new case of HCC later than 450 days after treatment initiation. In multivariate analysis, higher MELD-Scores and AFP-levels were independently associated with HCC development. Transplant-free patient survival was similar in both groups. IFN-free direct-acting antiviral therapy of chronic hepatitis C does not alter the short-term risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become evident after more than 1.5 years of follow-up. © 2017 John Wiley & Sons Ltd.

Alterations in Cerebral White Matter and Neuropsychology in Patients with Cirrhosis and Falls

PubMed Central

Gómez-Ansón, Beatriz; Román, Eva; Fernández de Bobadilla, Ramón; Pires-Encuentra, Patricia; Díaz-Manera, Jordi; Núñez, Fidel; Martinez-Horta, Saül; Vives-Gilabert, Yolanda; Pagonabarraga, Javier; Kulisevsky, Jaume; Guarner, Carlos; Soriano, Germán

2015-01-01

Background & Aim Falls are frequent in patients with cirrhosis but underlying mechanisms are unknown. The aim was to determine the neuropsychological, neurological and brain alterations using magnetic resonance-diffusion tensor imaging (MR-DTI) in cirrhotic patients with falls. Patients and methods Twelve patients with cirrhosis and falls in the previous year were compared to 9 cirrhotic patients without falls. A comprehensive neuropsychological and neurological evaluation of variables that may predispose to falls included: the Mini-Mental State Examination, Psychometric Hepatic Encephalopathy Score (PHES), Parkinson’s Disease-Cognitive Rating Scale, specific tests to explore various cognitive domains, Unified Parkinson’s Disease Rating Scale to evaluate parkinsonism, scales for ataxia and muscular strength, and electroneurography. High-field MR (3T) including DTI and structural sequences was performed in all patients. Results The main neuropsychological findings were impairment in PHES (p = 0.03), Parkinson’s Disease-Cognitive Rating Scale (p = 0.04) and in executive (p<0.05) and visuospatial-visuoconstructive functions (p<0.05) in patients with falls compared to those without. There were no statistical differences between the two groups in the neurological evaluation or in the visual assessment of MRI. MR-DTI showed alterations in white matter integrity in patients with falls compared to those without falls (p<0.05), with local maxima in the superior longitudinal fasciculus and corticospinal tract. These alterations were independent of PHES as a covariate and correlated with executive dysfunction (p<0.05). Conclusions With the limitation of the small sample size, our results suggest that patients with cirrhosis and falls present alterations in brain white matter tracts related to executive dysfunction. These alterations are independent of PHES impairment. PMID:25793766

Effect of Sea buckthorn on liver fibrosis: A clinical study

PubMed Central

Gao, Ze-Li; Gu, Xiao-Hong; Cheng, Feng-Tao; Jiang, Fo-Hu

2003-01-01

AIM: To appraise the effect of sea buckthorn (Hippophae rhamnoides) on cirrhotic patients. METHODS: Fifty cirrhotic patients of Child-Pugh grade A and B were randomly divided into two groups: Group A as the treated group (n = 30), taking orally the sea buckthorn extract, 15 g 3 times a day for 6 mo. Group B as the control group (n = 18), taking vitamin B complex one tablet, 3 times a day for 6 mo. The following tests were performed before and after the treatment in both groups to determine LN, HA, collagens types III and IV, cytokines IL-6 and TNFα, liver serum albumin, total bile acid, ALT, AST and prothrombin time. RESULTS: The serum levels of TNFα, IL-6, laminin and type IV collagen in group A were significantly higher than those in the control group. After a course of sea buckthorn treatment, the serum levels of LN, HA, collagen types III and IV, total bile acid (TBA) decreased significantly as compared with those before and after treatment in the control group. The sea buckthorn notably shortened the duration for normalization of aminotransferases. CONCLUSION: Sea buckthorn may be a hopeful drug for prevention and treatment of liver fibrosis. PMID:12854177

Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis.

PubMed

Chiva, Maite; Soriano, Germán; Rochat, Isabelle; Peralta, Carmen; Rochat, Florence; Llovet, Teresa; Mirelis, Beatriz; Schiffrin, Eduardo J; Guarner, Carlos; Balanzó, Joaquim

2002-10-01

Probiotics and antioxidants could be alternatives to antibiotics in the prevention of bacterial infections in cirrhosis. The aim of the present study was to determine the effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora, endotoxemia, and bacterial translocation in cirrhotic rats. Twenty-nine Sprague-Dawley rats with cirrhosis induced by CCl(4) and ascites received Lactobacillus johnsonii La1 10(9)cfu/day in vehicle (antioxidants: vitamin C+glutamate) (n=10), vehicle alone (n=11), or water (n=8) by gavage. Another eight non-cirrhotic rats formed the control group. After 10 days of treatment, a laparotomy was performed to determine microbiological study of ileal and cecal feces, bacterial translocation, endotoxemia, and intestinal malondialdehyde (MDA) levels as index of intestinal oxidative damage. Intestinal enterobacteria and enterococci, bacterial translocation (0/11 and 0/10 vs. 5/8, P<0.01), and ileal MDA levels (P<0.01) were lower in cirrhotic rats treated with antioxidants alone or in combination with Lactobacillus johnsonii La1 compared to cirrhotic rats receiving water. Only rats treated with antioxidants and Lactobacillus johnsonii La1 showed a decrease in endotoxemia with respect to cirrhotic rats receiving water (P<0.05). Antioxidants alone or in combination with Lactobacillus johnsonii La1 can be useful in preventing bacterial translocation in cirrhosis.

Inhibition of soluble epoxide hydrolase lowers portal hypertension in cirrhotic rats by ameliorating endothelial dysfunction and liver fibrosis.

PubMed

Deng, Wensheng; Zhu, Yiming; Lin, Jiayun; Zheng, Lei; Zhang, Chihao; Luo, Meng

2017-07-01

Epoxyeicostrienoic acids (EETs) are arachidonic acid derived meditators which are catalyzed by soluble epoxide hydrolase (sEH) to less active dihydroeicostrienoics acids (DHETS). The aim of our study is to investigate the effects of sEH inhibition on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl4 cirrhotic rats. The sEH inhibitor,trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB) was administered to stabilize hepatic EETs by gavage at a dose of 1mg/kg/d. Our results showed that hepatic sEH expression was markedly increased in portal hypertension, and led to a lower ratio of EETs/DHETs which was effectively reversed by t-TUCB administration. t-TUCB significantly decreased portal pressure without significant changes in systemic hemodynamics, which was associated with the attenuation of intrahepatic vascular resistance (IHVR) and liver fibrosis. t-TUCB ameliorated endothelial dysfunction, increased hepatic endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. In addition, t-TUCB significantly reduced alpha-Smooth Muscle Actin (α-SMA) expression and liver fibrosis, which was associated with a decrease in NF-κB signaling. Taken together, inhibition of sEH reduces portal pressure, liver fibrosis and attenuates hepatic endothelial dysfunction in cirrhotic rats. Our results indicate that sEH inhbitors may be useful in the treatment of portal hypertension in patients with cirrhosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Nutritional status and liver transplantation.

PubMed

Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero

2011-12-01

Chronic liver disease has a profound effect on nutritional status and undernourishment is almost universally present in patients with end-stage liver disease undergoing liver transplantation. In the last decades, due to epidemiological changes, a trend showing an increase in patients with end-stage liver disease and associated obesity has also been reported in developed countries. Nutrition abnormalities may influence the outcome after transplantation therefore, the importance to carefully assess the nutritional status in the work-up of patients candidates for liver transplantation is widely accepted. More attention has been given to malnourished patients as they represent the greater number. The subjective global nutritional assessment and anthropometric measurements are recognized in current guidelines to be adequate in identifying those patients at risk of malnutrition. Cirrhotic patients with a depletion in lean body mass and fat deposits have an increased surgical risk and malnutrition may impact on morbidity, mortality and costs in the post-transplantation setting. For this reason an adequate calorie and protein intake should always be ensured to malnourished cirrhotic patient either through the diet, or using oral nutritional supplements or by enteral or parenteral nutrition although studies supporting the efficacy of nutritional supplementation in improving the clinical outcomes after transplantation are still scarce. When liver function is restored, an amelioration in the nutritional status is expected. After liver transplantation in fact dietary intake rapidly normalizes and fat mass is progressively regained while the recovery of muscle mass can be slower. In some patients unregulated weight gain may lead to over-nutrition and may favor metabolic disorders (hypertension, hyperglycemia, hyperlipidemia). This condition, defined as 'metabolic syndrome', may play a negative role on the overall survival of liver transplant patients. In this report we review data on nutrition and liver transplantation.

Preservation of nutritional-status in patients with refractory ascites due to hepatic cirrhosis who are undergoing repeated paracentesis.

PubMed

Sorrentino, Paolo; Castaldo, Giuseppe; Tarantino, Luciano; Bracigliano, Alessandra; Perrella, Alessandro; Perrella, Oreste; Fiorentino, Francesco; Vecchione, Raffaela; D' Angelo, Salvatore

2012-04-01

Refractory ascites in liver-cirrhosis is associated with a poor prognosis. We performed a prospective study to investigate whether aggressive nutritional-support could improve outcomes in cirrhotic patients. Cirrhotic patients undergoing serial large-volume paracentesis for refractory-ascites were enrolled and randomized into three groups. Group A received post-paracentesis intravenous nutritional-support in addition to a balanced oral diet and a late-evening protein snack, group B received the same oral nutritional-protocol as the first group but without parenteral support, and group C (the control group) received a low-sodium or sodium-free diet. Clinical, anthropometric and laboratory nutritional parameters and biochemical tests of liver and renal function were reported for 12 months of follow-up. We enrolled 120 patients, who were randomized into three groups of equal size. Patients on the nutritional-protocol showed better preservation of clinical, anthropometric and laboratory nutritional parameters that were associated with decreased deterioration of liver function compared with patients on the low-sodium or sodium-free diet (group C). Groups A and B had lower morbidity and mortality rates than the control group (C). Mortality rates were significantly better in patients who were treated with parenteral-nutritional-support than for the other two groups. In patients who were on the nutritional-protocol, there was a reduction in the requirement of taps for the treatment of refractory ascites. Post-paracentesis parenteral-nutritional-support with a balanced oral diet and an evening protein snack appears to be the best care protocol for patients with liver-cirrhosis that has been complicated by refractory-ascites. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.

PubMed

Kang, S H; Lee, Y B; Lee, J-H; Nam, J Y; Chang, Y; Cho, H; Yoo, J-J; Cho, Y Y; Cho, E J; Yu, S J; Kim, M Y; Kim, Y J; Baik, S K; Yoon, J-H

2017-11-01

Rifaximin might decrease the risk of portal hypertension-related complications by controlling small intestinal bacterial overgrowth. To evaluate whether rifaximin was associated with the risk of death and cirrhotic complications. We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non-HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding. In the non-HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio [aHR], 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile-associated diarrhoea was not different between the groups (aHR, 0.028; P = .338). In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy. © 2017 John Wiley & Sons Ltd.

Treatment of Chronic HCV Infection with the New Direct Acting Antivirals (DAA): First Report of a Real World Experience in Southern Brazil.

PubMed

Cheinquer, Hugo; Sette, Hoel; Wolff, Fernando H; de Araujo, Alexandre; Coelho-Borges, Silvia; Soares, Silvia R P; Barros, Mauricio F A

2017-01-01

There is almost no data regarding the efficacy of direct acting antivirals (DAAs) therapy in Brazil. The aim of this historical cohort study is to describe the sustained virologic response (SVR) rate among real-world compensated chronic hepatitis C patients in three hepatology centers from Southern Brazil. Patients were included if they had at least 12 weeks follow-up after the end of therapy. Patients that were lost to follow-up or had treatment prematurely interrupted for any reason were considered treatment failure in this intention to treat analysis. 219 patients were analyzed. Mean age was 57.4 ± 10.9 years and 142/219 (64.8%) were male. Genotype 1 was present in 166 patients (75.8%; 1a 29.2%, 1b 46.6%); Genotypes 2, 3 and 4 in 8 (3.7%), 43 (19.6%) and 2 (0.9%), respectively. 96 (43.8%) were cirrhotic. 134 (59.5%) were treatment experienced. DAA therapies were: sofosbuvir (SOF) + ribavirin (RBV) in 10 patients; SOF + simeprevir (SMV) ± RBV in 73; SOF + pegylated interferon (PEG-IFN) + RBV in 6; SOF + daclatasvir (DCV) ± RBV in 51, SOF + ledipasvir (LDV) ± RBV in 61, and paritaprevir/ ritonavir + ombitasvir + dasabuvir (PTVr/OBV/DSV) ± RBV in 18 patients. SVR-12 was achieved in 208/219 (95%). Ten patients had virologic failure: 6 cirrhotic, 7 treatment experienced, and 6 either genotype 3 or 1a. No adverse event was attributed to the DAA therapy. Real world experience with DAA therapy in Southern Brazil showed a high rate of SVR and excellent tolerability. Failure to achieve SVR was mainly observed among patients with at least one negative predictor of response: cirrhosis and/or genotypes 1a or 3.

Cost-Effectiveness of Treating Hepatitis C with Sofosbuvir/Ledipasvir in Germany.

PubMed

Stahmeyer, Jona T; Rossol, Siegbert; Liersch, Sebastian; Guerra, Ines; Krauth, Christian

2017-01-01

Infections with the hepatitis C virus (HCV) are a global public health problem. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. Newly introduced direct acting antivirals, especially interferon-free regimens, have improved rates of sustained viral response above 90% in most patient groups and allow treating patients who were ineligible for treatment in the past. These new regimens have replaced former treatment and are recommended by current guidelines. However, there is an ongoing discussion on high pharmaceutical prices. Our aim was to assess the long-term cost-effectiveness of treating hepatitis C genotype 1 patients with sofosbuvir/ledipasvir (SOF/LDV) treatment in Germany. We used a Markov cohort model to simulate disease progression and assess cost-effectiveness. The model calculates lifetime costs and outcomes (quality-adjusted life years, QALYs) of SOF/LDV and other strategies. Patients were stratified by treatment status (treatment-naive and treatment-experienced) and absence/presence of cirrhosis. Different treatment strategies were compared to prior standard of care. Sensitivity analyses were performed to evaluate model robustness. Base-case analyses results show that in treatment-naive non-cirrhotic patients treatment with SOF/LDV dominates the prior standard of care (is more effective and less costly). In cirrhotic patients an incremental cost-effectiveness ratio (ICER) of 3,383 €/QALY was estimated. In treatment-experienced patients ICERs were 26,426 €/QALY and 1,397 €/QALY for treatment-naive and treatment-experienced patients, respectively. Robustness of results was confirmed in sensitivity analyses. Our analysis shows that treatment with SOF/LDV is cost-effective compared to prior standard of care in all patient groups considering international costs per QALY thresholds.

Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

DOE PAGES

Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; ...

2014-06-10

HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to ε max) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001).more » A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, ε max, was significantly (p≤0.032) associated with increasing severity of liver disease (ε max[s.e.]=0.86[0.05], ε max=0.69[0.06] and ε max=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log 10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

Association between sarcopenia and osteoporosis in chronic liver disease.

PubMed

Hayashi, Manabu; Abe, Kazumichi; Fujita, Masashi; Okai, Ken; Takahashi, Atsushi; Ohira, Hiromasa

2018-05-07

Sarcopenia and osteoporosis are important complications in chronic liver disease (CLD). The aim of this study was to investigate the relationship between sarcopenia and osteoporosis in patients with CLD. We retrospectively investigated the relationship between sarcopenia and osteoporosis in 112 CLD patients (57 males and 55 females), including 40 cirrhotic patients (36%), by measuring the appendicular skeletal muscle mass index (ASMI) using bio-impedance analysis. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The sarcopenia rate was 13% (14/112), and the osteoporosis and osteopenia rates were 17% (19/112) and 65% (73/112), respectively. The rate of osteoporosis was significant and high in patients with sarcopenia or cirrhosis. In linear regression analysis, sarcopenia was significantly associated with the BMD of the lumbar spine (Coefficient = -0.149, P = 0.014) and the femur neck (Coefficient = -0.110, P = 0.003). Cirrhosis was also significantly associated with low BMD of the lumbar spine (Coefficient = -0.160, P < 0.001) and the femur neck (Coefficient = -0.066, P = 0.015). In the logistic analysis, sarcopenia (odds ratio = 6.16, P = 0.039) and cirrhosis (odds ratio = 15.8, P = 0.002) were independent risk factors for osteoporosis. The ASMI cut-off values for osteoporosis were 7.33 kg/m 2 in males and 5.71 kg/m 2 in females. Sarcopenia was closely associated with osteoporosis, and a low ASMI was a potential predictor of osteoporosis in CLD patients. Screening for BMD may be required to detect osteoporosis in cirrhotic patients. This article is protected by copyright. All rights reserved.

Is Interferon-Based Treatment of Viral Hepatitis C Genotype 3 Infection Still of Value in the Era of Direct-Acting Antivirals?

PubMed

Zarębska-Michaluk, Dorota; Flisiak, Robert; Jaroszewicz, Jerzy; Janczewska, Ewa; Czauż-Andrzejuk, Agnieszka; Berak, Hanna; Horban, Andrzej; Staniaszek, Agnieszka; Gietka, Andrzej; Tudrujek, Magdalena; Tomasiewicz, Krzysztof; Dybowska, Dorota; Halota, Waldemar; Piekarska, Anna; Sitko, Marek; Garlicki, Aleksander; Orłowska, Iwona; Simon, Krzysztof; Belica-Wdowik, Teresa; Baka-Ćwierz, Barbara; Mazur, Włodzimierz; Białkowska, Jolanta; Socha, Łukasz; Wawrzynowicz-Syczewska, Marta; Laurans, Łukasz; Deroń, Zbigniew; Lorenc, Beata; Dobracka, Beata; Tronina, Olga; Pawłowska, Małgorzata

2018-02-01

The aim of the study is to analyze treatments available for patients infected with genotype (G) 3 hepatitis C virus (HCV) in Poland at the beginning of the interferon (IFN)-free era and evaluate the efficacy and safety of different therapeutic options administered in a real-world setting. We analyzed data of 198 patients who started antiviral therapy after July 1, 2015, and completed it before December 31, 2016; 57.6% of them had liver cirrhosis and 46% were treatment experienced. Fifty percent of patients were assigned to sofosbuvir (SOF)+pegylated IFN alfa (PegIFNa)+ribavirin (RBV), 9% to PegIFNa+RBV, 36% received SOF+RBV, and 5% SOF+daclatasvir (DCV)±RBV. Cirrhotic patients were assigned more frequently to IFN-free regimens. Overall, a sustained virological response was achieved by 84.3% of patients in intent-to-treat (ITT) analysis and 87% in modified ITT analysis. For SOF+PegIFNa+RBV and SOF+DCV±RBV regimens, the sustained virologic response (SVR) rate reached at least 90%, whereas the two other therapeutic options demonstrated efficacy <80%. The SVR rate in noncirrhotics was higher than in cirrhotics, irrespective of regimen. Adverse events were documented in 52.5%, with the most common being weakness/fatigue and anemia. We confirmed effectiveness and safety of the SOF-based treatment in a real-world cohort of patients with chronic HCV G3 infection. Most notably, we demonstrated good tolerability and high efficacy of the SOF+PegIFNa+RBV regimen.

Cockcroft-Gault revisited: New de-liver-ance on recommendations for use in cirrhosis.

PubMed

Scappaticci, Gianni B; Regal, Randolph E

2017-01-28

The Cockcroft-Gault (CG) equation has become perhaps the most popular practical approach for estimating renal function among health care professionals. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine (SCr) based equation, but also may not appreciate the validity of the many variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying pathophysiology of the disease contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population. We reviewed the original CG trial from 1976 along with data surrounding clinician specific alterations to the CG equation that followed through time. These alterations included different formulas for body weight in obese patients and the "rounding up" approach in patients with low SCr. Additionally, we described the pathophysiology and hemodynamic changes that occur in cirrhosis; and reviewed several studies that attempted to estimate renal function in this population. The evidence we reviewed regarding the most accurate manipulation of the original CG equation to estimate creatinine clearance (CrCl) was inconclusive. Unfortunately, the homogeneity of the patient population in the original CG trial limited its external validity. Elimination of body weight in the CG equation actually produced the estimate closest to the measure CrCl. Furthermore, "rounding up" of SCr values often underestimated CrCl. This approach could lead to suboptimal dosing of drug therapies in patients with low SCr. In cirrhotic patients, utilization of SCr based methods overestimated true renal function by about 50% in the literature we reviewed.

Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: a randomized and controlled double blind study.

PubMed

Malaguarnera, Mariano; Risino, Corrado; Cammalleri, Lisa; Malaguarnera, Lucia; Astuto, Marinella; Vecchio, Ignazio; Rampello, Liborio

2009-07-01

Our earlier study has demonstrated that the administration of L-acetylcarnitine (LAC) improves neurological symptoms and serum parameters in hepatic coma. The aim of this work has been to evaluate the efficacy of the LAC and branched chain amino acids (BCAA) versus BCAA, administered in intravenous infusion, in patients with cirrhotic hepatic coma. Forty-eight highly selected patients were enrolled in the study and, after randomization, received blindly LAC+BCAA (n=24) versus BCAA (n=24). The two groups were similar in age, sex, pathogenesis of cirrhosis, and severity of liver disease. The comparison between values before and after LAC planned treatment showed statistical significant differences in neurological findings, evaluated by the Glasgow Scale, ammonia serum levels, blood urea nitrogen, and EEG. After 60 min of the study period, the LAC+BCAA treated patients compared with BCCA treated showed a significant decrease of ammonia serum levels: 41.20 versus 10.40 mumol P<0.05. After 1 day of the study period, the LAC+BCAA treated patients compared with BCCA treated patients showed a significant increase of Glasgow's score: 3.60 versus 1.50 score P<0.05; a significant decrease of ammonia serum levels: 63.30 versus 27.00 mumol P<0.01; a significant improvement of EEG cps/s: 2.70 versus 0.6 P<0.001. No side-effects were observed in our study series. Our study demonstrated that the administration of BCAA supplemented with LAC might improve neurological symptoms and serum ammonium levels in selected cirrhotic patients with hepatic coma.

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy

PubMed Central

Gjeorgjievski, Mihajlo; Cappell, Mitchell S

2016-01-01

AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. METHODS: Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: “portal” and “gastropathy”; or “portal” and “hypertensive”; or “congestive” and “gastropathy”; or “congestive” and “gastroenteropathy”. The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. CONCLUSION: PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy. PMID:26855694

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

PubMed Central

Callefi, Luciana Azevedo; Villela-Nogueira, Cristiane Alves; de Barros Tenore, Simone; Carnaúba-Júnior, Dimas; Coelho, Henrique Sérgio Moraes; Pinto, Paulo de Tarso A.; Nabuco, Letícia Cancella; Pessoa, Mário Guimarães; Ferraz, Maria Lucia Cardoso Gomes; Ferreira, Paulo Roberto Abrão; de Lourdes Candolo Martinelli, Ana; Chachá, Silvana Gama Florencio; de Souza Paiva Ferreira, Adalgisa; de Macedo Bisio, Alessandra Porto; Brandão-Mello, Carlos Eduardo; Álvares-Da-Silva, Mário Reis; Reuter, Tânia; Ivantes, Claudia Alexandra Pontes; de Mello Perez, Renata; Mendes-Correa, Maria Cássia Jacintho

2017-01-01

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts. PMID:28658438

Hepatocellular carcinoma risk assessment by the measurement of liver stiffness variations in HCV cirrhotics treated with direct acting antivirals.

PubMed

Ravaioli, Federico; Conti, Fabio; Brillanti, Stefano; Andreone, Pietro; Mazzella, Giuseppe; Buonfiglioli, Federica; Serio, Ilaria; Verrucchi, Gabriella; Bacchi Reggiani, Maria Letizia; Colli, Agostino; Marasco, Giovanni; Colecchia, Antonio; Festi, Davide

2018-06-01

Direct-acting antivirals (DAA) are an effective treatment for hepatitis C virus infection. However, sustained virologic response (SVR) after DAA treatment does not seem to reduce the risk of hepatocellular carcinoma (HCC) development in these patients. Liver stiffness measurement (LSM) may predict the risk of developing HCC in liver cirrhosis patients. The aim of our study was to evaluate the role of LSM variation as predictor of HCC development in patients treated with DAA. In 139 HCV-related cirrhotic patients, LSM and laboratory tests were carried out at baseline (BL) and at the end of DAA treatment (EOT). Patients were followed for at least 6 months after the EOT. LSM reduction was expressed as Delta LS (∆LS). Cox regression analysis was used to identify prognostic factors for HCC development after DAA. Median LSM values were significantly reduced from BL to EOT (from 18.6 to 13.8 kPa; p < 0.001). The median ∆LS was -26.7% (IQR: -38.4% -13.6%). During a median follow-up of 15 months after DAA treatment, 20 (14.4%) patients developed HCC. Significant LSM reduction was observed both in patients who developed HCC and in those who did not, but this was significantly lower in the patients who developed HCC (-18.0% vs -28.9% p = 0.005). At multivariate analysis, ∆LS lower than -30%, Child-Turcotte-Pugh-B and history of HCC were independently associated with HCC development. Our results indicate that ∆LS is a useful non-invasive marker for predicting HCC development after DAA treatment. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Liver transplantation for hepatocellular cancer: UCL experience in 137 adult cirrhotic patients. Alpha-foetoprotein level and locoregional treatment as refined selection criteria.

PubMed

Ciccarelli, Olga; Lai, Quirino; Goffette, Pierre; Finet, Patrice; De Reyck, Chantal; Roggen, Francine; Sempoux, Christine; Doffagne, Erik; Reding, Raymond; Lerut, Jan

2012-08-01

Liver transplantation (LT) is a validated treatment for selected cirrhotics with hepatocellular cancer (HCC). A retrospective single center study including 137 recipients having proven HCC was done to refine inclusion criteria for LT as well as to look at impact of locoregional treatment (LRT) on outcome. At pre-LT imaging, 42 (30.6%) patients were Milan criteria (MC)-OUT; 28 (20.4%) were University of California San Francisco criteria (UCSFC)-OUT. Pre-LT LRT was performed in 109 (79.6%) patients. Multivariate analysis identified four factors to be independently predictive of recurrence: tumour number >3, AFP level ≥400 ng/ml, microvascular invasion and rejection needing anti-lymphocytic antibodies. When considering pre-transplant variables only, AFP level ≥400 ng/ml (HR = 5.13; P < 0.0001) was the unique risk factor for recurrence; conversely, application of LRT was protective (HR = 0.42; P = 0.04). MC-IN patients having LRT (n = 79) had the best 5-year tumour-free survival (TFS) (91.6%). MC-IN patients without LRT (n = 16) and MC-OUT patients with LRT (n = 30) had similar good TFS (72.7% vs.77.5%); finally MC-OUT patients without LRT (n = 12) had the worst results (45.0%; vs. 1st group: P < 0.0001). Immediate pre-LT AFP and aggressive pre-transplant LRT strategy, especially in MC-OUT patients, are both important elements to further expand inclusion criteria without compromising long-term results of HCC liver recipients. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Biomarkers for acute kidney injury in decompensated cirrhosis: A Prospective Study.

PubMed

Jaques, David A; Spahr, Laurent; Berra, Gregory; Poffet, Vincent; Lescuyer, Pierre; Gerstel, Eric; Garin, Nicolas; Martin, Pierre-Yves; Ponte, Belen

2018-01-25

Acute kidney injury (AKI) is a frequent complication in cirrhotic patients. As serum creatinine is a poor marker of renal function in this population, we aimed to study the utility of several biomarkers in this context. A prospective study was conducted in hospitalized patients with decompensated cirrhosis. Serum creatinine (SCr), Cystatin C (CystC), NGAL and urinary NGAL, KIM-1, protein, albumin and sodium were measured on three separate occasions. Renal resistive index (RRI) was obtained. We analyzed the value of these biomarkers to determine the presence of AKI, its etiology [prerenal, acute tubular necrosis (ATN), or hepatorenal (HRS)], its severity and a composite clinical outcome at 30 days (death, dialysis and intensive care admission). We included 105 patients, of which 55 had AKI. SCr, CystC, NGAL (plasma and urinary), urinary sodium and RRI at inclusion were independently associated with the presence of AKI. SCr, CystC and plasma NGAL were able to predict the subsequent development of AKI. Pre-renal state showed lower levels of SCr, NGAL (plasma and urinary) and RRI. ATN patients had high levels of NGAL (plasma and urinary) as well as urinary protein and sodium. HRS patients presented an intermediate pattern. All biomarkers paralleled the severity of AKI. SCr, CystC and plasma NGAL predicted the development of the composite clinical outcome with the same performance as the MELD score. In patients with decompensated cirrhosis, early measurement of renal biomarkers provides valuable information on AKI etiology. It could also improve AKI diagnosis and prognosis. This article is protected by copyright. All rights reserved.

Relative effects of heavy alcohol use and hepatitis C in decompensated chronic liver disease in a hospital inpatient population.

PubMed

Mankal, Pavan Kumar; Abed, Jean; Aristy, Jose David; Munot, Khushboo; Suneja, Upma; Engelson, Ellen S; Kotler, Donald P

2015-03-01

Heavy alcohol use has been hypothesized to accelerate disease progression to end-stage liver disease in patients with hepatitis C virus (HCV) infection. In this study, we estimated the relative influences of heavy alcohol use and HCV in decompensated chronic liver disease (CLD). Retrospectively, 904 patients with cirrhotic disease admitted to our hospitals during January 2010-December 2012 were identified based on ICD9 codes. A thorough chart review captured information on demographics, viral hepatitis status, alcohol use and progression of liver disease (i.e. decompensation). Decompensation was defined as the presence of ascites due to portal hypertension, bleeding esophageal varices, hepatic encephalopathy or hepatorenal syndrome. Heavy alcohol use was defined as a chart entry of greater than six daily units of alcohol or its equivalent. 347 patients were included based on our selection criteria of documented heavy alcohol use (n = 215; 62.0%), hepatitis titers (HCV: n = 182; 52.5%) and radiological evidence of CLD with or without decompensation (decompensation: n = 225; 64.8%). Independent of HCV infection, heavy alcohol use significantly increased the risk of decompensation (OR = 1.75, 95% CI 1.11-2.75, p < 0.02) relative to no heavy alcohol use. No significance was seen with age, sex, race, HIV, viral hepatitis and moderate alcohol use for risk for decompensation. Additionally, dose-relationship regression analysis revealed that heavy, but not moderate alcohol use, resulted in a three-fold increase (p = 0.013) in the risk of decompensation relative to abstinence. While both heavy alcohol use and HCV infection are associated with risk of developing CLD, our data suggest that heavy, but not moderate, alcohol consumption is associated with a greater risk for hepatic decompensation in patients with cirrhosis than does HCV infection.

Amelioration of cirrhotic portal hypertension by targeted cyclooxygenase-1 siRNA delivery to liver sinusoidal endothelium with polyethylenimine grafted hyaluronic acid.

PubMed

Lin, Liteng; Cai, Mingyue; Deng, Shaohui; Huang, Wensou; Huang, Jingjun; Huang, Xinghua; Huang, Mingsheng; Wang, Yong; Shuai, Xintao; Zhu, Kangshun

2017-10-01

Portal hypertension (PH), a leading cause of mortality in cirrhosis, lacks effective clinical therapeutic strategies. The increased thromboxane A 2 (TXA 2 ), derived primarily from the upregulation of cyclooxygenase-1 (COX-1) in cirrhotic liver sinusoidal endothelial cells (LSECs), is responsible for hepatic endothelial dysfunction and PH. Thus, blocking the COX-1 pathway in cirrhotic LSECs may benefit the treatment of PH. In this study, hyaluronate-graft-polyethylenimine (HA-PEI) was synthesized for the targeted delivery of COX-1 siRNA to LSECs. Compared to non-targeted PEI, HA-PEI mediated much more efficient siRNA delivery, which resulted in potent targeted gene silencing in LSECs. In vivo, HA-PEI notably increased the accumulation of siRNA along the sinusoidal lining of the liver, inhibited over-activation of the COX-1/TXA 2 pathway in LSECs, and successfully reduced portal pressure in cirrhotic mice. These results highlight the potential of HA-PEI complexed siRNA to serve as a LSECs-specific nanomedical system for effective gene therapy in PH. Copyright © 2017 Elsevier Inc. All rights reserved.

Glycogen content in hepatocytes is related with their size in normal rat liver but not in cirrhotic one.

PubMed

Bezborodkina, Natalia N; Chestnova, Anna Yu; Vorobev, Mikhail L; Kudryavtsev, Boris N

2016-04-01

Hepatocytes differ from one another by the degree of the ploidy, size, position in the liver lobule, and level of the DNA-synthetic processes. It is believed, that the cell size exerts substantial influence on the metabolism of the hepatocytes and the glycogen content in them. The aim of the present study was to test this hypothesis. Dry weight of hepatocytes, their ploidy and glycogen content were determined in the normal and the cirrhotic rat liver. Liver cirrhosis in rats was produced by chronic inhalation of CCl4 vapours in the course of 6 months. A combined cytophotometric method was used. Dry weight of the cell, its glycogen and DNA content were successively measured on a mapped preparation. Hepatocytes of each ploidy class in the normal and the cirrhotic rat liver accumulated glycogen at the same rate. In the normal liver, there was a distinct correlation between the size of hepatocytes and glycogen content in them. This correlation was observed in each ploidy class, and was especially pronounced in the class of mononucleate tetraploid hepatocytes. In the cirrhotic liver, there was no correlation between the size of the cells and their glycogen content. The impairment of liver lobular structure probably explains the observed lack of correlation between hepatocyte size and their glycogen content in the cirrhotic liver. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

Treatment of Patients With Hepatitis C Virus Infection With Ledipasvir-Sofosbuvir in the Liver Transplant Setting.

PubMed

Abaalkhail, Faisal; Elsiesy, Hussein; Elbeshbeshy, Hany; Shawkat, Mohamed; Yousif, Sarra; Ullah, Waheed; Alabbad, Saleh; Al-Jedai, Ahmed; Ajlan, Aziza; Broering, Dieter; Saab, Sammy; Al Sebayel, Mohammed; Al-Hamoudi, Waleed

2017-11-01

Hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir (LDV)-sofosbuvir (SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation. This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (cohort A) and a cohort of postliver transplantation patients (cohort B). Patients received LDV/SOF (90-400 mg) once daily for 12 to 24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded. A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in King Faisal Specialist Hospital and Research Center; 55% cohort A and 44% cohort B received RBV. Sustained virological response sustain virological response (SVR)12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, P value = 0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia. LDV/SOF without RBV is an effective and safe treatment option for patients with HCV genotype 4 infection in preliver and postliver transplant settings.

Hepatic inflammatory pseudotumor: A case series

PubMed Central

Calomeni, Guilherme D.; Ataíde, Elaine B.; Machado, Ricardo R.; Escanhoela, Cecília A.F.; Costa, Larissa B.E.; Boin, Ilka F.F.

2013-01-01

INTRODUCTION Inflammatory pseudotumor (IPT) is a rare lesion consisted of inflammatory and myofibroblastic cells. These lesions may be found in different organs. There are less than 300 described cases. PRESENTATION OF CASE Case 1. 64-year-old cirrhotic male with a palpable epigastric mass. CT showed a lesion in liver segments 2 and 3 and left hepatic artery aneurism. Percutaneous embolization and wide spectrum antibiotics were tried, however the lesion grew. Left lateral hepatectomy was performed, and HIPT diagnosed. The patient died due to multiple organ dysfunction. Case 2. 30-year-old male with abdominal pain and fever. CT showed a hepatic hilar lesion. Surgical resection was performed after an ineffectual antibiotic trial, and HIPT was confirmed. The patient is doing well. Case 3. 73-year-old female with abdominal pain and fever. CT showed a 7 cm lesion in the left liver lobe. Unrewarding cancerous screening was performed, and unsuccessful antibiotic course was tried. Resection was performed, and HIPT diagnosed. The patient is doing well. Case 4. 50-year-old cirrhotic male with abdominal pain. CT showed a segment 6 lesion and portal vein thrombosis. Considering cancer as the first hypothesis and the MELD score of 9, segmentectomy was performed. HIPT was the final diagnosis. The patient died due to abdominal sepsis. DISCUSSION HIPT is a lesion with a vast list of differential diagnosis. Antibiotics are the first line of therapy, although surgery is often necessary. Overall prognosis is good, although comorbidities may worsen it. CONCLUSION HIPT is a rare and misleading entity. PMID:23399515

Influence of genetic variations in the SOD1 gene on the development of ascites and spontaneous bacterial peritonitis in decompensated liver cirrhosis.

PubMed

Schwab, Sebastian; Lehmann, Jennifer; Lutz, Philipp; Jansen, Christian; Appenrodt, Beate; Lammert, Frank; Strassburg, Christian P; Spengler, Ulrich; Nischalke, Hans-Dieter; Trebicka, Jonel

2017-07-01

The balance between generation and elimination of reactive oxygen species by superoxide dismutase (SOD) is crucially involved in the pathophysiology of liver cirrhosis. Reactive oxygen species damage cells and induce inflammation/fibrosis, but also play a critical role in immune defense from pathogens. As both processes are involved in the development of liver cirrhosis and its complications, genetic variation of the SOD1 gene was investigated. Two SOD1 single nucleotide polymorphisms (rs1041740 and rs3844942) were analyzed in 49 cirrhotic patients undergoing liver transplantation. In addition, 344 cirrhotic patients with ascites were analyzed in a cohort of 521 individuals in terms of the relationship of these polymorphisms with spontaneous bacterial peritonitis (SBP). Although rs3844942 showed no associations with complications of cirrhosis, we observed a significant association between rs1041740 and the presence of ascites and SBP in the discovery cohort of patients with cirrhosis. Importantly, the association with SBP was not confirmed in the validation cohort of patients with ascites. By contrast, a trend toward lower SBP rates was observed in carriers of rs1041740. In this cohort, rs1041740 was not associated with survival. These data suggest a complex role of SOD1 in different processes leading to complications of liver cirrhosis. rs1041740 might be associated with the development of ascites and possibly plays a role in SBP once ascites has developed.

Umbilical hernia repair in the presence of cirrhosis and ascites: results of a survey and review of the literature.

PubMed

McKay, A; Dixon, E; Bathe, O; Sutherland, F

2009-10-01

Umbilical hernias are common in cirrhotics, yet, their management poses several challenges. The objective of this paper was to evaluate the indications, selection criteria, and technical aspects of umbilical hernia repair in patients with cirrhosis and ascites. An extensive review of the literature since 1980 was performed. A survey was also conducted to obtain expert consensus to supplement any available conclusions from the literature. Nineteen surgeons (45%) responded to the survey. For asymptomatic hernias, all would consider hernia repair in Child's A cirrhosis, but not in more advanced disease, whereas the vast majority would consider the repair of complicated hernias. This seems to reflect the respondents' higher estimates of morbidity and mortality with more advanced liver disease. However, because the recent literature demonstrates much lower morbidity and mortality than in the past, many authors now advocate early elective repair. In addition, uncontrolled ascites appear to be strongly predictive of hernia recurrence (relative risk [RR] 8.5; 95% confidence interval [CI] 2.7-26.9). While acknowledging the limitations of this study, it appears that the early repair of umbilical hernias in patients with cirrhosis and ascites is safer than it was in the past and can be considered for selected patients. This may avoid increased morbidity and mortality associated with urgent repair later on. The control of ascites is critical to a successful outcome. Urgent repair of umbilical hernia in cirrhotic patients is indicated when complications develop.

Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications

PubMed Central

Ponziani, Francesca Romana; Gerardi, Viviana; Pecere, Silvia; D’Aversa, Francesca; Lopetuso, Loris; Zocco, Maria Assunta; Pompili, Maurizio; Gasbarrini, Antonio

2015-01-01

Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial “fingerprint”, characterized by the reduced ratio of “good” to “potentially pathogenic” bacteria has recently been outlined, and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover, in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and, portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic, immune-modulating and anti-inflammatory activity, a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE, and also to prevent the development of SBP, to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality, triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease. PMID:26604640

Pharmaceutical and nutraceutical approaches for preventing liver carcinogenesis: chemoprevention of hepatocellular carcinoma using acyclic retinoid and branched-chain amino acids.

PubMed

Shimizu, Masahito; Shirakami, Yohei; Hanai, Tatsunori; Imai, Kenji; Suetsugu, Atsushi; Takai, Koji; Shiraki, Makoto; Moriwaki, Hisataka

2014-01-01

The poor prognosis for patients with hepatocellular carcinoma (HCC) is associated with its high rate of recurrence in the cirrhotic liver. Therefore, more effective strategies need to be urgently developed for the chemoprevention of this malignancy. The malfunction of retinoid X receptor α, a retinoid receptor, due to phosphorylation by Ras/mitogen-activated protein kinase is closely associated with liver carcinogenesis and may be a promising target for HCC chemoprevention. Acyclic retinoid (ACR), a synthetic retinoid, can prevent HCC development by inhibiting retinoid X receptor α phosphorylation and improve the prognosis for this malignancy. Supplementation with branched-chain amino acids (BCAA), which are used to improve protein malnutrition in patients with liver cirrhosis, can also reduce the risk of HCC in obese cirrhotic patients. In experimental studies, both ACR and BCAA exert suppressive effects on HCC development and the growth of HCC cells. In particular, combined treatment with ACR and BCAA cooperatively inhibits the growth of HCC cells. Furthermore, ACR and BCAA inhibit liver tumorigenesis associated with obesity and diabetes, both of which are critical risk factors for HCC development. These findings suggest that pharmaceutical and nutraceutical approaches using ACR and BCAA may be promising strategies for preventing HCC and improving the prognosis of this malignancy. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Liver Full Reference Set Application: David Lubman - Univ of Michigan (2011) — EDRN Public Portal

Cancer.gov

In this work we will perform the next step in the biomarker development and validation. This step will be the Phase 2 validation of glycoproteins that have passed Phase 1 blinded validation using ELISA kits based on target glycoproteins selected based on our previous work. This will be done in a large Phase 2 sample set obtained in a multicenter study funded by the EDRN. The assays will be performed in our research lab located in the Center for Cancer Proteomics in the University of Michigan Medical Center. This study will include patients in whom serum was stored for future validation and includes samples from early HCC (n = 158), advanced cases (n=214) and cirrhotic controls (n = 417). These samples will be supplied by the EDRN (per Dr. Jo Ann Rinaudo) and will be analyzed in a blinded fashion by Dr. Feng from the Fred Hutchinson Cancer Center. This phase 2 study was designed to have above 90% power at one-sided 5% type-I error for comparing the joint sensitivity and specificity for differentiating early stage HCC from cirrhotic patients between AFP and a new marker. Sample sizes of 200 for early stage HCC and 400 for cirrhotics were required to achieve the stated power (14). We will select our candidates for this larger phase validation set based on the results of previous work. These will include HGF and CD14 and the results of these assays will be used to evaluate the performance of each of these markers and combinations of HGF and CD14 and AFP and HGF. It is expected that each assay will be repeated three times for each marker and will also be performed for AFP as the standard for comparison. 250 uL of each sample is requested for analysis.

[Influence of non-sodium restricted diet with diuretics on plasma rennin, renal blood flow and in patients with cirrhotic ascites].

PubMed

Zhu, Yin-fang; Gu, Xi-bing; Zhu, Hong-ying; Yang, Xiao-juan; Wang, Dong; Yu, Ping

2013-02-01

To explore influence of sodium restricted diet and non-sodium restricted diet on plasma rennin (PRA), angiotensin II (All), ALD, renal blood flow (RBF) and subside of ascites in patients with cirrhotic ascites. Eighty cases of hepatitis B with cirrhotic ascites were randomly divided into sodium restricted diet group and non-sodium restricted diet group. 39 cases were in non-sodium restricted diet group, taking sodium chloride 6500-8000 mg daily; 41 cases were in sodium restricted diet group, taking sodium chloride 5000 mg daily. Both groups received diuretics furosemide and spironolactone. Blood sodium, urine sodium, PRA, AII, ALD, RBF ascites subsiding were compared after treatment. In non-sodium restricted diet group, blood sodium and urine sodium increased 10 days after treatment compared with those before treatment, and compared with those of sodium restricted diet group 10 days after treatment, P <0. 01. RBF increased compared with that before treatment, and compared with that of sodium restricted diet group 10 days after treatment, P < 0. 01. Renal damage induced by low blood sodium after treatment was less in non-sodium restricted diet group than that in sodium restricted diet group, P <0. 05. Ascites disappearance upon discharge was more in sodium restricted diet group than that in non-sodium restricted diet group, P <0. 01. Time of ascites disappearance was shorter in non-sodium restricted diet group than that in sodium restricted diet group, P < 0. 01. Compared with sodium restricted diet, while using diuretics of both groups, non-sodium restricted diet can increase level of blood sodium, thus increasing excretion of urine sodium and diuretic effect. It can also decrease levels of PRA, AII and ALD, increase renal blood flow and prevent renal damage induced by low blood sodium and facilitate subsiding of ascites.

A case of pelvic organ prolapse in the setting of cirrhotic ascites.

PubMed

Shah, Nima M; Ginzburg, Natasha; Whitmore, Kristene

2016-01-01

Ascites is commonly found in patients with liver cirrhosis. Although conservative therapy is often the ideal choice of care with these patients who also have symptomatic pelvic organ prolapse, this may fail and surgical methods may be needed. Literature is limited regarding surgical repair of prolapse in the setting of ascites. The authors present the surgical evaluation and management of a 63-year-old woman with recurrent ascites from liver cirrhosis who failed conservative therapy. With adequate multidisciplinary care and medical optimization, this patient underwent surgical therapy with resolution of her symptomatic prolapse and improved quality of life.

Hepatocellular Carcinoma in the Cirrhotic Liver: Evaluation Using Computed Tomography and Magnetic Resonance Imaging.

PubMed

Coskun, Mehmet

2017-03-01

Hepatocellular carcinoma is the fifth most common tumor in patients worldwide and the third most common cause of cancer-related death, after lung and stomach cancer. Cirrhosis of the liver is the strongest predisposing factor for hepatocellular carcinoma, with approximately 80% of cases of hepatocellular carcinoma developing in a cirrhotic liver. The annual incidence of hepatocellular carcinoma is 2.0% to 6.6% in patients with cirrhosis compared with 0.4% in patients without cirrhosis. The 5-year survival rates of patients undergoing curative therapies for hepatocellular carcinoma, including liver transplant, hepatic resection, and percutaneous ablative techniques, range between 40% and 75%. Orthotropic liver transplant offers the prima facie cure for both hepatocellular carcinoma and liver cirrhosis. In hepatocellular carcinoma confined to the liver without macrovascular invasion, patients with a single tumor ≤ 5 cm or up to 3 tumors ≤ 3 cm each had a 5-year survival rate of 75% and a disease-free survival rate of 83%. In the adult population, liver transplant for hepatocellular carcinoma yields good results for patients whose tumor masses do not exceed the Milan criteria. The diagnosis of hepatocellular carcinoma using imaging tests has had a substantial impact on transplant decisions. Radiologists should be aware of this responsibility and exercise the utmost scrutiny before making a diagnosis of hepatocellular carcinoma. Erroneous diagnosis of hepatocellular carcinoma based on imaging tests could deny deserving patients the opportunity of a life-saving liver transplant and result in unnecessary liver transplants for others. Contrast-enhanced magnetic resonance imaging and helical computed tomography are the best imaging techniques currently available for the noninvasive diagnosis of hepatocellular carcinoma. With technological advances in hardware and software, diffusion-weighted imaging can be readily applied to the liver with resulting improved image quality.

Umbilical paracentesis for incarcerated umbilical hernia in patients with end-stage liver disease.

PubMed

Alonso, S; Donat, M; Carrion, L; Rodriguez, J M; Diego, L; Acin, D; Serrano, A; Perez, E; Pereira, F

2016-08-01

Patients with cirrhosis and ascites are prone to abdominal wall complications largely predominate by umbilical hernia. Elective surgery is indicated in select patients but a high morbidity and mortality rate occurs if it is performed in emergency conditions. We present a clinical case of a patient with advanced alcoholic liver disease who came to the emergency room for an acutely incarcerated umbilical hernia. Due to the high surgical risk, we had to discuss other treatment options. The use of umbilical paracentesis for incarcerated hernia reduction in cirrhotic patients with tense ascites is a safe and reproducible technique. Umbilical paracentesis could be considered as an alternative to emergency surgery in these high-risk patients.

The nanomechanical signature of liver cancer tissues and its molecular origin

NASA Astrophysics Data System (ADS)

Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

2015-07-01

Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC. Electronic supplementary information (ESI) available: Detailed experimental procedures and supplementary figures. See DOI: 10.1039/c5nr02192h

Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS.

PubMed

Nielsen, M J; Lehmann, J; Leeming, D J; Schierwagen, R; Klein, S; Jansen, C; Strassburg, C P; Bendtsen, F; Møller, S; Sauerbruch, T; Karsdal, M A; Krag, A; Trebicka, J

2015-11-01

Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS). We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated. Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients. This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.

Polyunsaturated fatty acids balance affects platelet NOX2 activity in patients with liver cirrhosis.

PubMed

Basili, Stefania; Raparelli, Valeria; Napoleone, Laura; Del Ben, Maria; Merli, Manuela; Riggio, Oliviero; Nocella, Cristina; Carnevale, Roberto; Pignatelli, Pasquale; Violi, Francesco

2014-07-01

NADPH-oxidase-2 up-regulation has been suggested in liver damage perpetuation via an oxidative stress-mediated mechanism. n-6/n-3 polyunsaturated fatty acids ratio derangement has been reported in liver disease. To explore polyunsaturated fatty acids balance and its interplay with platelet oxidative stress in liver cirrhosis. A cross-sectional study in 51 cirrhotic patients and sex- and age-matched controls was performed. Serum polyunsaturated fatty acids and oxidative stress markers (urinary isoprostanes and serum soluble NADPH-oxidase-2-derived peptide) were measured. The effect on platelet oxidative stress of n-6/n-3 polyunsaturated fatty acids ratio in vitro and in vivo (1-week supplementation with 3g/daily n-3-polyunsaturated fatty acids) was tested. Compared to controls, cirrhotic patients had significantly higher n-6/n-3 polyunsaturated fatty acids ratio. n-6/n-3 polyunsaturated fatty acids ratio correlated significantly with disease severity and oxidative stress markers. In vitro experiments showed that in Child-Pugh C patients' platelets incubation with low n-6/n-3 polyunsaturated fatty acids ratio resulted in dose-dependent decrease of radical oxigen species (-39%), isoprostanes (-25%) and NADPH-oxidase-2 regulation (-51%). n-3 polyunsaturated fatty acids supplemented patients showed significant oxidative stress indexes reduction. In cirrhosis, n-6/n-3 polyunsaturated fatty acids imbalance up-regulates platelet NADPH-oxidase-2 with ensuing oxidative stress. Further study to evaluate if n-3 supplementation may reduce disease progression is warranted. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: A single center study.

PubMed

Ziada, Dina H; El Sadany, Sherif; Soliman, Hanan; Abd-Elsalam, Sherief; Salama, Marwa; Hawash, Nehad; Selim, Amal; Hamisa, Manal; Elsabagh, Hala M

2016-12-01

Hepatocellular carcinoma (HCC) has an increasing incidence worldwide. In this study we aimed to assess the prevalence of HCC among HCV patients in our center in Mid Delta, Egypt. During the period between April 2013 and January 2015, we screened sequentially chronic HCV patients attending inpatient wards or outpatient Clinic of Tropical Medicine Department in Tanta University Hospital for HCC. Individuals with focal lesion in Ultrasound (US) and/or serum α-fetoprotein (AFP) level >200ng/ml were examined by triphasic computed tomography scanning (CT), and/or magnetic resonance imaging (MRI). Among 514 HCV patients interviewed and accepted sharing in this study, 90 (17.5%), 144 (28%), and 280 (54.5%) were Child A, B, and C, respectively. We found that 108/514 patients (21%) had focal lesion detected by US. Also, 89/514 (17.3%) had elevated AFP >200, 13 of them (14.6%) had no focal lesion on US, but further work up showed HCC in 2 of them. Overall HCC diagnosis was confirmed in 103 cases, 94 of them (91.3%) were Child B or C. Occurrence of HCC was significantly higher in smokers, diabetics, patients with decompensated liver and those with positive family history of HCC. Only 20/103 (19.4%) were candidates to curative treatments, 8 of them were Child A asymptomatic and discovered accidentally during screening. The high prevalence of HCC in our HCV patients (22%) was mainly associated with decompensated cirrhosis. A national surveillance program for the detection of HCC in cirrhotic HCV Egyptian patients by combining ultrasound examination and AFP is highly recommended. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Acute-on-Chronic Liver Failure: Getting ready for prime-time.

PubMed

Bajaj, Jasmohan S; Moreau, Richard; Kamath, Patrick S; Vargas, Hugo E; Arroyo, Vicente; Reddy, K Rajender; Szabo, Gyongyi; Tandon, Puneeta; Olson, Jody; Karvellas, Constantine; Gustot, Thierry; Lai, Jennifer C; Wong, Florence

2018-04-24

Acute on chronic liver failure (ACLF) is a culmination of chronic liver disease and extra-hepatic organ failures, which is associated with a high short-term mortality and immense healthcare expenditure. There are varying definitions for organ failures and ACLF in Europe, North America and Asia. These differing definitions need to be reconciled to enhance progress in the field. The pathogenesis of ACLF is multi-factorial and related to interactions between the immuno-inflammatory system, microbiota and the precipitating factors. Individual organ failures related to the kidney, brain, lungs and circulation have cumulative adverse effects on mortality and are often complicated or precipitated by infections. Strategies to prevent and rapidly treat these organ failures are paramount in improving survival. With the aging population and paucity of organs for liver transplant, the prognosis of ACLF patients is poor, highlighting the need for novel therapeutic strategies. The role of liver transplant in ACLF is evolving and needs further investigation across large consortia. A role for early palliative care and management of frailty as approaches to alleviate disease burden and improve patient-reported outcomes is being increasingly recognized. ACLF is a clinically relevant syndrome that is epidemic worldwide and which requires a dedicated multi-national approach focused on prognostication and management. Investigations are underway worldwide to get ACLF ready for prime time. Compensated cirrhosis with >90% 1-year survival can transition into the decompensated stage with the onset of jaundice, ascites, variceal bleeding and hepatic encephalopathy (HE) (1)Acute on chronic liver failure (ACLF) is associated with rapid deterioration of liver function leading to liver failure, multiple extra-hepatic organ failures and high short-term mortality (2). Even if patients survive the acute insult, they may never return to their pre-episode functional state (3). The term "acute decompensation" has been used to characterize ascites, gastrointestinal bleeding, hepatic encephalopathy or infections without organ failure(4). There are several gaps in knowledge surrounding ACLF, which will be highlighted in this review. The prevalence of ACLF is difficult to assess due to varying regional definitions (5). ACLF, once thought to occur only in decompensated cirrhosis, has been recognized even in chronic liver disease without cirrhosis (5). ACLF occurs in approximately 10-30% of hospitalized cirrhotic patients (6-8). Because of its acuity, patients are frequently admitted into the intensive care unit (ICU), and every effort is made to stabilize these patients for liver transplantation (LT). This drives healthcare costs(9). Despite this intensive management, ACLF is associated with substantial morbidity and mortality. Because curative LT is only available to <10% of cirrhotic patients each year and ACLF patients are often delisted, the morbidity and mortality rates remain high, especially with an increasing number of organ failures (10). This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Risk factor analysis for massive lymphatic ascites after laparoscopic retroperitonal lymphadenectomy in gynecologic cancers and treatment using intranodal lymphangiography with glue embolization

PubMed Central

2016-01-01

Objective To evaluate risk factors for massive lymphatic ascites after laparoscopic retroperitoneal lymphadenectomy in gynecologic cancer and the feasibility of treatments using intranodal lymphangiography (INLAG) with glue embolization. Methods A retrospective analysis of 234 patients with gynecologic cancer who received laparoscopic retroperitonal lymphadenectomy between April 2006 and November 2015 was done. In June 2014, INLAG with glue embolization was initiated to manage massive lymphatic ascites. All possible clinicopathologic factors related to massive lymphatic ascites were determined in the pre-INLAG group (n=163). Clinical courses between pre-INLAG group and post-INLAG group (n=71) were compared. Results In the pre-INLAG group (n=163), four patients (2.5%) developed massive lymphatic ascites postoperatively. Postoperative lymphatic ascites was associated with liver cirrhosis (three cirrhotic patients, p<0.001). In the post-INLAG group, one patient with massive lymphatic ascites had a congestive heart failure and first received INLAG with glue embolization. She had pelvic drain removed within 7 days after INLAG. The mean duration of pelvic drain and hospital stay decreased after the introduction of INLAG (13.2 days vs. 10.9 days, p=0.001; 15.2 days vs. 12.6 days, p=0.001). There was no evidence of recurrence after this procedure. Conclusion Underlying medical conditions related to the reduced effective circulating volume, such as liver cirrhosis and heart failure, may be associated with massive lymphatic ascites after retroperitoneal lymphadenectomy. INLAG with glue embolization can be an alternative treatment options to treat leaking lymphatic channels in patients with massive lymphatic leakage. PMID:27171674

Pulmonary changes in liver transplant candidates with hepatitis C cirrhosis.

PubMed

Al-Moamary, M S; Gorka, T; Al-Traif, I H; Al-Jahdali, H H; Al-Shimemeri, A A; Al-Kanway, B; Abdulkareeem, A A; Abdulkareeem, A A

2001-12-01

Several studies have shown that pulmonary abnormalities are common in patients with end-stage liver disease. However, most of these studies were conducted on patients with heterogeneous etiologies. Therefore, we studied these changes in a homogenous group of hepatitis C cirrhotic patients who were potential candidates for liver transplantation. The charts of 81 patients from King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with hepatitis C cirrhosis who were evaluated for liver transplantation were reviewed. The following data was retrieved: echocardiography with micro-bubble study, arterial blood gases, and pulmonary function tests of 81 candidates and reviewed over 3 years from 1994 to 1997. The mean age was 53 (+/-9) years with male to female ratio of 1.4:1. Echocardiographic micro-bubble study, revealed 4 of 62 (7%) had an intrapulmonary shunt. Arterial blood gases results were pH of 7.44 (+/-0.4), partial arterial tension of carbon dioxide of 33 mm Hg (+/-4), partial arterial tension of oxygen of 84 mm Hg (+/-12), and alveolar-arterial gradient of 30 mm Hg (+/-10). Eleven percent had obstructive airway disease, 17% had restrictive lung impairment, and 43% had reduced diffusion capacity. Seventy five percent of patients with reduced diffusion capacity had normal lung volumes. Various pulmonary function test abnormalities did not lead to significant differences in arterial blood gases. Pulmonary changes were frequent in liver transplant candidates with hepatitis C virus cirrhosis with reduced diffusion capacity being the most. Apart from the effect of hepatopulmonary syndrome on arterial oxygenation, other pulmonary abnormalities were not significantly different.

Interaction between hyaluronan and CD44 in the development of dimethylnitrosamine-induced liver cirrhosis.

PubMed

Satoh, T; Ichida, T; Matsuda, Y; Sugiyama, M; Yonekura, K; Ishikawa, T; Asakura, H

2000-04-01

A significant increase in serum hyaluronan (HA) levels has been reported in patients with liver cirrhosis. This mechanism is not yet clear, and receptors for HA have not been characterized. In this study, we examined the expression of both HA and its receptors, CD44 and intercellular adhesion molecule-1 (ICAM-1), in dimethylnitrosamine-induced liver cirrhosis. Using biotinylated HA binding protein, HA was detected in the area of periportal fibrosis and around the sinusoidal wall where hepatic fibrosis was developing. Electron microscopy revealed that HA was localized on Ito cells and sinusoidal endothelial cells (SEC). Conversely, CD44, which was only expressed weakly in normal liver, was present in large amounts in cirrhotic liver. The distribution pattern of CD44 was similar to that of HA, however, CD44 was mainly localized on the infiltrating lymphocytes and Kupffer cells. Moreover, CD44 was detected on part of factor VIII-positive SEC. Intercellular adhesion molecule-1, another receptor for HA, was detected on the surface of hepatocytes and around the sinusoidal wall in cirrhotic liver, but its distribution was not accompanied by expression of HA. With respect to CD44 isoforms, the standard form m-RNA predominated in both normal and cirrhotic liver. Variant pMeta-1 mRNA was detected at low levels. An interaction between HA and CD44 may play a role in the recruitment of numerous infiltrating cells and HA accumulation in hepatic sinusoids. Together with phenotypic changes in the SEC, these results may lead to a disturbance in the elimination of HA during the progression of liver cirrhosis.

[Autoimmune hepatitis].

PubMed

Färkkilä, Martti

2013-01-01

Autoimmune hepatitis is chronic liver disease with two subtypes, type 1 with anti nuclear or smooth muscle antibodies and type 2 with LKM1 or LC1 antibodies, and both with hypergammaglobulinemia and typical histology. Prevalence of AIH is between 10 to 17 per 100000 in Europe. Up to 20-40 % of cases present with acute hepatitis. Budesonide can be used as a first line induction therapy in non-cirrhotic patients, and tiopurines, mercaptopurine or mycophenolic acid as maintenance therapies. Patients not responding to conventional therapy can be treated with ciclosporin, tacrolimus or rituximab or finally with liver transplantation.

Sub-clinical hepatic encephalopathy in cirrhotic patients is not aggravated by sedation with propofol compared to midazolam: a randomized controlled study.

PubMed

Khamaysi, Iyad; William, Nseir; Olga, Alexandrov; Alex, Isakson; Vladimir, Mysh; Kamal, Dabbah; Nimer, Assy

2011-01-01

The risk of exacerbating sub-clinical hepatic encephalopathy (HE) by propofol has not been established. The aim of this study is to determine whether the use of propofol, for upper endoscopy in patients with cirrhosis, precipitates sub-clinical HE. Sixty-one patients with compensated HCV and HBV cirrhosis (CP score 5-6) were randomly selected and divided into two groups (intent-to-treat population) matched for age, gender, and BMI. The first group received a single propofol sedation (N = 31, age 57 ± 12, dose range 70-100 mg/procedure) and the second group (N = 30, age 56 ± 12, dose 3-6 mg/procedure) received a single midazolam sedation, all done by an anesthesiologist. All patients completed number connection test (NCT), cognitive function score, time to recovery, time to discharge sheets, and hemodynamic parameters before sedation, and at discharge from the endoscopy unit, 1h post-procedure. Thirty control subjects without cirrhosis were matched to the cirrhotic patients who received sedation with regard to age, gender, BMI, and education level. A total of 58/61 cirrhotic patients (95%) had sub-clinical encephalopathy before the endoscopy (mean NCT 84.7 ± 77 s, normal < 30 s). No patient developed overt HE after sedation. There were no differences between groups in the incidence of adverse effects, cognitive function, MELD score, CP score, oxygen saturation, or respiratory and heart rates before and after sedation. Propofol did not exacerbate minimal HE when compared to midazolam (NCT changed from 87.5 ± 62 s prior to sedation to 74.2 ± 58 s after sedation in the propofol group versus 72.8 ± 62 s before to 85.6 ± 72 s after sedation in the midazolam group; p < 0.01). Time to recovery (4.1 ± 1.9 min vs. 11.5 ± 5.0 min, p < 0.001), and time to discharge (38.0 ± 9 min vs. 110 ± 42 min, p < 0.001) were significantly shorter with propofol than midazolam. Pre- and post-procedure NCT (from 25 ± 20 s to 24 ± 20 s), cognitive function score (from 25 to 26), time to recovery (3.5 ± 1.0 min), and time to discharge (35 ± 10 min) did not change in the healthy controls. Sedation with propofol has a shorter time recovery and a shorter time to discharge than midazolam and does not exacerbate sub-clinical hepatic encephalopathy in patients with compensated liver cirrhosis. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Treatment of a TIPS-Biliary Fistula by Stent-Graft in a 9-Year-Old Boy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyvat, Fatih; Cekirge, Saruhan; Balkanci, Ferhun

1999-01-15

We report a 9-year-old male cirrhotic patient with acute occlusion of a transjugular intrahepatic portosystemic shunt (TIPS) due to a biliary-to-TIPS fistula which occurred 9 hr after the TIPS procedure. Immediate TIPS revision was performed and the fistula was treated by placement of an endoluminal stent-graft. At 12-month follow-up color Doppler examination demonstrated a patent shunt.

Insulin-Like Growth Factor-1 Deficiency and Cirrhosis Establishment

PubMed Central

de la Garza, Rocio G.; Morales-Garza, Luis Alonso; Martin-Estal, Irene; Castilla-Cortazar, Inma

2017-01-01

Cirrhosis represents the final stage of chronic liver damage, which can be due to different factors such as alcohol, metabolic syndrome with liver steatosis, autoimmune diseases, drugs, toxins, and viral infection, among others. Nowadays, cirrhosis is an important health problem and it is an increasing cause of morbidity and mortality, being the 14th most common cause of death worldwide. The physiopathological pathways that lead to fibrosis and finally cirrhosis partly depend on the etiology. Nevertheless, some common features are shared in this complex mechanism. Recently, it has been demonstrated that cirrhosis is a dynamic process that can be altered in order to delay or revert fibrosis. In addition, when cirrhosis has been established, insulin-like growth factor-1 (IGF-1) deficiency or reduced availability is a common condition, independently of the etiology of chronic liver damage that leads to cirrhosis. IGF-1 deprivation seriously contributes to the progressive malnutrition of cirrhotic patient, increasing the vulnerability of the liver to establish an inflammatory and oxidative microenvironment with mitochondrial dysfunction. In this context, IGF-1 deficiency in cirrhotic patients can justify some of the common characteristics of these individuals. Several studies in animals and humans have been done in order to test the replacement of IGF-1 as a possible therapeutic option, with promising results. PMID:28270882

Combining amplicon sequencing and metabolomics in cirrhotic patients highlights distinctive microbiota features involved in bacterial translocation, systemic inflammation and hepatic encephalopathy.

PubMed

Iebba, Valerio; Guerrieri, Francesca; Di Gregorio, Vincenza; Levrero, Massimo; Gagliardi, Antonella; Santangelo, Floriana; Sobolev, Anatoly P; Circi, Simone; Giannelli, Valerio; Mannina, Luisa; Schippa, Serena; Merli, Manuela

2018-05-29

In liver cirrhosis (LC), impaired intestinal functions lead to dysbiosis and possible bacterial translocation (BT). Bacteria or their byproducts within the bloodstream can thus play a role in systemic inflammation and hepatic encephalopathy (HE). We combined 16S sequencing, NMR metabolomics and network analysis to describe the interrelationships of members of the microbiota in LC biopsies, faeces, peripheral/portal blood and faecal metabolites with clinical parameters. LC faeces and biopsies showed marked dysbiosis with a heightened proportion of Enterobacteriaceae. Our approach showed impaired faecal bacterial metabolism of short-chain fatty acids (SCFAs) and carbon/methane sources in LC, along with an enhanced stress-related response. Sixteen species, mainly belonging to the Proteobacteria phylum, were shared between LC peripheral and portal blood and were functionally linked to iron metabolism. Faecal Enterobacteriaceae and trimethylamine were positively correlated with blood proinflammatory cytokines, while Ruminococcaceae and SCFAs played a protective role. Within the peripheral blood and faeces, certain species (Stenotrophomonas pavanii, Methylobacterium extorquens) and metabolites (methanol, threonine) were positively related to HE. Cirrhotic patients thus harbour a 'functional dysbiosis' in the faeces and peripheral/portal blood, with specific keystone species and metabolites related to clinical markers of systemic inflammation and HE.

Renal water handling in rats with decompensated liver cirrhosis.

PubMed

Jonassen, T E; Christensen, S; Kwon, T H; Langhoff, S; Salling, N; Nielsen, S

2000-12-01

The present study was performed to investigate the renal handling of water in rats with decompensated liver cirrhosis. Liver cirrhosis was induced by intraperitoneal administration of carbon tetrachloride twice weekly for 16 wk. Control rats were treated with vehicle. The cirrhotic rats developed severe disturbances in water homeostasis: urine production was decreased and hyperosmotic, the rats had significantly decreased plasma sodium concentration and ascites, and the ability to excrete an intravenous water load was significantly impaired. Plasma concentrations of vasopressin and aldosterone were increased. Mean arterial pressure, glomerular filtration rate (GFR), and fractional lithium excretion were decreased. Acute vasopressin type 2-receptor blockade with the selective nonpeptide antagonist OPC-31260 (800 microg. kg(-1). h(-1)) was performed during conditions whereby volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 150 mM glucose. The aquaretic response to OPC-31260 was similar in cirrhotic and control rats. However, the OPC 31260-induced rises in fractional water excretion (delta V/GFR; +24%) and fractional distal water excretion (delta V/C(Li); +46%) were significantly increased in the cirrhotic rats, where V is flow rate and delta is change. This suggests that vasopressin-mediated renal water reabsorption capacity was increased in the cirrhotic rats. Semiquantitative immunoblotting revealed that the expression of the vasopressin-regulated water channel aquaporin-2 was unchanged in membrane fractions of both whole kidney and inner medulla from cirrhotic rats. Together, these results suggest a relative escape from vasopressin on collecting duct water reabsorption in rats with decompensated liver cirrhosis.

Efficiency of herbal medicine Dai-kenchu-to on portal blood flow in rat models.

PubMed

Muraoka, Izumi; Takatsuki, Mitsuhisa; Soyama, Akihiko; Yamaguchi, Izumi; Tanaka, Shiro; Tanaka, Takayuki; Kinoshita, Ayaka; Hara, Takanobu; Kuroki, Tamotsu; Eguchi, Susumu

2015-09-01

To clarify the influence of Dai-Kenchu-To (DKT) on portal blood flow (PBF), PBF was continuously measured with Doppler ultrasound. Normal liver rats were divided into a DKT 90 mg/kg, DKT 270 mg/kg administered group, and control, while cirrhotic liver rats were divided into a DKT-LC 90 mg/kg administered group and Control-LC. The PBF was measured after the administration of either DKT or water for 60 min by laser Doppler flowmetry system. The PBF in the DKT 90 increased approximately 10 min after DKT was administrated, and elevated levels were maintained for approximately 10 min. A comparison of the increase in PBF by the calculating the area under the curve (AUC) revealed that flow was significantly higher in the DKT 90 compared to either the control or the DKT 270 (p < 0.05). The cirrhotic liver group showed stable PBF in both the DKT-LC and Control-LC. The AUC, revealed no significant difference between the DKT-LC and Control-LC. DKT induced an increase in PBF in normal livers; however, its effects were insufficient to increase PBF in the cirrhotic livers. No increase in the portal blood flow in the cirrhotic liver rats was probably the result of the cirrhotic liver, which had fibrotic change, and, therefore, may not have had sufficient compliance to accept the increasing blood flow volume from the intestinal tract. We suggested DKT has the potential to protect the liver by increasing PBF when the liver has either normal or mild to moderate dysfunction.

Ledipasvir-Sofosbuvir for 8 Weeks in Non-Cirrhotic Patients with Previously Untreated Genotype 1 HCV Infection ± HIV-1 Co-Infection.

PubMed

Isakov, Vasily; Gankina, Natalia; Morozov, Viacheslav; Kersey, Kathryn; Lu, Sophia; Osinusi, Anu; Svarovskaia, Evguenia; Brainard, Diana M; Salupere, Riina; Orlova-Morozova, Elena; Zhdanov, Konstantin

2018-03-01

BACKGROUND AND OBJECTIVES: The efficacy of < 12 weeks of hepatitis C virus (HCV) treatment in patients co-infected with HCV and human immunodeficiency virus type 1 (HIV-1) has not been established. We assessed the efficacy and safety of ledipasvir-sofosbuvir for 8 weeks in HCV mono-infected and HCV/HIV-1 co-infected patients. We enrolled patients mono-infected with genotype 1 HCV or co-infected with HCV and HIV-1 who were HCV treatment-naive and did not have cirrhosis. HCV/HIV-1 co-infected patients were either not receiving antiretroviral treatment and had a CD4 T-cell count > 500 cells/mm 3 or were receiving a protocol-approved antiretroviral regimen for ≥ 8 weeks (or ≥ 6 months for abacavir-containing regimens) and had HIV-1 RNA < 50 copies/mL and a CD4 T-cell count > 200 cells/mm 3 . Patients received ledipasvir-sofosbuvir (90/400 mg) once daily for 8 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment discontinuation (SVR12). The SVR12 rate was 100% (67/67) for HCV mono-infected patients and 97% (57/59) for HCV/HIV-1 co-infected patients. Two patients relapsed by the week 4 post-treatment visit. Overall, the most common adverse events were headache (52%) and upper abdominal pain (26%). There were no serious adverse events or treatment discontinuations due to adverse events. No HCV/HIV-1 co-infected patients receiving antiretroviral treatment experienced HIV virologic rebound, and no clinically meaningful changes in CD4 T-cell counts were observed in any co-infected patient. Non-cirrhotic, treatment-naive patients with genotype 1 HCV mono-infection and HCV/HIV-1 co-infection achieved high rates of SVR12 with 8 weeks of treatment with ledipasvir/sofosbuvir. ClinicalTrials.gov identifier: NCT02472886.

Genetic Polymorphisms of Cytochrome P4501A1 (CYP1A1) and Glutathione S-Transferase P1 (GSTP1) and Risk of Hepatocellular Carcinoma Among Chronic Hepatitis C Patients in Egypt.

PubMed

Abo-Hashem, Ekbal M; El-Emshaty, Wafaa M; Farag, Raghda El Sayed; Zakaria, Sahar; Abd El-Aziz, Mohammed; Ghonaim, Azza

2016-10-01

Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase P1 (GSTP1) genes are involved in the metabolism of many carcinogens. Polymorphisms in these genes with altered enzyme activity have been reported. The present study evaluated the synergistic effect between CYP1A1 and GSTP1 gene polymorphisms and smoking on development of HCV-related liver disease and hepatocellular carcinoma (HCC). The patients group comprised 40 patients with HCC and 40 patients with liver cirrhosis. The control group comprised 40 healthy subjects having no history of malignancy. The genetic polymorphisms were studied using polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) technique on blood samples. The number of current or former smoker among HCC and cirrhotic patients as well as the median Pack/year of cigarette smoked were significantly higher in HCC and liver cirrhotic patients than in control group. Subjects with CYP1A1 gene variants (m1 and m3) had no significant risk to develop cirrhosis or HCC compared to control group. Individuals carrying the Ile/Val genotype of GSTP1 had a significant increased risk of HCC (OR of 2.2, 95 % CI 1.143-4.261) and had larger tumor size. No significant risk was observed on combining both genes variants or on combining smoking with variants of both genes. In conclusion, the GSTP1 Ile/Val genotype and Val allele are associated with an increased risk of HCC. CYP1A1 and GSTP1 genes variants interaction did not increase the risk of HCC.

Rifaximin vs. lactulose in treatment of minimal hepatic encephalopathy.

PubMed

Sidhu, Sandeep S; Goyal, Omesh; Parker, Richard A; Kishore, Harsh; Sood, Ajit

2016-03-01

Lactulose and rifaximin have already been shown to improve both cognitive functions and health related quality of life (HRQOL) in MHE patients. We aimed to compare the efficacy of rifaximin with lactulose in reversal of MHE and improvement in HRQOL in cirrhotic patients with MHE. This prospective, randomized, open label, non-inferiority trial, was conducted at the Gastroenterology department of a tertiary care institute in Northern India. MHE was diagnosed if any two of the five neuro-psychometric (NP) tests were positive. HRQOL was assessed using the sickness impact profile (SIP) questionnaire (John Hopkins University, USA). Of 527 cirrhotics screened, 351 were found eligible and tested for MHE. A total of 112 (31.9%) patients were found to have MHE and then randomized into two groups group A (lactulose; 30-120 ml/day) and B (Tablet. rifaximin; 400 mg thrice a day). Based on the intention-to-treat population, the proportion of patients with MHE reversal at 3 months was 73.7% (42/57) in the rifaximin arm and 69.1% (38/55) in the lactulose arm [4.6% difference (90% CI -9.3% to 18.4%)]. However, non-inferiority of rifaximin over lactulose could not be established as the pre-specified non-inferiority margin (-5%) lies within the two-sided 90% confidence interval of the difference. HRQOL was significantly improved in both groups (P = 0.20). However, the proportion of patients with flatulence (P = 0.004) and diarrhoea (P = 0.0002) was significantly higher in patients who took lactulose. Non-inferiority of rifaximin over lactulose for MHE reversal was not established. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

PubMed

Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease.

PubMed

Bamias, Giorgos; Gizis, Michalis; Delladetsima, Ioanna; Laoudi, Eyfrosyni; Siakavellas, Spyros I; Koutsounas, Ioannis; Kaltsa, Garyfallia; Vlachogiannakos, John; Vafiadis-Zouboulis, Irene; Daikos, George L; Papatheodoridis, George V; Ladas, Spiros D

2016-01-01

Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease.

Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients

PubMed Central

Vilas-Boas, Walkíria Wingester; Jr, Antônio Ribeiro-Oliveira; da Cunha Ribeiro, Renata; Vieira, Renata Lúcia Pereira; Almeida, Jerusa; Nadu, Ana Paula; Silva, Ana Cristina Simões e; Santos, Robson Augusto Souza

2008-01-01

AIM: To evaluate the effect of β-blockade on angiotensins in the splanchnic and peripheral circulation of cirrhotic patients and also to compare hemodynamic parameters during liver transplantation according to propranolol pre-treatment or not. METHODS: Patients were allocated into two groups: outpatients with advanced liver disease(LD) and during liver transplantation(LT). Both groups were subdivided according to treatment with propranolol or not. Plasma was collected through peripheral venipuncture to determine plasma renin activity(PRA), Angiotensin(Ang) I, Ang II, and Ang-(1-7) levels by radioimmunoassay in LD group. During liver transplantation, hemodynamic parameters were determined and blood samples were obtained from the portal vein to measure renin angiotensin system(RAS) components. RESULTS: PRA, Ang I, Ang II and Ang-(1-7) were significantly lower in the portal vein and periphery in all subgroups treated with propranolol as compared to non-treated. The relationships between Ang-(1-7) and Ang I levels and between Ang II and Ang I were significantly increased in LD group receiving propranolol. The ratio between Ang-(1-7) and Ang II remained unchanged in splanchnic and peripheral circulation in patients under β-blockade, whereas the relationship between Ang II and Ang I was significantly increased in splanchnic circulation of LT patients treated with propranolol. During liver transplantation, cardiac output and index as well systemic vascular resistance and index were reduced in propranolol-treated subgroup. CONCLUSION: In LD group, propranolol treatment reduced RAS mediators, but did not change the ratio between Ang-(1-7) and Ang II in splanchnic and peripheral circulation. Furthermore, the modification of hemodynamic parameters in propranolol treated patients was not associated with changes in the angiotensin ratio. PMID:19058308

Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life.

PubMed

Cento, V; Barbaliscia, S; Lenci, I; Ruggiero, T; Magni, C F; Paolucci, S; Babudieri, S; Siciliano, M; Pasquazzi, C; Ciancio, A; Perno, C F; Ceccherini-Silberstein, F

2017-10-01

First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. After PI-failure, 121 patients (cirrhotic=86.8%) were retreated following three different strategies: A) with 'GRT-guided' regimens (N=18); B) with 'AASLD/EASL recommended, not GRT-guided' regimens (N=72); C) with 'not recommended, not GRT-guided' regimens (N=31). Overall SVR rate was 91%, but all 18 patients treated with 'GRT-guided' regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving 'AASLD/EASL recommended, not GRT-guided' regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a 'not recommended, not GRT-guided regimen' (p <0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of treatment duration and performance of a baseline-GRT. Retreatment of PI-experienced patients can induce maximal SVR rates in real life. Baseline-GRT could help to optimize retreatment strategy, allowing PIs to be reconsidered when chosen after a RASs evaluation. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians.

PubMed

Arends, Pauline; Sonneveld, Milan J; Zoutendijk, Roeland; Carey, Ivana; Brown, Ashley; Fasano, Massimo; Mutimer, David; Deterding, Katja; Reijnders, Jurriën G P; Oo, Ye; Petersen, Jörg; van Bömmel, Florian; de Knegt, Robert J; Santantonio, Teresa; Berg, Thomas; Welzel, Tania M; Wedemeyer, Heiner; Buti, Maria; Pradat, Pierre; Zoulim, Fabien; Hansen, Bettina; Janssen, Harry L A

2015-08-01

Hepatocellular carcinoma (HCC) risk-scores may predict HCC in Asian entecavir (ETV)-treated patients. We aimed to study risk factors and performance of risk scores during ETV treatment in an ethnically diverse Western population. We studied all HBV monoinfected patients treated with ETV from 11 European referral centres within the VIRGIL Network. A total of 744 patients were included; 42% Caucasian, 29% Asian, 19% other, 10% unknown. At baseline, 164 patients (22%) had cirrhosis. During a median follow-up of 167 (IQR 82-212) weeks, 14 patients developed HCC of whom nine (64%) had cirrhosis at baseline. The 5-year cumulative incidence rate of HCC was 2.1% for non-cirrhotic and 10.9% for cirrhotic patients (p<0.001). HCC incidence was higher in older patients (p<0.001) and patients with lower baseline platelet counts (p=0.02). Twelve patients who developed HCC achieved virologic response (HBV DNA <80 IU/mL) before HCC. At baseline, higher CU-HCC and GAG-HCC, but not REACH-B scores were associated with development of HCC. Discriminatory performance of HCC risk scores was low, with sensitivity ranging from 18% to 73%, and c-statistics from 0.71 to 0.85. Performance was further reduced in Caucasians with c-statistics from 0.54 to 0.74. Predicted risk of HCC based on risk-scores declined during ETV therapy (all p<0.001), but predictive performances after 1 year were comparable to those at baseline. Cumulative incidence of HCC is low in patients treated with ETV, but ETV does not eliminate the risk of HCC. Discriminatory performance of HCC risk scores was limited, particularly in Caucasians, at baseline and during therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study.

PubMed

Lampertico, Pietro; Invernizzi, Federica; Viganò, Mauro; Loglio, Alessandro; Mangia, Giampaolo; Facchetti, Floriana; Primignani, Massimo; Jovani, Manol; Iavarone, Massimo; Fraquelli, Mirella; Casazza, Giovanni; de Franchis, Roberto; Colombo, Massimo

2015-11-01

Esophageal varices (EV) are a marker of disease severity in compensated cirrhosis due to hepatitis B virus (HBV) which predicts also the risk of hepatocellular carcinoma (HCC), clinical decompensation and anticipated liver related death. The dynamics and prognostic significance of EV in patients under long-term HBV suppression by nucleos(t)ide analogs (NUC), are poorly known. A standardized protocol (Baveno) including 414 upper gastrointestinal (GI) endoscopies was applied to 107 HBeAg-negative compensated cirrhotic patients (93% Child-Pugh A) during a median of 12 (range 2 to 17) years of NUC therapy. Patients who initially started on lamivudine (LMV) and then developed resistance (LMV-R), were rescued by early administration of adefovir, or were switched to tenofovir. Surveillance included serum HBV DNA every three months and abdominal ultrasound every six months. Twenty-seven patients had baseline F1 EV which regressed in 18, remained unchanged in eight and progressed in one patient; the 12-year cumulative incidence of EV regression was 83% (95% CI: 52-92%). De novo F1/F2 EV developed in 6/80 patients with a 12-year cumulative incidence of 10% (95% CI: 5-20%). Six of seven patients with de novo varices or progression of pre-existing varices had either a clinical breakthrough due to LMV-R and/or developed a HCC. No bleedings from ruptured EV occurred, 12 patients died (9 HCC) and 15 were transplanted (13 HCC): the 12-year cumulative incidence of HCC and overall survival was 33% (95% CI: 24-42%) and 76% (95% CI: 67-83%), respectively. Long-term pharmacological suppression of HBV in HBeAg-seronegative patients with compensated cirrhosis leads to a significant regression of pre-existing EV accompanied by a negligible risk of developing de novo EV. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Randomised clinical trial: the effects of a multispecies probiotic vs. placebo on innate immune function, bacterial translocation and gut permeability in patients with cirrhosis.

PubMed

Horvath, A; Leber, B; Schmerboeck, B; Tawdrous, M; Zettel, G; Hartl, A; Madl, T; Stryeck, S; Fuchs, D; Lemesch, S; Douschan, P; Krones, E; Spindelboeck, W; Durchschein, F; Rainer, F; Zollner, G; Stauber, R E; Fickert, P; Stiegler, P; Stadlbauer, V

2016-11-01

Probiotics may correct intestinal dysbiosis and proinflammatory conditions in patients with liver cirrhosis. To test the effects of a multispecies probiotic on innate immune function, bacterial translocation and gut permeability. In a randomised, double blind, placebo-controlled study, stable cirrhotic out-patients either received a daily dose of a probiotic powder containing eight different bacterial strains (Ecologic Barrier, Winclove, Amsterdam, The Netherlands) (n = 44) or a placebo (n = 36) for 6 months and were followed up for another 6 months. We found a significant but subclinical increase in neutrophil resting burst (2.6-3.2%, P = 0.0134) and neopterin levels (7.7-8.4 nmol/L, P = 0.001) with probiotics but not with placebo. Probiotic supplementation did not have a significant influence on neutrophil phagocytosis, endotoxin load, gut permeability or inflammatory markers. Ten severe infections occurred in total; one during intervention in the placebo group, and five and four after the intervention has ended in the probiotic and placebo group, respectively. Liver function showed some improvement with probiotics but not with placebo. Probiotic supplementation significantly increased serum neopterin levels and the production of reactive oxygen species by neutrophils. These findings might explain the beneficial effects of probiotics on immune function. Furthermore, probiotic supplementation may be a well-tolerated method to maintain or even improve liver function in stable cirrhosis. However, its influence on gut barrier function and bacterial translocation in cirrhotic patients is minimal. © 2016 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.

The psoas muscle transversal diameter predicts mortality in patients with cirrhosis on a waiting list for liver transplantation: A retrospective cohort study.

PubMed

Huguet, Audrey; Latournerie, Marianne; Debry, Pauline Houssel; Jezequel, Caroline; Legros, Ludivine; Rayar, Michel; Boudjema, Karim; Guyader, Dominique; Jacquet, Edouard Bardou; Thibault, Ronan

2018-02-09

Malnutrition impairs prognosis in liver cirrhosis. Our aims were to determine (1) if transversal (TPTI) and axial (APTI) psoas thickness indices predict mortality in cirrhotic patients and (2) the feasibility and reproducibility of transversal (TDPM) and axial (ADPM) diameters of the psoas muscle measurements. This was a retrospective study. Inclusion criteria included cirrhosis diagnosis, on liver transplantation waiting list, and abdominal computed tomography (CT) scan within the 3 mo preceding list inscription. TDPM and ADPM were measured on a single umbilicus-targeted CT image by non-expert and expert operators. TPTI or APTI (mm/m) were calculated as TDPM or ADPM/height (m). Area under the receiver operating characteristic curve (AUC) and Cox proportional hazard models were assessed. TPTI and APTI interobserver agreement: κ correlation test. A total of 173 patients were included. Low TPTI was associated with increased mortality: AUC = 0.66 (95% confidence interval, 0.51-0.80). TPTI was the only factor associated with mortality (hazard ratio = 0.87, 95% confidence interval 0.76-0.99, P = 0.034). There was an almost perfect interobserver agreement between the two operators: TDPM, κ = 0.97; ADPM, κ = 0.94; P <0.0001. TPTI measured on umbilicus-targeted CT scan before inscription on the waiting list for liver transplantation predicts mortality of cirrhotic patients. TPTI measurement is easy and reliable, even by a non-trained operator, and this is highly feasible in daily clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

Cytokeratin-18 in Diagnosis of HCC in Patients with Liver Cirrhosis

PubMed

Ismail, Saber A; El Saadany, Sherif; Ziada, Dina H; Zakaria, Soha S; Mayah, Wael W; Elashry, Heba; Arafa, Mona; Elmashad, Nehal

2017-04-01

Background: Hepatocellular carcinoma (HCC) is a common malignancy that occurs secondary to viral hepatitis B and C cirrhosis under the influence of environmental factors. In early stages, clinical diagnosis is often difficult and distinguishing HCC from cirrhosis and other hepatic masses by conventional tests is frequently not feasible. Physicians usually depend on measuring serum alpha-fetoprotein (AFP), but this marker has low sensitivity and specificity. The aim of this research was to determine any role of serum cytokeratin-18(Ck-18) as a marker for diagnosis of HCC in patients with liver cirrhosis. Patients and methods: We used ELISA to measure the serum levels of AFP and CK 18 in 60 Egyptian patients (30 cirrhotic and 30 with HCC) and 30 controls. Results: The Ck-18 level was significantly elevated in the HCC group (1247.8± 105.3U/L) when compared to the liver cirrhosis (834.1± 38.8 U/L) and control groups (265.2±83.1U/L). Ck-18 as a marker showed 95.6% sensitivity, 93.3% specificity and 98.8% accuracy. The mean serum AFP was 4901.4±2185.8ng/ml in the HCC group, 100.7±71.7 ng/ml in the cirrhotic group, and 4.0±1.2ng/ ml in controls. AFP showed 55. 7% sensitivity, 97. 7% specificity and 84.4% accuracy. Combined use of both Ck-18 and AFP improved the sensitivity to 98%. Conclusion: Serum cytokeratin-18 level can be used as a diagnostic biomarker for HCC with a higher sensitivity than AFP. Creative Commons Attribution License

Cytokeratin-18 in Diagnosis of HCC in Patients with Liver Cirrhosis

PubMed Central

Ismail, Saber A; Saadany, Sherif El; Ziada, Dina H; Zakaria, Soha S; Mayah, Wael W; Elashry, Heba; Arafa, Mona; Elmashad, Nehal

2017-01-01

Background: Hepatocellular carcinoma (HCC) is a common malignancy that occurs secondary to viral hepatitis B and C cirrhosis under the influence of environmental factors. In early stages, clinical diagnosis is often difficult and distinguishing HCC from cirrhosis and other hepatic masses by conventional tests is frequently not feasible. Physicians usually depend on measuring serum alpha-fetoprotein (AFP), but this marker has low sensitivity and specificity. The aim of this research was to determine any role of serum cytokeratin-18(Ck-18) as a marker for diagnosis of HCC in patients with liver cirrhosis. Patients and methods: We used ELISA to measure the serum levels of AFP and CK 18 in 60 Egyptian patients (30 cirrhotic and 30 with HCC) and 30 controls. Results: The Ck-18 level was significantly elevated in the HCC group (1247.8± 105.3U/L) when compared to the liver cirrhosis (834.1± 38.8 U/L) and control groups (265.2±83.1U/L). Ck-18 as a marker showed 95.6% sensitivity, 93.3% specificity and 98.8% accuracy. The mean serum AFP was 4901.4±2185.8ng/ml in the HCC group, 100.7±71.7 ng/ml in the cirrhotic group, and 4.0±1.2ng/ml in controls. AFP showed 55. 7% sensitivity, 97. 7% specificity and 84.4% accuracy. Combined use of both Ck-18 and AFP improved the sensitivity to 98%. Conclusion: Serum cytokeratin-18 level can be used as a diagnostic biomarker for HCC with a higher sensitivity than AFP. PMID:28547948

Rapamycin Ameliorates Inflammation and Fibrosis in the Early Phase of Cirrhotic Portal Hypertension in Rats through Inhibition of mTORC1 but Not mTORC2

PubMed Central

Wang, Weijie; Yan, Jiqi; Wang, Huakai; Shi, Minmin; Zhang, Mingjun; Yang, Weiping; Peng, Chenghong; Li, Hongwei

2014-01-01

Objective Hepatic stellate cells (HSCs) transdifferentiation and subsequent inflammation are important pathological processes involved in the formation of cirrhotic portal hypertension. This study characterizes the pathogenetic mechanisms leading to cholestatic liver fibrosis and portal hypertension, and focuses on mammalian target of rapamycin (mTOR) pathway as a potential modulator in the early phase of cirrhotic portal hypertension. Methods Early cirrhotic portal hypertension was induced by bile duct ligation (BDL) for three weeks. One week after operation, sham-operated (SHAM) and BDL rats received rapamycin (2 mg/kg/day) by intraperitoneal injection for fourteen days. Vehicle-treated SHAM and BDL rats served as controls. Fibrosis, inflammation, and portal pressure were evaluated by histology, morphometry, and hemodynamics. Expressions of pro-fibrogenic and pro-inflammatory genes in liver were measured by RT-PCR; alpha smooth muscle actin (α-SMA) and antigen Ki67 were detected by immunohistochemistry; expressions of AKT/mTOR signaling molecules, extracellular-signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, and interleukin-1 beta (IL-1β) were assessed by western blot. Results The AKT/mTOR signaling pathway was markedly activated in the early phase of cirrhotic portal hypertension induced by BDL in rats. mTOR blockade by rapamycin profoundly improved liver function by limiting inflammation, fibrosis and portal pressure. Rapamycin significantly inhibited the expressions of phosphorylated 70KD ribosomal protein S6 kinase (p-P70S6K) and phosphorylated ribosomal protein S6 (p-S6) but not p-AKT Ser473 relative to their total proteins in BDL-Ra rats. Those results suggested that mTOR Complex 1 (mTORC1) rather than mTORC2 was inhibited by rapamycin. Interestingly, we also found that the level of p-ERK1/2 to ERK1/2 was significantly increased in BDL rats, which was little affected by rapamycin. Conclusions The AKT/mTOR signaling pathway played an important role in the early phase of cirrhotic portal hypertension in rats, which could be a potential target for therapeutic intervention in the early phase of such pathophysiological progress. PMID:24404143

Rapamycin ameliorates inflammation and fibrosis in the early phase of cirrhotic portal hypertension in rats through inhibition of mTORC1 but not mTORC2.

PubMed

Wang, Weijie; Yan, Jiqi; Wang, Huakai; Shi, Minmin; Zhang, Mingjun; Yang, Weiping; Peng, Chenghong; Li, Hongwei

2014-01-01

Hepatic stellate cells (HSCs) transdifferentiation and subsequent inflammation are important pathological processes involved in the formation of cirrhotic portal hypertension. This study characterizes the pathogenetic mechanisms leading to cholestatic liver fibrosis and portal hypertension, and focuses on mammalian target of rapamycin (mTOR) pathway as a potential modulator in the early phase of cirrhotic portal hypertension. Early cirrhotic portal hypertension was induced by bile duct ligation (BDL) for three weeks. One week after operation, sham-operated (SHAM) and BDL rats received rapamycin (2 mg/kg/day) by intraperitoneal injection for fourteen days. Vehicle-treated SHAM and BDL rats served as controls. Fibrosis, inflammation, and portal pressure were evaluated by histology, morphometry, and hemodynamics. Expressions of pro-fibrogenic and pro-inflammatory genes in liver were measured by RT-PCR; alpha smooth muscle actin (α-SMA) and antigen Ki67 were detected by immunohistochemistry; expressions of AKT/mTOR signaling molecules, extracellular-signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, and interleukin-1 beta (IL-1β) were assessed by western blot. The AKT/mTOR signaling pathway was markedly activated in the early phase of cirrhotic portal hypertension induced by BDL in rats. mTOR blockade by rapamycin profoundly improved liver function by limiting inflammation, fibrosis and portal pressure. Rapamycin significantly inhibited the expressions of phosphorylated 70KD ribosomal protein S6 kinase (p-P70S6K) and phosphorylated ribosomal protein S6 (p-S6) but not p-AKT Ser473 relative to their total proteins in BDL-Ra rats. Those results suggested that mTOR Complex 1 (mTORC1) rather than mTORC2 was inhibited by rapamycin. Interestingly, we also found that the level of p-ERK1/2 to ERK1/2 was significantly increased in BDL rats, which was little affected by rapamycin. The AKT/mTOR signaling pathway played an important role in the early phase of cirrhotic portal hypertension in rats, which could be a potential target for therapeutic intervention in the early phase of such pathophysiological progress.

TIPS treatment in a patient with severe lower gastrointestinal bleeding with a misdiagnosis of cirrhotic portal hypertension.

PubMed

Laborda, Alicia; Guirola, José Andrés; Medrano, Joaquín; Simón, Miguel Ángel; Ioakeim, Ignatios; de-Gregorio, Miguel Ángel

2015-12-01

Abernethy malformation is a rare abnormal embryological development of splanchnic venous system characterised by the presence of a congenital extrahepatic portosystemic shunt. We present a rare case of an adult male patient that was admitted with severe lower gastrointestinal bleeding, requiring multiple blood transfusions. The patient's medical history and the laboratory tests performed led to the misdiagnosis of a congenital Abernethy malformation. We present a rare case, discussing the reasons for the misdiagnosis and we conclude that management of clinical data and imaging are highly important to discard these types of congenital malformations that can mimic a portal hypertension condition.

Predictors of Cardiovascular Events After Liver Transplantation.

PubMed

Gallegos-Orozco, Juan F; Charlton, Michael R

2017-05-01

Indications for liver transplant have been extended, and older and sicker patients are undergoing transplantation. Infectious, malignant, and cardiovascular diseases account for the most posttransplant deaths. Cirrhotic patients can develop heart disease through systemic diseases affecting the heart and the liver, cirrhosis-specific heart disease, or common cardiovascular. No single factor can predict posttransplant cardiovascular complications. Patients with history of cardiovascular disease, and specific abnormalities on echocardiography, electrocardiography, or serum markers of heart disease seem to be at increased risk of complications. Pretransplant cardiovascular evaluation is essential to detecting these risk factors so their effects can be mitigated through appropriate intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Insufficient evidence of benefit regarding mortality due to albumin substitution in HCC-free cirrhotic patients undergoing large volume paracentesis.

PubMed

Kütting, Fabian; Schubert, Jens; Franklin, Jeremy; Bowe, Andrea; Hoffmann, Vera; Demir, Muenevver; Pelc, Agnes; Nierhoff, Dirk; Töx, Ulrich; Steffen, Hans-Michael

2017-02-01

Current guidelines for clinical practice recommend the infusion of human albumin after large volume paracentesis. After inspecting the current evidence behind this recommendation, we decided to conduct a systematic review and meta-analysis in order to address the effect of albumin on mortality and morbidity in the context of large volume paracentesis. We performed a comprehensive search of large databases and abstract books of conference proceedings up to March 15th 2016 for randomized controlled trials, testing the infusion of human albumin against alternatives (vs no treatment, vs plasma expanders; vs vasoconstrictors) in HCC-free patients suffering from cirrhosis. We analyzed these trials with regard to mortality, changes in plasma renin activity (PRA), hyponatremia, renal impairment, recurrence of ascites with consequential re-admission into hospital and additional complications. We employed trial sequential analysis in order to calculate the number of patients required in controlled trials to be able to determine a statistically significant advantage of the administration of one agent over another with regard to mortality. We were able to include 21 trials totaling 1277 patients. While the administration of albumin prevents a rise in PRA as well as hyponatremia, no improvement in strong clinical endpoints such as mortality could be demonstrated. Trial sequential analysis showed that at least 1550 additional patients need to be recruited into RCTs and analyzed with regard to this question in order to detect or disprove a 25% mortality effect. There is insufficient evidence that the infusion of albumin after LVP significantly lowers mortality in HCC-free patients with advanced liver disease. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Drinking patterns and beverage preferences of liver cirrhosis patients in Mexico.

PubMed

Campollo, O; Martínez, M D; Valencia, J J; Segura-Ortega, J

2001-02-01

The purpose of this study was to investigate the pattern of alcoholism in a special group of alcoholics (alcoholic cirrhotics) in a hospital-based population in west central Mexico and assess the role of regional spirits such as tequila. A complete alcohol drinking history and a structured questionnaire directed at investigating the pattern of alcohol consumption was applied to 124 adult patients with chronic liver disease caused by alcohol during January 1995 to January 1996. The mean age of onset was 27 +/- 3 years in women and 18 +/- 0.5 years in men. The mean alcohol intake per week was 749 +/- 192 g for women and 1113 +/- 151 g for men. On average, patients consumed alcohol for a mean of 24.5 years. The overall patient drinking preference was for tequila followed by 96 degree Gay Lusac (G.L.), alcohol, and beer. In a subset of 70 patients three phases of alcoholism could be identified (prealcoholic, critical, and chronic). Each phase had a mean duration of at least 11 years. Beer was the dominant beverage in the prealcoholic phase while tequila was consumed more often in the other phases. In the critical phase of alcoholism an average of 337 g of alcohol were consumed per week and in the chronic phase 1765 g/week. Tequila was the overall preferred beverage in this group of alcoholics. Other beverages included beer and straight alcohol with a clear trend from less to higher concentration of alcohol throughout the drinking history. Subtle gender differences in the patterns of alcoholism may be suspected. In this group of patients the role of tequila drinking is highlighted.

Predictors of mental and physical health in non-cirrhotic patients with viral hepatitis: a case control study.

PubMed

Ashrafi, Mandana; Modabbernia, Amirhossein; Dalir, Mojtaba; Taslimi, Shervin; Karami, Maryam; Ostovaneh, Mohammad Reza; Malekzadeh, Reza; Poustchi, Hossein

2012-09-01

To identify independent predictors of mental and physical health in patients with viral hepatitis. Hepatitis C (HCV) and hepatitis B (HBV) infected patients, and community control subjects with equal age and sex distribution were recruited. All subjects filled in personal characteristics questionnaire, Hospital Anxiety and Depression Scale (HADS), Iowa Fatigue Scale (IFS), and Medical Outcomes Survey Short Form-12 (SF-12). All patients had measurement of routine laboratory values, and some had recent liver biopsy. Regression analyses were used to identify predictors of physical and mental health. One hundred eighty nine subjects (162 males, 27 females, for each group N=63) with mean (±SD) age of 39±11years were included. Anxiety and depression were important predictors of SF-12 (and its subscales MCS and PCS) and IFS scores, whereas IFS scores independently predicted HADS, PCS, MCS, and SF-12 scores. After controlling for confounders, HCV infection was independently associated with impairment of physical health. Moreover, creatinine showed an inverse strong relation with fatigue. Genotype 3a of HCV was independently associated with depressed and anxious states, whereas higher inflammation grade was significantly related to depression. Marital status, non-psychiatric comorbidities, and history of alcohol abuse also predicted health scores in the patients. Adjusted R(2)s for linear models were 0.571 to 0.709, whereas areas under the receiver operating characteristic (ROC) curve for logistic models were 0.90 to 0.93. In viral hepatitis patients, besides mental and medical comorbidities, marital status, and alcohol abuse, HCV infection itself is associated with impaired physical and possibly mental health. Copyright © 2012 Elsevier Inc. All rights reserved.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma.

PubMed

Porcu, Cristiana; Antonucci, Laura; Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-02-06

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies.

Serum Liver Fibrosis Markers in the Prognosis of Liver Cirrhosis: A Prospective Observational Study.

PubMed

Qi, Xingshun; Liu, Xu; Zhang, Yongguo; Hou, Yue; Ren, Linan; Wu, Chunyan; Chen, Jiang; Xia, Chunlian; Zhao, Jiajun; Wang, Di; Zhang, Yanlin; Zhang, Xia; Lin, Hao; Wang, Hezhi; Wang, Jinling; Cui, Zhongmin; Li, Xueyan; Deng, Han; Hou, Feifei; Peng, Ying; Wang, Xueying; Shao, Xiaodong; Li, Hongyu; Guo, Xiaozhong

2016-08-02

BACKGROUND The prognostic role of serum liver fibrosis markers in cirrhotic patients remains unclear. We performed a prospective observational study to evaluate the effect of amino-terminal pro-peptide of type III pro-collagen (PIIINP), collagen IV (CIV), laminin (LN), and hyaluronic acid (HA) on the prognosis of liver cirrhosis. MATERIAL AND METHODS All patients who were diagnosed with liver cirrhosis and admitted to our department were prospectively enrolled. PIIINP, CIV, LN, and HA levels were tested. RESULTS Overall, 108 cirrhotic patients were included. Correlation analysis demonstrated that CIV (coefficient r: 0.658, p<0.001; coefficient r: 0.368, p<0.001), LN (coefficient r: 0.450, p<0.001; coefficient r: 0.343, p<0.001), and HA (coefficient r: 0.325, p=0.001; coefficient r: 0.282, p=0.004) levels, but not PIIINP level (coefficient r: 0.081, p=0.414; coefficient r: 0.090, p=0.363), significantly correlated with Child-Pugh and MELD scores. Logistic regression analysis demonstrated that HA (odds ratio=1.00003, 95% confidence interval [CI]=1.000004-1.000056, p=0.022) was significantly associated with the 6-month mortality. Receiver operating characteristics analysis demonstrated that the area under the curve (AUC) of HA for predicting the 6-month mortality was 0.612 (95%CI=0.508-0.709, p=0.1531). CONCLUSIONS CIV, LN, and HA levels were significantly associated with the severity of liver dysfunction, but might be inappropriate for the prognostic assessment of liver cirrhosis.

Correlation of serum liver fibrosis markers with severity of liver dysfunction in liver cirrhosis: a retrospective cross-sectional study

PubMed Central

Zhu, Cuihong; Qi, Xingshun; Li, Hongyu; Peng, Ying; Dai, Junna; Chen, Jiang; Xia, Chunlian; Hou, Yue; Zhang, Wenwen; Guo, Xiaozhong

2015-01-01

Hyaluronic acid (HA), laminin (LN), amino-terminal pro-peptide of type III pro-collagen (PIIINP), and collagen IV (CIV) are four major serum markers of liver fibrosis. This retrospective cross-sectional study aimed to evaluate the correlations of the four serum markers with the severity of liver dysfunction in cirrhotic patients. Between January 2013 and June 2014, a total of 228 patients with a clinical diagnosis with liver cirrhosis and without malignancy underwent the tests of HA, LN, PIIINP, and CIV levels. Laboratory data were collected. Child-Pugh and model for the end-stage of liver diseases (MELD) scores were calculated. Of them, 32%, 40%, and 18% had Child-Pugh class A, B, and C, respectively. MELD score was 7.58±0.50. HA (coefficient r: 0.1612, P=0.0203), LN (coefficient r: 0.2445, P=0.0004), and CIV (coefficient r: 0.2361, P=0.0006) levels significantly correlated with Child-Pugh score, but not PIIINP level. Additionally, LN (coefficient r: 0.2588, P=0.0002) and CIV (coefficient r: 0.1795, P=0.0108) levels significantly correlated with MELD score, but not HA or PIIINP level. In conclusions, HA, LN, and CIV levels might be positively associated with the severity of liver dysfunction in cirrhotic patients. However, given a relatively weak correlation between them, our findings should be cautiously interpreted and further validated. PMID:26131195

Minimal hepatic encephalopathy matters in daily life

PubMed Central

Bajaj, Jasmohan S

2008-01-01

Minimal hepatic encephalopathy is a neuro-cognitive dysfunction which occurs in an epidemic proportion of cirrhotic patients, estimated as high as 80% of the population tested. It is characterized by a specific, complex cognitive dysfunction which is independent of sleep dysfunction or problems with overall intelligence. Although named “minimal”, minimal hepatic encephalopathy (MHE) can have a far-reaching impact on quality of life, ability to function in daily life and progression to overt hepatic encephalopathy. Importantly, MHE has a profound negative impact on the ability to drive a car and may be a significant factor behind motor vehicle accidents. A crucial aspect of the clinical care of MHE patients is their driving history, which is often ignored in routine care and can add a vital dimension to the overall disease assessment. Driving history should be an integral part of care in patients with MHE. The lack of specific signs and symptoms, the preserved communication skills and lack of insight make MHE a difficult condition to diagnose. Diagnostic strategies for MHE abound, but are usually limited by financial, normative or time constraints. Recent studies into the inhibitory control and critical flicker frequency tests are encouraging since these tests can increase the rates of MHE diagnosis without requiring a psychologist. Although testing for MHE and subsequent therapy is not standard of care at this time, it is important to consider this in cirrhotics in order to improve their ability to live their life to the fullest. PMID:18595126

Infarction and Laceration of Liver Parenchyma Caused by Wedged CO{sub 2} Venography Before TIPS Insertion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Theuerkauf, Ingo; Strunk, Holger; Brensing, Karl August

2001-01-15

We describe the fatal outcome of an elective TIPS procedure performed in a 43-year-old man with alcoholic cirrhosis. Wedged hepatic venography with CO{sub 2} was the reason for infarction and laceration of liver parenchyma resulting in a subcapsular hematoma and subsequent intra-abdominal bleeding. This is the first report of this complication after the use of CO{sub 2} in a cirrhotic patient.

Efficiency of herbal medicine Dai-kenchu-to on portal blood flow in rat models

PubMed Central

Muraoka, Izumi; Takatsuki, Mitsuhisa; Soyama, Akihiko; Yamaguchi, Izumi; Tanaka, Shiro; Tanaka, Takayuki; Kinoshita, Ayaka; Hara, Takanobu; Kuroki, Tamotsu; Eguchi, Susumu

2015-01-01

Introduction To clarify the influence of Dai-Kenchu-To (DKT) on portal blood flow (PBF), PBF was continuously measured with Doppler ultrasound. Methods Normal liver rats were divided into a DKT 90 mg/kg, DKT 270 mg/kg administered group, and control, while cirrhotic liver rats were divided into a DKT-LC 90 mg/kg administered group and Control-LC. The PBF was measured after the administration of either DKT or water for 60 min by laser Doppler flowmetry system. Results The PBF in the DKT 90 increased approximately 10 min after DKT was administrated, and elevated levels were maintained for approximately 10 min. A comparison of the increase in PBF by the calculating the area under the curve (AUC) revealed that flow was significantly higher in the DKT 90 compared to either the control or the DKT 270 (p < 0.05). The cirrhotic liver group showed stable PBF in both the DKT-LC and Control-LC. The AUC, revealed no significant difference between the DKT-LC and Control-LC. Discussion DKT induced an increase in PBF in normal livers; however, its effects were insufficient to increase PBF in the cirrhotic livers. No increase in the portal blood flow in the cirrhotic liver rats was probably the result of the cirrhotic liver, which had fibrotic change, and, therefore, may not have had sufficient compliance to accept the increasing blood flow volume from the intestinal tract. Conclusion We suggested DKT has the potential to protect the liver by increasing PBF when the liver has either normal or mild to moderate dysfunction. PMID:26155361

Factors affecting outcome of treatment of chronic hepatitis C: result of an open label study from eastern India.

PubMed

Ray, Gautam

2016-01-01

Standard treatment of hepatitis C involves the use of pegylated interferon (PEGIFN) and ribavirin but directly acting antiviral agents (DAA) with seemingly greater efficacy have now appeared on the market. Thus closer detail needs to be given to optimise the use of the former. Fifty-two chronic hepatitis C patients (Child class A) were administered PEGIFN and ribavirin in a prospective, open label study in standard dose and duration. Complete therapy was ensured for the best chance of achieving a sustained viral response (SVR) and delineating its controlling factors. Seventy-five percent had genotype 3 virus. Compensated cirrhosis was present in 38.5%. Response overall and in cirrhotics were 65.4% and 30%, respectively, without difference between genotypes 1 and 3. Non-cirrhotics had higher response in all groups, especially genotype 1 (83.3%). The factors associated with positive response were age less than 50 years, absence of cirrhosis and presence of risk factors for transmission. Treatment outcome and factors affecting it are similar to studies from Europe and America. © The Author(s) 2015.

Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

PubMed

Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

2015-08-01

To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

Nutritional status and quality of life in current patients with liver cirrhosis as assessed in 2007-2011.

PubMed

Shiraki, Makoto; Nishiguchi, Shuhei; Saito, Masaki; Fukuzawa, Yoshitaka; Mizuta, Toshihiko; Kaibori, Masaki; Hanai, Tatsunori; Nishimura, Kayoko; Shimizu, Masahito; Tsurumi, Hisashi; Moriwaki, Hisataka

2013-02-01

Current guidelines recommended adequate nutritional support for patients with liver cirrhosis to improve clinical outcome and quality of life (QOL). However, these evidences were obtained more than 10 years ago when malnutrition prevailed. In recent years, the impact of obesity on liver damage and carcinogenesis has grown. We attempted to elucidate the nutritional state and QOL in present cirrhotics. A research group supported by the Ministry of Health, Labor and Welfare of Japan recruited 294 cirrhotics between 2007 and 2011. Subjects comprised 171 males and 123 females, 158 of whom had hepatocellular carcinoma (HCC) and Child-Pugh grades A : B : C were 154:91:49. Anthropometry, blood biochemistry and indirect calorimetry were conducted, and QOL was measured using Short Form-8. The mean body mass index (BMI) of all patients was 23.1 ± 3.4 kg/m(2) , and 31% showed obesity (BMI ≥ 25.0). In subjects without ascites, edema or HCC, mean BMI was 23.6 ± 3.6, and 34% had obesity. Protein malnutrition defined as serum albumin of less than 3.5 g/dL and energy malnutrition as respiratory quotient of less than 0.85 appeared in 61% and 43%, respectively, and protein-energy malnutrition (PEM) in 27% of all subjects. Among subjects without HCC, each proportion was 67%, 48% and 30%, respectively. QOL was significantly lower on all subscales than Japanese national standard values, but was similar regardless the presence or absence of HCC. While PEM is still present in liver cirrhosis, an equal proportion has obesity in recent patients. Thus, in addition to guidelines for PEM, establishment of nutrition and exercise guidelines seems essential for obese patients with liver cirrhosis. © 2013 The Japan Society of Hepatology.

Infections in patients affected by liver cirrhosis: an update.

PubMed

Ascione, Tiziana; Di Flumeri, Giusy; Boccia, Giovanni; De Caro, Francesco

2017-06-01

Patients with liver cirrhosis present an increased incidence of infections. The main cause has been founded in alterations of the enteric flora and of the intestinal barrier probably due to portal hypertension, in addition to a reticulo-endothelial system dysfunction. Furthermore, those living with cirrhosis can report a high predisposition to sepsis and septic shock, due to the excessive response of pro-inflammatory cytokines and a complessive hemodynamic derangement. By the analysis in the experimental model of the cirrhotic rat, it was demonstrated that radio-labelled Escherichia coli given by the oral route resulted in the location of the bacteria in the gut, the ascitic fluid and mesenteric lymph nodes, a phenomenon known as bacterial translocation. Bacteria encountered with the highest frequency are those colonizing the intestinal tract, such as E. coli, Klebsiella pneumoniae and Enterobacteriaceae, intracellular bacteria and parasites are reported with a lower frequency. Multi-drug resistant bacteria are cultured with the highest frequency in those with frequent hospitalisations and report both high septic shock and mortality rates. Spontaneous bacterial peritonitis (SBP) is the commonest infection in cirrhotic, estimated to occur in 10-30% of the cases with ascites. A practical approach may include administration of a protected penicillin, III generation cephalosporin or quinolones in uncomplicated cases. Instead, in complicated cases and in nosocomial SBP, administration of cephalosporin or quinolones can be burned by the high resistance rate and drugs active against ESBL-producing bacteria and multi-drug resistant Gram positive bacteria have to be considered as empiric therapy, until cultures are available. When cultures are not readily available and patients fail to improve a repeated diagnostic paracentesis should be performed. Current investigations suggest that norfloxacin 400 mg/day orally has been reported to successfully prevent SBP in patients with low-protein ascites and patients with prior SBP.

Amprenavir and ritonavir plasma concentrations in HIV-infected patients treated with fosamprenavir/ritonavir with various degrees of liver impairment.

PubMed

Seminari, Elena; De Bona, Anna; Gentilini, Gianluca; Galli, Laura; Schira, Giulia; Gianotti, Nicola; Uberti-Foppa, Caterina; Soldarini, Armando; Dorigatti, Fernanda; Lazzarin, Adriano; Castagna, Antonella

2007-10-01

The purpose of this study was to evaluate the steady-state pharmacokinetics of amprenavir and ritonavir in HIV-infected patients with different degrees of hepatic impairment. HIV-positive patients receiving fosamprenavir/ritonavir (700/100 mg twice daily) were included. Patients were classified into three groups: (i) chronic hepatitis; (ii) liver cirrhosis; (iii) normal liver function. Serial blood samples for steady-state amprenavir and ritonavir pharmacokinetics (>14 days on treatment) were collected in the fasting state before the morning dose (C(trough)) and then 1, 2, 3, 4, 6, 8, 10 and 12 h after drug intake. Amprenavir and ritonavir plasma concentrations were determined by HPLC. Twenty-one HIV-infected patients were included. Seven had chronic hepatitis, eight had liver cirrhosis and six patients were in the control group. Amprenavir AUC(0-12), AUC(0-infinity), C(max) and C(ss) were increased by 50% to 60% in the cirrhotic group when compared with controls, whereas CL/F was decreased by 40%. Patients with chronic hepatitis showed a significant increase in AUC(0-12), C(max) and C(ss) values when compared with controls. Ritonavir pharmacokinetics was different only in cirrhotic patients when compared with controls. Liver function parameters at weeks 4, 12 and 24 were not different from baseline in any of the groups. Overall, a significant correlation between amprenavir AUC(0-12) and total bilirubin values on the day of pharmacokinetic analysis was found (r = 0.64, P = 0.003). On the basis of these data and also of data available in the literature, it seems reasonable to adapt the dose of fosamprenavir and/or ritonavir exclusively in the presence of adverse events, possibly related to protease inhibitors (i.e. liver toxicity), in subjects with high drug plasma levels. Therapeutic drug monitoring is advised in the management of these patients.

Impact of universal access to hepatitis C therapy on HIV-infected patients: implementation of the Spanish national hepatitis C strategy.

PubMed

Rivero-Juarez, A; Lopez-Cortes, L F; Castaño, M; Merino, D; Marquez, M; Mancebo, M; Cuenca-Lopez, F; Jimenez-Aguilar, P; Lopez-Montesinos, I; Lopez-Cardenas, S; Collado, A; Lopez-Ruz, M A; Omar, M; Tellez, F; Perez-Stachowski, X; Hernandez-Quero, J; Girón-Gonzalez, J A; Fernandez-Fuertes, E; Rivero, A

2017-03-01

In April 2015, the Spanish National Health System (SNHS) developed a national strategic plan for the diagnosis, treatment, and management of hepatitis C virus (HCV). Our aim was to analyze the impact of this on human immunodeficiency virus (HIV)-infected patients included in the HERACLES cohort during the first 6 months of its implementation. The HERACLES cohort (NCT02511496) was set up in March 2015 to evaluate the status and follow-up of chronic HCV infection in patients co-infected with HIV in the south of Spain. In September 2015, the data were analyzed to identify clinical events (death, liver decompensation, and liver fibrosis progression) and rate of treatment implementation in this population. The study population comprised a total of 3474 HIV/HCV co-infected patients. The distribution according to liver fibrosis stage was: 1152 F0-F1 (33.2 %); 513 F2 (14.4 %); 641 F3 (18.2 %); 761 F4 (21.9 %); and 407 whose liver fibrosis was not measured (12.3 %). During follow-up, 248 patients progressed by at least one fibrosis stage [7.1 %; 95 % confidence interval (CI): 6.3-8 %]. Among cirrhotic patients, 52 (6.8 %; 95 % CI: 5.2-8.9 %) developed hepatic decompensation. In the overall population, 50 patients died (1.4 %; 95 % CI: 1.1-1.9 %). Eight hundred and nineteen patients (23.56 %) initiated interferon (IFN)-free treatment during follow-up, of which 47.8 % were cirrhotic. In our study, during 6 months of follow-up, 23.56 % of HIV/HCV co-infected patients included in our cohort received HCV treatment. However, we observed a high incidence of negative short-term outcomes in our population.

[Resting-state functional magnetic resonance study of brain function changes after TIPS operation in patients with liver cirrhosis].

PubMed

Liu, C; Wang, H B; Yu, Y Q; Wang, M Q; Zhang, G B; Xu, L Y; Wu, J M

2016-12-20

Objective: To investigate the brain function changes in cirrhosis patients after transjugular intrahepatic portosystemic shunt (TIPS), resting-state functional MRI (rs-fMRI) performed and fractional amplitude of low frequency fluctuation (fALFF) was analyzed. Methods: From January 2014 to February 2016, a total of 96 cirrhotic patients from invasive technology department and infection department in the First Affiliated Hospital of Anhui Medical University were selected , the blood ammonia data of 96 cirrhotic patients with TIPS operation in four groups were collected after 1, 3, 6 and 12 month, and all subjects performed rs-fMRI scans. The rs-fMRI data processed with DPARSF and SPM12 softwares, whole-brain fALFF values were calculated, and One-Way analysis of variance , multiple comparison analysis and correlation analysis were performed. Results: There were brain regions with significant function changes in four groups patients with TIPS operation after 1, 3, 6 and 12 month, including bilateral superior temporal gyrus, right middle temportal gyrus , right hippocampus, right island of inferior frontal gyrus, left fusiform gyrus, left olfactory cortex, left orbital superior frontal gyrus (all P <0.005). Multiple comparison analysis showed that compared with patients in the 1-month follow-up, patients in the 3-month follow-up showed that brain function areas increased in left olfactory cortex, left inferior temporal gyrus, left fusiform gyrus, left orbital middle frontal gyrus, left putamen, left cerebelum, and decreased in left lingual gyrus; patients in the 6-month follow-up showed that brain function areas increased in left middle temportal gyrus, right supramarginal gyrus, right temporal pole, right central operculum, and decreased in left top edge of angular gyrus, left postcentral gyrus; patients in the 12-month follow-up showed that brain function areas increased in right hippocampus, right middle cingulate gyrus, and decreased in right middle temportal gyrus.Compared with patients in the 3-month follow-up, patients in the 6-month follow-up showed that brain function areas increased in left superior temporal gyrus, left middle temporal gyrus, right temporal pole, right island of inferior frontal gyrus, and decreased in left cerebelum, left orbital inferior frontal gyrus; patients in the 12-month follow-up showed that there were no obvious increase and decrease brain function areas.Compared with patients in the 6-month follow-up, patients in the 12-month follow-up showed that there were no obvious increase brain function areas , but brain function areas decreased in bilateral middle temportal gyrus( P <0.001). Brain regions were positively related to blood ammonia in right middle cingulate gyrus, right central operculum, left parahippocampal gyrus, while as brain regions were negatively related to blood ammonia in bilateral medial prefrontal lobe, anterior cingulate and paracingulate gyrus, right top edge of angular gyrus, right middle temportal gyrus, left anterior central gyrus, left posterior central gyrus (all P <0.005). Conclusion: The resting state brain function increased or decreased with course of disease in cirrhosis patients after TIPS operation. The brain activity of limbic system and sensorimotor system all had significant correlation with blood ammonia levels. The blood ammonia level and the function of relative brain regions after 6-month with TIPS operation can be gradually improved.

Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial.

PubMed

Hézode, Christophe; Asselah, Tarik; Reddy, K Rajender; Hassanein, Tarek; Berenguer, Marina; Fleischer-Stepniewska, Katarzyna; Marcellin, Patrick; Hall, Coleen; Schnell, Gretja; Pilot-Matias, Tami; Mobashery, Niloufar; Redman, Rebecca; Vilchez, Regis A; Pol, Stanislas

2015-06-20

Hepatitis C virus (HCV) genotype 4 accounts for about 13% of global HCV infections. Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability, an unmet need exists for effective all-oral regimens. We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir, an NS5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (ombitasvir plus paritaprevir plus ritonavir), given with or without ribavirin. In this multicentre ongoing phase 2b, randomised, open-label combination trial (PEARL-I), patients were recruited from academic, public, and private hospitals and clinics in France, Hungary, Italy, Poland, Romania, Spain, Turkey, and the USA. Eligible participants were aged 18-70 years with non-cirrhotic, chronic HCV genotype 4 infection (documented ≥6 months before screening) and plasma HCV RNA levels higher than 10,000 IU/mL. Previously untreated (treatment-naive) patients were randomly assigned (1:1) by computer-generated randomisation lists to receive once-daily ombitasvir (25 mg) plus paritaprevir (150 mg) plus ritonavir (100 mg) with or without weight-based ribavirin for 12 weeks. Previously treated (treatment-experienced) patients who had received pegylated interferon plus ribavirin all received the ribavirin-containing regimen. The primary endpoint was a sustained virological response (HCV RNA <25 IU/mL) 12 weeks after the end of treatment (SVR12). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01685203. Between Aug 14, 2012, and Nov 19, 2013, 467 patients with HCV infection were screened, of whom 174 were infected with genotype 4. 135 patients were randomly assigned to treatment and received at least one dose of study medication; 86 patients were treatment-naive, of whom 44 received ombitasvir plus paritaprevir plus ritonavir and 42 received ombitasvir plus paritaprevir plus ritonavir with ribavirin, and 49 treatment-experienced patients received the ribavirin-containing regimen. In previously untreated patients, SVR12 rates were 100% (42/42 [95% CI 91·6-100]) in the ribavirin-containing regimen and 90·9% (40/44 [95% CI 78·3-97·5]) in the ribavirin-free regimen. No statistically significant differences in SVR12 rates were noted between the treatment-naive groups (mean difference -9·16% [95% CI -19·61 to 1·29]; p=0·086). All treatment-experienced patients achieved SVR12 (49/49; 100% [95% CI 92·7-100]). In the ribavirin-free group, two (5%) of 42 treatment-naive patients had virological relapse, and one (2%) of 44 had virological breakthrough; no virological failures were recorded in the ribavirin-containing regimen. The most common adverse event was headache (14 [29%] of 49 treatment-experienced patients and 14 [33%] of 42 treatment-naive patients). No adverse event-related discontinuations or dose interruptions of study medications, including ribavirin, were noted, and only four patients (4%) of 91 receiving ribavirin required dose modification for haemoglobin less than 100 g/L or anaemia. An interferon-free regimen of ombitasvir plus paritaprevir plus ritonavir with or without ribavirin achieved high sustained virological response rates at 12 weeks after the end of treatment and was generally well tolerated, with low rates of anaemia and treatment discontinuation in non-cirrhotic previously untreated and previously treated patients with HCV genotype 4 infection. AbbVie. Copyright © 2015 Elsevier Ltd. All rights reserved.

Coagulopathy in liver disease: Lack of an assessment tool.

PubMed

Blasi, Annabel

2015-09-21

There is a discrepancy between the information from clotting tests which have routinely been used in clinical practice and evidence regarding thrombotic and bleeding events in patients with liver disease. This discrepancy leads us to rely on other variables which have been shown to be involved in haemostasis in these patients and/or to extrapolate the behaviour of these patients to other settings in order to decide the best clinical approach. The aims of the present review are as follows: (1) to present the information provided by clotting tests in cirrhotic patients; (2) to present the factors that may influence clotting in these patients; (3) to review the clinical evidence; and (4) to put forward a clinical approach based on the first 3 points.

Coagulopathy in liver disease: Lack of an assessment tool

PubMed Central

Blasi, Annabel

2015-01-01

There is a discrepancy between the information from clotting tests which have routinely been used in clinical practice and evidence regarding thrombotic and bleeding events in patients with liver disease. This discrepancy leads us to rely on other variables which have been shown to be involved in haemostasis in these patients and/or to extrapolate the behaviour of these patients to other settings in order to decide the best clinical approach. The aims of the present review are as follows: (1) to present the information provided by clotting tests in cirrhotic patients; (2) to present the factors that may influence clotting in these patients; (3) to review the clinical evidence; and (4) to put forward a clinical approach based on the first 3 points. PMID:26401071