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Sample records for liver cirrhosis identified

  1. Liver cirrhosis.

    PubMed Central

    Williams, E. J.; Iredale, J. P.

    1998-01-01

    Liver fibrosis and its related complications continue to represent a significant worldwide healthcare burden. Over the past decade there has been considerable improvement in our understanding of the cellular mechanisms and pathophysiology underlying hepatic fibrosis. This greater insight into the relevant basic sciences may lead to the development of novel treatment strategies designed to block the fibrogenic cascade or even enhance matrix degradation. In addition, there have been significant advances in the management of the complications of cirrhosis, with specific treatments now available for some conditions. Perhaps most notably, liver transplantation is now a highly successful treatment for end-stage liver disease and should be considered in all patients with chronic liver disease. PMID:9683971

  2. Pathogenesis of liver cirrhosis.

    PubMed

    Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

    2014-06-21

    Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

  3. Pathogenesis of liver cirrhosis

    PubMed Central

    Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

    2014-01-01

    Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions. PMID:24966602

  4. Identifying nursing interventions associated with the accuracy used nursing diagnoses for patients with liver cirrhosis 1

    PubMed Central

    Gimenes, Fernanda Raphael Escobar; Motta, Ana Paula Gobbo; da Silva, Patrícia Costa dos Santos; Gobbo, Ana Flora Fogaça; Atila, Elisabeth; de Carvalho, Emilia Campos

    2017-01-01

    ABSTRACT Objective: to identify the nursing interventions associated with the most accurate and frequently used NANDA International, Inc. (NANDA-I) nursing diagnoses for patients with liver cirrhosis. Method: this is a descriptive, quantitative, cross-sectional study. Results: a total of 12 nursing diagnoses were evaluated, seven of which showed high accuracy (IVC ≥ 0.8); 70 interventions were identified and 23 (32.86%) were common to more than one diagnosis. Conclusion: in general, nurses often perform nursing interventions suggested in the NIC for the seven highly accurate nursing diagnoses identified in this study to care patients with liver cirrhosis. Accurate and valid nursing diagnoses guide the selection of appropriate interventions that nurses can perform to enhance patient safety and thus improve patient health outcomes.

  5. [Diabetes in liver cirrhosis].

    PubMed

    García-Compeán, Diego; Jáquez-Quintana, Joel O; González-González, José A; Lavalle-González, Fernando J; Villarreal-Pérez, Jesús Z; Maldonado-Garza, Hector J

    2013-01-01

    The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes». Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease. Copyright © 2013 Elsevier España, S.L. y AEEH y AEG. All rights reserved.

  6. Use of analytic morphomics of liver, spleen, and body composition to identify patients at risk for cirrhosis.

    PubMed

    Krishnamurthy, Venkat; Zhang, Peng; Ethiraj, Sampath; Enchakalody, Binu; Waljee, Akbar K; Wang, Lu; Wang, Stewart C; Su, Grace L

    2015-02-01

    A diagnosis of cirrhosis can be made on the basis of findings from imaging studies, but these are subjective. Analytic morphomics uses computational image processing algorithms to provide precise and detailed measurements of organs and body tissues. We investigated whether morphomic parameters can be used to identify patients with cirrhosis. In a retrospective study, we performed analytic morphomics on data collected from 357 patients evaluated at the University of Michigan from 2004 to 2012 who had a liver biopsy within 6 months of a computed tomography scan for any reason. We used logistic regression with elastic net regularization and cross-validation to develop predictive models for cirrhosis, within 80% randomly selected internal training set. The other 20% data were used as internal test set to ensure that model overfitting did not occur. In validation studies, we tested the performance of our models on an external cohort of patients from a different health system. Our predictive models, which were based on analytic morphomics and demographics (morphomics model) or analytic morphomics, demographics, and laboratory studies (full model), identified patients with cirrhosis with area under the receiver operating characteristic curve (AUROC) values of 0.91 and 0.90, respectively, compared with 0.69, 0.77, and 0.76 for aspartate aminotransferase-to-platelet ratio, Lok Score, and FIB-4, respectively, by using the same data set. In the validation set, our morphomics model identified patients who developed cirrhosis with AUROC value of 0.97, and the full model identified them with AUROC value of 0.90. We used analytic morphomics to demonstrate that cirrhosis can be objectively quantified by using medical imaging. In a retrospective analysis of multi-protocol scans, we found that it is possible to identify patients who have cirrhosis on the basis of analyses of preexisting scans, without significant additional risk or cost. Copyright © 2015 AGA Institute. Published by

  7. Albumin and magnetic resonance imaging-liver volume to identify hepatitis B-related cirrhosis and esophageal varices

    PubMed Central

    Li, Hang; Chen, Tian-Wu; Li, Zhen-Lin; Zhang, Xiao-Ming; Li, Cheng-Jun; Chen, Xiao-Li; Chen, Guang-Wen; Hu, Jia-Ni; Ye, Yong-Quan

    2015-01-01

    AIM: To investigate whether liver lobe volume and albumin (ALB) could predict the presence and severity of liver cirrhosis, and esophageal varices. METHODS: Seventy-one cirrhotic patients with hepatitis B and 21 healthy individuals were enrolled in this study. All the participants underwent abdominal enhanced magnetic resonance imaging to measure each liver lobe volume, and biochemical workup for testing ALB and Child-Pugh class. All cirrhotic patients underwent upper gastrointestinal endoscopy to show the presence of cirrhotic esophageal varices. Right liver lobe volume (RV), left medial liver lobe volume (LMV), left lateral liver lobe volume (LLV), and caudate lobe volume (CV) were measured using enhanced magnetic resonance imaging. The ratios of RV to ALB (RV/ALB), LMV to ALB (LMV/ALB), LLV to ALB (LLV/ALB) and CV to ALB (CV/ALB) were calculated. Statistical analyses were performed to determine whether and how the combination of liver lobe volume measured using magnetic resonance imaging and albumin could predict the presence and severity of liver cirrhosis, and the presence of esophageal varices. RESULTS: RV, LMV, LLV and CV decreased (r = -0.51-0.373; all P < 0.05), while RV/ALB increased (r = 0.424; P < 0.05), with the progress of Child-Pugh class of liver cirrhosis. RV, LMV, CV, LLV/ALB and CV/ALB could identify presence of liver cirrhosis; LLV and LMV could distinguish Child-Pugh class A from B; RV, LMV, LLV, CV, RV/ALB and LLV/ALB could distinguish class A from C; RV and LLV/ALB could differentiate B from C; and RV, RV/ALB and CV/ALB could identify presence of esophageal varices (all P < 0.05). Among these parameters, CV/ALB could best identify the presence of liver cirrhosis, with an area under receiver operating characteristic curve (AUC) of 0.860, a sensitivity of 82.0% and a specificity of 83.0%. LLV could best distinguish class A from B, with an AUC of 0.761, a sensitivity of 74.4% and a specificity of 73.1%. RV could best distinguish class A from C

  8. Cirrhosis

    MedlinePlus

    Liver cirrhosis; Chronic liver disease; End-stage liver disease; Liver failure - cirrhosis; Ascites - cirrhosis ... Cirrhosis is the end result of chronic liver damage caused by ... liver disease in the United States are: Hepatitis B or hepatitis ...

  9. [Liver cirrhosis in metabolic disorders].

    PubMed

    Tazawa, Y

    1994-01-01

    The most early cirrhosis is observed in newborns with neonatal hemachromatosis. Early cirrhosis occurs in hereditary tyrosinemia type I, peroxisomal diseases and glycogen storage disease (type IV). In Wilson's disease, a case complicated with cirrhosis was reported in a 4-year-old patient. Slowly progressive cirrhosis is seen in patients with familial progressive intrahepatic cholestasis. Focal biliary cirrhosis is found in cystic fibrosis of the pancreas. Moreover, many other metabolic disorders, except for urea cycle disorders, are occasionally or rarely complicated with cirrhosis. Early diagnosis and proper management could prevent the development of cirrhosis in patients with galactosemia, hereditary fructose intolerance, etc. The occurrence of hepatoma must be monitored in these patients. Liver transplantation is indicated in a part of the patients with cirrhosis.

  10. Reversal of liver cirrhosis in autoimmune hepatitis.

    PubMed

    Shah, Anish M; Malhotra, Ashish; Kothari, Shivangi; Baddoura, Walid; Depasquale, Joseph; Spira, Robert

    2011-01-01

    Liver cirrhosis is generally considered irreversible but there are reports in which there is documented reversal of fibrosis/cirrhosis in various clinical conditions like Wilson's disease, hemochromatosis, primary biliary cirrhosis and autoimmune hepatitis. The subgroup of patients with autoimmune hepatitis that will have reversal of cirrhosis is not known. We present two cases with documented liver cirrhosis that had reversal of cirrhosis after treatment with immunosuppressive agents. We postulate that patients presenting with acute hepatitis and no other fibrogenic factors have higher chances of reversal of liver cirrhosis as compared to those presenting as chronic liver injury.

  11. Hepatic Encephalopathy in Liver Cirrhosis.

    PubMed

    Djiambou-Nganjeu, Herbert

    2017-03-01

    Liver cirrhosis is a worldwide gastroenterological condition, characterized by a slow, progressive and irreversible replacement of liver cells by fibrous tissue (scar) that prevents liver function. This condition often leads to the development of other syndromes. Cardiac complications can be indicated through abnormal QTc interval and arrhythmias, thereby their analysis aids in the prevention of cardiovascular events. Most cirrhotic cases have abnormal laboratory values (bilirubin, albumin, AST, ALT, AST/ALT, INR) indicating the presence of concomitant infection, inflammation and coagulopathy. In this case report, the usage Halstead-Reitan and Child-Pugh score helped in the assessment of the status of deterioration of brain. The knowledge of liver cirrhosis aetiologies help to determine the predisposition to development of hepatic encephalopathy and cardiomyopathy. The different values of liver enzymes and other blood laboratory analyses indicated the level of liver damage and poor prognosis.

  12. Cirrhosis and Liver Disease in Latina Women

    MedlinePlus

    ... Home > Minority Women's Health > Latinas Minority Women's Health Cirrhosis and liver disease Health conditions common in Latinas: More information on cirrhosis and liver disease in English Más recursos en ...

  13. Insulin resistance in liver cirrhosis.

    PubMed

    Goral, Vedat; Atalay, Roni; Kucukoner, Mehmet; Kucukoren, Mehmet

    2010-01-01

    Liver cirrhosis is a chronic disease by degeneration, regeneration and fibrosis in the liver parenchyma, caused by many diseases. Insulin resistance can be defined as any type of decrease in the effect that may occur at the phases following insulin's secretion from beta-cells of the pancreas, where it is produced, until it has the expected effects in the target cells. The aim of the present study is to demonstrate the presence of insulin resistance in LC, which is common in our country and region, and investigate the existence of association between insulin resistance occuring in LC and cytokine levels, age, gender, CRP, Hs-CRP, Child-Pugh score and etiology of LC. A total of 79 patients with liver cirrhosis (group 1) were included in the study, and 50 subjects as controls (group 2). Of liver cirrhosis patients, 49 (62%) were male and 30 (38%) were female, with a mean age of 54.71 +/- 14.68. Of the controls, 23 (46%) were male and 27 (54%) were female, with a mean age of 41.9 +/- 11.54. Severity of cirrhosis was assessed by Modified Child-Turcoutte-Pugh score. Seven cases (8.9%) were at the Child-Pugh stage A, 35 cases (44.3%) at the Child-Pough stage B, and 37 cases (46.8%) at the Child-Pough stage C. HOMA-IR was calculated and values > 2.7 were regarded as presence of insulin resistance (HOMA-IR +). Serum glucose, albumin, bilirubin values were studied with enzymatic method (Architect C-16000); serum CRP, Hs-CRP values with nephelometric method by Beckman Coulter Image Nephelometer (immunochemistry system); insulin, C-peptide with electrochemiluminance immunological method; prothrombin time with radiation method by ACL-Advance brand device. In this study, glucose (p = 0.004), insulin (p = 0.010), C-peptide (p < 0.001), HOMA-IR (p < 0.001), TNF-alpha (p < 0.001), IL-2RES (p < 0.001), IL-6 (p = 0.002), CRP (p < 0.001) and HsCRP (p = 0.006) levels are elevated in LC patients, compared to control group. Consequently, high HOMA-IR in LC supports the fact that insulin

  14. Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: comparison with concurrent cohort diagnosed antemortem.

    PubMed

    Singh, Nina; Sifri, Costi D; Silveira, Fernanda P; Miller, Rachel; Gregg, Kevin S; Huprikar, Shirish; Lease, Erika D; Zimmer, Andrea; Dummer, J Stephen; Spak, Cedric W; Koval, Christine; Banach, David B; Shroff, Miloni; Le, Jade; Ostrander, Darin; Avery, Robin; Eid, Albert; Razonable, Raymund R; Montero, Jose; Blumberg, Emily; Alynbiawi, Ahlaam; Morris, Michele I; Randall, Henry B; Alangaden, George; Tessier, Jeffrey; Cacciarelli, Thomas V; Wagener, Marilyn M; Sun, Hsin Yun

    2016-09-06

    Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.

  15. Periodontal disease and liver cirrhosis: A systematic review.

    PubMed

    Grønkjær, Lea Ladegaard

    2015-01-01

    Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease and liver cirrhosis and to identify opportunities and directions for future research in this area. A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conducted using search terms including 'liver cirrhosis', 'end-stage liver disease', 'liver diseases', 'oral health', 'periodontal disease', 'mouth disease', 'gingivitis', and 'periodontitis'. Thirteen studies published between 1981 and 2014 were found to include data on oral health and periodontal disease in cirrhotic patients. Studies indicated an increased incidence of periodontal disease in patients with liver cirrhosis, measured with several different periodontal indices. The reported prevalence of periodontal disease in cirrhosis patients ranged from 25.0% to 68.75% in four studies and apical periodontitis was found in 49%-79% of the patients. One study found that mortality was lower among patients who underwent dental treatment versus non-treated patients. Another study suggested an association between periodontal disease and the progression of liver cirrhosis, but data are sparse and conflicting as to whether periodontal disease is correlated to cirrhosis aetiology and severity. Despite the clinical reality of periodontal disease in liver cirrhosis patients, there are few published studies. Before clinical implications can be addressed, more data on the prevalence of and correlation between periodontal disease and liver cirrhosis aetiology, duration, and progression are needed.

  16. Liver progenitor cells-mediated liver regeneration in liver cirrhosis.

    PubMed

    Shang, Haitao; Wang, Zhijun; Song, Yuhu

    2016-05-01

    Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury. In cirrhotic liver where hepatocytes proliferation is compromised, liver progenitor cells (LPCs) are activated and then differentiated into hepatocytes and cholangiocytes, leading to the generation of regenerative nodules and functional restoration. Here, we summarize and discuss recent findings on the mechanisms underlying LPCs-mediated regeneration in liver cirrhosis. Firstly, we provide recent research on the mechanism underlying LPCs activation in severe or chronic liver injury. Secondly, we present new and exciting data on exploring the origin of LPCs, which reveal that the hepatocytes give rise to duct-like progenitors that then differentiate back into hepatocytes in chronic liver injury or liver cirrhosis. Finally, we highlight recent findings from the literature exploring the role of LPCs niche in directing the behavior and fate of LPCs. This remarkable insight into the cellular and molecular mechanisms of LPCs-mediated regeneration in liver cirrhosis will provide a basis for translating this knowledge into clinical application.

  17. Periodontal disease and liver cirrhosis: A systematic review

    PubMed Central

    2015-01-01

    Objectives: Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease and liver cirrhosis and to identify opportunities and directions for future research in this area. Methods: A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conducted using search terms including ‘liver cirrhosis’, ‘end-stage liver disease’, ‘liver diseases’, ‘oral health’, ‘periodontal disease’, ‘mouth disease’, ‘gingivitis’, and ‘periodontitis’. Results: Thirteen studies published between 1981 and 2014 were found to include data on oral health and periodontal disease in cirrhotic patients. Studies indicated an increased incidence of periodontal disease in patients with liver cirrhosis, measured with several different periodontal indices. The reported prevalence of periodontal disease in cirrhosis patients ranged from 25.0% to 68.75% in four studies and apical periodontitis was found in 49%–79% of the patients. One study found that mortality was lower among patients who underwent dental treatment versus non-treated patients. Another study suggested an association between periodontal disease and the progression of liver cirrhosis, but data are sparse and conflicting as to whether periodontal disease is correlated to cirrhosis aetiology and severity. Conclusion: Despite the clinical reality of periodontal disease in liver cirrhosis patients, there are few published studies. Before clinical implications can be addressed, more data on the prevalence of and correlation between periodontal disease and liver cirrhosis aetiology, duration, and progression are needed. PMID:26770799

  18. MiRNA-target network analysis identifies potential biomarkers for Traditional Chinese Medicine (TCM) syndrome development evaluation in hepatitis B caused liver cirrhosis.

    PubMed

    Liu, Yamin; Wang, Mei; Luo, Yunquan; Chen, ChenJian; Lu, Yiyu; Shi, Yulin; Tang, Chenchen; Zhou, Qianmei; Zhang, Hui; Hu, Yuanjia; Su, Shibing; Chen, Qilong

    2017-09-08

    Hepatitis B is one of most etiologies of Liver cirrhosis in China, and clinically lacks the effective strategy for Hepatitis B caused cirrhosis (HBC) therapy. As a complementary and alternative medicine, Chinese Traditional Medicine (TCM) has special therapeutic effects for HBC. Here, we focus on the evolution process of HBC TCM syndromes, which was from Excessive (Liver-Gallbladder Dampness-Heat Syndrome, LGDHS) to Deficient (Liver-Kidney Deficiency Syndrome, LKYDS) via Excessive-Deficient syndrome (Liver-Depression and Spleen-Deficiency Syndrome, LDSDS). Using R package, 16 miRNAs in LGDHS/Normal, 48 miRNAs in LDSDS/LGDHS, and 16 miRNAs in LKYDS/LDSDS were identified, respectively. The miRNA-target networks show that the LDSDS was most stability and complicated. Subsequently, 4 kernel miRNAs with LGDHS-LDSDS process, and 5 kernel miRNAs with LDSDS-LKYDS process were screened. Using RT-qPCR data, p1 (hsa-miR-17-3p, -377-3p, -410-3p and -495) and p2 miRNA panel (hsa-miR-377-3p, -410-3p, -27a-3p, 149-5p and 940) were identified by Logistic Regression Model, which clearly improve the accuracy of TCM syndrome classification. The rebuilt miRNA-target network shows that the LDSDS is a critical point and might determine the evolution directions of HBC TCM syndrome. This study suggests that the identified kernel miRNAs act as potential biomarkers and benefit to evaluate the evolution tendency of HBC TCM syndromes.

  19. Efficiency of Cell Therapy in Liver Cirrhosis.

    PubMed

    Shevela, E Ya; Starostina, N M; Pal'tsev, A I; Shipunov, M V; Zheltova, O I; Meledina, I V; Khvan, L A; Leplina, O Yu; Ostanin, A A; Chernykh, E R; Kozlov, V A

    2016-02-01

    We studied safety and clinical efficacy of transplantation of autologous bone marrow cell in complex therapy of 158 patients with chronic hepatitis and cirrhosis of the liver. The efficiency of cell therapy was assessed in 12 months after single injection of the cells. The positive response (alleviation of liver cirrhosis or stabilization of the pathological process) was observed in 70% cases. The efficacy of therapy correlated with the severity and etiology of the disease and was maximum in patients with Child-Pugh class A (in 82.5% cases) and class B liver cirrhosis (in 79% cases); in patients with class C liver cirrhosis, the positive response was achieved in 42.5% cases. In 39 patients, ultrasonic examination performed in 3 years after transplantation revealed no focal lesions or ectopic ossification foci.

  20. Prediction of liver cirrhosis, using diagnostic imaging tools

    PubMed Central

    Yeom, Suk Keu; Lee, Chang Hee; Cha, Sang Hoon; Park, Cheol Min

    2015-01-01

    Early diagnosis of liver cirrhosis is important. Ultrasound-guided liver biopsy is the gold standard for diagnosis of liver cirrhosis. However, its invasiveness and sampling bias limit the applicability of the method. Basic imaging for the diagnosis of liver cirrhosis has developed over the last few decades, enabling early detection of morphological changes of the liver by ultrasonography (US), computed tomography, and magnetic resonance imaging (MRI). They are also accurate diagnostic methods for advanced liver cirrhosis, for which early diagnosis is difficult. There are a number of ways to compensate for this difficulty, including texture analysis to more closely identify the homogeneity of hepatic parenchyma, elastography to measure the stiffness and elasticity of the liver, and perfusion studies to determine the blood flow volume, transit time, and velocity. Amongst these methods, elastography using US and MRI was found to be slightly easier, faster, and able to provide an accurate diagnosis. Early diagnosis of liver cirrhosis using MRI or US elastography is therefore a realistic alternative, but further research is still needed. PMID:26301049

  1. Cirrhosis and autoimmune liver disease: Current understanding

    PubMed Central

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  2. New prognostic markers in liver cirrhosis

    PubMed Central

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-01-01

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of “inflammatory stress” and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value. PMID:26019739

  3. New prognostic markers in liver cirrhosis.

    PubMed

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-05-28

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of "inflammatory stress" and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value.

  4. 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.

  5. [PRIMARY BILIARY LIVER CIRRHOSIS: MODERN CONCEPTS].

    PubMed

    Tsimmerman, Ya S

    2015-01-01

    Modern data on primary biliary liver cirrhosis are presented including the definition, prevalence, possible etiological factors, and detailed description of pathogenesis (autoimmune mechanisms, intrahepatic cholestasis, hereditary predisposition, environmental factors) and clinical picture. Also considered are complications and concomitant diseases, methods of laboratory, instrumental and morphological diagnostics, approaches to medicamental treatment and its effectiveness, indications for liver transplantation.

  6. The role of zinc in liver cirrhosis.

    PubMed

    Grüngreiff, Kurt; Reinhold, Dirk; Wedemeyer, Heiner

    2016-01-01

    Zinc is an essential trace element playing fundamental roles in cellular metabolism. It acts mostly by binding a wide range of proteins, thus affecting a broad spectrum of biological processes, which include cell division, growth and differentiation. Zinc is critical to a large number of structural proteins, enzymatic processes, and transcription factors. Zinc deficiency can result in a spectrum of clinical manifestations, such as poor of appetite, loss of body hair, altered taste and smell, testicular atrophy, cerebral and immune dysfunction, and diminished drug elimination capacity. These are common symptoms in patients with chronic liver diseases, especially liver cirrhosis. The liver is the main organ responsible for the zinc metabolism which can be affected by liver diseases. On the other hand, zinc deficiency may alter hepatocyte functions and also immune responses in inflammatory liver diseases. Liver cirrhosis represents the most advanced stage of chronic liver diseases and is the common outcome of chronic liver injury. It is associated with energy malnutrition, with numerous metabolic disorders, such as hypoalbuminemia, with imbalance between branched-chain amino acids and aromatic amino acids, and with reduced zinc serum concentrations. All these processes can influence the clinical outcome of patients, such ascites, hepatic encephalopathy and hepatocellular carcinoma. In the present review, we summarize the emerging evidence on the pitoval role of zinc in the pathogenesis of liver cirrhosis.

  7. BACTERIAL INFECTIONS IN PATIENTS WITH LIVER CIRRHOSIS.

    PubMed

    Preveden, Tomislav

    2015-01-01

    Liver cirrhosis is characterized by a reduced defensive reaction to bacterial infections and patients with cirrhosis are at increased risk of developing infections, sepsis and death. The most common bacterial infections in these patients are spontaneous bacterial peritonitis, urinary tract infection, pneumonia, skin and soft tissue infection and bacteremia. The most common causes are Gram negative bacteria. The aim of this study was to determine the prevalence, localization and etiology of bacterial infections in hospitalized patients with liver cirrhosis. This retrospective study included 401 patients with liver cirrhosis hospitalized at the Department of Infectious Diseases, Clinical Center of Vojvodina Novi Sad in the period from 2006 to 2010. Bacterial infection was diagnosed according to clinical examination, laboratory findings, radiological examination and bacterial positive culture. The prevalence of bacterial infection was 38.15% (153/401). The most common infections were pneumonia (21.56%), urinary tract infection (20.91%), and spontaneous bacterial peritonitis (18.95%). Localization of infection remained undetermined in as many as 37 patients (24.18%). Bacterial cultures were positive in 32 patients (20.91%), Gram negative bacteria were commonly isolated, mostly Escherichia coli (71.87%). The mortality rate among patients with bacterial infections was 31.37% (48/153). Bacterial infections are often found in patients with liver cirrhosis, the most frequent being pneumonia, urinary tract infection and spontaneous bacterial peritonitis. Gram negative bacteria, especially Escherichia coli were predominant in the etiology. The extent to which bacterial infections are taken into consideration in cases with liver cirrhosis is rather high; however, they are not proved etiologically to the satisfactory level.

  8. Cirrhosis

    MedlinePlus

    Cirrhosis is scarring of the liver. Scar tissue forms because of injury or long-term disease. Scar ... the blood, help digest food and store energy. Cirrhosis can lead to Easy bruising or bleeding, or ...

  9. [Nutritional support in patients with liver cirrhosis].

    PubMed

    Rivera Irigoin, Robin; Abilés, Jimena

    2012-10-01

    Given the liver's multiple synthetic, regulatory and detoxifying functions, one of the characteristics accompanying severe hepatocellular dysfunction is the presence of malnutrition. This disorder is highly frequent in liver cirrhosis, even in the relatively early stages of the disease. Independently of the cause of the cirrhosis, poor nutritional status is associated with a worse prognosis and therefore early intervention to correct nutrient deficiency can prolong life expectancy, improve quality of life, reduce complications and increase the probability of successful transplantation. The present article reviews current knowledge of the diagnosis and management of malnutrition in patients with cirrhosis. Special attention is paid to the concept of the late evening snack and its characteristics, composition and probable benefits in the course of the disease.

  10. Bloodstream infections in patients with liver cirrhosis

    PubMed Central

    Bartoletti, Michele; Giannella, Maddalena; Lewis, Russell Edward; Viale, Pierluigi

    2016-01-01

    ABSTRACT Bloodstream infections are a serious complication in patients with liver cirrhosis. Dysregulated intestinal bacterial translocation is the predominant pathophysiological mechanism of infections in this setting. For this reason enteric Gram-negative bacteria are commonly encountered as the first etiological cause of infection. However, through the years, the improvement in the management of cirrhosis, the recourse to invasive procedures and the global spread of multidrug resistant pathogens have importantly changed the current epidemiology. Bloodstream infections in cirrhotic patients are characterized by high mortality rate and complications including metastatic infections, infective endocarditis, and endotipsitis (or transjugular intrahepatic portosystemic shunt-related infection). For this reason early identification of patients at risk for mortality and appropriated therapeutic management is mandatory. Liver cirrhosis can significantly change the pharmacokinetic behavior of antimicrobials. In fact hypoproteinaemia, ascitis and third space expansion and impairment of renal function can be translated in an unpredictable drug exposure. PMID:26864729

  11. Bacterial translocation markers in liver cirrhosis

    PubMed Central

    Alexopoulou, Alexandra; Agiasotelli, Danai; Vasilieva, Larisa E.; Dourakis, Spyros P.

    2017-01-01

    Bacterial translocation (BT) is an important mechanism in the development of infection in liver cirrhosis. The migration and colonization of bacteria and/or bacterial products from the bowel to mesenteric lymph nodes is a controlled process in healthy persons. Increased intestinal permeability, bacterial overgrowth and defect of gut-associated lymphatic tissue promote impaired BT in cirrhotics. We reviewed the reports on markers used for the evaluation of BT published between 1987 and 2016. We focused on the clinical consequences of BT in cirrhosis, as indicated by the values of the BT markers. Patients with cirrhosis are reported to have elevated levels of surrogate markers associated with BT compared with controls. The most widely used BT parameters are C-reactive protein, procalcitonin, bacterial DNA, endotoxin or lipopolysaccharide, lipopolysaccharide binding protein, calprotectin, and bactericidal/permeability increasing protein. High levels of these factors in serum and/or ascitic fluid in humans may be associated with advanced liver disease, hemodynamic instability, high levels of proinflammatory cytokines, susceptibility to the development of severe or recurrent infections, acute-on-chronic liver failure, hepatic encephalopathy, hepatorenal syndrome and poor prognosis during follow up. In conclusion, high levels of BT markers are associated with a high inflammatory response, increased complications of liver cirrhosis and occasionally high fatality rates. PMID:28845103

  12. Cardiovascular dysfunction in patients with liver cirrhosis

    PubMed Central

    Fede, Giuseppe; Privitera, Graziella; Tomaselli, Tania; Spadaro, Luisa; Purrello, Francesco

    2015-01-01

    Hyperdynamic syndrome is a well-known clinical condition found in patients with cirrhosis and portal hypertension, characterized by increased heart rate and cardiac output, and reduced systemic vascular resistance and arterial blood pressure. The leading cause of hyperdynamic circulation in cirrhotic patients is peripheral and splanchnic vasodilatation, due to an increased production/activity of vasodilator factors and decreased vascular reactivity to vasoconstrictors. The term “cirrhotic cardiomyopathy” describes impaired contractile responsiveness to stress, diastolic dysfunction and electrophysiological abnormalities in patients with cirrhosis without known cardiac disease. Underlying circulatory and cardiac dysfunctions are the main determinant in the development of hepatorenal syndrome in advanced cirrhosis. Moreover, the clinical consequences of cirrhosis-related cardiovascular dysfunction are evident during and after liver transplantation, and after transjugular intrahepatic portosystemic shunt insertion. Cardiovascular complications following these procedures are common, with pulmonary edema being the most common complication. Other complications include overt heart failure, arrhythmia, pulmonary hypertension, pericardial effusion, and cardiac thrombus formation. This review discusses the circulatory and cardiovascular dysfunctions in cirrhosis, examining the pathophysiologic and clinical implications in light of the most recent published literature. PMID:25608575

  13. [Nutritional care for patients with liver cirrhosis].

    PubMed

    Aceves-Martins, Magaly

    2014-02-01

    The liver is an important organ with specific functions that influence directly on the nutritional and physiological status of every person. At the presence of any illness or injury in this organ, liver cirrhosis is always its final phase. In this pathology, patients present carbohydrate utilization and storage diminishment, as well as protein and fat catabolism increase. This situation, plus a low ingest and a bad nutrient absorption, results in a high prevalence of malnutrition. Many studies prove the importance of an opportune nutritional treatment in these patients, bringing general benefits and improving their quality of life. It's important to considerate the possible nutritional risks and deficiencies that could appear in the course of the cirrhosis to take opportune actions. The nutritional assessment and treatment is transcendental both in compensated phase (without complications) and in decompensated phase (with complications) of the illness.

  14. Falls in Patients With Liver Cirrhosis.

    PubMed

    Yildirim, Meric

    Health-related quality of life (HRQOL) has become an important outcome for patients with liver cirrhosis as the number of transplantation candidates increases by the progression of treatment strategies. Falls and fall-related injuries are common in patients with liver cirrhosis and negatively affect HRQOL. Many factors increase the risk for falls such as minimal hepatic encephalopathy, psychoactive drugs, muscle strength, autonomic dysfunction, hyponatremia, and sleep problems. It is important to understand the underlying mechanisms for falls in cirrhotic patients to prevent severe injuries such as fractures, decrease healthcare costs, and improve HRQOL. Healthcare professionals, including physiotherapists and nurses, should be aware of the higher risk for falls in this population and therapeutic interventions must be designed for patients, especially those waiting on the transplant list.

  15. Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis

    PubMed Central

    Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-hua; Xue, Dongbo

    2017-01-01

    Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including “immune response” as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma. PMID:28355233

  16. Hypergammaglobulinaemic purpura associated with alcoholic liver cirrhosis.

    PubMed

    Futei, Y; Chen, K R

    2009-12-01

    Hypergammaglobulinaemic purpura (HP) is commonly found in Sjögren's syndrome. We report a rare association of HP arising in a patient with alcoholic liver cirrhosis. A 65-year-old man presented with palpable purpura on the legs. Histological examination of a biopsy taken from the purpura found leucocytoclastic vasculitis in the superficial and mid-dermis. The activity of the vasculitic skin lesions correlated with liver dysfunction. Increased IgA and IgG levels, and hypocomplementaemia, may account for the pathogenesis of the hypergammaglobulinaemic immune complex-mediated vasculitis in this case.

  17. Nutrition in cirrhosis and chronic liver disease.

    PubMed

    Juakiem, Wassem; Torres, Dawn M; Harrison, Stephen A

    2014-02-01

    Nutrition has not been a primary focus of many medical conditions despite its importance in the development and the severity of these diseases. This is certainly the case with nutrition and end-stage liver disease despite the well-established association of nutritional deficiencies and increased rates of complications and mortality in cirrhosis. This review provides an overview of nutrition in chronic liver disease with an emphasis on its pathogenesis as well as ways to assess nutritional status and intervene in an effort to improve nutrition.

  18. [Endotoxinaemia in liver cirrhosis (author's transl)].

    PubMed

    Nilius, R; Bernhardt, H; Zipprich, B; Knoke, M

    1980-01-01

    23 patients with liver cirrhosis of diverse etiology and of different activity levels and grades of compensation of the portal circulation were examined with regard to the systemic endotoxinaemia. The endotoxin was determined using the Limulus-Amoebocyte-Lysat-test. Endotoxin was traceable in the venous blood of 7 out of 23 patients (= 30,4%). No relation was found between endotoxaemia and the activity or grade of severity of liver cirrhosis; nor were there any accumulation of endotoxinaemia in patients with collateral circulation or portal decompensation. Consequently, as a result of our findings, the prognostic value of the symptom endotoxinaemia remains debatable, then endotoxinaemia does not always mean endotoxicosis. Particularly high immunoglobulin concentration and low albumin values in serum of endotoxin-positive cirrhotics indicate a "spillovet" of antigen substances and also of endotoxines in the body circulation resulting from insufficiency of the liver-RHS. Parallel analysis of microbian small bowel flora in 10 patients indicate that coli-dysbiosis appears to play a role in the development of systemic endoxinaemia, although the latter was also traceable in borderline cases of eubiosis/dysbiosis. Our findings strengthen the view that it is not possible to simply translate the findings in animals on to human liver diseases. Quite a number of the mechanisms being discussed are still with uncleared details and they give only a blurred picture of the pathophysiology of endotoxinaemia.

  19. Challenges and Management of Liver Cirrhosis: Practical Issues in the Therapy of Patients with Cirrhosis due to NAFLD and NASH.

    PubMed

    Traussnigg, Stefan; Kienbacher, Christian; Halilbasic, Emina; Rechling, Christian; Kazemi-Shirazi, Lili; Hofer, Harald; Munda, Petra; Trauner, Michael

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH.

  20. Proteomic analysis of HCV cirrhosis and HCV-induced HCC: Identifying biomarkers for monitoring HCV-cirrhotic patients awaiting liver transplantation

    PubMed Central

    Mas, Valeria R; Maluf, Daniel G; Archer, Kellie J; Yanek, Kenneth; Bornstein, Karen; Fisher, Robert A

    2009-01-01

    Background Progression from chronic Hepatitis C virus (HCV) infection to cirrhosis and hepatocellular carcinoma (HCC) results in protein changes in the peripheral blood. We evaluated global protein expression in plasma samples of HCV-cirrhotic and HCV-cirrhotic-HCC patients. Patients and Methods Plasma samples from 25 HCV-cirrhotic-HCC and 10 HCV-cirrhotic patients were quantitatively evaluated for protein expression. Tryptic peptides were analyzed using Thermo linear ion-trap mass specttometer (LTQ) coupled with a Surveyoy HPLC system (Thermo). SEQUEST and X!Tandem database search algorithms were used for peptide sequence identification. Protein relative quantification was performed using the area under the curve from the select ion chromatogram. A significant fold change between groups was based on controlling the False Discovery Rate (FDR) at less than 5%. Results We identified and quantified 2,320 proteins from the analysis of the different protein pattern between HCV-cirrhosis and HCV-HCC samples. Gene ontology terms (GO) classified the more important biologic process related to these proteins as signal transduction, regulation of transcription DNA-dependent, protein amino acid phosphorylation, cell adhesion, transport, and immune response. Seven proteins showed significant expression changes with a FDR<5% between cirrhosis and tumor groups. Moreover, 18 proteins showed significant expression changes (FDR<5%) when plasma samples from HCV-cirrhosis were compared with early HCV-HCC. Conclusions Differential protein expression was observed between samples from HCV patients with cirrhosis with and without HCC. Also, differences were observed between early and advanced HCV-HCC samples. This study provides important information for discovery of potential biomarkers for early HCC diagnosis in HCV cirrhotic patients. PMID:19136905

  1. 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

  2. Cancer and liver cirrhosis: implications on prognosis and management

    PubMed Central

    Pinter, Matthias; Trauner, Michael; Peck-Radosavljevic, Markus; Sieghart, Wolfgang

    2016-01-01

    Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies. PMID:27843598

  3. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis.

    PubMed

    Mokdad, Ali A; Lopez, Alan D; Shahraz, Saied; Lozano, Rafael; Mokdad, Ali H; Stanaway, Jeff; Murray, Christopher J L; Naghavi, Mohsen

    2014-09-18

    identifies areas with high and/or rapidly increasing mortality where preventive measures to control and reduce liver cirrhosis risk factors should be urgently strengthened.

  4. Nursing Assessment Tool for People With Liver Cirrhosis

    PubMed Central

    Reis, Renata Karina; da Silva, Patrícia Costa dos Santos; Silva, Ana Elisa Bauer de Camargo; Atila, Elisabeth

    2016-01-01

    The aim of this study was to describe the process of developing a nursing assessment tool for hospitalized adult patients with liver cirrhosis. A descriptive study was carried out in three stages. First, we conducted a literature review to develop a data collection tool on the basis of the Conceptual Model of Wanda Horta. Second, the data collection tool was assessed through an expert panel. Third, we conducted the pilot testing in hospitalized patients. Most of the comments offered by the panel members were accepted to improve the tool. The final version was in the form of a questionnaire with open-closed questions. The panel members concluded that the tool was useful for accurate nursing diagnosis. Horta's Conceptual Model assisted with the development of this data collection tool to help nurses identify accurate nursing diagnosis in hospitalized patients with liver cirrhosis. We hope that the tool can be used by all nurses in clinical practice. PMID:26425862

  5. Liver Cirrhosis: Evaluation, Nutritional Status, and Prognosis.

    PubMed

    Nishikawa, Hiroki; Osaki, Yukio

    2015-01-01

    The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes.

  6. Liver Cirrhosis: Evaluation, Nutritional Status, and Prognosis

    PubMed Central

    Nishikawa, Hiroki; Osaki, Yukio

    2015-01-01

    The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes. PMID:26494949

  7. Schistosomiasis and hepatopulmonary syndrome: the role of concomitant liver cirrhosis

    PubMed Central

    Gonçalves-Macedo, Liana; Lopes, Edmundo Pessoa; Domingues, Ana Lucia Coutinho; Markman, Brivaldo; Mota, Vitor Gomes; Luna, Carlos Feitosa

    2017-01-01

    BACKGROUND Hepatopulmonary syndrome (HPS) is defined as an oxygenation defect induced by intrapulmonary vasodilation in patients with liver disease or portal hypertension. It is investigated in patients with liver cirrhosis and less frequently in those with portal hypertension without liver cirrhosis, as may occur in hepatosplenic schistosomiasis (HSS). OBJECTIVES To investigate the prevalence of HPS in patients with HSS, and to determine whether the occurrence of HPS is influenced by concomitant cirrhosis. METHODS We evaluated patients with HSS with or without concomitant liver cirrhosis. All patients underwent laboratory testing, ultrasound, endoscopy, contrast echocardiography, and arterial blood gas analysis. FINDINGS Of the 121 patients with HSS, 64 were also diagnosed with liver cirrhosis. HPS was diagnosed in 42 patients (35%) and was more frequent among patients with concomitant liver cirrhosis than in those without cirrhosis (42% vs. 26%), but the difference was not significant (p = 0.069). HPS was more common in those with spider naevi, Child-Pugh classes B or C and high model for end stage liver disease (MELD) scores (p < 0.05 each). MAIN CONCLUSIONS The prevalence of HPS was 35% in this study. The occurrence of liver cirrhosis concomitantly with HSS may have influenced the frequency of patients presenting with HPS. PMID:28591307

  8. Schistosomiasis and hepatopulmonary syndrome: the role of concomitant liver cirrhosis.

    PubMed

    Gonçalves-Macedo, Liana; Lopes, Edmundo Pessoa; Domingues, Ana Lucia Coutinho; Markman, Brivaldo; Mota, Vitor Gomes; Luna, Carlos Feitosa

    2017-07-01

    Hepatopulmonary syndrome (HPS) is defined as an oxygenation defect induced by intrapulmonary vasodilation in patients with liver disease or portal hypertension. It is investigated in patients with liver cirrhosis and less frequently in those with portal hypertension without liver cirrhosis, as may occur in hepatosplenic schistosomiasis (HSS). To investigate the prevalence of HPS in patients with HSS, and to determine whether the occurrence of HPS is influenced by concomitant cirrhosis. We evaluated patients with HSS with or without concomitant liver cirrhosis. All patients underwent laboratory testing, ultrasound, endoscopy, contrast echocardiography, and arterial blood gas analysis. Of the 121 patients with HSS, 64 were also diagnosed with liver cirrhosis. HPS was diagnosed in 42 patients (35%) and was more frequent among patients with concomitant liver cirrhosis than in those without cirrhosis (42% vs. 26%), but the difference was not significant (p = 0.069). HPS was more common in those with spider naevi, Child-Pugh classes B or C and high model for end stage liver disease (MELD) scores (p < 0.05 each). The prevalence of HPS was 35% in this study. The occurrence of liver cirrhosis concomitantly with HSS may have influenced the frequency of patients presenting with HPS.

  9. Protein-protein interaction network analysis of cirrhosis liver disease.

    PubMed

    Safaei, Akram; Rezaei Tavirani, Mostafa; Arefi Oskouei, Afsaneh; Zamanian Azodi, Mona; Mohebbi, Seyed Reza; Nikzamir, Abdol Rahim

    2016-01-01

    Evaluation of biological characteristics of 13 identified proteins of patients with cirrhotic liver disease is the main aim of this research. In clinical usage, liver biopsy remains the gold standard for diagnosis of hepatic fibrosis. Evaluation and confirmation of liver fibrosis stages and severity of chronic diseases require a precise and noninvasive biomarkers. Since the early detection of cirrhosis is a clinical problem, achieving a sensitive, specific and predictive novel method based on biomarkers is an important task. Essential analysis, such as gene ontology (GO) enrichment and protein-protein interactions (PPI) was undergone EXPASy, STRING Database and DAVID Bioinformatics Resources query. Based on GO analysis, most of proteins are located in the endoplasmic reticulum lumen, intracellular organelle lumen, membrane-enclosed lumen, and extracellular region. The relevant molecular functions are actin binding, metal ion binding, cation binding and ion binding. Cell adhesion, biological adhesion, cellular amino acid derivative, metabolic process and homeostatic process are the related processes. Protein-protein interaction network analysis introduced five proteins (fibroblast growth factor receptor 4, tropomyosin 4, tropomyosin 2 (beta), lectin, Lectin galactoside-binding soluble 3 binding protein and apolipoprotein A-I) as hub and bottleneck proteins. Our result indicates that regulation of lipid metabolism and cell survival are important biological processes involved in cirrhosis disease. More investigation of above mentioned proteins will provide a better understanding of cirrhosis disease.

  10. Protein-protein interaction network analysis of cirrhosis liver disease

    PubMed Central

    Safaei, Akram; Rezaei Tavirani, Mostafa; Arefi Oskouei, Afsaneh; Zamanian Azodi, Mona; Mohebbi, Seyed Reza; Nikzamir, Abdol Rahim

    2016-01-01

    Aim: Evaluation of biological characteristics of 13 identified proteins of patients with cirrhotic liver disease is the main aim of this research. Background: In clinical usage, liver biopsy remains the gold standard for diagnosis of hepatic fibrosis. Evaluation and confirmation of liver fibrosis stages and severity of chronic diseases require a precise and noninvasive biomarkers. Since the early detection of cirrhosis is a clinical problem, achieving a sensitive, specific and predictive novel method based on biomarkers is an important task. Methods: Essential analysis, such as gene ontology (GO) enrichment and protein-protein interactions (PPI) was undergone EXPASy, STRING Database and DAVID Bioinformatics Resources query. Results: Based on GO analysis, most of proteins are located in the endoplasmic reticulum lumen, intracellular organelle lumen, membrane-enclosed lumen, and extracellular region. The relevant molecular functions are actin binding, metal ion binding, cation binding and ion binding. Cell adhesion, biological adhesion, cellular amino acid derivative, metabolic process and homeostatic process are the related processes. Protein-protein interaction network analysis introduced five proteins (fibroblast growth factor receptor 4, tropomyosin 4, tropomyosin 2 (beta), lectin, Lectin galactoside-binding soluble 3 binding protein and apolipoprotein A-I) as hub and bottleneck proteins. Conclusion: Our result indicates that regulation of lipid metabolism and cell survival are important biological processes involved in cirrhosis disease. More investigation of above mentioned proteins will provide a better understanding of cirrhosis disease. PMID:27099671

  11. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    PubMed Central

    Gehling, Ursula M; Willems, Marc; Schlagner, Kathleen; Benndorf, Ralf A; Dandri, Maura; Petersen, Jörg; Sterneck, Martina; Pollok, Joerg-Matthias; Hossfeld, Dieter K; Rogiers, Xavier

    2010-01-01

    AIM: To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS: Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry. Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1 (SDF-1) were measured using an enzyme linked immunosorbent assay. RESULTS: Progenitor cells with a CD133+/CD45+/CD14+ phenotype were observed in 61% of the patients. Between 1% and 26% of the peripheral blood mononuclear cells (MNCs) displayed this phenotype. Furthermore, a distinct population of c-kit+ progenitor cells (between 1% and 38 % of the MNCs) could be detected in 91% of the patients. Additionally, 18% of the patients showed a population of progenitor cells (between 1% and 68% of the MNCs) that was characterized by expression of breast cancer resistance protein-1. Further phenotypic analysis disclosed that the circulating precursors expressed CXC chemokine receptor 4, the receptor for SDF-1. In line with this finding, elevated plasma levels of SDF-1 were present in all patients and were found to correlate with the number of mobilized CD133+ progenitor cells. CONCLUSION: These data indicate that in humans, liver cirrhosis leads to recruitment of various populations of hematopoietic progenitor cells that display markers of intrahepatic progenitor cells. PMID:20066741

  12. Cirrhosis

    MedlinePlus

    ... This procedure involves using an endoscope—a small, flexible tube with a light—to look for varices. ... providers use blood tests, ultrasound, or both to screen for liver cancer in people with cirrhosis. He ...

  13. Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis

    PubMed Central

    Mueller, Sebastian

    2016-01-01

    Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a major health problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis (SPH), which identifies an elevated sinusoidal pressure (SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts (SPH part I: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmHg and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures (SPH part II: perpetuation). It also defines the “point of no return” where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies. PMID:28082801

  14. Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan.

    PubMed

    Tung, Chien-Hsueh; Lai, Ning-Seng; Lu, Ming-Chi; Lee, Ching-Chih

    2016-02-01

    The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis.

  15. [Nutrition in liver cirrhosis: diagnostic aspects and treatment].

    PubMed

    Gundling, F; Schepp, W

    2008-04-01

    Malnutrition is very common in patients with liver cirrhosis and includes especially protein-calorie malnutrition. The pathophysiological reasons vary and are caused by metabolic modifications and characteristics of enteral absorption and digestion cause by the cirrhosis. Malnutrition contributes to overall mortality and complication rate of the chronic liver disease. An adequate daily energy and protein supply should be ensured in patients with liver cirrhosis, which is higher than that in the normal population, because of higher amino-acid turnover. Ascites may benefit from daily low-salt fluid intake. Nutritional substitution of vitamins and trace elements is indicated when symptoms of deficiency occur.

  16. Virus-related liver cirrhosis: molecular basis and therapeutic options.

    PubMed

    Lin, Ji; Wu, Jian-Feng; Zhang, Qi; Zhang, Hong-Wei; Cao, Guang-Wen

    2014-06-07

    Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8(+) T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.

  17. Virus-related liver cirrhosis: Molecular basis and therapeutic options

    PubMed Central

    Lin, Ji; Wu, Jian-Feng; Zhang, Qi; Zhang, Hong-Wei; Cao, Guang-Wen

    2014-01-01

    Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8+ T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis. PMID:24914367

  18. [Treatment of liver cirrhosis - actually possibility of ambulant internist].

    PubMed

    Ehrmann, Jiří; Aiglová, Květa; Konečný, Michal; Procházka, Vlastimil; Vrzalová, Drahomíra

    There are 40 000-60 000 patients with cirrhosis in the Czech Republic. 2 000 die of this disease yearly. This group of patients needs a complex treatment and it is mostly an internist cooperating with other specialists. The most important for an ambulant internist is to diagnose the disease as soon as possible and start with treatment of chronic liver disease that could lead to a cirrhosis. It means especially chronic viral hepatitis, alcoholic or non-alcoholic steatosis/steatohepatitis, auto-immune liver damage and metabolic disease. The next step is to diagnose the cirrhosis in time when it is in no manifest stage. The third step is to diagnose and treat the liver decompensation. It means consequences of the portal hypertension, it is ascit, esophageal or gastric varices, hepatorenal syndrome. Next there are consequences of the metabolic insufficiency, it is icterus, coagulopathy and hepatic encephalopathy. It is necessary to diagnose and cure cholestasis from the very first extrahepatic causes. For a successful treatment of the hepatocellular carcinoma originated almost exclusively in the grounds of the cirrhosis must be early diagnosed. The ambulant internist respective hepatologist must diagnose the stage of the cirrhosis and decide when a hospitalization is necessary. Also a close cooperation with other specialists is urgent if it is about a liver transplantation. The treatment of successive stages of the cirrhosis is a topic of the showed educational article. compensated/decompensated liver cirrhosis - diet/nutrition in liver cirrhosis - etiology and diagnose of liver cirrhosis - treatment of liver insufficiency/failure - treatment of portal hypertension and its complications.

  19. Unilateral pleural effusion without ascites in liver cirrhosis

    SciTech Connect

    Faiyaz, U.; Goyal, P.C.

    1983-09-01

    The source of massive pleural effusion was not apparent in a 58-year-old man who had cirrhosis but no demonstrable ascites. Intraperitoneal injection of technetium Tc 99m sulfur colloid established the presence of peritoneopleural communication. This diagnostic technique can be helpful in evaluating patients with cirrhosis of the liver and pleural effusion with or without ascites.

  20. Gut microbiota and host metabolism in liver cirrhosis

    PubMed Central

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-01-01

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  1. Gut microbiota and host metabolism in liver cirrhosis.

    PubMed

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-11-07

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  2. Management of coagulopathy in patients with decompensated liver cirrhosis.

    PubMed

    Amarapurkar, Pooja D; Amarapurkar, Deepak N

    2011-01-01

    Patients with decompensated liver cirrhosis have significantly impaired synthetic function. Many proteins involved in the coagulation process are synthesized in the liver. Routinely performed tests of the coagulation are abnormal in patients with decompensated liver cirrhosis. This has led to the widespread belief that decompensated liver cirrhosis is prototype of acquired hemorrhagic coagulopathy. If prothrombin time is prolonged more than 3 seconds over control, invasive procedures like liver biopsy, splenoportogram, percutaneous cholangiography, or surgery were associated with increased risk of bleeding, and coagulopathy should be corrected with infusion of fresh frozen plasma. These practices were without any scientific evidence and were associated with significant hazards of fresh frozen plasma transfusion. Now, it is realized that coagulation is a complex process involving the interaction of procoagulation and anticoagulation factors and the fibrinolytic system. As there is reduction in both anti and procoagulant factors, global tests of coagulation are normal in patients with acute and chronic liver disease indicating that coagulopathy in liver disease is more of a myth than a reality. In the last few years, surgical techniques have substantially improved, and complex procedures like liver transplantation can be done without the use of blood or blood products. Patients with liver cirrhosis may also be at increased risk of thrombosis. In this paper, we will discuss coagulopathy, increased risk of thrombosis, and their management in decompensated liver cirrhosis.

  3. [Activity of antioxidant enzymes in patients with liver cirrhosis].

    PubMed

    Czeczot, Hanna; Scibior, Dorota; Skrzycki, Michał; Podsiad, Małgorzata

    2006-01-01

    The aim of our studies was the estimation of activities of antioxidant enzymes in patients with liver cirrhosis. We investigated activities of superoxide dismutases (CuZnSOD, MnSOD), catalase (CAT), selenium dependent GSH peroxidase (Se-GSH-Px), selenium independent GSH peroxidase (non-Se-GSH-Px), GSH-S-transferase (GST), GSH reductase (GSHR) and the level ofreduced gutathione (GSH) in cirrhotic and healthy liver tissues. The activities of CuZnSOD, MnSOD, CAT and GSH-dependent enzymes (except GSHR) were found to be lower in cirrhotic tissue compared to healthy liver. Those changes were associated with decrease of GSH level in cirrhotic tissue compared with control liver tissue. Our results show that antioxidant barrier in liver cirrhosis is impaired. It is associated with decrease of glutathione level and changes of activities of antioxidant enzymes (SOD, CAT, GSHPx, GST, GSHR) in liver cirrhosis compared with healthy liver.

  4. Biomechanics and functionality of hepatocytes in liver cirrhosis.

    PubMed

    Sun, Shan; Song, Zhenyuan; Cotler, Scott J; Cho, Michael

    2014-06-27

    Cirrhosis is a life-threatening condition that is generally attributed to overproduction of collagen fibers in the extracellular matrix that mechanically stiffens the liver. Chronic liver injury due to causes including viral hepatitis, inherited and metabolic liver diseases and external factors such as alcohol abuse can result in the development of cirrhosis. Progression of cirrhosis leads to hepatocellular dysfunction. While extensive studies to understand the complexity underlying liver fibrosis have led to potential application of anti-fibrotic drugs, no such FDA-approved drugs are currently available. Additional studies of hepatic fibrogenesis and cirrhosis primarily have focused on the extracellular matrix, while hepatocyte biomechanics has received limited attention. The role of hepatocyte biomechanics in liver cirrhosis remains elusive, and how the cell stiffness is correlated with biological functions of hepatocytes is also unknown. In this study, we demonstrate that the biomechanical properties of hepatocytes are correlated with their functions (e.g., glucose metabolism), and that hepatic dysfunction can be restored through modulation of the cellular biomechanics. Furthermore, our results indicate the hepatocyte functionality appears to be regulated through a crosstalk between the Rho and Akt signaling. These novel findings may lead to biomechanical intervention of hepatocytes and the development of innovative tissue engineering for clinical treatment to target liver cells rather than exclusively focusing on the extracellular matrix alone in liver cirrhosis.

  5. Clinico-hemato-biochemical profile of dogs with liver cirrhosis

    PubMed Central

    Elhiblu, M. A.; Dua, K.; Mohindroo, J.; Mahajan, S. K.; Sood, N. K.; Dhaliwal, P. S.

    2015-01-01

    Aim: The aim of this study was to determine the relevant tools in the diagnosis of liver cirrhosis in dogs. Material and Methods: A total of 140 dogs presented at Veterinary Teaching Hospital, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, showing clinical signs of hepatic insufficiency were subjected to clinico-hemato biochemical, urological, ultrasonographic (USG), and USG guided fine-needle biopsy examinations by standard methods. On the basis of these results, 6 dogs out of 140 dogs were found to be suffering from liver cirrhosis. Six clinically healthy dogs constituted the control group. Results: The dogs suffering from liver cirrhosis manifested inappetence, halitosis, abdominal distension, weight loss, melena, icterus, anemia, and neutrophilic leukocytosis with the left shift. Levels of hemoglobin, lymphocytes, packed cell volume, mean corpuscular volume, mean corpuscular Hb (MCH), and platelet count were significantly lower in liver cirrhosis group than control group while total leukocyte count, neutrophils, and MCH concentration were significantly higher. Glucose, total protein, albumin, A/G ratio, and fibrinogen were significantly lower, and creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, prothrombin time, and APTT were significantly higher than the control values. Ultrasound revealed diffuse increase in echogenicity with rounded and irregular liver margins. Cytological examination of the ascitic fluid and fine-needle aspiration biopsy of liver was not fruitful in the diagnosis of liver cirrhosis. Conclusions: Liver cirrhosis causes clinical and hemo-biochemical alterations, which require special consideration when treating diseased animals. USG, diffuse increase in echogenicity of liver, rounding and irregularity of liver margins and microhepatica were the consistent findings. It is suggested that USG along with hemo-biochemical alterations may be used as a diagnostic tool for liver cirrhosis

  6. Predictors of liver failure in primary biliary cirrhosis.

    PubMed

    Zhao, Pan; Liu, Wei-wei; Li, Jin-feng; Wang, Chun-ya; Wang, Hao; Xu, Jun; Wang, Rui-fang; Yang, Hao-zhen; Jin, Cheng; Wei, Zhen-man

    2015-03-01

    The disease progression of patients with primary biliary cirrhosis (PBC) varies significantly, and the prognostic markers that identify those patients who will develop liver failure have been scarcely studied from a Chinese cohort. Aims. We aimed to determine the predictive factors of liver failure in patients with PBC. Patients who were first diagnosed as PBC with hepatic compensation between January 2007 and December 2009 were enrolled in this cohort study. Altogether 398 patients were finally included. Of these patients, 80% were women, 98% had positive antimitochondrial antibodies, and 45% had positive antinuclear antibodies (ANA). To December 2012, a total of 38 patients developed liver failure. According to the outcome, patients who developed liver failure had had higher serum concentration of baseline total bilirubin (TBil) (p = 0.013) and total bile acid (TBA) (p < 0.001), and lower concentrations of baseline total cholesterol (Tch) (p = 0.008), than patients who did not develop liver failure. Additionally, the proportion of ANA positivity was statistically different between the two groups (p = 0.009). In the established model for predicting liver failure in PBC, three variables were finally selected out, including Tch (odds ratio (OR) 0.552, 95% confidence interval (CI) 0.394-0.774, p < 0.001), TBA (OR 1.006, 95% CI 1.002-1.010, p = 0.002), and ANA (+ versus -, OR 5.518, 95% CI 1.155-26.376, p = 0.032). ANA, Tch, and TBA are predictors of liver failure in PBC.

  7. 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

    2017-01-23

    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.

  8. Genetic markers in alcoholic liver cirrhosis.

    PubMed

    Lareu, M V; Alvarez-Prechous, A; Pardiñas, C; Concheiro, L; Carracedo, A

    1992-01-01

    11 genetic markers were typed in 157 individuals suffering from alcoholic cirrhosis, and compared with a random sample of healthy individuals. No significant differences were found for transferrin, specific group component, orosomucoid, esterase D, phosphogluconate dehydrogenase and adenylate kinase. Strong associations between alcoholic cirrhosis and alpha-1-antitrypsin PI*Z allele, haptoglobin HP*1 allele and acid phosphatase ACP AC phenotype were observed. The biological significance of these associations and their relationships with the development of alcoholic cirrhosis are also discussed.

  9. [Pain management in patients with liver cirrhosis].

    PubMed

    Ojeda, Antonio; Moreno, Luis A

    2014-01-01

    Pain management in patients with liver cirrhosis is a real challenge and is often inadequate due to a lack of therapeutic efficacy or the high incidence of adverse effects. The focus of treatment differs depending on whether the pain is acute or chronic and involves understanding the causative pathophysiological mechanism. Analgesics should be started with the minimum effective dose and should be titrated slowly with avoidance of polypharmacy. Adverse effects must be monitored, especially sedation and constipation, which predispose the patient to the development of hepatic encephalopathy. The first-line drug is paracetamol, which is safe at doses of 2-3g/day. Non-steroidal anti-inflammatory agents are contraindicated because they can cause acute renal failure and/or gastrointestinal bleeding. Tramadol is a safe option for moderate-severe pain. The opioids with the best safety profile are fentanyl and hydromorphone, with methadone as an alternative. Topical treatment can reduce oral drug consumption. In neuropathic pain the first-line therapeutic option is gabapentin. The use of antidepressants such as amitriptyline can be considered in some patients. Interventional techniques are a valuable tool in moderate to severe pain, since they allow a reduction in drug therapy and consequently its adverse effects. Psychological treatment, physical therapy and rehabilitation should be considered as part of multimodality therapy in the management of chronic pain. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  10. Factors predicting early postoperative liver cirrhosis-related complications after lung cancer surgery in patients with liver cirrhosis.

    PubMed

    Iwata, Takashi; Inoue, Kiyotoshi; Nishiyama, Noritoshi; Nagano, Koshi; Izumi, Nobuhiro; Tsukioka, Takuma; Hanada, Shoji; Suehiro, Shigefumi

    2007-12-01

    We aimed to determine the factors predicting liver cirrhosis-related complications in the early postoperative period after lung cancer surgery in patients with liver cirrhosis. We retrospectively reviewed the medical records of patients who underwent curative surgery for primary lung cancer in our institute from January 1990 to March 2007, finding 37 cases with comorbid liver cirrhosis. These patients were divided into two groups, according to whether liver failure, bleeding, and critical infection had occurred postoperatively. Various clinical parameters were analyzed statistically between the bigeminal groups. Liver cirrhosis-related complications occurred in seven of the 37 patients (18.9%). Transient liver failure occurred in two patients (5.4%) after pulmonary resection. Acute intrathoracic bleeding occurred in four cases (10.8%). Two patients died (5.4%) in both cases due to sepsis. Preoperative total bilirubin (P<0.05), and indocyanine green retention rate at 15 min (P<0.05) were significantly higher in patients with liver failure. Only serum value of total bilirubin was an independent risk factor (P<0.05) by multivariate analysis. In predicting death from infection, only preoperative nutritional status was a significant risk factor (P<0.05). To avoid postoperative cirrhosis-related complications, preoperative preparation to improve their liver function and nutrition status is essential.

  11. Incidence and prognosis of tuberculosis in patients with cirrhosis of the liver. A Danish nationwide population based study.

    PubMed Central

    Thulstrup, A. M.; Mølle, I.; Svendsen, N.; Sørensen, H. T.

    2000-01-01

    We examined the incidence rate and prognosis of tuberculosis in a cohort of patients with liver cirrhosis in Denmark. In a study cohort of 22675 patients with liver cirrhosis, we identified 151 cases of tuberculosis from 1977 to 1993. The incidence rate was 168.6 per 100000 person-years of risk, and the highest incidence rate was among men above 65 years of age, with an incidence rate of 246.0 per 100000 person-years of risk. The 30-day case-fatality rate was 27.3% and the 1-year case fatality rate was 47.7%. The results demonstrate that patients with liver cirrhosis are at increased risk of tuberculosis. Additionally, it is suggested that liver cirrhosis is an independent risk factor for tuberculosis, and that patients with liver cirrhosis who acquire tuberculosis have a poor prognosis. PMID:10813146

  12. Nutritional assessment and treatment of patients with liver cirrhosis.

    PubMed

    Moctezuma-Velázquez, Carlos; García-Juárez, Ignacio; Soto-Solís, Rodrigo; Hernández-Cortés, Juan; Torre, Aldo

    2013-01-01

    Prevalence of chronic liver diseases, including liver cirrhosis, is increasing worldwide. The nutritional state assessment in these patients is complicated, and besides anthropometry is based on several other tools in order to be more accurate. Specific dietary recommendations are needed in patients with chronic liver diseases in order to help prevent and treat liver decompensation because malnutrition is an independent predictor of mortality. This review focuses on essential aspects in the nutritional assessment of cirrhotic patients and some general recommendations for their treatment.

  13. Occult endocrine dysfunction in patients with cirrhosis of liver

    PubMed Central

    Kumar, K. V. S. Hari; Pawah, A. K.; Manrai, Manish

    2016-01-01

    Background: Liver dysfunction leads to endocrine disturbance due to the alteration in protein metabolism or synthesis. We studied the presence of occult endocrine dysfunction in liver cirrhosis and compared the same with underlying etiology. Materials and Methods: We evaluated thirty patients with liver cirrhosis in this cross-sectional, observational study. All subjects were assessed for pituitary, thyroid, adrenal, and gonadal function. The patients were divided into Group 1 (cirrhosis, n = 30) and Group 2 (controls, n = 15) and the data were analyzed with appropriate statistical tests. Results: The study participants (20 males, 10 females) had a mean age of 54.5 ± 12.4 years and duration of the cirrhosis 5.1 ± 2.7 years. Four patients were in Child Class A, 11 and 15 patients were in Child Classes B and C, respectively. Eleven out of thirty patients (37%) had endocrine disorders, that include subclinical hypothyroidism (n = 3), primary hypothyroidism (n = 1), Sick Euthyroid syndrome (n = 3), central hypothyroidism (n = 2), secondary hypogonadism (n = 3) and growth hormone deficiency in three patients. Two patients had partial hypopituitarism and one patient had complete hypopituitarism. Conclusion: Occult endocrine dysfunction of thyroid and gonadal axes is common in patients with cirrhosis of the liver. The hormonal abnormalities are not different based on the etiology of the cirrhosis. PMID:28217586

  14. Transcriptional Profiling and miRNA-Target Network Analysis Identify Potential Biomarkers for Efficacy Evaluation of Fuzheng-Huayu Formula-Treated Hepatitis B Caused Liver Cirrhosis

    PubMed Central

    Chen, Qilong; Wu, Feizhen; Wang, Mei; Dong, Shu; Liu, Yamin; Lu, Yiyu; Song, Yanan; Zhou, Qianmei; Liu, Ping; Luo, Yunquan; Su, Shibing

    2016-01-01

    Fuzheng-Huayu (FZHY) formula has been found to have a satisfactory effect on hepatitis B-caused cirrhosis (HBC) treatment. However, the efficacy evaluation of FZHY is often challenging. In this study, a randomized, double-blind and placebo-controlled trial was used to evaluate the therapeutic efficacy of FZHY in HBC treatment. In the trial, 35 medical indexes were detected, and 14 indexes had a statistically-significant difference before compared to after the trial. Importantly, the Child-Pugh score also demonstrated FZHY having therapeutic efficacy. Furthermore, the microRNA (miRNA) profiles of 12 serum samples were detected in FZHY groups, and 112 differential-expressed (DE) miRNAs were determined. Using predicted miRNA targets, 13 kernel miRNAs were identified from the established miRNA-target network. Subsequently, quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used to validate the expression level of 13 identified miRNAs in the trials. The results showed that nine miRNAs have a statistically-significant difference before compared to after FZHY treatment. By means of a logistic regression model, a miRNA panel with hsa-miR-18a-5p, -326, -1182 and -193b-5p was established, and it can clearly improve the accuracy of the efficacy evaluation of FZHY. This study suggested that the particular miRNAs can act as potential biomarkers and obviously increase the diagnostic accuracy for drug evaluation in HBC treatment progression. PMID:27271613

  15. Probiotics in Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, and Cirrhosis.

    PubMed

    Qamar, Amir A

    2015-01-01

    With the growing epidemic of obesity, the incidence of both nonalcoholic fatty liver disease (NAFL) and nonalcoholic steatohepatitis (NASH) is increasing. The intestinal microbiota differs between individuals who are obese or have normal body mass indices. Animal studies have shown increased intestinal permeability in NAFL, NASH, and cirrhosis. This increases the risk of oxidative and inflammatory injury to the liver from intestinal microbacteria. It may also increase the risk of fatty acid injury and fatty deposition. Bacterial translocation is associated with increased portal hypertension and hepatic encephalopathy in cirrhosis. By preventing bacterial adhesion and translocation, probiotics may have a role in the management of patients with NAFL, NASH, and cirrhosis. Multiple small studies have suggested that probiotics improve some of the clinical markers of activity in patients with NAFL and NASH. Controlled studies have also shown improved outcomes in patients with cirrhosis who were treated with probiotics.

  16. Amiodarone-Induced Cirrhosis of Liver: What Predicts Mortality?

    PubMed Central

    Hussain, Nasir

    2013-01-01

    Introduction. Amiodarone has been used for more than 5 decades for the treatment of various tachyarrhythmias and previously for the treatment of refractory angina. There are multiple well-established side effects of amiodarone. However, amiodarone-induced cirrhosis (AIC) of liver is an underrecognized complication. Methods. A systematic search of Medline from January 1970 to November 2012 by using the following terms, amiodarone and cirrhosis, identified 37 reported cases of which 30 were used in this analysis. Patients were divided into 2 subsets, survivors versus nonsurvivors, at 5 months. Results. Aspartate aminotransferase was significantly lower (P = 0.03) in patients who survived at 5-months (mean 103.33 IU/L) compared to nonsurvivors (mean 216.88 IU/L). There was no statistical difference in the levels of prothrombin time, total bilirubin, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, cumulative dose, and latency period between the two groups. The prevalence of DM, HTN, HLD, CAD, and CHF was similar in the two groups. None of the above-mentioned variables could be identified as a predictor of survival at 5 months. Conclusion. AIC carries a mortality risk of 60% at 5 months once the diagnosis is established. Further prospective studies are needed to identify predictors of AIC and of mortality or survival in cases of AIC. PMID:23577267

  17. Coffee prevents CCl(4)-induced liver cirrhosis in the rat.

    PubMed

    Moreno, Mario G; Chávez, Enrique; Aldaba-Muruato, Liseth R; Segovia, José; Vergara, Paula; Tsutsumi, Víctor; Shibayama, Mineko; Rivera-Espinoza, Yadira; Muriel, Pablo

    2011-09-01

    Previous clinical observations suggested that coffee may have beneficial effects on the liver. In fact, an inverse relationship between coffee consumption and liver cirrhosis has been reported in humans. However, the causative role of coffee has not been established; therefore, the aim of this work was to study the effect of coffee in an experimental model of liver damage. In this work, cirrhosis was induced by chronic CCl(4) administration and soluble or grain coffee (SC, GC, respectively) were co-administered for 8 weeks. CCl(4) administration elevated serum alkaline phosphatase and alanine aminotranspherase, liver lipid peroxidation, collagen content (fourfold) and TGF-β mRNA, and protein levels; depleted liver glycogen and reduced glutathione (GSH) content. Coffee prevented most of the changes produced by CCl(4). Histopathological analysis was in agreement with biochemical and molecular data. The best effect was produced by GC. It is worth noting that GC preserved the normal collagen content as well as the normal TGF-β mRNA and protein levels. Our results suggest (1) that coffee plays a causative role in preventing cirrhosis (at least experimental cirrhosis); (2) that action mechanisms are probably associated with down regulation of the profibrogenic cytokine TGF-β and to its antioxidant properties and, (3) that GC is more potent than SC. These findings suggest a beneficial effect of coffee on the liver. However, more clinical and basic studies must be performed before reaching a final recommendation.

  18. Management of thrombocytopenia due to liver cirrhosis: a review.

    PubMed

    Hayashi, Hiromitsu; Beppu, Toru; Shirabe, Ken; Maehara, Yoshihiko; Baba, Hideo

    2014-03-14

    Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis, limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding. Multiple factors, including splenic sequestration, reduced activity of the hematopoietic growth factor thrombopoietin, bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents, and antiviral treatment with interferon-based therapy, can contribute to the development of thrombocytopenia in cirrhotic patients. Of these factors, the major mechanisms for thrombocytopenia in liver cirrhosis are (1) platelet sequestration in the spleen; and (2) decreased production of thrombopoietin in the liver. Several treatment options, including platelet transfusion, interventional partial splenic embolization, and surgical splenectomy, are now available for severe thrombocytopenia in cirrhotic patients. Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis, their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials. In this review, we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume, and we describe the current management of thrombocytopenia due to liver cirrhosis.

  19. Chronic hepatitis and cirrhosis of the liver in cryoglobulinaemia

    PubMed Central

    Jori, G. P.; Buonanno, G.

    1972-01-01

    Hepatic biopsy showed either persistent or aggressive chronic hepatitis in 11 patients with cryoglobulinaemia not attributable to known disease entities, whereas liver impairment was not in every case suggested by either physical examination or functional abnormalities. The incidence was predominantly in women and cryoglobulin behaviour was similar in these patients and in five subjects with cirrhosis-associated cryoglobulinaemia. It is concluded that liver disease should be included among the constant features of the cryoglobulin-associated syndrome, and the speculation is advanced that in cryoglobulinaemic patients both cirrhosis and chronic hepatitis may be caused by the same pathogenic mechanism(s). PMID:4627774

  20. Evidence-based clinical practice guidelines for liver cirrhosis 2015.

    PubMed

    Fukui, Hiroshi; Saito, Hidetsugu; Ueno, Yoshiyuki; Uto, Hirofumi; Obara, Katsutoshi; Sakaida, Isao; Shibuya, Akitaka; Seike, Masataka; Nagoshi, Sumiko; Segawa, Makoto; Tsubouchi, Hirohito; Moriwaki, Hisataka; Kato, Akinobu; Hashimoto, Etsuko; Michitaka, Kojiro; Murawaki, Toshikazu; Sugano, Kentaro; Watanabe, Mamoru; Shimosegawa, Tooru

    2016-07-01

    The Japanese Society of Gastroenterology revised the evidence-based clinical practice guidelines for liver cirrhosis in 2015. Eighty-three clinical questions were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. Manual searching of the latest important literature was added until August 2015. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This digest version in English introduces selected clinical questions and statements related to the management of liver cirrhosis and its complications. Branched-chain amino acids relieve hypoalbuminemia and hepatic encephalopathy and improve quality of life. Nucleoside analogues and peginterferon plus ribavirin combination therapy improve the prognosis of patients with hepatitis B virus related liver cirrhosis and hepatitis C related compensated liver cirrhosis, respectively, although the latter therapy may be replaced by direct-acting antivirals. For liver cirrhosis caused by primary biliary cirrhosis and active autoimmune hepatitis, urosodeoxycholic acid and steroid are recommended, respectively. The most adequate modalities for the management of variceal bleeding are the endoscopic injection sclerotherapy for esophageal varices and the balloon-occluded retrograde transvenous obliteration following endoscopic obturation with cyanoacrylate for gastric varices. Beta-blockers are useful for primary prophylaxis of esophageal variceal bleeding. The V2 receptor antagonist tolvaptan is a useful add-on therapy in careful diuretic therapy for ascites. Albumin infusion is useful for the prevention of paracentesis-induced circulatory disturbance and renal failure. In addition to disaccharides, the nonabsorbable antibiotic rifaximin is useful for the management of encephalopathy. Anticoagulation therapy is proposed for

  1. Alterations of the human gut microbiome in liver cirrhosis.

    PubMed

    Qin, Nan; Yang, Fengling; Li, Ang; Prifti, Edi; Chen, Yanfei; Shao, Li; Guo, Jing; Le Chatelier, Emmanuelle; Yao, Jian; Wu, Lingjiao; Zhou, Jiawei; Ni, Shujun; Liu, Lin; Pons, Nicolas; Batto, Jean Michel; Kennedy, Sean P; Leonard, Pierre; Yuan, Chunhui; Ding, Wenchao; Chen, Yuanting; Hu, Xinjun; Zheng, Beiwen; Qian, Guirong; Xu, Wei; Ehrlich, S Dusko; Zheng, Shusen; Li, Lanjuan

    2014-09-04

    Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.

  2. Intestinal permeability in a patient with liver cirrhosis

    PubMed Central

    Aguirre Valadez, Jonathan Manuel; Rivera-Espinosa, Liliana; Méndez-Guerrero, Osvely; Chávez-Pacheco, Juan Luis; García Juárez, Ignacio; Torre, Aldo

    2016-01-01

    Liver cirrhosis is a worldwide public health problem, and patients with this disease are at high risk of developing complications, bacterial translocation from the intestinal lumen to the mesenteric nodes, and systemic circulation, resulting in the development of severe complications related to high mortality rate. The intestinal barrier is a structure with a physical and biochemical activity to maintain balance between the external environment, including bacteria and their products, and the internal environment. Patients with liver cirrhosis develop a series of alterations in different components of the intestinal barrier directly associated with the severity of liver disease that finally increased intestinal permeability. A “leaky gut” is an effect produced by damaged intestinal barrier; alterations in the function of tight junction proteins are related to bacterial translocation and their products. Instead, increasing serum proinflammatory cytokines and hemodynamics modification, which results in the appearance of complications of liver cirrhosis such as hepatic encephalopathy, variceal hemorrhage, bacterial spontaneous peritonitis, and hepatorenal syndrome. The intestinal microbiota plays a fundamental role in maintaining the proper function of the intestinal barrier; bacterial overgrowth and dysbiosis are two phenomena often present in people with liver cirrhosis favoring bacterial translocation. Increased intestinal permeability has an important role in the genesis of these complications, and treating it could be the base for prevention and partial treatment of these complications. PMID:27920543

  3. Accuracy of Ultrasound and Noninvasive Markers of Fibrosis to Identify Patients with Cirrhosis

    PubMed Central

    Martin, Jason; Khatri, Gaurav; Gopal, Purva; Singal, Amit G.

    2015-01-01

    Background Accurate identification of patients with cirrhosis using non-invasive markers of fibrosis is useful for esophageal varices and hepatocellular carcinoma surveillance programs. The aims of our study were to characterize the accuracy of ultrasonography, AST to platelet ratio index (APRI), and FIB-4 as non-invasive markers to identify the presence of cirrhosis. Methods We conducted a retrospective cohort study of patients who underwent liver biopsy at a large urban safety-net institution between November 2008 and July 2011. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy using receiver operator characteristic curve analysis for the detection of cirrhosis were calculated for each non-invasive marker. Results Liver biopsy was performed in 388 patients, of whom 93 (24.0%) had cirrhosis. C-statistics for APRI and FIB-4 predicting the presence of cirrhosis were 0.68 (95%CI 0.63 – 0.74) and 0.73 (95%CI 0.68 – 0.78), respectively. The c-statistic for a nodular appearance on ultrasound was 0.78 (95%CI 0.72-0.83). The PPV of a shrunken nodular-appearing liver was 64.8%; however, PPV was significantly higher in the subset with a cirrhotic-appearing liver and signs of portal hypertension (PPV 83.6%, p=0.01) as well as in the subset with a non-invasive fibrosis marker also suggesting cirrhosis (PPV 77.8%, p<0.001). Conclusion Serum and imaging non-invasive markers of fibrosis may have insufficient accuracy when used in isolation; however, a combination of markers may allow sufficient accuracy to systematically identify patients with cirrhosis. PMID:25586089

  4. Reversal of liver cirrhosis: current evidence and expectations

    PubMed Central

    Jung, Young Kul; Yim, Hyung Joon

    2017-01-01

    In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fibrosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are associated with liver fibrosis via integrated signaling pathways, a comprehensive understanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the reversibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis. PMID:28171717

  5. Incidence, predictors and outcomes of acute-on-chronic liver failure in outpatients with cirrhosis.

    PubMed

    Piano, Salvatore; Tonon, Marta; Vettore, Elia; Stanco, Marialuisa; Pilutti, Chiara; Romano, Antonietta; Mareso, Sara; Gambino, Carmine; Brocca, Alessandra; Sticca, Antonietta; Fasolato, Silvano; Angeli, Paolo

    2017-07-19

    Acute-on-chronic liver failure (ACLF) is the most life-threatening complication of cirrhosis. Prevalence and outcomes of ACLF have recently been described in hospitalized patients with cirrhosis. However, no data is currently available on the prevalence and the risk factors of ACLF in outpatients with cirrhosis. The aim of this study was to evaluate incidence, predictors and outcomes of ACLF in a large cohort of outpatients with cirrhosis. A total of 466 patients with cirrhosis consecutively evaluated in the outpatient clinic of a tertiary hospital were included and followed up until death and/or liver transplantation for a mean of 45±44months. Data on development of hepatic and extrahepatic organ failures were collected during this period. ACLF was defined and graded according to the EASL-CLIF Consortium definition. During the follow-up, 118 patients (25%) developed ACLF: 57 grade-1, 33 grade-2 and 28 grade-3. The probability of developing ACLF was 14%, 29%, and 41% at 1year, 5years, and 10years, respectively. In the multivariate analysis, baseline mean arterial pressure (hazard ratio [HR] 0.96; p=0.012), ascites (HR 2.53; p=0.019), model of end-stage liver disease score (HR 1.26; p<0.001) and baseline hemoglobin (HR 0.07; p=0.012) were found to be independent predictors of the development of ACLF at one year. As expected, ACLF was associated with a poor prognosis, with a 3-month probability of transplant-free survival of 56%. Outpatients with cirrhosis have a high risk of developing ACLF. The degree of liver failure and circulatory dysfunction are associated with the development of ACLF, as well as low values of hemoglobin. These simple variables may help to identify patients at a high risk of developing ACLF and to plan a program of close surveillance and prevention in these patients. There is a need to identify predictors of acute-on-chronic liver failure (ACLF) in patients with cirrhosis in order to identify patients at high risk of developing ACLF and to

  6. Liver Cirrhosis/Severe Fibrosis Is a Risk Factor for Anastomotic Leakage after Colorectal Surgery

    PubMed Central

    Hofmann, Irina; Willi, Niels; Stickel, Felix

    2016-01-01

    Purpose. Liver cirrhosis associated with high perioperative morbidity/mortality. This retrospective study determines whether liver cirrhosis represents a risk factor for anastomotic leakage after colonic anastomosis or not. Methods. Based on a prospective database with all consecutive colorectal resections performed at the authors' institution from 07/2002 to 07/2012 (n = 2104) all colonic and rectal anastomoses were identified (n = 1875). A temporary loop ileostomy was constructed in 257 cases (13.7%) either due to Mannheimer Peritonitis-Index > 29 or rectal anastomosis below 6 cm from the anal verge. More than one-third of the patients (n = 691) had postoperative contrast enema, either at the occasion of another study or prior to closure of ileostomy. The presence of liver cirrhosis and the development of anastomotic leakage were assessed by chart review. Results. The overall anastomotic leakage rate was 2.7% (50/1875). In patients with cirrhosis/severe fibrosis, the anastomotic leakage rate was 12.5% (3/24), while it was only 2.5% (47/1851) in those without (p = 0.024). The difference remained statistically significant after correction for confounding factors by multivariate analysis. Conclusion. Patients with liver cirrhosis/severe fibrosis have an increased risk of leakage after colonic anastomosis. PMID:28105046

  7. Liver cirrhosis and thyroid function: Friend or foe?

    PubMed

    Vincken, Stefanie; Reynaert, Hendrik; Schiettecatte, Johan; Kaufman, Leon; Velkeniers, Brigitte

    2017-04-01

    The liver plays a central role in thyroid hormone metabolism, transport, and clearance. A normal function of both the thyroid gland and the liver is therefore necessary to maintain normal thyroid hormone levels and action. Data regarding thyroid function in patients with liver cirrhosis are scarce and variable. The most consistent finding is a decreased free triiodothyronine (fT3) level, which correlates with the severity of liver disease and has been proposed as a prognostic factor for liver-related complications. To evaluate thyroid hormone values in patients with stable liver cirrhosis and to compare them with healthy controls without liver disease. We also assessed the prevalence of thyroid autoimmunity and whether liver function tests correlated with thyroid function. We performed a prospective case-control study in an endocrinological setting. Twenty-nine patients with stable cirrhosis (20 males and 9 females, mean age 60.97 ± 7.17 years) were included in the case group and 50 healthy subjects (22 males and 28 females, mean age 61.70 ± 13.00 years) in the control group. We excluded patients with confounding factors known to influence thyroid function. Levels of serum thyroid-stimulating hormone (TSH), fT3, free thyroxine (fT4) and anti-TPO-antibodies (TPO-Ab) were measured. These thyroid hormone values were compared in both groups. Biochemical indices of liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [AP], gamma-glutamyl transpeptidase [GGT], INR, total bilirubin, and albumin levels) were correlated with thyroid function tests. fT3 en fT4 levels were significantly lower in patients with cirrhosis than in healthy subjects (p = 0.001 and 0.002, respectively). TSH levels were not statistically significantly different in the two groups. The level of TPO-Ab was not increased in patients with cirrhosis compared to healthy controls. fT3 correlated negatively with the Child-Pugh score. These results

  8. Molecular Mechanisms Involved in the Interaction Effects of Alcohol and Hepatitis C Virus in Liver Cirrhosis

    PubMed Central

    Mas, Valeria R; Fassnacht, Ryan; Archer, Kellie J; Maluf, Daniel

    2010-01-01

    The mechanisms by which alcohol consumption accelerates liver disease in patients with chronic hepatitis C virus (HCV) are not well understood. To identify the characteristics of molecular pathways affected by alcohol in HCV patients, we fit probe-set level linear models that included the additive effects as well as the interaction between alcohol and HCV. The study included liver tissue samples from 78 patients, 23 (29.5%) with HCV-cirrhosis, 13 (16.7%) with alcohol-cirrhosis, 23 (29.5%) with HCV/alcohol cirrhosis and 19 (24.4%) with no liver disease (no HCV/no alcohol group). We performed gene-expression profiling by using microarrays. Probe-set expression summaries were calculated by using the robust multiarray average. Probe-set level linear models were fit where probe-set expression was modeled by HCV status, alcohol status, and the interaction between HCV and alcohol. We found that 2172 probe sets (1895 genes) were differentially expressed between HCV cirrhosis versus alcoholic cirrhosis groups. Genes involved in the virus response and the immune response were the more important upregulated genes in HCV cirrhosis. Genes involved in apoptosis regulation were also overexpressed in HCV cirrhosis. Genes of the cytochrome P450 superfamily of enzymes were upregulated in alcoholic cirrhosis, and 1230 probe sets (1051 genes) had a significant interaction estimate. Cell death and cellular growth and proliferation were affected by the interaction between HCV and alcohol. Immune response and response to the virus genes were downregulated in HCV-alcohol interaction (interaction term alcohol*HCV). Alcohol*HCV in the cirrhotic tissues resulted in a strong negative regulation of the apoptosis pattern with concomitant positive regulation of cellular division and proliferation. PMID:20386865

  9. Mortality after cardiac surgery in patients with liver cirrhosis classified by the Child-Pugh score.

    PubMed

    Jacob, Kirolos A; Hjortnaes, Jesper; Kranenburg, Guido; de Heer, Frederiek; Kluin, Jolanda

    2015-04-01

    Liver cirrhosis is a known risk factor for postoperative mortality in patients undergoing cardiac surgery. Clinical assessment of liver cirrhosis using the widely accepted Child-Pugh (CP) score is thus vital for evaluation of surgical options and perioperative care. However, detailed mortality rates as a consequence of liver cirrhosis are unclear. This review aimed to stratify the risk of short-term (<30 days) and overall (up to 10 years) mortality after cardiac surgery in patients with liver cirrhosis, classified by the CP score. Thus, PubMed, Embase, CINAHL and the Cochrane Library were systematically reviewed by two independent investigators for studies published up to February 2014, in which mortality in cirrhotic patients, classified by the CP classification, undergoing cardiac surgery was evaluated postoperatively. A total of 993 articles were identified. After critical appraisal of 21 articles, 19 were selected for final analysis. Weighted short-term mortality of cirrhotic patients undergoing cardiac surgery was 19.3% [95% confidence interval (CI): 16.4-22.5%]. Across the different CP groups, short-term mortality appeared to be 9.0% (95% CI: 6.6-12.2%), 37.7% (95% CI: 30.8-44.3%) and 52.0% (95% CI: 33.5-70.0%) in Groups A, B and C, respectively. Weighted overall mortality within 1 year was 42.0% (95% CI: 36.0-48.3%) in all cirrhotic patients. Subdivided in groups, overall mortality within that 1 year was 27.2% (95% CI: 20.9-34.7%), 66.2% (95% CI: 54.3-76.3%) and 78.9% (95% CI: 56.1-92.1%) in Groups A, B and C, respectively. In conclusion, short-term mortality is considerably increased in patients with liver cirrhosis CP class B and C. Overall mortality is significantly high in all classes of liver cirrhosis.

  10. Influence of unrecorded alcohol consumption on liver cirrhosis mortality

    PubMed Central

    Lachenmeier, Dirk W; Monakhova, Yulia B; Rehm, Jürgen

    2014-01-01

    Unrecorded alcohol includes illegally distributed alcohol as well as homemade or surrogate alcohol which is unintended for consumption by humans (e.g., cosmetics containing alcohol). The highest unrecorded alcohol consumption occurs in Eastern Europe and some of these countries have an over proportional liver cirrhosis mortality. Compounds besides ethanol have been hypothesized as being responsible for this observation. On the other hand, chemical investigations were unable to prove that unrecorded alcohol regularly contains contaminants above toxicological thresholds. However, illegally produced spirits regularly contain higher percentages of alcohol (above 45% by volume), but for considerably less costs compared with licit beverages, potentially causing more problematic patterns of drinking. In this review, it is investigated whether patterns of drinking rather than product composition can explain the liver cirrhosis mortality rates. Statistical examination of World Health Organization country data shows that the originally detected correlation of the percentage of unrecorded alcohol consumption and liver cirrhosis mortality rates disappears when the data is adjusted for the prevalence of heavy episodic drinking. It may be concluded that there is currently a lack of data to demonstrate causality between the composition of illicit spirits (e.g., higher levels of certain contaminants in home-produced products) and liver toxicity on a population scale. Exceptions may be cases of poisoning with antiseptic liquids containing compounds such as polyhexamethyleneguanidine, which were reported to be consumed as surrogate alcohol in Russia, leading to an outbreak of acute cholestatic liver injury, histologically different from conventional alcoholic liver disease. PMID:24966592

  11. Non invasive tools for the diagnosis of liver cirrhosis.

    PubMed

    Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe

    2014-12-28

    Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis.

  12. Non invasive tools for the diagnosis of liver cirrhosis

    PubMed Central

    Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe

    2014-01-01

    Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis. PMID:25561782

  13. The Burden of Rehospitalization for Patients With Liver Cirrhosis.

    PubMed

    Desai, Archita P; Reau, Nancy

    2016-01-01

    Advanced liver disease is becoming more prevalent in the United States. This increase has been attributed largely to the growing epidemic of nonalcoholic fatty liver disease and an aging population infected with hepatitis C. Complications of cirrhosis are a major cause of hospital admissions and readmissions. It is important to target efforts for preventing rehospitalization toward patients with cirrhosis who are at the highest risk for readmission, such as those who have high Model for End-Stage Liver Disease scores, are at risk for fluid/electrolyte abnormalities or overt hepatic encephalopathy recurrence, and those who have comorbid conditions (e.g. diabetes). The heart failure management paradigm may provide valuable insights for managing patients with cirrhosis, given the extensive research on preventing hospital readmission and improving health care utilization in this subpopulation. As quality measures related to hospital readmissions for cirrhosis and its complications are adopted by the Centers for Medicare & Medicaid Services and private payers in the future, understanding drivers of hospital readmissions and health care utilization in this vulnerable population are key to improving quality measure performance.

  14. Can computerized brain training games be used to identify early cognitive impairment in cirrhosis?

    PubMed

    Tartaglione, Erica V; Derleth, Mark; Yu, Lei; Ioannou, George N

    2014-03-01

    We evaluated whether commercially available, computerized "brain-training" games can be used to identify subtle cognitive impairments in patients with cirrhosis. We compared patients with cirrhosis who did not have overt encephalopathy (n=31), patients with pre-cirrhotic chronic liver disease (n=28), and normal controls without liver disease (n=16) with respect to their scores on the number connection test-A (NCT-A), the Inhibitory Control Test (ICT), and five, short (∼2.5 min), brain-training games that were administered on an Apple iPad and tested different cognitive domains. Patients with cirrhosis had similar scores to patients with pre-cirrhotic liver disease and slightly worse scores than normal controls in the NCT-A and the ICT, although these differences were not statistically significant. In contrast, patients with cirrhosis had significantly worse scores than patients with pre-cirrhotic liver disease and even more so than normal controls in all five of the brain-training games. After adjustment for age and educational attainment, these differences remained significant for two of the tests, "Color Match" which is a version of the Stroop test and measures selective attention, and "Memory Matrix", which measures visuospatial memory. The area under the receiver operating characteristic curve discriminating cirrhosis from pre-cirrhotic liver disease was 0.56 (95% confidence interval (CI) 0.41-0.72) for the ICT and 0.58 (95% CI 0.43-0.73) for the NCT-A, indicating no discrimination, while it was 0.75 (95% CI 0.63-0.87) for "Color Match" and 0.77 (95% CI 0.64-0.90) for "Memory Matrix", indicating good discrimination. Short, brain-training games administered on an iPad can be used as psychometric tests to detect subtle cognitive impairments in patients with cirrhosis without overt encephalopathy that could not be detected by the NCT-A or the ICT.

  15. Ultrasonography for diagnosis of alcoholic cirrhosis in people with alcoholic liver disease.

    PubMed

    Pavlov, Chavdar S; Casazza, Giovanni; Semenistaia, Marianna; Nikolova, Dimitrinka; Tsochatzis, Emmanuel; Liusina, Ekaterina; Ivashkin, Vladimir T; Gluud, Christian

    2016-03-02

    , nodularity of the liver surface, size of the lymph nodes around the hepatic artery, irregularity and narrowness of the inferior vena cava, portal vein velocity, and spleen size.Diagnosis of cirrhosis by ultrasound, especially in people who are asymptomatic, may have its advantages for the prognosis, motivation, and treatment of these people to decrease their alcohol consumption or become abstinent.Timely diagnosis of alcoholic cirrhosis in people with alcoholic liver disease is the cornerstone for evaluation of prognosis or choosing treatment strategies. To determine the diagnostic accuracy of ultrasonography for detecting the presence or absence of cirrhosis in people with alcoholic liver disease compared with liver biopsy as reference standard.To determine the diagnostic accuracy of any of the ultrasonography tests, B-mode or echo-colour Doppler ultrasonography, used singly or combined, or plus ultrasonography signs, or a combination of these, for detecting hepatic cirrhosis in people with alcoholic liver disease compared with liver biopsy as a reference standard, irrespective of sequence. We performed searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, The Cochrane Library (Wiley), MEDLINE (OvidSP), EMBASE (OvidSP), and the Science Citation Index Expanded to 8 January 2015. We applied no language limitations.We screened study references of the retrieved studies to identify other potentially relevant studies for inclusion in the review and read abstract and poster publications. Three review authors independently identified studies for possible inclusion in the review. We excluded references not fulfilling the inclusion criteria of the review protocol. We sent e-mails to study authors.The included studies had to evaluate ultrasound in the diagnosis of hepatic cirrhosis using only liver biopsy as the reference standard.The maximum time interval of investigation with liver

  16. Primary biliary cirrhosis in the era of liver transplantation.

    PubMed

    Raczyńska, Joanna; Habior, Andrzej; Pączek, Leszek; Foroncewicz, Bartosz; Pawełas, Andrzej; Mucha, Krzysztof

    2014-09-29

    Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by the presence of antimitochondrial antibodies (AMA) and progressive immune-mediated destruction of biliary ductules, which lead to cirrhosis. Theories of the PBC etiopathogenesis assume that the disease develops secondarily as an improper immunological reaction to undefined environmental and/or infectious factors in genetically predisposed individuals. Ursodeoxycholic acid (UDCA) is the only drug recommended to treat PBC; it delays the progression of liver disease, but remains only a symptomatic treatment. In the advanced stage of PBC, the treatment of choice is liver transplantation (LTx). Nowadays, PBC is the third indication for LTx, after viral-related and alcoholic liver cirrhosis. Unfortunately, PBC recurs in 21-37% of patients at 10 years after LTx, and in 43% at 15 years after LTx, with the median time to recurrence of 3-5.5 years. Diagnosis of recurrent PBC (rPBC) is based on the liver histopathology. Although various risk factors of rPBC have been investigated, the cause of the recurrence is not clear. There is no specific treatment of rPBC. Together with immunosuppression after LTx, UDCA remains the treatment of choice. New diagnostic technologies (e.g., genomics, proteomics, cell-based therapy, and clinical study of the rPBC patients) may be helpful in understanding the pathogenesis of PBC and the development of new treatment modalities.

  17. Perioperative Care of Patients With Liver Cirrhosis: A Review

    PubMed Central

    Abbas, Naeem; Makker, Jasbir; Abbas, Hafsa; Balar, Bhavna

    2017-01-01

    The incidence of cirrhosis is rising, and identification of these patients prior to undergoing any surgical procedure is crucial. The preoperative risk stratification using validated scores, such as Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease, perioperative optimization of hemodynamics and metabolic derangements, and postoperative monitoring to minimize the risk of hepatic decompensation and complications are essential components of medical management. The advanced stage of cirrhosis, emergency surgery, open surgeries, old age, and coexistence of medical comorbidities are main factors influencing the clinical outcome of these patients. Perioperative management of patients with cirrhosis warrants special attention to nutritional status, fluid and electrolyte balance, control of ascites, excluding preexisting infections, correction of coagulopathy and thrombocytopenia, and avoidance of nephrotoxic and hepatotoxic medications. Transjugular intrahepatic portosystemic shunt may improve the CTP class, and semielective surgeries may be feasible. Emergency surgery, whenever possible, should be avoided. PMID:28469455

  18. Iliopsoas muscle hematoma secondary to alcoholic liver cirrhosis.

    PubMed

    Yamashita, Suguru; Tanaka, Nobutaka; Nomura, Yukihiro; Miyahara, Takuya; Furuya, Takatoshi

    2012-09-01

    Iliopsoas muscle hematoma in a patient with alcoholic liver cirrhosis is rarely seen, however it has a high mortality. Thus we should cautiously make a diagnosis and treatment. This is the case of a 60-year-old male. He had a 15-year history of alcoholic liver disease and emphysema. He presented with low back pain after a fall that had happened 2 months before. Due to persistent back pain, he went to see a local physician who, after detailed examination, suspected rupture of bilateral common iliac artery aneurysms and transferred the patient to our hospital. The same presumptive diagnosis was made, and on this basis, an aortic bifemoral Y-graft was implanted. He developed aspiration pneumonia and hepatic and renal dysfunction postoperatively, which led to multiple organ failure and subsequent in-hospital death on postoperative day 62. This was believed to be a case of iliopsoas muscle hematoma developed in a patient with liver cirrhosis, and considering it was a case with poor surgical risk, a conservative treatment option such as transcatheter arterial embolization should also have been considered. Although iliopsoas muscle hematoma with alcoholic liver cirrhosis is rare, an appropriate treatment plan should be determined on a case-by-case basis despite its poor prognosis.

  19. 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

  20. Non-invasive evaluation of liver cirrhosis using ultrasound.

    PubMed

    Goyal, N; Jain, N; Rachapalli, V; Cochlin, D L; Robinson, M

    2009-11-01

    Ultrasound (US) is essential in both assessment of the potentially cirrhotic liver and surveillance of selected patients with chronic hepatitis as liver biopsy can be misleading or inaccurate in up to 25% of cases. Various techniques are already in routine use, such as grey-scale imaging, Doppler US, and contrast-enhanced US (CEUS), while newer techniques such as elastography and hepatic vein transit time (HVTT) have the potential to exclude patients without significant fibrosis or cirrhosis; however, they are operator dependent and require specific software. Grey-scale imaging may demonstrate changes, such as volume redistribution, capsule nodularity, parenchymal nodularity, and echotexture changes. The Doppler findings in the hepatic and portal veins, hepatic artery, and varices allow assessment of liver cirrhosis. However, the operator needs to be aware of limitations of these techniques. Low mechanical index CEUS plays an important role in the assessment of complications of cirrhosis, such as hepatocellular carcinoma and portal vein thrombus. Optimized US technique is crucial for accurate diagnosis of the cirrhotic liver and its complications.

  1. 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.

  2. Liver stiffness predicts variceal bleeding in HIV/HCV-coinfected patients with compensated cirrhosis.

    PubMed

    Merchante, Nicolás; Rivero-Juárez, Antonio; Téllez, Francisco; Merino, Dolores; Ríos-Villegas, Maria José; Ojeda-Burgos, Guillermo; Omar, Mohamed; Macías, Juan; Rivero, Antonio; Pérez-Pérez, Monserrat; Raffo, Miguel; López-Montesinos, Inmaculada; Márquez-Solero, Manuel; Gómez-Vidal, Maria Amparo; Pineda, Juan A

    2017-02-20

    A liver stiffness below 21 kPa has a high negative predictive value to exclude the presence of esophageal varices at risk of bleeding in HIV/hepatitis C virus (HCV)-coinfected patients. Consequently, upper gastrointestinal endoscopy (UGE) for the screening of esophageal varices could be avoided in these patients. However, this strategy has not been widely accepted due to concerns about its safety. To assess the ability of liver stiffness to predict the risk of portal hypertensive gastrointestinal bleeding (PHGB) in HIV/HCV-coinfected patients with compensated cirrhosis. Prospective study of 446 HIV/HCV-coinfected patients with a new diagnosis of cirrhosis and no previous decompensation. All patients underwent a UGE for the screening of esophageal varices at entry in the cohort before November 2009. From this date, UGE was not recommended in patients with liver stiffness below 21 kPa. The time from diagnosis of cirrhosis to the emergence of PHGB was evaluated. After a median (quartile1-quartile3) follow-up of 49 (25-68) months, 15 (3.4%, 95% confidence interval 1.7-5%) patients developed a first PHGB episode. In all cases, baseline liver stiffness was at least 21 kPa. Thus, the negative predictive value of a liver stiffness below 21 kPa to predict PHGB during follow-up was 100%. At the time of the bleeding episode, liver stiffness was above this threshold in all patients. Liver stiffness identifies HIV/HCV-coinfected patients with compensated cirrhosis with a very low risk of PHGB. In fact, no individual with liver stiffness below 21 kPa developed this outcome. Our results confirm that UGE can be safely spared in patients with liver stiffness below 21 kPa.

  3. [Hemoperitoneum supporting difficult diagnosis of diffuse hepatocarcinoma in liver cirrhosis].

    PubMed

    Vignoli, A; Cioni, G; Sardini, C; Tincani, E; Cristani, A; Ventura, E

    1994-04-01

    The cases of two patients with liver cirrhosis HCV-related, admitted in our Department in consequence of the development of ascites, anemia and clinical deterioration, are reported. Both patients had all major risk factors for hepatocellular carcinoma and anamnestic and physical findings suggesting this diagnosis; nevertheless, the alpha-1-fetoprotein serum levels and the ultrasonographic findings were not diagnostic for primary hepatic neoplasm. Explorative paracentesis was diagnostic, demonstrating the presence of hemoperitoneum (the hematocrit ratio in the ascitic fluid was 12 and 10, respectively). Magnetic resonance revealed extensive diffuse hepatocellular carcinoma on both cases. Hemoperitoneum, in patients with liver cirrhosis, in face of non diagnostic levels of alpha-1-fetoprotein and ultrasonographic findings, can be indicative of the spontaneous rupture of a diffuse type of hepatocellular carcinoma.

  4. Analysis of serum haptoglobin fucosylation in hepatocellular carcinoma and liver cirrhosis of different etiologies.

    PubMed

    Zhu, Jianhui; Lin, Zhenxin; Wu, Jing; Yin, Haidi; Dai, Jianliang; Feng, Ziding; Marrero, Jorge; Lubman, David M

    2014-06-06

    We have developed herein a quantitative mass spectrometry-based approach to analyze the etiology-related alterations in fucosylation degree of serum haptoglobin in patients with liver cirrhosis and hepatocellular carcinoma (HCC). The three most common etiologies, including infection with hepatitis B virus (HBV), infection with hepatitis C virus (HCV), and heavy alcohol consumption (ALC), were investigated. Only 10 μL of serum was used in this assay in which haptoglobin was immunoprecipitated using a monoclonal antibody. The N-glycans of haptoglobin were released with PNGase F, desialylated, and permethylated prior to MALDI-QIT-TOF MS analysis. In total, N-glycan profiles derived from 104 individual patient samples were quantified (14 healthy controls, 40 cirrhosis, and 50 HCCs). A unique pattern of bifucosylated tetra-antennary glycan, with both core and antennary fucosylation, was identified in HCC patients. Quantitative analysis indicated that the increased fucosylation degree was highly associated with HBV- and ALC-related HCC patients compared to that of the corresponding cirrhosis patients. Notably, the bifucosylation degree was distinctly increased in HCC patients versus that in cirrhosis of all etiologies. The elevated bifucosylation degree of haptoglobin can discriminate early stage HCC patients from cirrhosis in each etiologic category, which may be used to provide a potential marker for early detection and to predict HCC in patients with cirrhosis.

  5. [Basics of nutrition in cirrhosis of the liver].

    PubMed

    Mörk, H

    2007-04-26

    Liver cirrhosis is associated with complex metabolic disorders, and regularly leads to a catabolic state. Catabolism, malassimilation, but also loss of protein and, frequently, malnutrition, are the main reasons underlying reduced the nutritional status frequently encountered in these patients. This promotes such complications as ascites, diabetes mellitus, encephalopathy, infections and the hepatorenal syndrome. Dietary therapy individually tailored to the course of the disease provides the often increased energy requirement, while also serving to prevent and treat complications.

  6. Tolvaptan for the treatment of liver cirrhosis oedema.

    PubMed

    Sakaida, Isao

    2014-07-01

    No alternative therapeutic option exists if liver cirrhosis patients have insufficient response to conventional diuretics and/or experience conventional diuretic-related adverse events. In 2013, tolvaptan (7.5 mg/day), an arginine vasopressin V2 receptor antagonist, was approved in Japan for the treatment of liver cirrhosis with oedema. Short-term use of tolvaptan produced decreases in body weight, reduction in ascites volume and increases in urine volume when compared to placebo, despite the use of conventional diuretics. Additionally, approximately 60% of patients with oedema-related symptoms improved. Low-dose tolvaptan, 3.75 mg, was also efficacious. Even in patients with low serum albumin (<2.5 g/dL), decrease in body weight was greater with tolvaptan than with placebo. For future research, the efficacy and safety of lower tolvaptan doses for the treatment of liver cirrhosis patients with oedema should be confirmed in Japan. The results of this research could be used as an indicator or a guideline for physicians around the world.

  7. Fleroxacin pharmacokinetics in patients with liver cirrhosis.

    PubMed Central

    Blouin, R A; Hamelin, B A; Smith, D A; Foster, T S; John, W J; Welker, H A

    1992-01-01

    In this open-label study, the disposition of fleroxacin in liver disease in 12 healthy male volunteers, 6 male cirrhotics without ascites (group A), and 6 male cirrhotics with ascites (group B) was evaluated. Fleroxacin (400 mg) was administered orally and intravenously to each subject in a random crossover fashion. Fleroxacin was completely absorbed and achieved similar peak concentrations in plasma in all three study groups (P greater than 0.05). The volume of distribution exceeded 1 liter/kg in healthy controls and was not affected by liver impairment (P greater than 0.05). Only group B demonstrated differences in the pharmacokinetic parameters evaluated: the systemic and renal clearances of fleroxacin and the renal clearances and clearances of the two major metabolites of fleroxacin formed, N-demethyl fleroxacin and fleroxacin N-oxide, were significantly lower and the half-lives of the parent drug and its metabolites were significantly longer in group B than in healthy controls and group A (P less than 0.05). The elimination of the two metabolites appeared to be formation rate limited in all three study groups. It was concluded from this study that a 50% reduction in the fleroxacin maintenance dose in patients with liver disease appears justified only in patients with ascites. However, no change in the fleroxacin loading dose is needed in patients with compromised liver function. PMID:1622175

  8. [Chronic Budd-Chiari syndrome can cause liver cirrhosis].

    PubMed

    Karlsen, Stine; Nielsen, Dennis Tønner; Grønbæk, Henning

    2012-06-11

    Budd-Chiari syndrome (BCS) is a rare disease defined by congestive hepatopathy with obstruction of the hepatic venous outflow tract. Classical symptoms and signs include ascites, hepatomegaly, abdominal pain and various degrees of liver dysfunction. BCS is predominantly caused by thrombosis, malformations and venous compression. We present a case, in which BCS was the cause of liver cirrhosis complicated with refractory ascites and which can be misinterpreted as hepatocellular carcinoma nodules. The diagnosis was confirmed during the transjugular intrahepatic portosystemic shunt procedure with successful vascular stenting resolving the ascites formation.

  9. Diagnosis and therapy of ascites in liver cirrhosis

    PubMed Central

    Biecker, Erwin

    2011-01-01

    Ascites is one of the major complications of liver cirrhosis and is associated with a poor prognosis. It is important to distinguish noncirrhotic from cirrhotic causes of ascites to guide therapy in patients with noncirrhotic ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. The diuretic of choice is spironolactone. A combination treatment with furosemide might be necessary in patients who do not respond to spironolactone alone. Tense ascites is treated by paracentesis, followed by albumin infusion and diuretic therapy. Treatment options for refractory ascites include repeated paracentesis and transjugular intrahepatic portosystemic shunt placement in patients with a preserved liver function. Potential complications of ascites are spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). SBP is diagnosed by an ascitic neutrophil count > 250 cells/mm3 and is treated with antibiotics. Patients who survive a first episode of SBP or with a low protein concentration in the ascitic fluid require an antibiotic prophylaxis. The prognosis of untreated HRS type 1 is grave. Treatment consists of a combination of terlipressin and albumin. Hemodialysis might serve in selected patients as a bridging therapy to liver transplantation. Liver transplantation should be considered in all patients with ascites and liver cirrhosis. PMID:21455322

  10. Hyponatremia in Patients with Cirrhosis of the Liver

    PubMed Central

    Bernardi, Mauro; Ricci, Carmen Serena; Santi, Luca

    2014-01-01

    Hyponatremia is common in cirrhosis. It mostly occurs in an advanced stage of the disease and is associated with complications and increased mortality. Either hypovolemic or, more commonly, hypervolemic hyponatremia can be seen in cirrhosis. Impaired renal sodium handling due to renal hypoperfusion and increased arginine-vasopressin secretion secondary to reduced effective volemia due to peripheral arterial vasodilation represent the main mechanisms leading to dilutional hyponatremia in this setting. Patients with cirrhosis usually develop slowly progressing hyponatremia. In different clinical contexts, it is associated with neurological manifestations due to increased brain water content, where the intensity is often magnified by concomitant hyperammonemia leading to hepatic encephalopathy. Severe hyponatremia requiring hypertonic saline infusion is rare in cirrhosis. The management of asymptomatic or mildly symptomatic hyponatremia mainly rely on the identification and treatment of precipitating factors. However, sustained resolution of hyponatremia is often difficult to achieve. V2 receptor blockade by Vaptans is certainly effective, but their long-term safety, especially when associated to diuretics given to control ascites, has not been established as yet. As in other conditions, a rapid correction of long-standing hyponatremia can lead to irreversible brain damage. The liver transplant setting represents a condition at high risk for the occurrence of such complications. PMID:26237020

  11. Nutrient intakes, nutritional patterns and the risk of liver cirrhosis: an explorative case-control study.

    PubMed

    Corrao, Giovanni; Zambon, Antonella; Bagnardi, Vinccnzo; Aricò, Sarino; Loguercio, Carmelina; D'Amicis, Amleto

    2004-01-01

    Several experimental studies have suggested that specific nutrients might play a role on the risk of liver damage. Nevertheless, few epidemiological studies have evaluated the role of diet on the risk of symptomatic liver cirrhosis, giving contradictory results. To evaluate the role of the intake of nutritional factors and dietary patterns on the risk of symptomatic liver cirrhosis and to examine their combined action with alcohol consumption we used data from the Italian Study on Liver Cirrhosis Determinants project. From 1994 to 1998 all the consecutive cirrhotic inpatients admitted to 19 Italian collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (259 cases) and one or two gender, age and area of residence matched individuals (416 controls) were recruited. Data on lifetime alcohol intake, usual consumption of 191 food items and on markers of hepatitis B and C viral infection were collected. The analysis of principal components identified a nutritional pattern positively correlated with vegetable and fruit intakes and negatively with animal and no-fruit sugar products. With respect to abstainers, relative risks in consumers of use < or = 25 and > or = 51 g/day of alcohol increased from 0.4 [95% confidence interval 0.0, 5.9] to 9.3 [1.3, 69.0] and from 2.1 [1.1, 4.2] to 18.1 [2.8, 118.3] for the lowest and the highest value of this nutritional pattern, respectively. Diet might therefore modulate the damaging effect of alcohol on the liver.

  12. Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study

    PubMed Central

    2012-01-01

    Background Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. Methods This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. Results A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 ± 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P < 0.001). Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal syndrome (P < 0.0001), and spontaneous bacterial peritonitis (P = 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular (≤18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with reduced overall survival were high CRP (≥2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258, CI (0.077 to 0.862)), model of end stage liver disease (MELD) score ≥20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 0.955, CI (0.922 to 0.989)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). Conclusions In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus

  13. Pharmacokinetics of metoclopramide in patients with liver cirrhosis.

    PubMed Central

    Magueur, E; Hagege, H; Attali, P; Singlas, E; Etienne, J P; Taburet, A M

    1991-01-01

    The pharmacokinetics of metoclopramide were investigated after intravenous and oral administration in eight patients with severe alcoholic cirrhosis and in eight healthy volunteers. As a consequence of a 50% lower clearance (0.16 +/- 0.07 vs 0.34 +/- 0.09 l h-1 kg-1, plasma drug concentrations and the half-life of metoclopramide were greater in patients following both routes of drug administration. Volume of distribution (3.1 +/- 0.8 vs 3.4 +/- 1.2 l kg-1) and absolute bioavailability (79 +/- 19 vs 84 +/- 15%) were similar in the two groups. The adverse effects of metoclopramide observed in patients with marked hepatic impairment are likely to result from increased accumulation of the drug as a result of impaired clearance. Consequently a reduction in dose of 50% is recommended in patients with severe liver cirrhosis. PMID:2049236

  14. Peripheral blood monocytes from patients with HBV related decompensated liver cirrhosis can differentiate into functional hepatocytes.

    PubMed

    Yan, Li; Han, Ying; Wang, Jingbo; Liu, Jingmei; Hong, Liu; Fan, Daiming

    2007-11-01

    Peripheral blood monocytes (PBMCs) have the potential to differentiate into various progenitor cells. Here we have investigated the differentiation potential of PBMCs derived from patients with HBV related decompensated liver cirrhosis into hepatocyte-like cells. In our clinical trial, the PBMCs from 2 patients were mobilized by the recombinant human granulocyte colony stimulating factor, followed by leukapheresis and transplantation of PBMCs. PBMCs, induced by recombinant human hepatocyte growth factors, were identified by the expression of hepatocyte markers and specific biological functions with biochemical assays in vitro. Patients showed a lasting clinical amelioration for more than one year after transplantation, and hepatocyte-like cells were identified by expressing liver specific genes, synthesizing albumin, urea, aspirate transaminase, and glycogen, which were all similar to the human normal hepatic cell line QZG. Our results clearly demonstrated that mobilized PBMCs from patients with HBV related decompensated liver cirrhosis could differentiate into functional hepatocyte-like cells, indicating the possibility of autologous cell transplantation for treating patients with HBV related decompensated liver cirrhosis.

  15. Liver transplantation for hepatic cirrhosis in cystic fibrosis.

    PubMed Central

    Noble-Jamieson, G; Barnes, N; Jamieson, N; Friend, P; Calne, R

    1996-01-01

    About 10% of children with CF develop hepatic cirrhosis and progressive portal hypertension. As the portal hypertension worsens these children are likely to develop serious variceal bleeding and other complications including malnutrition and a decline in respiratory function. Indices of lung function may fall as much as 50% in a year and chest infections may require frequent admissions to hospital. The respiratory symptoms are often attributed to CF related lung disease and affected children may therefore be considered unsuitable for liver transplantation. We propose a simple scoring system which can help to select patients who should be referred for assessment of liver transplantation. After careful assessment and preparation children with lung function indices as low as 30% predicted can have a successful outcome after liver transplantation. With good graft function portal hypertension is relieved and absorption, nutrition and respiratory function all improve. The improved quality of life of these children is remarkable. PMID:8778448

  16. Molecular Mechanisms Leading to Splanchnic Vasodilation in Liver Cirrhosis.

    PubMed

    Di Pascoli, Marco; Sacerdoti, David; Pontisso, Patrizia; Angeli, Paolo; Bolognesi, Massimo

    2017-01-01

    In liver cirrhosis, portal hypertension is a consequence of enhanced intrahepatic vascular resistance and portal blood flow. Significant vasodilation in the arterial splanchnic district is crucial for an increase in portal flow. In this pathological condition, increased levels of circulating endogenous vasodilators, including nitric oxide, prostacyclin, carbon monoxide, epoxyeicosatrienoic acids, glucagon, endogenous cannabinoids, and adrenomedullin, and a decreased vascular response to vasoconstrictors are the main mechanisms underlying splanchnic vasodilation. In this review, the molecular pathways leading to splanchnic vasodilation will be discussed in detail. © 2017 S. Karger AG, Basel.

  17. 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.

  18. [Usefulness of procalcitonin for diagnosing infection in critically ill patients with liver cirrhosis].

    PubMed

    Villarreal, E; Vacacela, K; Gordon, M; Calabuig, C; Alonso, R; Ruiz, J; Kot, P; Babiloni, D; Ramírez, P

    2016-03-01

    To evaluate the usefulness of procalcitonin (PCT) for diagnosing infection in patients with liver cirrhosis admitted to an Intensive Care Unit. A retrospective study was carried out. Intensive Care Unit. Versatile, twenty-four beds. Participants Patients with liver cirrhosis admitted to our Intensive Care Unit in the last four years with suspected infection and measurement of PCT. Among the 255 patients with cirrhosis admitted to our unit, PCT was determined for the differential diagnosis of infection in 69 cases (27%). Three patients were excluded from analysis due to a lack of clinical data. The average stay was 10.6 ± 9.2 days, with a mortality rate of 65%. The origin of cirrhosis was mainly viral (57%) or alcoholic (37%). The Child-Pugh and MELD scores were 9.5 ± 2 and 23 ± 8, respectively. Infection was diagnosed in 54 patients (82%). The most common infection was pneumonia (72%), followed by intraabdominal infections (18%) and bacteremia (5%). In patients without infection, the median PCT concentration was 0.57 ng/ml (range 0.28 to 1.14) versus 2.99 (1.31 to 9.4) in those with infection (p<.001). Diagnostic capacity was maintained in patients with intraabdominal infections. The diagnostic cutoff point was set at 0.8 ng/ml (sensitivity 83%, specificity 75%, AUC 0.82 [0.702-0.93]). In patients with liver cirrhosis, PCT is useful for identifying bacterial infections, including intraabdominal processes. Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  19. Factors Influencing Surveillance for Hepatocellular Carcinoma in Patients with Liver Cirrhosis

    PubMed Central

    Ahmed Mohammed, Hager A.; Yang, Ju Dong; Giama, Nasra H.; Choi, Jonggi; Ali, Hawa M.; Mara, Kristin C.; Harmsen, William S.; Wiesner, Russell H.; Leise, Michael D.; Therneau, Terry M.; Roberts, Lewis R.

    2017-01-01

    Objective Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide, and a rising cause of cancer mortality in the U.S. Liver cirrhosis is the major risk factor for HCC. Surveillance of persons with cirrhosis facilitates early detection and improves outcomes. We assessed the surveillance rate for HCC within a major academic health system and identified factors influencing surveillance. Patients and Methods We examined the surveillance rate for HCC using liver ultrasound, CT, or MRI, and factors influencing surveillance in a cohort of 369 Minnesota residents with cirrhosis seen at the Mayo Clinic between 2007 and 2009. Results Ninety-three percent of cirrhosis patients received at least one surveillance study, but only 14% received the recommended uninterrupted semiannual surveillance. Thirty percent received ≥75% of recommended surveillance, and 59% received ≥50% of recommended surveillance. Factors increasing surveillance included gastroenterology or hepatology specialist visits (p < 0.0001), advanced liver disease as assessed by hepatic encephalopathy (p = 0.0008), and comorbid illness as assessed by diabetes mellitus (p = 0.02). Age, sex, race, residence, cirrhosis etiology, or number of primary care visits did not significantly affect the rate of surveillance. Conclusions While the rate of surveillance in a major academic health system was higher than reported in other studies, surveillance was heavily dependent on visits to a subspecialist. This suggests a major and urgent national need to improve identification of individuals at risk for HCC in the primary care setting and the initiation and maintenance of surveillance by primary care practitioners. PMID:28275579

  20. Liver Cancer: Connections with Obesity, Fatty Liver, and Cirrhosis.

    PubMed

    Marengo, Andrea; Rosso, Chiara; Bugianesi, Elisabetta

    2016-01-01

    The burden of hepatocellular carcinoma (HCC), the most common form of liver cancer, is steadily growing because obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD) are replacing viral- and alcohol-related liver disease as major pathogenic promoters. The most worrisome aspects of these new risk factors are their large spread in the general population and their link with HCC arising in noncirrhotic livers. HCC may be the presenting feature of an asymptomatic nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD. The HCC risk connected to metabolic factors has been underestimated so far, and a poorer surveillance has prevented an adequate treatment. Systemic and hepatic molecular mechanisms involved in obesity- and NAFLD-induced hepatocarcinogenesis as well as potential early markers of HCC are being extensively investigated. This review summarizes current evidence linking obesity, NAFLD and liver cancer, discusses its clinical impact and describes the main mechanisms underlying this complex relationship.

  1. Left-sided infective endocarditis in patients with liver cirrhosis.

    PubMed

    Ruiz-Morales, J; Ivanova-Georgieva, R; Fernández-Hidalgo, N; García-Cabrera, E; Miró, Jose M; Muñoz, P; Almirante, B; Plata-Ciézar, A; González-Ramallo, V; Gálvez-Acebal, J; Fariñas, M C; Bravo-Ferrer, J M; Goenaga-Sánchez, M A; Hidalgo-Tenorio, C; Goikoetxea-Agirre, J; de Alarcón-González, A

    2015-12-01

    To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery. Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals. A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p < 0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p < 0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery. Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  2. Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia

    PubMed Central

    Fukui, Hiroshi

    2015-01-01

    A “leaky gut” may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis. PMID:25848468

  3. Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia.

    PubMed

    Fukui, Hiroshi

    2015-03-27

    A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.

  4. Metronidazole-induced encephalopathy in a patient with liver cirrhosis

    PubMed Central

    Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul

    2011-01-01

    Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis. PMID:21757988

  5. Liver transplantation for hepatic cirrhosis in cystic fibrosis.

    PubMed Central

    Noble-Jamieson, G; Valente, J; Barnes, N D; Friend, P J; Jamieson, N V; Rasmussen, A; Calne, R Y

    1994-01-01

    Five children with cystic fibrosis complicated by hepatic cirrhosis received liver grafts. They all had portal hypertension with varices and three had variceal bleeding; respiratory function was only moderately impaired, but four were colonised with pseudomonas and one with aspergillus. Liver transplantation was well tolerated and there was no increase in respiratory or other early postoperative complications. Four of the children were fully well from 14 to 35 months after transplantation; the most recently transplanted had problems from a biliary stricture. In spite of the need for immunosuppression there was no increase in infection and respiratory function improved or remained stable. Once the children were stabilised after transplantation their nutrition and general health were greatly improved. PMID:7979532

  6. Increased prevalence of intestinal inflammation in patients with liver cirrhosis

    PubMed Central

    Saitoh, Osamu; Sugi, Kazunori; Kojima, Keishi; Matsumoto, Hisashi; Nakagawa, Ken; Kayazawa, Masanobu; Tanaka, Seigou; Teranishi, Tsutomu; Hirata, Ichiro; Katsu, Ken-ichi

    1999-01-01

    AIM: To investigate the pathophysiology of the digestive tract in patients with liver cirrhosis. METHODS: In 42 cirrhotic patients and 20 control subjects, the following fecal proteins were measured by enzyme-linked immunosorbent assay: albumin (Alb), transferrin (Tf), and α1-antitrypsin (α1-AT) as a marker for intestinal protein loss, hemoglobin (Hb) for bleeding, PMN-elastase for intestinal inflammation, and secretory IgA for intestinal immunity. RESULTS: The fecal concentrations of Hb, Alb, Tf, α1-AT, an d PMN-elastase were increased in 13 (31%), 8 (19%), 10 (24%), 6 (14%), and 11 (26%) cases among 42 patients, respectively. Fecal concentration of secretory IgA was decreased in 7 (17%) of 42 patients. However, these fecal concentrations were not related to the severity or etiology of liver cirrhosis. The serum Alb level was significantly decreased in patients with intestinal protein loss compared to that in patients without intestinal protein loss. CONCLUSION: These findings suggest that: ① besides the well-known pathological conditions, such as bleeding and protein loss, intestinal inflammation and decreased intestinal immunity are found in cirrhotic patients; ② intestinal protein loss contributes to hypoalbuminemia in cirrhotic patients, and ③ intestinal inflammation should not be over looked in cirrhotic patients, since it may contribute to or cause intestinal protein loss and other various path ological conditions. PMID:11819475

  7. Concentrations of fetuin-A, osteoprotegerin and α-Klotho in patients with alcoholic liver cirrhosis

    PubMed Central

    Prystupa, Andrzej; Dąbrowska, Anna; Sak, Jarosław Jerzy; Tarach, Jerzy; Toruń-Jurkowska, Anna; Lachowska-Kotowska, Patrycja; Dzida, Grzegorz

    2016-01-01

    The aim of the present study was to evaluate the concentrations of fetuin-A, osteoprotegerin (OPG) and α-Klotho protein in patients with alcoholic cirrhosis at different stages of the disease, and to demonstrate that fetuin-A, osteoprotegin and α-Klotho may be used as markers of the severity of cirrhosis. A total of 54 patients with alcoholic liver cirrhosis treated in various hospitals in the Lublin region of Poland were randomly enrolled. The control group consisted of 18 healthy individuals without liver disease, who did not drink alcohol. Serum levels of fetuin-A, OPG and α-Klotho were measured by ELISA kits. Levels of fetuin-A were significantly reduced in patients with alcoholic liver cirrhosis compared with the control group. OPG levels were higher in patients with alcoholic liver cirrhosis than in the controls, whereas the levels of α-Klotho were comparable in the cirrhosis and control groups. No statistically significant differences in the concentrations of fetuin-A, OPG and α-Klotho protein were demonstrated according to type of liver cirrhosis. The findings of the present study revealed a significant negative correlation between the level of α-Klotho protein and C-reactive protein in the patients with alcoholic liver cirrhosis. Concentrations of fetuin-A were lower, whereas those of OPG were higher, in the alcoholic liver cirrhosis group compared with the control group. Fetuin-A, OPG and α-Klotho may not be good indicators of liver cirrhosis severity. In conclusion, fetuin-A and OPG may be used in the diagnosis of liver cirrhosis. PMID:27882180

  8. Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis.

    PubMed

    Arroyo, Vicente; Moreau, Richard; Jalan, Rajiv; Ginès, Pere

    2015-04-01

    Acute-on-chronic liver failure (ACLF) is a recently recognized syndrome characterized by acute decompensation (AD) of cirrhosis and organ/system failure(s) (organ failure: liver, kidney, brain, coagulation, circulation and/or respiration) and extremely poor survival (28-day mortality rate 30-40%). ACLF occurs in relatively young patients. It is especially frequent in alcoholic- and untreated hepatitis B associated-cirrhosis, in addition it is related to bacterial infections and active alcoholism, although in 40% of cases no precipitating event can be identified. It may develop at any time during the course of the disease in the patient (from compensated to long-standing cirrhosis). The development of ACLF occurs in the setting of a systemic inflammation, the severity of which correlates with the number of organ failures and mortality. Systemic inflammation may cause ACLF through complex mechanisms including an exaggerated inflammatory response and systemic oxidative stress to pathogen- or danger/damage-associated molecular patterns (immunopathology) and/or alteration of tissue homeostasis to inflammation caused either by the pathogen itself or through a dysfunction of tissue tolerance. A scoring system composed of three scores (CLIF-C OFs, CLIF-C AD, and CLIF-C ACLFs) specifically designed for patients with AD, with and without ACLF, allows a step-wise algorithm for a rational indication of therapy. The management of ACLF should be carried out in enhanced or intensive care units. Current therapeutic measures comprise the treatment for associated complications, organ failures support and liver transplantation.

  9. alpha 2-Plasmin inhibitor metabolism in patients with liver cirrhosis.

    PubMed

    Knot, E A; Drijfhout, H R; ten Cate, J W; de Jong, E; Iburg, A H; Kahlé, L H; Grijm, R

    1985-03-01

    We describe the metabolism of purified human alpha 2-plasmin inhibitor in patients with liver cirrhosis to determine whether low plasma concentrations of alpha 2-plasmin inhibitor are the result of impaired synthesis or increased catabolism or both. A kinetic study was performed with 131I-alpha 2-plasmin inhibitor as a sensitive parameter of fibrinolysis in 14 patients with histologically proved liver cirrhosis compared with six healthy control subjects. Eight patients had macronodular cirrhosis (with positive hepatitis B surface antigen), and six had micronodular cirrhosis as a result of alcohol abuse. None of the patients had clinical signs of ascites, and in all the disease was stabilized. alpha 2-Plasmin inhibitor levels biologically and immunologically measured were decreased in all patients. Ten microCi 131I-alpha 2PI was injected intravenously, the disappearance of plasma radioactivity was measured, and turnover data were calculated according to the function x(t) = A1e-alpha 1t + A2e-alpha 2t + Be-beta t. Mean (+/- SD) turnover data in the control subjects were plasma radioactivity half-life 60.1 +/- 5.3 hours, fractional catabolic rate constant of the plasma pool 0.0318 +/- 0.0106 hr-1, and absolute catabolic (synthetic) rate constant 2.10 +/- 0.60 mg/kg/day. The alpha 1-phase was 1.26 +/- 0.23, and the transcapillary influx constant (k2,1) was 0.974 +/- 0.109 hr-1. In the patients, plasma radioactivity half-life was 58.7 +/- 12.09 hr, and fractional catabolic rate constant of the plasma pool 0.0283 +/- 0.0043 hr-1. The alpha 1-phase 4.74 +/- 6.48 and the transcapillary influx (k2,1) 3.08 +/- 3.9 hr-1 were both significantly increased compared with control values (p less than 0.05 and p less than 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Non-invasive diagnosis of liver fibrosis and cirrhosis.

    PubMed

    Lurie, Yoav; Webb, Muriel; Cytter-Kuint, Ruth; Shteingart, Shimon; Lederkremer, Gerardo Z

    2015-11-07

    The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.

  11. Outcomes of abdominal surgery in patients with liver cirrhosis.

    PubMed

    Lopez-Delgado, Juan C; Ballus, Josep; Esteve, Francisco; Betancur-Zambrano, Nelson L; Corral-Velez, Vicente; Mañez, Rafael; Betbese, Antoni J; Roncal, Joan A; Javierre, Casimiro

    2016-03-07

    Patients suffering from liver cirrhosis (LC) frequently require non-hepatic abdominal surgery, even before liver transplantation. LC is an important risk factor itself for surgery, due to the higher than average associated morbidity and mortality. This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors, such as coagulopathy, poor nutritional status, adaptive immune dysfunction, cirrhotic cardiomyopathy, and renal and pulmonary dysfunction, which all lead to poor outcomes. Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery. In the emergency setting, with the presence of decompensated LC, alcoholic hepatitis, severe/advanced LC, and significant extrahepatic organ dysfunction conservative management is preferred. A multidisciplinary, individualized, and specialized approach can improve outcomes; preoperative optimization after risk stratification and careful management are mandatory before surgery. Laparoscopic techniques can also improve outcomes. We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before, during, and after surgery.

  12. Outcomes of abdominal surgery in patients with liver cirrhosis

    PubMed Central

    Lopez-Delgado, Juan C; Ballus, Josep; Esteve, Francisco; Betancur-Zambrano, Nelson L; Corral-Velez, Vicente; Mañez, Rafael; Betbese, Antoni J; Roncal, Joan A; Javierre, Casimiro

    2016-01-01

    Patients suffering from liver cirrhosis (LC) frequently require non-hepatic abdominal surgery, even before liver transplantation. LC is an important risk factor itself for surgery, due to the higher than average associated morbidity and mortality. This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors, such as coagulopathy, poor nutritional status, adaptive immune dysfunction, cirrhotic cardiomyopathy, and renal and pulmonary dysfunction, which all lead to poor outcomes. Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery. In the emergency setting, with the presence of decompensated LC, alcoholic hepatitis, severe/advanced LC, and significant extrahepatic organ dysfunction conservative management is preferred. A multidisciplinary, individualized, and specialized approach can improve outcomes; preoperative optimization after risk stratification and careful management are mandatory before surgery. Laparoscopic techniques can also improve outcomes. We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before, during, and after surgery. PMID:26973406

  13. Non-invasive diagnosis of liver fibrosis and cirrhosis

    PubMed Central

    Lurie, Yoav; Webb, Muriel; Cytter-Kuint, Ruth; Shteingart, Shimon; Lederkremer, Gerardo Z

    2015-01-01

    The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this “gold-standard” is imperfect; even according to its proponents, it is only “the best” among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future. PMID:26556987

  14. Differential Sympathetic Vasomotor Activation Induced by Liver Cirrhosis in Rats

    PubMed Central

    Bergamaschi, Cássia T.; Campos, Ruy R.

    2016-01-01

    We tested the hypothesis that there is a topographical sympathetic activation in rats submitted to experimental cirrhosis. Baseline renal (rSNA) and splanchnic (sSNA) sympathetic nerve activities were evaluated in anesthetized rats. In addition, we evaluated main arterial pressure (MAP), heart rate (HR), and baroreceptor reflex sensitivity (BRS). Cirrhotic Wistar rats were obtained by bile duct ligation (BDL). MAP and HR were measured in conscious rats, and cardiac BRS was assessed by changes in blood pressure induced by increasing doses of phenylephrine or sodium nitroprusside. The BRS and baseline for the control of sSNA and rSNA were also evaluated in urethane-anesthetized rats. Cirrhotic rats had increased baseline sSNA (BDL, 102 vs control, 58 spikes/s; p<0.05), but no baseline changes in the rSNA compared to controls. These data were accompanied by increased splanchnic BRS (p<0.05) and decreased cardiac (p<0.05) and renal BRS (p<0.05). Furthermore, BDL rats had reduced basal MAP (BDL, 93 vs control, 101 mmHg; p<0.05) accompanied by increased HR (BDL, 378 vs control, 356; p<0.05). Our data have shown topographical sympathetic activation in rats submitted to experimental cirrhosis. The BDL group had increased baseline sSNA, independent of dysfunction in the BRS and no changes in baseline rSNA. However, an impairment of rSNA and HR control by arterial baroreceptor was noted. We suggest that arterial baroreceptor impairment of rSNA and HR is an early marker of cardiovascular dysfunction related to liver cirrhosis and probably a major mechanism leading to sympathoexcitation in decompensated phase. PMID:27055088

  15. Identification of circulating CD90+ CD73+ cells in cirrhosis of liver

    PubMed Central

    Sasikala, Mitnala; Surya, Pugazhelthi; Radhika, Gaddipati; Kumar, Pondugala Pavan; Rao, Mekala Subba; Mukherjee, Rathindra Mohan; Rao, Padaki Nagaraja; Reddy, D Nageshwar

    2011-01-01

    AIM: To identify circulating CD90+ CD73+ CD45- cells and evaluate their in vitro proliferating abilities. METHODS: Patients with cirrhosis (n = 43), and healthy volunteers (n = 40) were recruited to the study. Mononuclear cells were isolated and cultured from the peripheral blood of controls and cirrhosis patients. Fibroblast-like cells that appeared in cultures were analyzed for morphological features, enumerated by flow cytometry and confirmed by immunocytochemistry (ICC). Colony forming efficiency (CFE) of these cells was assessed and expressed as a percentage. RESULTS: In comparison to healthy volunteers, cells obtained from cirrhotic patients showed a significant increase (P < 0.001) in the percentage of CD90+ CD73+ CD45- cells in culture. Cultured cells also showed 10 fold increases in CFE. Flow cytometry and ICC confirmed that the proliferating cells expressed CD90+ CD73+ in the cultures from cirrhosis patients. CONCLUSION: These results indicate the presence of circulating CD90+ CD73+ CD45- cells in patients with liver cirrhosis that have the potential to proliferate at a higher rate. PMID:21860671

  16. Acute kidney injury in liver cirrhosis: new definition and application

    PubMed Central

    Wong, Florence

    2016-01-01

    The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression. PMID:27987536

  17. Acute kidney injury in liver cirrhosis: new definition and application.

    PubMed

    Wong, Florence

    2016-12-01

    The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression.

  18. Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients

    PubMed Central

    Galicia-Moreno, Marina; Rosique-Oramas, Dorothy; Medina-Avila, Zaira; Álvarez-Torres, Tania; Falcón, Dalia; Higuera-de la tijera, Fátima; Béjar, Yadira L.; Cordero-Pérez, Paula; Muñoz-Espinosa, Linda; Pérez-Hernández, José Luis; Kershenobich, David

    2016-01-01

    Alcohol is the most socially accepted addictive substance worldwide, and its metabolism is related with oxidative stress generation. The aim of this work was to evaluate the role of oxidative stress in alcoholic liver cirrhosis (ALC). This study included 187 patients divided into two groups: ALC, classified according to Child-Pugh score, and a control group. We determined the levels of reduced and oxidized glutathione (GSH and GSSG) and the GSH/GSSG ratio by an enzymatic method in blood. Also, protein carbonyl and malondialdehyde (MDA) content were estimated in serum. MDA levels increased in proportion to the severity of damage, whereas the GSH and GSSG levels decreased and increased, respectively, at different stages of cirrhosis. There were no differences in the GSH/GSSG ratio and carbonylated protein content between groups. We also evaluated whether the active consumption of or abstinence from alcoholic beverages affected the behavior of these oxidative markers and only found differences in the MDA, GSH, and GSSG determination and the GSH/GSSG ratio. Our results suggest that alcoholic cirrhotic subjects have an increase in oxidative stress in the early stages of disease severity and that abstinence from alcohol consumption favors the major antioxidant endogen: GSH in patients with advanced disease severity. PMID:28074118

  19. Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients.

    PubMed

    Galicia-Moreno, Marina; Rosique-Oramas, Dorothy; Medina-Avila, Zaira; Álvarez-Torres, Tania; Falcón, Dalia; Higuera-de la Tijera, Fátima; Béjar, Yadira L; Cordero-Pérez, Paula; Muñoz-Espinosa, Linda; Pérez-Hernández, José Luis; Kershenobich, David; Gutierrez-Reyes, Gabriela

    2016-01-01

    Alcohol is the most socially accepted addictive substance worldwide, and its metabolism is related with oxidative stress generation. The aim of this work was to evaluate the role of oxidative stress in alcoholic liver cirrhosis (ALC). This study included 187 patients divided into two groups: ALC, classified according to Child-Pugh score, and a control group. We determined the levels of reduced and oxidized glutathione (GSH and GSSG) and the GSH/GSSG ratio by an enzymatic method in blood. Also, protein carbonyl and malondialdehyde (MDA) content were estimated in serum. MDA levels increased in proportion to the severity of damage, whereas the GSH and GSSG levels decreased and increased, respectively, at different stages of cirrhosis. There were no differences in the GSH/GSSG ratio and carbonylated protein content between groups. We also evaluated whether the active consumption of or abstinence from alcoholic beverages affected the behavior of these oxidative markers and only found differences in the MDA, GSH, and GSSG determination and the GSH/GSSG ratio. Our results suggest that alcoholic cirrhotic subjects have an increase in oxidative stress in the early stages of disease severity and that abstinence from alcohol consumption favors the major antioxidant endogen: GSH in patients with advanced disease severity.

  20. Oral health and liver function in children and adolescents with cirrhosis of the liver

    PubMed Central

    Kowalczyk, Wojciech; Krasuska-Sławińska, Ewa; Dądalski, Maciej; Kostewicz, Krzysztof; Pawłowska, Joanna

    2014-01-01

    Introduction People with cirrhosis of the liver are predisposed to developing oral lesions. The occurrence and type of lesion depend on the degree of liver function impairment and its type, and on the severity and duration of systemic diseases. In children, the age at which the early symptoms of liver disease are experienced is also of great importance. Aim To assess the prevalence of oral pathological lesions in children and adolescents with cirrhosis of the liver, and their correlation with the degree of liver function impairment. Material and methods Clinical and laboratory results of liver function tests (Model of End-Stage Liver Disease/Score of Paediatric End-Stage Liver Disease, Child-Pugh score) were assessed in 35 patients with cirrhosis of the liver. The average age of the patients was 10.7 ±4.74 years. All patients also had their oral cavities examined (mucosa, gingiva – GI, hygiene – PLI, teeth – dmft/dmfs and DMFt/DMFs, DDE Index and Candida spp. presence) and this was then correlated to the degree of liver function impairment. Results According to the Child-Pugh scale, 16 patients were class A and 19 were class B/C. Jaundice during the first 3 years of life occurred in 9 patients. Mucosal lesions were found in 26 out of 35 patients (74%), including 10 out of 16 (63%) in Child-Pugh group A, and 16 out of 19 (84%) in group B/C (NS – non significant). Oral candidiasis occurred more often in class B/C than in class A (47.4% vs. 12.5%; p < 0.05). The GI index (Gingival Index) and PLI index (Dental Plaque Index) did not differ between the groups (A vs. B/C) but correlated in the whole group (R = 0.58) as well as in subgroups A (R = 0.65) and B/C (R = 0.59). Dmft/dmfs and DMFt/DMFs indexes did not differ between groups A and B/C, and neither did the DMFt/DMFs in patients with/without enamel defects. Conclusions Oral mucosal lesions are commonly found in children with cirrhosis of the liver. Advanced liver disease promotes oral candidiasis. Severity

  1. Terahertz spectroscopy of liver cirrhosis: investigating the origin of contrast

    NASA Astrophysics Data System (ADS)

    Sy, Stanley; Huang, Shengyang; Wang, Yi-Xiang J.; Yu, Jun; Ahuja, Anil T.; Zhang, Yuan-ting; Pickwell-MacPherson, Emma

    2010-12-01

    We have previously demonstrated that terahertz pulsed imaging is able to distinguish between rat tissues from different healthy organs. In this paper we report our measurements of healthy and cirrhotic liver tissues using terahertz reflection spectroscopy. The water content of the fresh tissue samples was also measured in order to investigate the correlations between the terahertz properties, water content, structural changes and cirrhosis. Finally, the samples were fixed in formalin to determine whether water was the sole source of image contrast in this study. We found that the cirrhotic tissue had a higher water content and absorption coefficient than the normal tissue and that even after formalin fixing there were significant differences between the normal and cirrhotic tissues' terahertz properties. Our results show that terahertz pulsed imaging can distinguish between healthy and diseased tissue due to differences in absorption originating from both water content and tissue structure.

  2. UDP-glucuronosyltransferase 1A7 polymorphisms are associated with liver cirrhosis.

    PubMed

    Tang, Kung-Sheng; Lee, Chuan-Mo; Teng, Hsiu-Chen; Huang, May-Jen; Huang, Ching-Shan

    2008-02-15

    Variations in the UDP-glucuronosyltransferase (UGT) 1A7 gene have been found to be related to the development of hepatocellular carcinoma (HCC). Since the pathogenesis of liver cirrhosis is not dissimilar to that of HCC, we hypothesized that UGT1A7 genetic polymorphisms may be associated with liver cirrhosis. PCR-restriction fragment length polymorphism was utilized to determine UGT for 1A7 genotypes for the 159 patients with liver cirrhosis and 263 gender/age matched controls. Simple logistic regression analysis revealed that significant risk factors for liver cirrhosis were (1) hepatitis B virus (HBV) infection, (2) hepatitis C virus (HCV) infection, (3) HBV infection plus HCV infection and (4) low-activity UGT1A7 genotypes. The results of further multivariate logistic regression confirmed these associations. Interaction of low-activity UGT1A7 genotypes and HBV (or HCV) infection produced an additive effect upon the risk for the development of liver cirrhosis [observed odds ratio (OR) (54.59) greater than the expected OR (18.05)]. UGT1A7 low/low genotype was also related to advanced liver cirrhosis (Child-Pugh classes C and/or B) (OR=7.50, P=0.009). This study demonstrates the novel findings that carriage of low-activity UGT1A7 genotypes represents a risk factor for the development and functional severity of liver cirrhosis.

  3. The immunopathology of liver granulomas in primary biliary cirrhosis.

    PubMed

    You, Zhengrui; Wang, Qixia; Bian, Zhaolian; Liu, Yuan; Han, Xiaofeng; Peng, Yanshen; Shen, Lei; Chen, Xiaoyu; Qiu, Dekai; Selmi, Carlo; Gershwin, M Eric; Ma, Xiong

    2012-09-01

    Liver granulomas and elevated serum IgM are commonly observed in patients with primary biliary cirrhosis (PBC) but their pathogenetic significance remains largely unknown. To address this issue we performed an extensive immunostaining and colocalization study of markers associated with dendritic cells and IgM in a large cohort of tissue samples from PBC and control livers as well as from non-hepatic granulomatous diseases. First, the classical dendritic cell CD11c marker is highly expressed and more sensitive than classical hematoxylin-eosin staining in detecting granulomas associated with PBC and other conditions. Second, PBC cases with CD11c-positive granulomas have significantly higher serum IgM levels and earlier disease stages. Third, granulomas from PBC and other diseases demonstrate markers of dendritic cell immaturity, i.e. CD11b, reduced MHC II, IL-23, CCR7 and CD83 expression, and elevated C1q expression. Lastly, B cells and IgM-positive plasma cells are largely represented around PBC granulomas along with macrophages. In conclusion, our comprehensive immunohistochemical study suggests that dendritic cells are key to the pathogenesis of granulomas, regardless of their origin. More specifically, PBC liver granulomas may result from the interaction between immature dendritic cells and IgM.

  4. Changes in platelet functional parameters and CD62 P expression in liver cirrhosis.

    PubMed

    Xianghong, G; Guanping, C; Fenghua, Y; Jiayin, W

    2013-12-01

    Hepatic impairment, portal hypertension, and multi-systemic damage could occur during liver cirrhosis's late stage. Bleeding is a complication of hepatic cirrhosis along with several changes including blood platelet count (BPC), mean platelet volume (MPV), platelet crit (PCT) and expression of platelet CD62P. Blood platelet count (BPC), mean platelet volume (MPV), platelet distribution width, and other indices are indirect reflections of CD62P parameters. To investigate the changes in platelet functional parameters and CD62 P expression in liver cirrhosis as a possible guide in clinical treatments and prognoses of liver cirrhosis. CD62P was tested by flow cytometry in liver cirrhosis. BPC, MPV, and PCT in peripheral blood were tested using an auto blood cell analyzer. Data were analyzed using SPSS11.0. The values of CD62P and MPV in patients was significantly higher than those of healthy donors (P<0.01), while the values of BPC and PCT were significantly lower than those of the control group (P<0.01). CD62P, BPC, MPV, and platelet crit (PCT) show several changes in liver cirrhosis. It is useful to understand the relationship between hepatic cirrhosis severity and CD62P, BPC, MPV, PCT, timely monitoring of CD62P for treatment of hepatic cirrhosis in clinical treatment and prognosis.

  5. Case Report of Cirrhosis following Yttrium-90 Radioembolization for Pancreatic Neuroendocrine Liver Metastases.

    PubMed

    Loree, Jonathan M; Hiruki, Tadaaki; Kennecke, Hagen F

    2016-01-01

    Management options for pancreatic neuroendocrine tumors (pNETs) metastatic to the liver include surgical, ablative, cytotoxic, and radioisotope approaches. One potential local treatment option includes selective internal radiotherapy utilizing yttrium-90 ((90)Y) microspheres. (90)Y has also been used in the treatment of hepatocellular carcinoma and tumors metastatic to the liver. It appears to be well tolerated; however, there is no randomized controlled trial reporting long-term toxicities. Previous retrospective reports have described biliary damage as a potential complication of therapy with (90)Y and chemoembolization; however, the long-term sequelae of (90)Y treatment are poorly understood. We present the case of a 65-year-old Caucasian woman who suffered biliary damage following (90)Y administration for metastatic pNETs and subsequently developed cirrhosis. Given the timeline of her various treatments and the lack of any other identifiable etiology for her cirrhosis, we believe this to be a potential long-term complication of (90)Y therapy. This case provides pathologic confirmation of cirrhosis as a potential long-term sequela of (90)Y treatment. This long-term risk needs to be considered when sequencing therapy for patients with neuroendocrine tumors who have a good prognosis. There are now several other systemic and ablative treatment options available to these patients, and long-term complications must be considered during treatment.

  6. Case Report of Cirrhosis following Yttrium-90 Radioembolization for Pancreatic Neuroendocrine Liver Metastases

    PubMed Central

    Loree, Jonathan M.; Hiruki, Tadaaki; Kennecke, Hagen F.

    2016-01-01

    Background Management options for pancreatic neuroendocrine tumors (pNETs) metastatic to the liver include surgical, ablative, cytotoxic, and radioisotope approaches. One potential local treatment option includes selective internal radiotherapy utilizing yttrium-90 (90Y) microspheres. 90Y has also been used in the treatment of hepatocellular carcinoma and tumors metastatic to the liver. It appears to be well tolerated; however, there is no randomized controlled trial reporting long-term toxicities. Previous retrospective reports have described biliary damage as a potential complication of therapy with 90Y and chemoembolization; however, the long-term sequelae of 90Y treatment are poorly understood. Case Presentation We present the case of a 65-year-old Caucasian woman who suffered biliary damage following 90Y administration for metastatic pNETs and subsequently developed cirrhosis. Given the timeline of her various treatments and the lack of any other identifiable etiology for her cirrhosis, we believe this to be a potential long-term complication of 90Y therapy. Conclusion This case provides pathologic confirmation of cirrhosis as a potential long-term sequela of 90Y treatment. This long-term risk needs to be considered when sequencing therapy for patients with neuroendocrine tumors who have a good prognosis. There are now several other systemic and ablative treatment options available to these patients, and long-term complications must be considered during treatment. PMID:26933423

  7. Cirrhosis, Liver Transplantation and HIV Infection Are Risk Factors Associated with Hepatitis E Virus Infection

    PubMed Central

    Riveiro-Barciela, Mar; Buti, María; Homs, María; Campos-Varela, Isabel; Cantarell, Carmen; Crespo, Manuel; Castells, Lluís; Tabernero, David; Quer, Josep; Esteban, Rafael; Rodriguez-Frías, Francisco

    2014-01-01

    Background Acute and chronic hepatitis E have been associated with high mortality and development of cirrhosis, particularly in solid-organ recipients and patients infected by human immunodeficiency virus. However, data regarding the epidemiology of hepatitis E in special populations is still limited. Aims Investigate seroprevalence and possible factors associated with HEV infection in a large cohort of immunosuppressed patients. Methods Cross-sectional study testing IgG anti-HEV in serum samples from 1373 consecutive individuals: 332 liver-transplant, 296 kidney-transplant, 6 dual organ recipients, 301 non-transplanted patients with chronic liver disease, 238 HIV-infected patients and 200 healthy controls. Results IgG anti-HEV was detected in 3.5% controls, 3.7% kidney recipients, 7.4% liver transplant without cirrhosis and 32.1% patients who developed post-transplant cirrhosis (p<0.01). In patients with chronic liver disease, IgG anti-HEV was also statistically higher in those with liver cirrhosis (2% vs 17.5%, p<0.01). HIV-infected patients showed an IgG anti-HEV rate of 9.2%, higher than those patients without HIV infection (p<0.03). Multivariate analysis showed that the factors independently associated with anti-HEV detection were liver cirrhosis, liver transplantation and HIV infection (OR: 7.6, 3.1 and 2.4). HCV infection was a protective factor for HEV infection (OR: 0.4). Conclusions HEV seroprevalence was high in liver transplant recipients, particularly those with liver cirrhosis. The difference in anti-HEV prevalence between Liver and Kidney transplanted cases suggests an association with advanced liver disease. Further research is needed to ascertain whether cirrhosis is a predisposing factor for HEV infection or whether HEV infection may play a role in the pathogeneses of cirrhosis. PMID:25068388

  8. The Frequency of Complications and the Etiology of Disease in Patients with Liver Cirrhosis in Erzurum

    PubMed Central

    Topdagi, Omer; Okcu, Nihat; Bilen, Nurhan

    2014-01-01

    Objective: This study included 100 patients diagnosed with liver cirrhosis who presented at Atatürk University Faculty of Medicine Gastroenterology clinic and polyclinic. Materials and Methods: The etiology of liver cirrhosis and the incidence of its complications have been investigated. Results: The etiological classification of liver cirrhosis in our patients was as follows: 47 hepatitis B virus hepatitis, 11 hepatitis C virus hepatitis, 5 HBV+HDV hepatitis, 4 Budd Chiari syndrome, 2 chronic alcohol abuse, 2 ischemic heart disease, 1 autoimmune hepatitis, 1 sclerosing cholangitis, 1 hydatid cyst. In 26 patients we could not find any etiological condition. These patients were called cryptogenic cirrhosis patients.When we examined the complications of liver cirrhosis, it appeared that there were ascites in 83 patient. In 56 patients, esophageal variceal bleeding occurred. There was spontaneous bacterial peritonitis in 42 patients. Hepatorenal syndrome occurred in 26 patients. Finally, in 3 patients we detected hepatorenal syndrome. Conclusion: The most common causes in the etiology of liver cirrhosis are viral, especially HBV. Many of the patients were in decompensated phase when diagnosed. We found that there was a close relation between the frequency of complications and mortality in liver cirrhosis. PMID:25610308

  9. The frequency of complications and the etiology of disease in patients with liver cirrhosis in erzurum.

    PubMed

    Topdagi, Omer; Okcu, Nihat; Bilen, Nurhan

    2014-06-01

    This study included 100 patients diagnosed with liver cirrhosis who presented at Atatürk University Faculty of Medicine Gastroenterology clinic and polyclinic. The etiology of liver cirrhosis and the incidence of its complications have been investigated. The etiological classification of liver cirrhosis in our patients was as follows: 47 hepatitis B virus hepatitis, 11 hepatitis C virus hepatitis, 5 HBV+HDV hepatitis, 4 Budd Chiari syndrome, 2 chronic alcohol abuse, 2 ischemic heart disease, 1 autoimmune hepatitis, 1 sclerosing cholangitis, 1 hydatid cyst. In 26 patients we could not find any etiological condition. These patients were called cryptogenic cirrhosis patients.When we examined the complications of liver cirrhosis, it appeared that there were ascites in 83 patient. In 56 patients, esophageal variceal bleeding occurred. There was spontaneous bacterial peritonitis in 42 patients. Hepatorenal syndrome occurred in 26 patients. Finally, in 3 patients we detected hepatorenal syndrome. The most common causes in the etiology of liver cirrhosis are viral, especially HBV. Many of the patients were in decompensated phase when diagnosed. We found that there was a close relation between the frequency of complications and mortality in liver cirrhosis.

  10. Alcohol Cirrhosis Alters Nuclear Receptor and Drug Transporter Expression in Human Liver

    PubMed Central

    More, Vijay R.; Cheng, Qiuqiong; Donepudi, Ajay C.; Buckley, David B.; Lu, Zhenqiang James; Cherrington, Nathan J.

    2013-01-01

    Unsafe use of alcohol results in approximately 2.5 million deaths worldwide, with cirrhosis contributing to 16.6% of reported deaths. Serum insulin levels are often elevated in alcoholism and may result in diabetes, which is why alcoholic liver disease and diabetes often are present together. Because there is a sizable population with these diseases alone or in combination, the purpose of this study was to determine whether transporter expression in human liver is affected by alcoholic cirrhosis, diabetes, and alcoholic cirrhosis coexisting with diabetes. Transporters aid in hepatobiliary excretion of many drugs and toxic chemicals and can be determinants of drug-induced liver injury. Drug transporter expression and transcription factor–relative mRNA and protein expression in normal, diabetic, cirrhotic, and cirrhosis with diabetes human livers were quantified. Cirrhosis significantly increased ABCC4, 5, ABCG2, and solute carrier organic anion (SLCO) 2B1 mRNA expression and decreased SLCO1B3 mRNA expression in the liver. ABCC1, 3–5, and ABCG2 protein expression was also upregulated by alcoholic cirrhosis. ABCC3-5 and ABCG2 protein expression was also upregulated in diabetic cirrhosis. Cirrhosis increased nuclear factor E2–related factor 2 mRNA expression, whereas it decreased pregnane-X-receptor and farnesoid-X-receptor mRNA expression in comparison with normal livers. Hierarchical cluster analysis indicated that expressions of ABCC2, 3, and 6; SLCO1B1 and 1B3; and ABCC4 and 5 were more closely related in the livers from this cohort. Overall, alcoholic cirrhosis altered transporter expression in human liver. PMID:23462698

  11. Alcohol cirrhosis alters nuclear receptor and drug transporter expression in human liver.

    PubMed

    More, Vijay R; Cheng, Qiuqiong; Donepudi, Ajay C; Buckley, David B; Lu, Zhenqiang James; Cherrington, Nathan J; Slitt, Angela L

    2013-05-01

    Unsafe use of alcohol results in approximately 2.5 million deaths worldwide, with cirrhosis contributing to 16.6% of reported deaths. Serum insulin levels are often elevated in alcoholism and may result in diabetes, which is why alcoholic liver disease and diabetes often are present together. Because there is a sizable population with these diseases alone or in combination, the purpose of this study was to determine whether transporter expression in human liver is affected by alcoholic cirrhosis, diabetes, and alcoholic cirrhosis coexisting with diabetes. Transporters aid in hepatobiliary excretion of many drugs and toxic chemicals and can be determinants of drug-induced liver injury. Drug transporter expression and transcription factor-relative mRNA and protein expression in normal, diabetic, cirrhotic, and cirrhosis with diabetes human livers were quantified. Cirrhosis significantly increased ABCC4, 5, ABCG2, and solute carrier organic anion (SLCO) 2B1 mRNA expression and decreased SLCO1B3 mRNA expression in the liver. ABCC1, 3-5, and ABCG2 protein expression was also upregulated by alcoholic cirrhosis. ABCC3-5 and ABCG2 protein expression was also upregulated in diabetic cirrhosis. Cirrhosis increased nuclear factor E2-related factor 2 mRNA expression, whereas it decreased pregnane-X-receptor and farnesoid-X-receptor mRNA expression in comparison with normal livers. Hierarchical cluster analysis indicated that expressions of ABCC2, 3, and 6; SLCO1B1 and 1B3; and ABCC4 and 5 were more closely related in the livers from this cohort. Overall, alcoholic cirrhosis altered transporter expression in human liver.

  12. Kallistatin, a new and reliable biomarker for the diagnosis of liver cirrhosis.

    PubMed

    Cheng, Zhiyun; Lv, Yinghui; Pang, Suqiu; Bai, Ruyu; Wang, Mingxi; Lin, Shuyu; Xu, Tianwen; Spalding, Duncan; Habib, Nagy; Xu, Ruian

    2015-05-01

    Kallistatin, which protects organs and cells against inflammation, fibrosis and oxidative stress, is mainly synthesized and secreted in liver. However, its relationship to human liver disease remains unclear. The purpose of this study was to explore the relationship between serum kallistatin and clinical evidence of both cirrhosis and hepatocellular carcinoma (HCC), and to determine if serum kallistatin levels could be used as a diagnostic indicator of hepatic health status, especially human liver cirrhosis (LC). Our cohort consisted of 115 patients with clinically proven liver fibrosis (LF), LC, or HCC by liver biopsies, and 31 healthy controls (CON). Serum kallistatin levels were quantified by ELISA. Results of the present study demonstrated that irrespective of the underlying etiology, serum kallistatin levels were significantly lower in the LF/LC group when compared with the CON group. A decrease in serum kallistatin levels appeared to reflect the extent of cirrhosis, with the lowest levels associated with higher grades of cirrhosis. Patients with LC had a noticeable correlation between serum kallistatin levels and other serum biochemical indicators. The area under the curve (AUC) for LC, viral liver cirrhosis (VLC) and alcoholic liver cirrhosis (ALC) was 0.845, 0.757 and 0.931, respectively. In conclusion, our findings demonstrated that kallistatin, a plasma protein produced by the liver, can be a useful and reliable diagnostic indicator of hepatic health status, especially for LC.

  13. A profile of volatile organic compounds in exhaled air as a potential non-invasive biomarker for liver cirrhosis.

    PubMed

    Pijls, Kirsten E; Smolinska, Agnieszka; Jonkers, Daisy M A E; Dallinga, Jan W; Masclee, Ad A M; Koek, Ger H; van Schooten, Frederik-Jan

    2016-01-29

    Early diagnosis of liver cirrhosis may prevent progression and development of complications. Liver biopsy is the current standard, but is invasive and associated with morbidity. We aimed to identify exhaled volatiles within a heterogeneous group of chronic liver disease (CLD) patients that discriminates those with compensated cirrhosis (CIR) from those without cirrhosis, and compare this with serological markers. Breath samples were collected from 87 CLD and 34 CIR patients. Volatiles in exhaled air were measured by gas chromatography mass spectrometry. Discriminant Analysis was performed to identify the optimal panel of serological markers and VOCs for classifying our patients using a random training set of 27 CIR and 27 CLD patients. Two randomly selected independent internal validation sets and permutation test were used to validate the model. 5 serological markers were found to distinguish CIR and CLD patients with a sensitivity of 0.71 and specificity of 0.84. A set of 11 volatiles discriminated CIR from CLD patients with sensitivity of 0.83 and specificity of 0.87. Combining both did not further improve accuracy. A specific exhaled volatile profile can predict the presence of compensated cirrhosis among CLD patients with a higher accuracy than serological markers and can aid in reducing liver biopsies.

  14. A profile of volatile organic compounds in exhaled air as a potential non-invasive biomarker for liver cirrhosis

    PubMed Central

    Pijls, Kirsten E.; Smolinska, Agnieszka; Jonkers, Daisy M. A. E.; Dallinga, Jan W.; Masclee, Ad A. M.; Koek, Ger H.; van Schooten, Frederik-Jan

    2016-01-01

    Early diagnosis of liver cirrhosis may prevent progression and development of complications. Liver biopsy is the current standard, but is invasive and associated with morbidity. We aimed to identify exhaled volatiles within a heterogeneous group of chronic liver disease (CLD) patients that discriminates those with compensated cirrhosis (CIR) from those without cirrhosis, and compare this with serological markers. Breath samples were collected from 87 CLD and 34 CIR patients. Volatiles in exhaled air were measured by gas chromatography mass spectrometry. Discriminant Analysis was performed to identify the optimal panel of serological markers and VOCs for classifying our patients using a random training set of 27 CIR and 27 CLD patients. Two randomly selected independent internal validation sets and permutation test were used to validate the model. 5 serological markers were found to distinguish CIR and CLD patients with a sensitivity of 0.71 and specificity of 0.84. A set of 11 volatiles discriminated CIR from CLD patients with sensitivity of 0.83 and specificity of 0.87. Combining both did not further improve accuracy. A specific exhaled volatile profile can predict the presence of compensated cirrhosis among CLD patients with a higher accuracy than serological markers and can aid in reducing liver biopsies. PMID:26822454

  15. Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis.

    PubMed

    Goldberg, David S; Taddei, Tamar H; Serper, Marina; Mehta, Rajni; Dieperink, Eric; Aytaman, Ayse; Baytarian, Michelle; Fox, Rena; Hunt, Kristel; Pedrosa, Marcos; Pocha, Christine; Valderrama, Adriana; Kaplan, David E

    2017-03-01

    Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in cirrhosis patients. This provides an opportunity to target the highest-risk population, yet surveillance rates in the United States and Europe range from 10% to 40%. The goal of this study was to identify barriers to HCC surveillance, using data from the Veterans Health Administration, the largest provider of liver-related health care in the United States. We included all patients 75 years of age or younger who were diagnosed with cirrhosis from January 1, 2008, until December 31, 2010. The primary outcome was a continuous measure of the percentage of time up-to-date with HCC surveillance (PTUDS) based on abdominal ultrasound (secondary outcomes included computed tomography and magnetic resonance imaging). Among 26,577 patients with cirrhosis (median follow-up = 4.7 years), the mean PTUDS was 17.8 ± 21.5% (ultrasounds) and 23.3 ± 24.1% when any liver imaging modality was included. The strongest predictor of increased PTUDS was the number of visits to a specialist (gastroenterologist/hepatologist and/or infectious diseases) in the first year after cirrhosis diagnosis; the association between visits to a primary care physician and increasing surveillance was very small. Increasing distance to the closest Veterans Administration center was associated with decreased PTUDS. There was an inverse association between ultrasound lead time (difference between the date an ultrasound was ordered and requested exam date) and the odds of it being performed: odds ratio = 0.77, 95% confidence interval 0.72-0.82 when ordered > 180 days ahead of time; odds ratio = 0.90, 95% confidence interval 0.85-0.94 if lead time 91-180 days.

  16. The impacts of liver cirrhosis on head and neck cancer patients undergoing microsurgical free tissue transfer: an evaluation of flap outcome and flap-related complications.

    PubMed

    Kao, Huang-Kai; Chang, Kai-Ping; Ching, Wei-Cheng; Tsao, Chung-Kan; Cheng, Ming-Huei; Wei, Fu-Chan

    2009-12-01

    Several authors have cited liver cirrhosis as a risk factor for surgery but no study performed statistical correlation between flap outcome and severity of liver cirrhosis in patients with head and neck cancer. We performed a retrospective analysis of 3108 patients who underwent free tissue transfer after head and neck cancer ablation between January 2000 and December 2008. Liver cirrhosis was identified in 62 patients. Forty-two patients (67.7%) were classified as having Child's class A cirrhosis, seventeen (27.4%) as having class B, and three (4.9%) as having class C cirrhosis. The overall complete flap survival rate was 90.3% (56/62). The flap-related complications of patients with Child's class A, B, and C were 38.1% (16/42), 47.1% (8/17), and 100% (3/3), respectively and showed no significant difference between these three groups (p=0.2758). The rate of postoperative neck hematoma was 14.5%; the risk of postoperative neck hematoma was significantly higher in patients with more advanced liver cirrhosis (p=0.0003). The recipient-site complications of patients with Child's class A cirrhosis, Child's class B, and Child's class C cirrhosis were 35.7%, 41.1%, and 66.6%, respectively, with no significant difference among the three groups. The statistical analysis demonstrated that diabetes mellitus is significantly associated with a negative prognosis for free flap reconstruction (p=0.0364). The flap survival rate and patency of microvascular anastomosis have no association with liver cirrhosis. To achieve a superior surgical outcome, preoperative optimization and a multidisciplinary team responsible for the evaluation and treatment of head and neck cancer patients with cirrhosis are necessary.

  17. Evaluation of Aspartate Aminotransferase-to-Platelet Ratio Index as a Non-Invasive Marker for Liver Cirrhosis

    PubMed Central

    Tripathi, B.K.; Gupta, B.; Bhandari, Bharti; Jalan, Divesh

    2015-01-01

    Introduction Liver biopsy is considered as a gold standard for the diagnosis of cirrhosis. Till date there is no non-invasive marker to replace it. Aim To investigate the effectiveness of Aspartate aminotransferase-to-platelet ratio index (APRI) as a non-invasive marker for liver cirrhosis. Materials and Methods Fifty-one patients with cirrhosis, identified on USG abdomen were included in study. Platelet count and Aspartate aminotransferase (AST) were done using haematology automatic analyser and automatic HITACHI-912 Auto Analyser respectively. APRI was calculated for every patient using the formula {(AST / ULN) x 100}/platelet count (109/L). Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Results APRI correctly classified 49 (96.1%) patients of cirrhosis with area under the ROC curve of 0.973 (95% CI) at cut-off 0.65 with negative predictive value (NPV) and Positive predictive value (PPV) of 96% and 96.1% respectively. The sensitivity and specificity of the test was found to be 96% and 96.1% respectively. Conclusion APRI could identify cirrhosis with high degree of accuracy in the studied patients. PMID:26672800

  18. Transketolase-TPP-effect in chronic alcoholics with various degrees of liver cirrhosis.

    PubMed

    Somogyi, J C; Kopp, P M; Filippini, L; Monnat, A

    1980-01-01

    A re-investigation of the use of the transketolase-TPP-effect for the assessment of the thiamine status of chronic alcoholics with various degrees of liver cirrhosis was carried out on 36 alcoholics. The extent of the liver damage in these patients was established by clinical examinations and biochemical tests. Fourteen persons showed no significant hepatic abnormalities, 5 patients had compensated liver cirrhosis, 7 slightly decompensated, and 10 patients suffered from severely decompensated liver cirrhosis. This investigation shows that the transketolase-TPP-effect is also present in patients even with severe liver cirrhosis and that a decrease of the TPP-effect can be observed after oral thiamine administration in these subjects. The TPP-effect of patients with compensated liver cirrhosis was markedly smaller than that of the subjects with slightly or severely decompensated cirrhosis. Accordingly a relationship exists between the TPP-effect and the degree of liver damage. No other correlations however could be established in this respect.

  19. Study of trace elements in liver cirrhosis patients and their role in prognosis of disease.

    PubMed

    Nangliya, Vijaylaxmi; Sharma, Anjali; Yadav, Dharamveer; Sunder, Shyam; Nijhawan, Sandeep; Mishra, Sandhya

    2015-05-01

    The objectives of this study are to evaluate trace elements in patients with liver cirrhosis and to assess their association with severity of the disease. One hundred fifty cirrhotic subjects of either sex ranging in age from 20-70 years were included in the study, and the results were compared with 50 age- and sex-matched healthy control subjects. All cirrhotic subjects were assessed for severity of disease as mild (Child A), moderate (Child B), and severe (Child C) as per Child-Pugh classification. Routine investigations were done and trace elements (Cu, Zn, Se, and Mg) were analyzed on atomic absorption spectrophotometer. Serum level of copper was found significantly increased in patients with liver cirrhosis as compared to control group. Whereas serum zinc, selenium, and magnesium levels were significantly decreased in cirrhotic subjects as compared to controls. Trace elements were compared with severity of liver cirrhosis. Serum copper concentration was slightly increased in patients with more severe clinical state of liver cirrhosis; however, mean level difference of copper among the Child-Pugh groups were statistically not significant. Moreover, there was no significant correlation between copper and Child-Pugh Score. However, copper showed a significant negative correlation with zinc. Serum zinc, magnesium, and selenium levels were significantly decreased with advancement of liver disease as compared to early stage of liver cirrhosis and showed a significant negative correlation with Child-Pugh Score. Trace element abnormalities may reflect the condition of liver dysfunction. These results suggest that liver dysfunction may alter the metabolism of trace elements. Our study shows that micronutrients status in liver cirrhosis correlates well with severity of liver cirrhosis. Micronutrients supplementation in liver cirrhotic patients may prevent progression of disease and development of complications; however, further research needs to be done.

  20. Torsion of the gallbladder, localized in right subphrenic space in a patient with liver cirrhosis.

    PubMed

    Maruyama, Yuichiro; Tanaka, Yuya; Yasunaga, Masafumi; Ogata, Kei; Tanaka, Hiroyuki; Akagi, Yoshito; Okuda, Koji

    2015-12-01

    We report a case of torsion of the gallbladder displaced under the right subphrenic space in a patient with liver cirrhosis. An 82-year-old Japanese woman was admitted to our hospital for acute pain in the right upper quadrant. Clinical features suggested gallbladder torsion. She was under treatment for hepatitis C virus-related cirrhosis at our hospital. Abdominal CT showed the swollen fundus and body of the gallbladder under the right subphrenic space. Emergency laparoscopic cholecystectomy was performed. Intraoperative findings included a grossly necrotic gallbladder in the right subphrenic space with 360° clockwise torsion, together with liver cirrhosis and localized peritonitis. The clinical features and imaging findings in this rare case of misplaced gallbladder in right subphrenic space resembled those described in typical strangulated gallbladder. The displacement was probably related to right liver lobe atrophy associated with liver cirrhosis. Appropriate diagnosis and prompt surgical treatment are essential for a positive outcome.

  1. [Metabolic disturbances in liver cirrhosis (part 1)--hepatic osteopathy and malnutrition].

    PubMed

    Gundling, F; Seidl, H; Löffler, N; Strassen, I; Schepp, W

    2009-11-01

    Medical treatment of patients with liver cirrhosis consists mainly of symptomatic therapy of associated complications. Apart from the classical complications of cirrhosis, e. g. ascites, portal hypertension or hepatic encephalopathy, other frequent complications are neglected in everyday medicine. The incidence of metabolic disturbances seems to be similar to the prevalence of classical complications of liver cirrhosis, such as portal hypertension or ascites. Osteoporosis is an important manifestation of hepatic osteopathy, especially in chronic cholestatic diseases and in candidates for liver transplantation, which necessitates timely adequate diagnostic test (e. g. osteodensitometry) and treatment (pre-emptive and causal). Malnutrition, especially when related to protein- and energy supply, is very common in patients with liver cirrhosis and has prognostic significance regarding mortality and complication rates. A sufficient daily energy and protein supply should be ensured, one which is higher than that for the normal population. Additional substitution of vitamins and trace elements is indicated when symptoms of deficiency became apparent.

  2. The Evaluation of Adrenal Function in Two Cases of Hypocortisolism Accompanied by Liver Cirrhosis.

    PubMed

    Yamashita, Maki; Kageyama, Kazunori; Murakami, Hiroshi; Sugiyama, Aya; Yanagimachi, Miyuki; Sato, Eri; Murasawa, Shingo; Matsui, Jun; Tamasawa, Naoki; Daimon, Makoto

    2016-01-01

    Adrenal insufficiency may occur in patients with liver cirrhosis. The assessment of hypothalamus-pituitary-adrenal function is important in such patients, but there is no consensus as to how it should be performed. We herein report the results of our evaluation of the adrenal function in two patients with hypocortisolism accompanied by liver cirrhosis. The patients lacked the typical features of hypocortisolism. One was diagnosed with hypocortisolism accompanied by liver cirrhosis while the other had secondary adrenal insufficiency caused by a hypothalamic disorder. Hypocortisolism accompanied by liver cirrhosis should be evaluated by endocrine tests to determine its pathogenesis. A low-dose adrenocorticotropic hormone test may be appropriate for non-critically ill cirrhotic patients.

  3. Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis.

    PubMed

    González-Reimers, E; López-Lirola, A; Olivera, R Martín; Santolaria-Fernández, F; Galindo-Martín, L; Abreu-González, P; Sánchez-Sanchez, J J; Martínez-Riera, A

    2003-01-01

    In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl4)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl4 to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD

  4. Hepatic-associated immunoglobulin-A nephropathy in a child with liver cirrhosis and portal hypertension.

    PubMed

    Alghamdi, Sharifa A; Saadah, Omar I; Almatury, Nesreen; Al-Maghrabi, Jaudah

    2012-01-01

    Hepatic-associated immunoglobulin A (IgA) nephropathy is a relatively common condition that occurs in adults with liver cirrhosis and portal hypertension. However, it is rare in children. This condition is characterized by the deposition of IgA in the renal glomeruli. The present report describes a 14-year-old boy with cryptogenic liver cirrhosis and portal hypertension who presented with hematuria and proteinuria associated with histological changes of IgA nephropathy.

  5. Hepatic-Associated Immunoglobulin-A Nephropathy in a Child with Liver Cirrhosis and Portal Hypertension

    PubMed Central

    Alghamdi, Sharifa A.; Saadah, Omar I.; Almatury, Nesreen; Al-Maghrabi, Jaudah

    2012-01-01

    Hepatic-associated immunoglobulin A (IgA) nephropathy is a relatively common condition that occurs in adults with liver cirrhosis and portal hypertension. However, it is rare in children. This condition is characterized by the deposition of IgA in the renal glomeruli. The present report describes a 14-year-old boy with cryptogenic liver cirrhosis and portal hypertension who presented with hematuria and proteinuria associated with histological changes of IgA nephropathy. PMID:22626802

  6. 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.

  7. Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis B.

    PubMed

    Tang, Kuo-Tung; Hung, Wei-Ting; Chen, Yi-Hsing; Lin, Ching-Heng; Chen, Der-Yuan

    2016-03-01

    A few studies showed that long-term methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis B (CHB)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 631 incident cases of RA among CHB patients (358 MTX users and 273 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 6 years since the diagnosis of CHB, a total of 41 (6.5%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHB patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among 56 MTX users with a cumulative dose ≧3 grams after 97 months' treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHB. However, interpretation of the results should be cautious due to potential bias in the cohort.

  8. Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis C

    PubMed Central

    Tang, Kuo-Tung; Chen, Yi-Hsing; Lin, Ching-Heng; Chen, Der-Yuan

    2016-01-01

    A few studies have shown that methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients, although the risk is low compared to psoriatics. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis C (CHC)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 450 incident cases of RA among CHC patients (255 MTX users and 195 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 5 years since the diagnosis of CHC, a total of 55 (12%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHC patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among the 43 MTX users with a cumulative dose ≧3 grams after 108 months of treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHC. However, these results should be interpreted with caution due to potential bias in the cohort. PMID:27609026

  9. Metabolism of Fibrinogen in Cirrhosis of the Liver

    PubMed Central

    Tytgat, G. N.; Collen, D.; Verstraete, M.

    1971-01-01

    The metabolism of human fibrinogen labeled with radioactive iodine was studied in 50 patients with documented cirrhosis of the liver and in 35 healthy control subjects. Results in cirrhotic subjects were the following: plasma volume 47 ± 10 ml/kg; plasma fibrinogen concentration 250 ± 102 mg/100 ml; total plasma fibrinogen pool 118 ± 59 mg/kg, representing 0.73 ± 0.10 of the total body pool; fibrinogen half-life 2.99 ± 0.59 days; fractional catabolic rate 0.34 ± 0.09 of the plasma pool per day; absolute catabolic rate 39 ± 20 mg/kg per day; fractional transcapillary efflux rate 0.82 ± 0.30 of the plasma pool per day. Results in the control subjects were the following: plasma volume 42 ± 7 ml/kg; plasma fibrinogen concentration 284 ± 71 mg/100 ml; total plasma fibrinogen pool 119 ± 40 mg/kg, representing 0.72 ± 0.07 of the total body pool; fibrinogen half-life 4.14 ± 0.56 days; fractional catabolic rate 0.24 ± 0.04 of the plasma pool per day; absolute catabolic rate 28 ± 9 mg/kg per day; fractional transcapillary efflux rate 0.60 ± 0.26 of the plasma pool per day. A significant difference between cirrhotics and controls was observed for plasma volume, fibrinogen half-life, fractional and total catabolic rates, and transcapillary efflux rate. During heparinization of 10 cirrhotic patients the fibrinogen half-life was prolonged from 3.15 ± 0.69 to 4.59 ± 0.79 days. This was associated with a rise in plasma fibrinogen in six out of eight patients. Heparinization did not influence the fibrinogen half-life in five control subjects. Inhibition of the fibrinolytic system in 17 patients resulted in prolongation of the plasma radioactivity half-life of more than 1 day in only three patients, an incidence comparable with that in five control subjects. These results strongly support the concept of accelerated fibrinogen consumption by a process of disseminated intravascular coagulation in cirrhosis of the liver. PMID:5163179

  10. A comparison of the accuracy of peritoneoscopy and liver biopsy in the diagnosis of cirrhosis

    PubMed Central

    Bruguera, M.; Bordas, J. M.; Mas, P.; Rodes, J.

    1974-01-01

    The accuracy of peritoneoscopy and liver biopsy in the diagnosis of hepatic cirrhosis was compared in 473 consecutive patients submitted to both procedures. One hundred and fifty-two of them had cirrhosis diagnosed by one or both methods. There was 73% agreement between the two procedures. `Apparent' false-negative results were 17·7% for peritoneoscopy and 9·3% for liver biopsy. The incidence of false-negative results in the diagnosis of cirrhosis can be reduced by combining both procedures. PMID:4279817

  11. Personalized management of cirrhosis by non-invasive tests of liver fibrosis

    PubMed Central

    Wong, Grace Lai-Hung; Espinosa, Wendell Zaragoza

    2015-01-01

    Owing to the high prevalence of various chronic liver diseases, cirrhosis is one of the leading causes of morbidity and mortality worldwide. In recent years, the development of non-invasive tests of fibrosis allows accurate diagnosis of cirrhosis and reduces the need for liver biopsy. In this review, we discuss the application of these non-invasive tests beyond the diagnosis of cirrhosis. In particular, their role in the selection of patients for hepatocellular carcinoma surveillance and varices screening is highlighted. PMID:26523265

  12. Identification and localization of xylose-binding proteins as potential biomarkers for liver fibrosis/cirrhosis.

    PubMed

    Zhong, Yaogang; Sun, Xiu-Xuan; Zhang, Peixin; Qin, Xinmin; Chen, Wentian; Guo, Yonghong; Jia, Zhansheng; Bian, Huijie; Li, Zheng

    2016-02-01

    In our recent study, we found that the expression levels of total xylose-binding proteins (XBPs) were up-regulated significantly in activated hepatic stellate cells (HSCs); however, the denomination, distribution, and function of the XBPs were uncharted. Herein, 70 XBPs from activated HSCs and 64 XBPs from quiescent HSCs were isolated, identified and annotated. A total of 30 XBPs were up-regulated (all fold change ≥ 1.5, p ≤ 0.05) and 14 XBPs were down-regulated (all fold change ≤ 0.67, p ≤ 0.05) in the activated HSCs. The XBPs were localized at the cytoplasm and cytoplasmic membrane in HSCs and cirrhotic liver tissues by cy/histochemistry. The XBPs (i.e. PDIA6 and CFL2) responsible for the regulation of protein binding were up-regulated and those responsible for the regulation of catalytic activity (i.e. TUBB and MX1) were up-regulated in the activated HSCs. 2 candidates (i.e. PDIA6 and APOA1) were then selected for further verification in the sera of patients with HBV-induced chronic hepatitis/cirrhosis using western blotting and serum microarrays. PDIA6 showed a higher discrimination (Area Under Curves, AUCs = 0.8985, p < 0.0001) relative to APOA1 (AUCs = 0.8738, p < 0.0001) in the sera of patients as biomarker candidate. In conclusion, the precision alteration of the XBPs associated with pathological changes in HSCs during liver fibrosis/cirrhosis may provide pivotal information needed to discover potential glycan-binding protein-related biomarkers for diagnosis of liver fibrosis/cirrhosis and for development of new anti-fibrotic strategies.

  13. Portal vein thrombosis relevance on liver cirrhosis: Italian Venous Thrombotic Events Registry.

    PubMed

    Violi, Francesco; Corazza, Roberto Gino; Caldwell, Stephen Hugh; Perticone, Francesco; Gatta, Angelo; Angelico, Mario; Farcomeni, Alessio; Masotti, Michela; Napoleone, Laura; Vestri, Annarita; Raparelli, Valeria; Basili, Stefania

    2016-12-01

    Portal vein thrombosis may occur in cirrhosis; nevertheless, its prevalence, and predictors are still elusive. To investigate this issue, the Italian Society of Internal Medicine undertook the "Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry" (PRO-LIVER). This prospective multicenter study includes consecutive cirrhotic patients undergoing Doppler ultrasound examination of the portal area to evaluate the prevalence and incidence of portal vein thrombosis over a 2-year scheduled follow-up. Seven hundred and fifty-three (68 % men; 64 ± 12 years) patients were included in the present analysis. Fifty percent of the cases were cirrhotic outpatients. Viral (44 %) etiology was predominant. Around half of the patients had a mild-severity disease according to the Child-Pugh score; hepatocellular carcinoma was present in 20 %. The prevalence of ultrasound-detected portal vein thrombosis was 17 % (n = 126); it was asymptomatic in 43 % of the cases. Notably, more than half of the portal vein thrombosis patients (n = 81) were not treated with anticoagulant therapy. Logistic step-forward multivariate analysis demonstrated that previous portal vein thrombosis (p < 0.001), Child-Pugh Class B + C (p < 0.001), hepatocellular carcinoma (p = 0.01), previous upper gastrointestinal bleeding (p = 0.030) and older age (p = 0.012) were independently associated with portal vein thrombosis. Portal vein thrombosis is a frequent complication of cirrhosis, particularly in patients with moderate-severe liver failure. The apparent undertreatment of patients with portal vein thrombosis is a matter of concern and debate, which should be addressed by planning interventional trials especially with newer oral anticoagulants. Clinicaltrials.gov identifier NCT01470547.

  14. Serum MicroRNA-122 Predicts Survival in Patients with Liver Cirrhosis

    PubMed Central

    Waidmann, Oliver; Köberle, Verena; Brunner, Friederike; Zeuzem, Stefan

    2012-01-01

    Background Liver cirrhosis is associated with high morbidity and mortality. MicroRNAs (miRs) circulating in the blood are an emerging new class of biomarkers. In particular, the serum level of the liver-specific miR-122 might be a clinically useful new parameter in patients with acute or chronic liver disease. Aim Here we investigated if the serum level of miR-122 might be a prognostic parameter in patients with liver cirrhosis. Methods 107 patients with liver cirrhosis in the test cohort and 143 patients in the validation cohort were prospectively enrolled into the present study. RNA was extracted from the sera obtained at the time of study enrollment and the level of miR-122 was assessed. Serum miR-122 levels were assessed by quantitative reverse-transcription PCR (RT-PCR) and were compared to overall survival time and to different complications of liver cirrhosis. Results Serum miR-122 levels were reduced in patients with hepatic decompensation in comparison to patients with compensated liver disease. Patients with ascites, spontaneous bacterial peritonitis and hepatorenal syndrome had significantly lower miR-122 levels than patients without these complications. Multivariate Cox regression analysis revealed that the miR-122 serum levels were associated with survival independently from the MELD score, sex and age. Conclusions Serum miR-122 is a new independent marker for prediction of survival of patients with liver cirrhosis. PMID:23029162

  15. Physiology-based simulations of a pathological condition: prediction of pharmacokinetics in patients with liver cirrhosis.

    PubMed

    Edginton, Andrea N; Willmann, Stefan

    2008-01-01

    Liver cirrhosis is a progressive disease characterized by loss of functional hepatocytes with concomitant connective tissue and nodule formation in the liver. The morphological and physiological changes associated with the disease substantially affect drug pharmacokinetics. Whole-body physiologically based pharmacokinetic (WB-PBPK) modelling is a predictive technique that quantitatively relates the pharmacokinetic parameters of a drug to such (patho-)physiological conditions. To extend an existing WB-PBPK model, based on the physiological changes associated with liver cirrhosis, which allows for prediction of drug pharmacokinetics in patients with liver cirrhosis. The literature was searched for quantitative measures of the physiological changes associated with the presence of Child-Pugh class A through C liver cirrhosis. The parameters that were included were the organ blood flows, cardiac index, plasma binding protein concentrations, haematocrit, functional liver volume, hepatic enzymatic activity and glomerular filtration rate. Predictions of pharmacokinetic profiles and parameters were compared with literature data for the model compounds alfentanil, lidocaine (lignocaine), theophylline and levetiracetam. The predicted versus observed plasma concentration-time profiles for alfentanil and lidocaine were similar, such that the pharmacokinetic changes associated with Child-Pugh class A, B and C liver cirrhosis were adequately described. The theophylline elimination half-life was greatly increased in Child-Pugh class B and C patients compared with controls, as predicted by the model. Levetiracetam urinary excretion was consistently reduced with disease progression and very closely resembled observed values. Consideration of the physiological differences between healthy individuals and patients with liver cirrhosis was important for the simulation of drug pharmacokinetics in this compromised group. The WB-PBPK model was altered to incorporate these physiological

  16. Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model.

    PubMed

    Nishibe, Y; Kaneko, H; Suzuki, H; Abe, T; Matsuura, Y; Takaku, H

    2008-07-01

    The wild-type baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects a range of mammalian cell types in vitro but does not replicate in these cells. The current study investigated the in vivo effect of AcMNPV in the mouse model of liver cirrhosis induced by the mutagen dimethylnitrosamine. Intraperitoneal injection of AcMNPV induced an immune response. The baculovirus was taken up by the liver and spleen where it suppressed liver injury and fibrosis through the induction of interferons. This study presents the first evidence of the feasibility of using baculovirus to treat liver cirrhosis.

  17. Learning to Diagnose Cirrhosis with Liver Capsule Guided Ultrasound Image Classification

    PubMed Central

    Liu, Xiang; Song, Jia Lin; Wang, Shuo Hong; Zhao, Jing Wen; Chen, Yan Qiu

    2017-01-01

    This paper proposes a computer-aided cirrhosis diagnosis system to diagnose cirrhosis based on ultrasound images. We first propose a method to extract a liver capsule on an ultrasound image, then, based on the extracted liver capsule, we fine-tune a deep convolutional neural network (CNN) model to extract features from the image patches cropped around the liver capsules. Finally, a trained support vector machine (SVM) classifier is applied to classify the sample into normal or abnormal cases. Experimental results show that the proposed method can effectively extract the liver capsules and accurately classify the ultrasound images. PMID:28098774

  18. Pharmacokinetics of oral brotizolam in patients with liver cirrhosis

    PubMed Central

    Jochemsen, Roeline; Joeres, R. P.; Wesselman, J. G. J.; Richter, E.; Breimer, D. D.

    1983-01-01

    1 Disposition of oral brotizolam (0.5 mg) was studied in male patients with liver cirrhosis (patients) and in other patients (control) matched for age, weight, smoking and drinking habits. 2 Absorption of brotizolam was relatively rapid in both groups with a median peak time (range) of 1.0 (0.5-2.0) h. Peak concentrations were also similar with median values of 7.1 (3.2-10.7) ng/ml in patients and 9.4 (2.9-19.0 ng/ml) in controls. 3 Elimination half-life was longer in patients than in controls. The median values were 12.8 (9.4-25) h and 6.9 (4.4-8.4) h respectively (P < 0.01). In two patients hardly any drug elimination was observed, indicating severe impairment of drug metabolizing activity. The prolongation of the elimination half-life was likely to be due to a decrease in clearance (45 ml/min in patients compared with 64 ml/min in controls), and an increase in volume of distribution (0.62 l/kg and 0.39 l/kg respectively). 4 Median values of protein unbound fraction of brotizolam were 9.2 (7.8-10.4)% in controls and 12.4 (10.4-18.9)% in patients. Clearance of unbound drug was 612 ml/min and 380 ml/min respectively. PMID:6661377

  19. Nutrition and exercise in the management of liver cirrhosis.

    PubMed

    Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

    2014-06-21

    Liver cirrhosis (LC) patients often have protein-energy malnutrition (PEM) and decreased physical activity. These conditions often lead to sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients. Nutrition and exercise management can improve PEM and sarcopenia in those patients. Nutrition management includes sufficient dietary intake and improved nutrient metabolism. With the current high prevalence of obesity, the number of obese LC patients has increased, and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients. Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients. Exercise management can increase skeletal muscle volume and strength and improve insulin resistance; however, nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients. The establishment of optimal exercise regimens for LC patients is currently required. In this review, we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients.

  20. Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis.

    PubMed

    Laish, Ido; Mannasse-Green, Batya; Hadary, Ruth; Biron-Shental, Tal; Konikoff, Fred M; Amiel, Aliza; Kitay-Cohen, Yona

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci. The expression of telomerase reverse transcriptase (hTERT) mRNA was measured using polymerase chain reaction, and telomere capture (TC) was assessed with 2 Cytocell probes, 15qter and 13qter. Shorter telomere length and increased cellular senescence was demonstrated in patients with NAFLD, compared to the CC patients and healthy controls. While hTERT mRNA was significantly decreased, TC was increased in CC patients, compared to the NAFLD group and healthy individuals. Thus, there is a correlation between hTERT mRNA expression and telomere length in patients with NAFLD, which might be related to associated metabolic disorders and the risk of malignant transformation. Patients with CC, on the contrary, elongate their telomeres through the TC mechanism.

  1. Nutrition and exercise in the management of liver cirrhosis

    PubMed Central

    Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

    2014-01-01

    Liver cirrhosis (LC) patients often have protein-energy malnutrition (PEM) and decreased physical activity. These conditions often lead to sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients. Nutrition and exercise management can improve PEM and sarcopenia in those patients. Nutrition management includes sufficient dietary intake and improved nutrient metabolism. With the current high prevalence of obesity, the number of obese LC patients has increased, and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients. Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients. Exercise management can increase skeletal muscle volume and strength and improve insulin resistance; however, nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients. The establishment of optimal exercise regimens for LC patients is currently required. In this review, we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients. PMID:24966599

  2. Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation.

    PubMed

    Tsien, Cynthia; Garber, Ari; Narayanan, Arvind; Shah, Shetal N; Barnes, David; Eghtesad, Bijan; Fung, John; McCullough, Arthur J; Dasarathy, Srinivasan

    2014-06-01

    Pre-transplant sarcopenia (reduced skeletal muscle mass) predicts poor outcome in cirrhosis. In contrast, whether muscle mass increases post-orthotopic liver transplantation (OLT) is not known and was studied prospectively. Consecutive patients who underwent a comprehensive nutritional evaluation in a liver transplant nutrition clinic were included. Core abdominal muscle area was measured on abdominal computed tomography obtained pre- and post-OLT. Age- and gender-based controls were used to define sarcopenia. Measures of body composition pre-transplant were correlated with computed tomography measurements. Predictors and clinical impact of post-OLT change in muscle area were examined. In three subjects post-OLT and three controls, expression of genes regulating skeletal muscle mass were quantified. During the study period, 53 patients (M:F 41:12; age 56.9 ± 7.5 years) were followed up after OLT for 19.3 ± 9 months. Five patients died and another five had acute graft rejection. Pre-OLT sarcopenia was present in 33 (66.2%). Pre-transplant clinical characteristics including Child's score, MELD score, and nutritional status or post-transplantation immunosuppression regimen did not predict post-transplant change in muscle mass. New onset post-OLT sarcopenia developed in 14 patients. Loss of muscle mass post-OLT increased risk of diabetes mellitus and a trend toward higher mortality. Skeletal muscle expression of myostatin was higher and that of ubiquitin proteasome proteolytic components lower post-OLT than in controls. Post-transplantation sarcopenia is common and could not be attributed to pre-transplant characteristics or the type or duration of post-OLT immunosuppression. Post-transplant sarcopenia contributes to adverse consequences and strategies targeting myostatin may be beneficial. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  3. Mortality and rebleeding following variceal haemorrhage in liver cirrhosis and periportal fibrosis

    PubMed Central

    Mohammed, Sara Elfadil Abbas; Abdo, Abdelmunem Eltayeb; Mudawi, Hatim Mohamed Yousif

    2016-01-01

    AIM To investigate mortality and rebleeding rate and identify associated risk factors at 6 wk and 5 d following acute variceal haemorrhage in patients with liver cirrhosis and schistosomal periportal fibrosis. METHODS This is a prospective study conducted during the period from March to December 2014. Patients with portal hypertension presenting with acute variceal haemorrhage secondary to either liver cirrhosis (group A) or schistosomal periportal fibroses (group B) presenting within 24 h of the onset of the bleeding were enrolled in the study and followed for a period of 6 wk. Analysis of data was done by Microsoft Excel and comparison between groups was done by Statistical Package of Social Sciences version 20 to calculate means and find the levels of statistical differences and define the mortality rates, the P value of < 0.05 was considered to be significant. RESULTS A total of 94 patients were enrolled in the study. Thirty-two patients (34%) had liver cirrhosis (group A) and 62 (66%) patients had periportal fibrosis (group B). Mortality: The 6-wk and 5-d mortality were 53% and 16% respectively in group A compared to 10% and 0% in group B (P value < 0.000 and < 0.004). In group A; a Child-Turcotte-Pugh class C and rebleeding within 5 d were significantly associated with 5-d mortality (P value < 0.029 and < 0.049 respectively) and Child- Turcotte-Pugh class C was also a significant risk factor for 6-wk mortality (P value < 0.018). In group B; mortality was significantly associated with rebleeding within the 6-wk follow-up period and requirement for blood transfusion on admission (P value < 0.005 and < 0.049). Rebleeding: The 6-wk and 5-d rebleeding rate in group A were 56% and 25% respectively compared to 32% and 3% in group B (P value < 0.015 and < 0.002). Clinical presentation with encephalopathy was a significant risk factor for 5 d rebleeding in group A (P value < 0.005) while grade III periportal fibrosis and requirement for blood transfusion on admission

  4. Rectal administration of 13N-ammonia in cirrhosis of the liver.

    PubMed

    Hazenberg, H J; Gips, C H; Beekhuis, H; Vaalburg, W

    1976-01-01

    13N-ammonia, applied rectally, after absorption and transportation visualises the liver. After release of 13N-aminoacids and 13N-urea by the liver, 13N-activity can be measured over other organs. In patients with porta-systemic shunts, 13N-ammonia will appear in the systemic circulation as well. In 16 controls and 26 patients with cirrhosis, activities were measured for 20 minutes over liver, spleen, heart, lungs and forearm. In all subjects, the liver was visualised within a minute, in some patients with cirrhosis faintly, however. Release by the liver of 13N-ammonia metabolites started within a few minutes. Liver/heart activity ratios proved to be more discriminating between the control- and the cirrhosis group than liver/lung and liver/spleen ratios. In the control group, the 20 minutes' liver/heart ratio was most suitable for determining the normal range. The lower normal level was found to be 2.25. Fourteen of the 26 patients with cirrhosis had a normal, 12 an abnormally low 20 minutes' liver/heart ratio.

  5. Beyond "cirrhosis": a proposal from the International Liver Pathology Study Group.

    PubMed

    Hytiroglou, Prodromos; Snover, Dale C; Alves, Venancio; Balabaud, Charles; Bhathal, Prithi S; Bioulac-Sage, Paulette; Crawford, James M; Dhillon, Amar P; Ferrell, Linda; Guido, Maria; Nakanuma, Yasuni; Paradis, Valerie; Quaglia, Alberto; Theise, Neil D; Thung, Swan N; Tsui, Wilson M S; van Leeuwen, Dirk J

    2012-01-01

    "Cirrhosis" is a morphologic term that has been used for almost 200 years to denote the end stage of a variety of chronic liver diseases. The term implies a condition with adverse prognosis due to the well-known complications of portal hypertension, hepatocellular carcinoma, and liver failure. However, recent advances in the diagnosis and treatment of chronic liver diseases have changed the natural history of cirrhosis significantly. This consensus document by the International Liver Pathology Study Group challenges the usefulness of the word cirrhosis in modern medicine and suggests that this is an appropriate time to consider discontinuing the use of this term. The role of pathologists should evolve to the diagnosis of advanced stage of chronic liver disease, with emphasis on etiology, grade of activity, features suggestive of progression or regression, presence of other diseases, and risk factors for malignancy, within the perspective of an integrated clinicopathologic assessment.

  6. Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Espírito Santo

    PubMed Central

    Gonçalves, Patricia Lofego; da Penha Zago-Gomes, Maria; Marques, Carla Couzi; Mendonça, Ana Tereza; Gonçalves, Carlos Sandoval; Pereira, Fausto Edmundo Lima

    2013-01-01

    OBJECTIVES: To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. METHODS: The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively) were pursued in all cases. RESULTS: The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.2±12.6 years). The following main etiological factors were observed: chronic alcoholism alone (39.7%), chronic alcoholism in association with HBV or HCV (16.1%), HCV alone (14.5%) and in association with alcoholism (8.6%) (total, 23.1%), and HBV alone (13.1%) and in association with alcoholism (7.5%, total 20.6%). The remaining etiologies included cryptogenic cases (9.8%) and other causes (6.0%). The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (p<0.001) with reduced age (at the time of cirrhosis diagnosis) and increased prevalence of hepatocellular carcinoma (p = 0.052). CONCLUSION: Alcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis. PMID:23644846

  7. Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Espírito Santo.

    PubMed

    Gonçalves, Patricia Lofego; Zago-Gomes, Maria da Penha; Marques, Carla Couzi; Mendonça, Ana Tereza; Gonçalves, Carlos Sandoval; Pereira, Fausto Edmundo Lima

    2013-01-01

    To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively) were pursued in all cases. The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.2 ± 12.6 years). The following main etiological factors were observed: chronic alcoholism alone (39.7%), chronic alcoholism in association with HBV or HCV (16.1 %), HCV alone (14.5%) and in association with alcoholism (8.6%) (total, 23.1 %), and HBV alone (13.1%) and in association with alcoholism (7.5%, total 20.6%). The remaining etiologies included cryptogenic cases (9.8%) and other causes (6.0%). The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (p<0.001) with reduced age (at the time of cirrhosis diagnosis) and increased prevalence of hepatocellular carcinoma (p = 0.052). Alcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis.

  8. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients.

    PubMed

    Zhang, Zheng; Lin, Hu; Shi, Ming; Xu, Ruonan; Fu, Junliang; Lv, Jiyun; Chen, Liming; Lv, Sa; Li, Yuanyuan; Yu, Shuangjie; Geng, Hua; Jin, Lei; Lau, George K K; Wang, Fu-Sheng

    2012-03-01

    Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.

  9. Body mass index and risk of liver cirrhosis in middle aged UK women: prospective study

    PubMed Central

    Balkwill, Angela; Reeves, Gillian; Beral, Valerie

    2010-01-01

    Objective To determine the relation between body mass index (BMI) and liver cirrhosis and the contribution that BMI and alcohol consumption make to the incidence of liver cirrhosis in middle aged women in the UK. Design Prospective cohort study (Million Women Study). Setting Women recruited from 1996 to 2001 in NHS breast screening centres and followed by record linkage to routinely collected information on hospital admissions and deaths. Participants 1 230 662 women (mean age 56 years at recruitment) followed for an average of 6.2 years. Main outcome measures Relative risk and absolute risk of first hospital admission with or death from liver cirrhosis adjusted for age, recruitment region, alcohol consumption, smoking, socioeconomic status, and physical activity. Results 1811 women had a first hospital admission with or died from liver cirrhosis during follow-up. Among women with a BMI of 22.5 or above, increasing BMI was associated with an increased incidence of liver cirrhosis: the adjusted relative risk of cirrhosis increased by 28% (relative risk 1.28, 95% confidence interval 1.19 to 1.38; P<0.001) for every 5 unit increase in BMI. Although the relative increase in the risk of liver cirrhosis per 5 unit increase in BMI did not differ significantly according to the amount of alcohol consumed, the absolute risk did. Among women who reported drinking less than 70 g alcohol per week, the absolute risk of liver cirrhosis per 1000 women over five years was 0.8 (0.7 to 0.9) for those with a BMI between 22.5 and 25 and 1.0 (0.9 to 1.2) for those with a BMI of 30 or more. Among women who reported drinking 150 g alcohol or more per week, the corresponding figures were 2.7 (2.1 to 3.4) and 5.0 (3.8 to 6.6). Conclusions Excess body weight increases the incidence of liver cirrhosis. In middle aged women in the UK, an estimated 17% of incident or fatal liver cirrhosis is attributable to excess body weight. This compares with an estimated 42% attributable to alcohol

  10. 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

  11. Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis.

    PubMed

    Sun, H Q; Zhang, J Y; Zhang, H; Zou, Z S; Wang, F S; Jia, J H

    2012-06-01

    T helper (Th) 17 cells have been demonstrated to participate in the pathogenesis of HBV-associated liver damage. However, little is known regarding the immunopathogenic role of liver fibrosis in patients with HBV-associated liver cirrhosis. The aims of this study were to evaluate whether Th17 cells are related to disease progression in patients and to explore the possible mechanisms. The frequencies of circulating Th17 cells were analysed in 78 patients with hepatitis B and cirrhosis (Child A: 34; Child B: 22; Child C 22) and matched controls. Liver samples were collected from 13 patients with HBV-associated cirrhosis, 23 patients with chronic hepatitis B and 12 healthy controls for immunohistochemical analysis. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by flow cytometry. Patients with hepatitis B-associated cirrhosis with more severe disease displayed significant increases in peripheral numbers of Th17 cells as well as in IL-17 plasma levels. The increased intrahepatic IL-17(+) cells correlated positively with fibrotic staging scores and clinical progression from CHB to cirrhosis. Moreover, many IL-17(+) cells were located in fibrotic areas in the liver of patients with cirrhosis. In vitro, IL-17 together with IL-17-activated monocytes, could promote the activation of stellate cells, which, in turn, aggravated liver fibrosis and the inflammatory response. In summary, increased peripheral and intrahepatic Th17 cells are enriched in patients with hepatitis B and cirrhosis and contribute further to the severity of disease progression through induction of stellate cell activation.

  12. New concepts in liver cirrhosis: clinical significance of sarcopenia in cirrhotic patients.

    PubMed

    Montano-Loza, A J

    2013-06-01

    The natural history of cirrhotic patients is highly variable due to several factors including hepatic synthetic function, presence and degree of portal hypertension, the cause of cirrhosis, the possibility of resolution of the underlying damaging process, and the occurrence of liver cancer. Currently, D'Amico stage classification and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of evaluation of the nutritional and functional status. Most widely recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma; however, sarcopenia or severe muscle wasting is one of the most common and frequently hidden complications which negatively impact survival, quality of life, and response to stressor, such as infection and surgery. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis, and also analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in cirrhosis and their impact after liver transplantation. We also discuss existing and potential novel therapeutic strategies for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in cirrhosis in an effort to improve survival and reduced morbidity related to cirrhosis. Finally, we propose that future studies including sarcopenia with the MELD score may allow better prediction of mortality among cirrhotic patients waiting for liver transplantation; however, due to the worldwide shortage of organs for transplants, one of the vital clinical questions is the feasibility to treat sarcopenia in cirrhosis without the need of liver transplant.

  13. Proinflammatory Cytokines (IL-1α, IL-6) and Hepatocyte Growth Factor in Patients with Alcoholic Liver Cirrhosis

    PubMed Central

    Prystupa, Andrzej; Kiciński, Paweł; Sak, Jarosław; Boguszewska-Czubara, Anna; Toruń-Jurkowska, Anna; Załuska, Wojciech

    2015-01-01

    Background. The aim of the study was to assess the activity of interleukin-1α, interleukin-6, and hepatocyte growth factor protein (HGF) in serum of patients with alcoholic liver cirrhosis. Materials and Methods. Sixty patients with alcoholic liver cirrhosis treated in various hospitals were randomly enrolled. The stage of cirrhosis was assessed according to the Child-Turcotte-Pugh scoring system. The control group consisted of ten healthy persons without liver disease, who did not drink alcohol. Additionally, the group of alcoholics without liver cirrhosis was included in the study. The activity of interleukin-1α, interleukin-6, and HGF in blood plasma of patients and controls was measured using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Results. Higher concentrations of HGF protein were demonstrated in patients with Child class B and Child class C liver cirrhosis, compared to controls and alcoholics without liver cirrhosis. Moreover, significantly higher concentrations of HGF protein were found in patients with Child class C liver cirrhosis compared to patients with Child class A liver cirrhosis (p < 0.05). The concentrations of interleukin-1α in patients with Child class B and Child class C liver cirrhosis were significantly higher in comparison with controls. Significantly higher concentrations of interleukin-6 were demonstrated in Child class C, compared to Child class A. PMID:26448742

  14. Injurious effect on rat liver mitochondria by lymphocytes from patients with primary biliary cirrhosis.

    PubMed Central

    Bootello, A; Fernandez-Cruz, E; Escartin, P; Blanco, M F; Gosalvez, M; Segovia De Arana, J M

    1976-01-01

    Lymphocytes from primary biliary cirrhosis (PBC) patients were shown to have an injurious effect on rat liver mitochondria, as was demonstrated by the inhibition of mitochondrial respiratory control by these cells. The incubation of the PBC patients' lymphocytes with isolated rat liver mitochondria produced a significant inhibition of mitochondrial respiration in the presence of ADP. However, no significant effect on respiration was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis and miscellaneous liver diseases. The results suggest that this injurious effect of PBC lymphocytes on mitochondria might be a consequence of sensitization in vivo of the PBC patients' lymphocytes by the mitochondrial antigens. PMID:1277585

  15. [Routes of resorption of peritoneal fluid in the diaphragm in liver cirrhosis (morphologic study)].

    PubMed

    Khoroshaev, V A; Vorozheĭkin, V M; Baĭbekov, I M

    1991-01-01

    The diaphragm peritoneum from 12 operated patients and 34 patients who died from liver cirrhosis with or without ascites was studied by means of light microscopy and electron transmission and scanning microscopy. Considerable lesions are found in the peritoneum: cuboidization of mesothelial cells, basal membrane thickening, dilation of stomata, lymphatic lacunae and collectors lumina. Liver cirrhosis with ascites is frequently followed by lymphatic vessels thrombosis and firm attachment of the diaphragm to the liver resulting in the inhibition of the ascitic liquid elimination. Thus both the enhancement of liquid transudation into the abdominal cavity and the disturbance of the drainage function of the diaphragm peritoneum take place.

  16. Gut-liver axis: an immune link between celiac disease and primary biliary cirrhosis.

    PubMed

    Volta, Umberto; Caio, Giacomo; Tovoli, Francesco; De Giorgio, Roberto

    2013-03-01

    The association between celiac disease and primary biliary cirrhosis is well established. The breakdown of gut-liver axis equilibrium plays a central role in the development of immune disorders involving the small bowel and liver. In celiac disease, immunologically active molecules generated from the cross-linking between tissue transglutaminase and food/bacterial antigens reach the liver through the portal circulation owing to the increased intestinal permeability. A molecular mimicry between bacterial antigens and the pyruvate dehydrogenase E2 component, recognized by antimitochondrial autoantibodies, may have a role in primary biliary cirrhosis pathogenesis. An aberrant intestinal T lymphocyte homing to the liver may contribute to trigger immune hepatic damage. Both celiac disease and primary biliary cirrhosis share several features, including a higher prevalence in females, autoimmune comorbidities and specific autoantibodies. Reciprocal screening for both diseases is recommended, as an early diagnosis with the appropriate treatment can improve the outcome of these patients.

  17. IMMUNOCYTOCHEMICAL STUDY OF GAMMA GLOBULIN IN LIVER IN HEPATITIS AND POSTNECROTIC CIRRHOSIS

    PubMed Central

    Cohen, Seymour; Ohta, Goroku; Singer, Edward J.; Popper, Hans

    1960-01-01

    Gamma globulin was demonstrated by immunocytochemical fluorescence technique in many reticuloendothelial cells of the hepatic sinusoids and of the fibrous tracts in various forms of hepatitis and in postnecrotic cirrhosis. In other liver diseases and in normal livers, even in the presence of hypergammaglobulinemia, few if any gamma globulin-containing cells were found. In contrast, spleen and lymph nodes showed no difference between postnecrotic cirrhosis or hepatitis and other types of cirrhosis or non-hepatic hypergammaglobulinemias. The gamma globulin-containing cells in the liver are on cytologic grounds considered reticuloendothelial cells showing transition to plasma cells and exhibiting little or no phagocytosis of tissue breakdown products. These cells are assumed to form rather than engulf gamma globulin. The possibility that the gamma globulin formed represents antibody to liver cell breakdown products is discussed. PMID:13694427

  18. Liver cirrhosis reversion is improved in hamsters with a neurointermediate pituitary lobectomy.

    PubMed

    Quintanar-Stephano, A; Ventura-Juárez, J; Sánchez-Alemán, E; Aldaba-Muruato, L R; Cervantes-García, D; Gonzalez-Blas, D; Muñoz-Ortega, M H

    2017-09-05

    Regulating mechanisms of fibrosis is an important goal in the treatment of fibrosis and liver cirrhosis. The role of arginine vasopressin (AVP) in promoting fibrosis in several organs has been well documented. However, the result of an AVP deficiency during liver fibrosis has not been reported. We herein study the effects of an AVP deficiency, which was induced by neurointermediate pituitary lobectomy (NIL), on liver cirrhosis and liver cirrhosis reversion. Hamsters were intact (control) or underwent CCl4-induced cirrhosis, the latter animals divided into four groups: Cirrhotic, NIL-cirrhotic, Cirrhotic-reversion (R) and NIL-cirrhotic-R. Liver function, liver histopathology (including the fibrosis area and collagen types) and liver expression of MMP-13 and TIMP-2 were assessed. Results show that the AVP deficiency decreased the levels of alkaline phosphatase in serum and the expression of type I collagen and TIMP-2, and increased type III collagen deposition, MMP-13 expression and the size of regeneration nodules in NIL-cirrhotic and NIL-cirrhotic-R animals. A significantly greater recovery was found in the NIL-cirrhotic-R than the Cirrhotic-R group. We conclude that an AVP deficiency participates importantly in hamster liver regeneration by: 1) prompting the fibroblasts to produce type III collagen deposit, 2) influencing the activity of AP from bile duct cells, and 3) inhibiting TIMP-2 expression while favoring the fibrolytic activity of MMP-13. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV.

    PubMed

    Qin, Yannan; Zhong, Yaogang; Ma, Tianran; Wu, Fei; Wu, Haoxiang; Yu, Hanjie; Huang, Chen; Li, Zheng

    2016-04-01

    The incidence of hepatocellular carcinoma (HCC) is closely correlated with hepatitis B virus (HBV)-induced liver cirrhosis. Structural changes in the glycans of serum and tissue proteins are reliable indicators of liver damage. However, little is known about the alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV infection. This study compared the differential expression of liver glycopatterns in 7 sets of normal pericarcinomatous tissues (PCTs), cirrhotic, and tumor tissues from patients with liver cirrhosis and HCC induced by HBV using lectin microarrays. Fluorescence-based lectin histochemistry and lectin blotting were further utilized to validate and assess the expression and distribution of certain glycans in 9 sets of corresponding liver tissue sections. Eight lectins (e.g., Jacalin and AAL) revealed significant difference in cirrhotic tissues versus PCTs. Eleven lectins (e.g., EEL and SJA) showed significant alteration during cirrhotic and tumor progression. The expression of Galα1-3(Fucα1-2)Gal (EEL) and fucosyltransferase 1 was mainly increasing in the cytoplasm of hepatocytes during PCTs-cirrhotic-tumor tissues progression, while the expression of T antigen (ACA and PNA) was decreased sharply in cytoplasm of tumor hepatocytes. Understanding the precision alteration of liver glycopatterns related to the development of hepatitis, cirrhosis, and tumor induced by HBV infection may help elucidate the molecular mechanisms underlying the progression of chronic liver diseases and develop new antineoplastic therapeutic strategies.

  20. Transient elastography improves detection of liver cirrhosis compared to routine screening tests

    PubMed Central

    Göbel, Thomas; Schadewaldt-Tümmers, Janine; Greiner, Lucas; Poremba, Christopher; Häussinger, Dieter; Erhardt, Andreas

    2015-01-01

    AIM: To investigate the diagnostic significance of transient elastography (TE) in a daily routine clinical setting in comparison to clinical signs, laboratory parameters and ultrasound. METHODS: TE, ultrasound, laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily routine. RESULTS: Sensitivity of TE for the detection of liver cirrhosis was 90.4%, compared to 80.1% for ultrasound, 58.0% for platelet count and 45.1% for cutaneous liver signs (P < 0.0001 for comparisons with histology). AUROC for TE was 0.760 (95%CI: 0.694-0.825). Combination of TE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825 (95%CI: 0.768-0.882). TE correlated with laboratory parameters of cirrhosis progression like albumin (r = -0.43), prothrombin time (r = -0.44), and bilirubin (r = 0.34; P < 0.001 for each). Particularly, in patients with Child Pugh score A or normal platelet count TE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1% (P < 0.04) and 16.3% (P < 0.02), respectively. CONCLUSION: Transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations. PMID:25624730

  1. Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery

    NASA Astrophysics Data System (ADS)

    Rudolph, Karl Lenhard; Chang, Sandy; Millard, Melissa; Schreiber-Agus, Nicole; DePinho, Ronald A.

    2000-02-01

    Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR-/- mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of ``telomerase therapy'' for such diseases.

  2. Role of Chymase in the Development of Liver Cirrhosis and Its Complications: Experimental and Human Data

    PubMed Central

    Sansoè, Giovanni; Aragno, Manuela; Mastrocola, Raffaella; Mengozzi, Giulio; Novo, Erica; Parola, Maurizio

    2016-01-01

    Background Tissue Angiotensin II (Ang-II), produced through local non ACE-dependent pathways, stimulates liver fibrogenesis, renal vasoconstriction and sodium retention. Aim To highlight chymase-dependent pathway of Ang-II production in liver and kidney during cirrhosis development. Methods Liver histology, portal pressure, liver and kidney function, and hormonal status were investigated in rat liver cirrhosis induced through 13 weeks of CCl4, with or without chymase inhibitor SF2809E, administered between 4th and 13th CCl4 weeks; liver and kidney chymase immunolocation and Ang-II content were assessed. Chymase immunohistochemistry was also assessed in normal and cirrhotic human liver, and chymase mRNA transcripts were measured in human HepG2 cells and activated hepatic stellate cells (HSC/MFs) in vitro. Results Rats receiving both CCl4 and SF2809E showed liver fibrotic septa focally linking portal tracts but no cirrhosis, as compared to ascitic cirrhotic rats receiving CCl4. SF2809E reduced portal pressure, plasma bilirubin, tissue content of Ang-II, plasma renin activity, norepinephrine and vasopressin, and increased glomerular filtration rate, water clearance, urinary sodium excretion. Chymase tissue content was increased and detected in α-SMA-positive liver myofibroblasts and in kidney tubular cells of cirrhotic rats. In human cirrhosis, chymase was located in hepatocytes of regenerative nodules. Human HepG2 cells and HSC/MFs responded to TGF-β1 by up-regulating chymase mRNA transcription. Conclusions Chymase, through synthesis of Ang-II and other mediators, plays a role in the derangement of liver and kidney function in chronic liver diseases. In human cirrhosis, chymase is well-represented and apt to become a future target of pharmacological treatment. PMID:27637026

  3. Serum lipid alterations identified in chronic hepatitis B, hepatitis B virus-associated cirrhosis and carcinoma patients

    PubMed Central

    Wu, Tao; Zheng, Xiaojiao; Yang, Ming; Zhao, Aihua; Li, Meng; Chen, Tianlu; Panee, Jun; Jia, Wei; Ji, Guang

    2017-01-01

    The incidences of chronic hepatitis B (CHB), Hepatitis B virus (HBV)-associated cirrhosis and HBV-associated carcinoma are high and increasing. This study was designed to evaluate serum lipid metabolite changes that are associated with the progression from CHB to HBV-associated cirrhosis and ultimately to HBV-associated HCC. A targeted metabolomic assay was performed in fasting sera from 136 CHB patients, 104 HBV-associated cirrhosis, and 95 HBV-associated HCC using ultra-performance liquid chromatography triple quadrupole mass spectrometry. A total of 140 metabolites were identified. Clear separations between each two groups were obtained using the partial least squares discriminate analysis of 9 lipid metabolites. Progressively lower levels of long-chain lysophosphatidylcholines (lysoPC a C18:2, lysoPC a C20:3, lysoPC a C20:4) were observed from CHB to cirrhosis to carcinoma; lower levels of lysoPC a C20:4 were found in patients with higher model for end-stage liver disease in the same disease group; and lysoPC a C20:3 levels were lower in Child-Pugh Class C than in Class A and Class B in HBV-associated cirrhosis and HBV-associated HCC groups. The octadecadienyl carnitine level was higher in HBV-associated cirrhosis group than in other two groups. Serum levels of selected long-chain lysoPCs are promising markers for the progression of HBV-associated liver diseases. PMID:28198443

  4. Autologous Stem Cells Transplantation in Egyptian Patients with Liver Cirrhosis on Top of Hepatitis C Virus

    PubMed Central

    Al Tayeb, Hoda; El Dorry, Ahmed; Amer, Nehad; Mowafy, Nadia; Zimaity, Maha; Bayoumy, Essam; Saleh, Shereen A.

    2015-01-01

    Background and Objectives Use of pluripotent stem cells is an ideal solution for liver insufficiencies. This work aims is to evaluate the safety and feasibility of autologous stem cells transplantation (SCT) in Egyptian patients of liver cirrhosis on top of hepatitis C virus (HCV). Subjects and Results 20 patients with HCV induced liver cirrhosis were divided into 2 groups. Group I: included 10 patients with liver cirrhosis Child score ≥9, for whom autologous stem cell transplantation was done using granulocyte colony stimulating factor (G-CSF) for stem cells mobilization. Separation and collection of the peripheral blood stem cells was done by leukapheresis. G-CSF mobilized peripheral blood mononuclear cells (G-CSF PB-MNCs) were counted by flow cytometry. Stem cell injection into the hepatic artery was done. Group II: included 10 patients with HCV induced liver cirrhosis as a control group. Follow up and comparison between both groups were done over a follow up period of 6 months. The procedure was well tolerated. Mobilization was successful and the total number of G-CSF PB-MNCs in the harvests ranged from 25×106 to 191×106. There was improvement in the quality of life, serum albumin, total bilirubin, liver enzymes and the Child-Pugh score of group I over the first two-three months after the procedure. Conclusion SCT in HCV induced liver cirrhosis is a safe procedure. It can improve the quality of life and hepatic functions transiently with no effect on the life expectancy or the fate of the liver cirrhosis. PMID:26634069

  5. Gene regulations in HBV-related liver cirrhosis closely correlate with disease severity.

    PubMed

    Lee, Seram; Kim, Soyoun

    2007-09-30

    Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

  6. Association Between TT Virus Infection and Cirrhosis in Liver Transplant Patients

    PubMed Central

    Kazemi, Mohammad Javad; Yaghobi, Ramin; Iravani Saadi, Mahdiyar; Geramizadeh, Bita; Moayedi, Javad

    2015-01-01

    Background: Cirrhosis is one of the most severe liver complications, with multiple etiologies. The torque teno virus (TTV), also known as transfusion transmitted virus, which has a high incidence in the world population, is one of the possible increasing risk factors in patients with idiopathic fulminant hepatitis and cryptogenic cirrhosis. Objectives: The aim of this study was to evaluate solitary and co-infection with TTV, in patients with cryptogenic and determined cause of cirrhosis. Patients and Methods: In this cross-sectional study, 200 liver transplant patients were consecutively recruited between years 2007 and 2011. Patients were classified, based on recognition of the etiology of cirrhosis to determined (n = 81) and cryptogenic (n = 119) patient groups. The existence of TTV infection was analyzed, using a semi-nested polymerase chain reaction method. The presence of hepatitis B virus (HBV) infective markers, including HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B core antibody (HBcAb), and hepatitis B e antibody (HBeAb), was evaluated using qualitative polymerase chain reaction and enzyme linked immunosorbent assay protocols, respectively. Results: The TTV infection was found in 37 of 200 (18.5%) and 53 of 200 (26.5%) plasma and tissue samples of studied liver transplanted patients, respectively. The TTV genomic DNA was found in 32 (26.9%) and 28 (23.5%) of 119 liver tissue and plasma samples of transplanted patients with cryptogenic cirrhosis, respectively. The genomic DNA of TTV was also diagnosed in 21 (25.9%) and nine (11.1%) of the 81 liver tissue and plasma samples of patients with determined cirrhosis, respectively. Significant associations were found between TTV infection with HBV molecular and immunologic infective markers, in liver transplanted patients, with determined and cryptogenic cirrhosis. Conclusions: The diagnosis of the high frequency of solitary TTV and co-infection with HBV, in both liver

  7. Semi-quantitative assessment of the presence and Child-Pugh class of hepatitis B related cirrhosis by using liver lobe-based dynamic contrast-enhanced MRI.

    PubMed

    Zhou, L; Wang, L-Y; Zhang, X-M; Zeng, N-L; Chen, T-W; Li, R; Huang, Y-C; Tang, Y-L

    2016-12-01

    To determine whether liver lobe-based DCE-MRI can be used to detect the presence and Child-Pugh class of hepatitis B-related cirrhosis. Fifty-six cirrhotic patients with hepatitis B and 20 healthy participants underwent liver DCE-MRI, and the positive enhancement integral (PEI), time to peak (TTP), maximum slope of increase (MSI) and maximum slope of decrease (MSD) of the left lateral liver lobe (LLL), left medial liver lobe (LML), right liver lobe (RL), and caudate lobe (CL) were measured and analysed statistically to evaluate cirrhosis. TTP values of the LLL, LML, RL and CL were positively correlated with the Child-Pugh class of cirrhosis (r=0.452 to 0.55, all p<0.05). PEI values of the LLL, LML, RL and CL, as well as the MSI of the CL and the MSD of the RL, were inversely correlated with the Child-Pugh class (r=-0.349 to -0.72, all p<0.05). PEI values of the LLL and CL, or TTP values of the RL had the most area under receiver operating characteristic curve (AUC) of 0.99 for identifying the presence of liver cirrhosis. The PEI of the RL had the largest AUC of 0.975 and 0.78 for distinguishing the Child-Pugh class A of cirrhosis from class B-C and class A-B of cirrhosis from class C, respectively. Liver lobe-based DCE-MRI parameters are associated with the presence and Child-Pugh class of hepatitis B-related cirrhosis. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  8. Association between interleukin-10 gene promoter polymorphisms and susceptibility to liver cirrhosis.

    PubMed

    Yao, Lanjie; Xing, Shuli; Fu, Xueqin; Song, Hongjie; Wang, Zhendong; Tang, Jianrong; Zhao, Yongjing

    2015-01-01

    We conducted a case-control study to investigate the association between three common SNPs in IL-10 gene (rs1800896, rs1800871 and rs1800872) and the development of liver cirrhosis in a Chinese population. Between January 2013 and December 2014, a total of 318 patients with liver cirrhosis and 318 health control subjects were enrolled into our study. The IL-10 rs1800896, rs1800871 and rs1800872 polymorphisms were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By multivariate logistic regression analysis, we found that individuals with the AA genotype and GA+AA genotype of IL-10 rs1800896 were more likely to have an increased risk of liver cirrhosis when compared with the GG genotype, and the ORs (95% CI) for the AA genotype and GA+AA genotype were 2.04 (1.20-3.50) and 1.41 (1.02-1.96), respectively. We found that the GA+AA genotype of IL-10 rs1800896 had higher risk of liver cirrhosis in individuals with chronic hepatitis B when compared with the GG genotype (OR = 1.95, 95% CI = 1.01-3.59). In conclusion, we found that IL-10 rs1800896 polymorphism was correlated with an increased risk of liver cirrhosis, especially in individuals with chronic hepatitis B.

  9. Activity of MMP1 and MMP13 and Amino Acid Metabolism in Patients with Alcoholic Liver Cirrhosis

    PubMed Central

    Prystupa, Andrzej; Szpetnar, Maria; Boguszewska-Czubara, Anna; Grzybowski, Andrzej; Sak, Jarosław; Załuska, Wojciech

    2015-01-01

    Background Alcoholic liver disease remains one of the most common causes of chronic liver disease worldwide. The aim of this study was to assess the usefulness of metalloproteinases (MMP1 and MMP13) as diagnostic markers of alcoholic liver disease and to determine the changes in free amino acid profile in the patients with alcoholic liver cirrhosis. Material/Methods Sixty patients with alcoholic liver cirrhosis treated in various hospitals of the Lublin region were randomly enrolled. The control group consisted of 10 healthy individuals without liver disease, who did not drink alcohol. Additionally, a group of alcoholics (22 persons) without liver cirrhosis was included in the study. The activity of MMP-1 and MMP-13 in blood plasma of patients and controls was measured using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Amino acids were determined by automated ion-exchange chromatography. Results No significant differences were observed in the activity of MMP-1 in alcoholics with or without liver cirrhosis or in controls. Increased serum MMP-13 was found in patients with liver cirrhosis (stage A, B, C) compared to the control group. Patients with alcoholic liver cirrhosis (stage A, B, C) demonstrated reduced concentrations of glutamic acid and glutamine compared to the control group. Plasma levels of valine, isoleucine, leucine, and tryptophan were significantly lower in patients with alcoholic liver cirrhosis (stage C) than in controls. Conclusions MMP-13 can be useful to confirm the diagnosis of alcoholic liver cirrhosis, but levels of MMP-1 are not significantly increased in patients with liver cirrhosis compared to controls. The serum branched-chain amino acid (BCAA) is markedly reduced in patients with stage C alcoholic liver cirrhosis. PMID:25863779

  10. Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis.

    PubMed

    López-Lirola, A; González-Reimers, E; Martín Olivera, R; Santolaria-Fernández, F; Galindo-Martín, L; Abreu-González, P; González-Hernández, T; Valladares-Parrilla, F

    2003-12-01

    Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.

  11. Association of Fasciola hepatica Infection with Liver Fibrosis, Cirrhosis, and Cancer: A Systematic Review

    PubMed Central

    Machicado, Claudia; Machicado, Jorge D.; Maco, Vicente; Terashima, Angelica; Marcos, Luis A.

    2016-01-01

    Background Fascioliasis has been sporadically associated with chronic liver disease on previous studies. In order to describe the current evidence, we carried out a systematic review to assess the association between fascioliasis with liver fibrosis, cirrhosis and cancer. Methodology and Principal Findings A systematic search of electronic databases (PubMed, LILACS, Scopus, Embase, Cochrane, and Scielo) was conducted from June to July 2015 and yielded 1,557 published studies. Among 21 studies that met inclusion and exclusion criteria, 12 studies explored the association of F. hepatica with liver fibrosis, 4 with liver cirrhosis, and 5 with cancer. Globally these studies suggested the ability of F. hepatica to promote liver fibrosis and cirrhosis. The role of F. hepatica in cancer is unknown. Given the heterogeneity of the studies, a meta-analysis could not be performed. Conclusions Future high-quality studies are needed to determine the role of F. hepatica on the development of liver fibrosis, liver cirrhosis, and cancer in humans. PMID:27681524

  12. Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review

    PubMed Central

    Rostirola Guedes, Renata; Kieling, Carlos Oscar; Rossato Adami, Marina; Cerski, Carlos Thadeu Schmidt

    2017-01-01

    Neonatal liver failure (NLF) is a major cause of neonatal morbidity and mortality, presenting as acute liver failure and/or congenital cirrhosis. Many affected patients show antenatal signs of fetal injury. There are several causes of NLF and early diagnosis is mandatory to elucidate the etiology and determine a specific treatment or the best management strategy. Gestational alloimmune liver disease associated with neonatal hemochromatosis (GALD-NH) is a rare but potentially treatable cause of NLF. It should be considered in any neonate with fetal signs of disease and postnatal signs of liver failure with no other identifiable causes. GALD-NH is often diagnosed late and patients are therefore referred late to specialized centers, delaying treatment. This case highlights the consequences of late diagnosis and treatment of GALD-NH and emphasizes the importance of a high grade of suspicion of this disease in order to refer the patient to a specialized center soon enough to perform the appropriate treatment. PMID:28251010

  13. NATIVE VALVE ENDOCARDITIS CAUSED BY METHICILLIN-RESISTANT STAPHYLOCOCCUS EPIDERMIDIS IN A PATIENT WITH ADVANCED LIVER CIRRHOSIS.

    PubMed

    Cavrić, Gordana; Ilić, Diana; Njers, Kristina; Prkacin, Ingrid; Hamp, Dubravka Bartolek

    2015-12-01

    We present a case of a 50-year-old man with advanced liver cirrhosis and native valve infective endocarditis caused by methicillin-resistant Staphylococcus epidermidis. Bacterial infections are one of the most common complications of liver cirrhosis, but reports of infective endocarditis in patients with liver cirrhosis are relatively rare. Because of vulnerability of patients with advanced cirrhosis for developing infections, it is necessary to pay attention to the pathogens that are sometimes considered contamination and actively seek for the seat of infection, even in less expected areas (e.g., native heart valves without a history of heart disease).

  14. Association of liver cirrhosis related IgA nephropathy with portal hypertension

    PubMed Central

    Kalambokis, Georgios; Christou, Leonidas; Stefanou, Dimitrios; Arkoumani, Evdokia; Tsianos, Epameinondas V

    2007-01-01

    A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed. PMID:17963311

  15. Association of liver cirrhosis related IgA nephropathy with portal hypertension.

    PubMed

    Kalambokis, Georgios; Christou, Leonidas; Stefanou, Dimitrios; Arkoumani, Evdokia; Tsianos, Epameinondas V

    2007-11-21

    A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed.

  16. Oxidative stress modulation by Rosmarinus officinalis in CCl4-induced liver cirrhosis.

    PubMed

    Gutiérrez, Rosalinda; Alvarado, José L; Presno, Manuel; Pérez-Veyna, Oscar; Serrano, Carmen J; Yahuaca, Patricia

    2010-04-01

    Rosmarinus officinalis (Lamiaceae) possesses antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative for chronic liver disease. The effect produced by a methanolic extract of Rosmarinus officinalis on CCl(4)-induced liver cirrhosis in rats was investigated using both prevention and reversion models. Over the course of the development of cirrhosis, the increased enzymatic activities of gamma-glutamyl transpeptidase and alanine aminotransferase, and the rise in bilirubin levels caused by CCl(4) administration, were prevented by Rosmarinus officinalis co-administration. When the cirrhosis by oxidative stress was evaluated as an increase on liver lipoperoxidation, total lipid peroxides, nitric oxide in serum, and loss of erythrocyte plasma membrane stability, R. officinalis was shown to prevent such alterations. On cirrhotic animals treated with CCl(4), histological studies showed massive necrosis, periportal inflammation and fibrosis which were modified by R. officinalis. These benefits on experimental cirrhosis suggest a potential therapeutic use for R. officinalis as an alternative for liver cirrhosis. Copyright (c) 2009 John Wiley & Sons, Ltd.

  17. Hepatocyte growth factor: a regenerative drug for acute hepatitis and liver cirrhosis.

    PubMed

    Mizuno, Shinya; Nakamura, Toshikazu

    2007-03-01

    Liver cirrhosis is a major cause of morbidity worldwide and is characterized by the loss of hepatocytes with interstitial fibrosis. In this review, we discuss the potential uses of hepatocyte growth factor for treating hepatic diseases, focusing on the molecular mechanisms whereby hepatocyte growth factor reverses liver cirrhosis. Hepatic myofibroblasts play a central role in the development of liver cirrhosis, while myofibroblasts acquire c-Met. Using a rat model of liver cirrhosis, we recently delineated the direct effect of hepatocyte growth factor toward myofibroblasts: the induction of apoptotic cell death associated with matrix degradation, the inhibition of overproliferation and the suppression of transforming growth factor-beta1 production in myofibroblasts. Hepatocyte growth factor elicits mitogenic, anti-apoptotic and anti-inflammatory functions in hepatocytes, therefore contributing to reversing liver dysfunction. Considering the insufficient production of hepatocyte growth factor is responsible for the manifestation of chronic hepatitis, supplementation with or reinduction of hepatocyte growth factor represents a new strategy for attenuating intractable liver diseases.

  18. Brief communication: Glomerulonephritis in patients with hepatitis C cirrhosis undergoing liver transplantation.

    PubMed

    McGuire, Brendan M; Julian, Bruce A; Bynon, J Steve; Cook, William J; King, Steven J; Curtis, John J; Accortt, Neil A; Eckhoff, Devin E

    2006-05-16

    Patients infected with hepatitis C virus (HCV) frequently develop renal failure after liver transplantation. To describe renal histologic characteristics and concomitant clinical features in HCV-infected patients with end-stage cirrhosis. Case series. Single-center liver transplant program in the United States. 30 patients who received liver transplants for HCV-induced cirrhosis. Kidney biopsy during liver engraftment. Clinical data and laboratory tests of renal function within 6 months before liver transplantation. Twenty-five patients had immune-complex glomerulonephritis: membranoproliferative glomerulonephritis type 1 (n = 12), IgA nephropathy (n = 7), and mesangial glomerulonephritis (n = 6). Of these patients, 10 had normal serum creatinine levels, normal urinalysis results, and normal quantitative proteinuria. For 5 others, the only renal abnormality was an increased serum creatinine level. No patient had cryoglobulins in the blood or kidney. This small observational study did not include patients with nonviral cirrhosis and did not document post-transplantation outcomes. Immune-complex glomerulonephritis was common in patients with end-stage HCV-induced cirrhosis and was often clinically silent. Its potential to cause renal failure after liver transplantation may be underappreciated.

  19. [Protein catabolism and malnutrition in liver cirrhosis - impact of oral nutritional therapy].

    PubMed

    Norman, K; Valentini, L; Lochs, H; Pirlich, M

    2010-07-01

    Malnutrition with loss of muscle is common in patients with liver cirrhosis and has negative impact on morbidity and mortality. The aetiology of malnutrition is multifactorial and includes inflammation, early onset of gluconeogenesis due to impaired glycogen storage and sometimes hypermetabolism. Reduced nutritional intake, however, plays the most important role in the pathogenesis of malnutrition. There is, however, ample evidence that nutritional intake and therapy are inadequate in liver cirrhosis although studies have clearly shown that dietary counselling and nutritional therapy with oral supplements improve intake in these patients. Protein requirement is considered to be increased in liver cirrhosis and high protein intake has been shown to be well tolerated and associated with an improvement of liver function and nutritional status. Protein intolerance on the other hand is uncommon and hepatic encephalopathy can thus rarely be attributed to high protein consumption. Recommendations for general protein restriction must therefore be considered obsolete and rather a risk factor for an impaired clinical outcome. Furthermore, the administration of late evening meals is highly beneficial in patients with liver disease since the rapid onset of the overnight catabolic state is counteracted. The serum concentration of branched-chain amino acids (BCAA) is decreased in patients with liver cirrhosis and long-term supplementation of BCAA has been shown to improve nutritional status and prolong event-free survival and quality of life.

  20. Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats

    PubMed Central

    2013-01-01

    Background Hepatology research has focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Thus, this study evaluated mechanisms of the hepatoprotective activity of Curcuma longa rhizome ethanolic extract (CLRE) on thioacetamide-induced liver cirrhosis in rats. Methods The hepatoprotective effect of CLRE was measured in a rat model of thioacetamide-induced liver cirrhosis over 8 weeks. Hepatic cytochrome P450 2E1 and serum levels of TGF-β1 and TNF-α were evaluated. Oxidative stress was measured by malondialdehyde, urinary 8-hydroxyguanosine and nitrotyrosine levels. The protective activity of CLRE free-radical scavenging mechanisms were evaluated through antioxidant enzymes. Protein expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in animal blood sera was studied and confirmed by immunohistochemistry of Bax, Bcl2 proteins and proliferating cell nuclear antigen. Results Histopathology, immunohistochemistry and liver biochemistry were significantly lower in the Curcuma longa-treated groups compared with controls. CLRE induced apoptosis, inhibited hepatocytes proliferation but had no effect on hepatic CYP2E1 levels. Conclusion The progression of liver cirrhosis could be inhibited by the antioxidant and anti-inflammatory activities of CLRE and the normal status of the liver could be preserved. PMID:23496995

  1. [Polymorphism of ornithine decarboxylase antizyme inhibitor 1 gene is associated with liver cirrhosis in Chinese hepatitis B patients].

    PubMed

    Peng, Li-Jun; Guo, Jin-Sheng; Zhang, Zhe; Shi, Hong; Wang, Jian; Friedman, Scott L; Sninsky, John J; Wang, Ji-Yao

    2011-03-01

    A cirrhosis risk score (CRS) comprised of single nucleotide polymorphisms (SNPs) in seven genes that predicts the risk of cirrhosis in Caucasian hepatitis C has been reported. The present study was to evaluate the association of 11 separate but related SNPs and the CRS with cirrhosis risk in Chinese hepatitis B patients. A total of 563 Chinese subjects with persistent HBV infection (349 with evident liver cirrhosis and 214 without cirrhosis clinically or pathologically) were studied. The candidate SNPs were detected with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The allele frequency and genotype distribution of each polymorphism as well as the CRS value within the cirrhosis and non-cirrhosis subjects were compared. The rs2679757 polymorphism of the antizyme inhibitor 1 (AZIN1) gene was associated with the risk of cirrhosis (x2 = 6.79, P = 0.03, odds ratio for GG+AG versus AA = 1.63, 95% confidence interval = 1.13-2.35). A gene variant (rs886277) in the transient receptor potential cation channel subfamily M, member 5 gene (TRPM5) was associated with liver cirrhosis, but did not reach statistical significance (x2 = 5.77, P = 0.06). Two SNPs (rs4986791, rs62522600) are not polymorphic in Chinese. Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups. The overall CRS values were not different between the cirrhotic and non-cirrhotic groups (median value 0.57 versus 0.62, Z = -1.05, P = 0.29). SNP rs2679757 in the AZIN1 gene is associated with the risk of HBV-related liver cirrhosis in Chinese. The CRS for Caucasian population has limited applicability for predicting liver cirrhosis in Chinese hepatitis B patients. SNPs associated with cirrhosis prognosis in hepatitis B patients and liver diseases with other etiologies warrant further clinical validation.

  2. Cirrhosis - discharge

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000290.htm Cirrhosis - discharge To use the sharing features on this page, please enable JavaScript. You have cirrhosis of the liver. Scar tissue forms and your ...

  3. Trace element analysis by PIXE in liver samples from dogs with chronic active hepatitis and liver cirrhosis

    NASA Astrophysics Data System (ADS)

    Andersson, Marianne; Ekholm, Ann-Kristin; Sevelius, Ewa

    1990-04-01

    Trace element levels of liver samples obtained from necropsied dogs suffering from hepatitis and/or liver cirrhosis were determined by PIXE. Two different techniques for preparation of the samples were compared: the pellet press method and wet digestion. Both methods gave similar results, but the pellet press method was chosen for the subsequent routine analyses because of its simplicity due to few preparation steps and little risk of contamination. Preliminary results indicate elevated levels of Cu in chronic hepatitis and cirrhosis. In hereditary copper-induced hepatitis (Bedlington hepatitis) Fe and Br levels were increased as well.

  4. [Studies on the mechanism of elevation of serum PIVKA-II levels in alcoholic liver cirrhosis].

    PubMed

    Sakizono, Kenji; Oita, Tatsuo; Eto, Masaaki; Bito, Sanae; Takegawa, Hiroshi; Kasakura, Shinpei

    2002-03-01

    We measured serum PIVKA-II concentrations in 18 patients with alcoholic liver cirrhosis. Alcoholic liver disease was diagnosed by the history of ethanol intake of more than 900 ml/day for over 10 years. Liver cirrhosis was diagnosed histologically. Infections with hepatitis B and C viruses were ruled out by assaying serum virus markers. No tumor was detected in liver by ultrasonography and computed tomography during observation period. None of the patients studied were positive for alpafetoprotein (AFP). Eight out of 18 (44.4%) patients with alcoholic liver cirrhosis showed elevated serum PIVKA-II levels. In contrast, only eight out of 93 (8.6%) patients with nonalcholic liver cirrhosis had elevated serum PIVKA-II levels. PIVKA-II is well known as a tumor marker of hepatocellular carcinoma (HCC). The rates of positive PIVKA-II found in alcoholic liver cirrhosis approached its rates in HCC. However, the time course for the elevation of serum PIVKA-II levels was different each other in alcoholic liver cirrhosis and HCC. In HCC, serum PIVKA-II "levels" continued to elevate until therapy. In contrast, its elevation was transient and its levels returned to baseline in alcoholic liver cirrhosis. The values of ALT (GPT), gamma-GTP, and ALP correlated poorly with serum PIVKA-II levels in patients with alcoholic liver cirrhosis. To investigate the mechanism by which elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis occurred, we studied the effect of vitamin K on production of PIVKA-II and AFP by hepatocytes. Hepatocytes(Alexander PLC/PRF/F cell line) were cultured in the presence of various concentrations of vitamin K (Kaytwo, Eisai, Tokyo). Vitamin K had no effect on AFP production. In contrast, PIVKA-II production was inhibited by addition of vitamin K in a dose dependent manner. Moreover, elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis was suppressed by administration of vitamin K (Kaytwo) to these patients. Taken

  5. Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection

    PubMed Central

    Weiler, Nina; Zeuzem, Stefan; Welker, Martin-Walter

    2016-01-01

    Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to (pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response (SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte (CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis. PMID:27895394

  6. Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells.

    PubMed

    Terai, Shuji; Takami, Taro; Yamamoto, Naoki; Fujisawa, Koichi; Ishikawa, Tsuyoshi; Urata, Yohei; Tanimoto, Haruko; Iwamoto, Takuya; Mizunaga, Yuko; Matsuda, Takashi; Oono, Takashi; Marumoto, Miho; Burganova, Guzel; Fernando Quintanilha, Luiz; Hidaka, Isao; Marumoto, Yoshio; Saeki, Issei; Uchida, Koichi; Yamasaki, Takahiro; Tani, Kenji; Taura, Yasuho; Fujii, Yasuhiko; Nishina, Hiroshi; Okita, Kiwamu; Sakaida, Isao

    2014-06-01

    In 2003, we started autologous bone marrow cell infusion (ABMi) therapy for treating liver cirrhosis. ABMi therapy uses 400 mL of autologous bone marrow obtained under general anesthesia and infused mononuclear cells from the peripheral vein. The clinical study expanded and we treated liver cirrhosis induced by HCV and HBV infection and alcohol consumption. We found that the ABMi therapy was effective for cirrhosis patients and now we are treating patients with combined HIV and HCV infection and with metabolic syndrome-induced liver cirrhosis. Currently, to substantiate our findings that liver cirrhosis can be successfully treated by the ABMi therapy, we are conducting randomized multicenter clinical studies designated "Advanced medical technology B" for HCV-related liver cirrhosis in Japan. On the basis of our clinical study, we developed a proof-of-concept showing that infusion of bone marrow cells (BMCs) improved liver fibrosis and sequentially activated proliferation of hepatic progenitor cells and hepatocytes, further promoting restoration of liver functions. To treat patients with severe forms of liver cirrhosis, we continued translational research to develop less invasive therapies by using mesenchymal stem cells derived from bone marrow. We obtained a small quantity of BMCs under local anesthesia and expanded them into mesenchymal stem cells that will then be used for treating cirrhosis. In this review, we present our strategy to apply the results of our laboratory research to clinical studies.

  7. Enoxaparin does not ameliorate liver fibrosis or portal hypertension in rats with advanced cirrhosis.

    PubMed

    Fortea, José I; Zipprich, Alexander; Fernandez-Mena, Carolina; Puerto, Marta; Bosoi, Cristina R; Almagro, Jorge; Hollenbach, Marcus; Bañares, Juan; Rodríguez-Sánchez, Belén; Cercenado, Emilia; Clément, Marc-André; Rose, Christopher F; Bañares, Rafael; Vaquero, Javier; Ripoll, Cristina

    2017-06-30

    Recent studies suggest that heparins reduce liver fibrosis and the risk of decompensation of liver disease. Here, we evaluated the effects of enoxaparin in several experimental models of advanced cirrhosis. Cirrhosis was induced in male Sprague-Dawley (SD) rats by: i. Oral gavage with carbon tetrachloride (CCl4ORAL ), ii. Bile duct ligation (BDL), and iii. CCl4 inhalation (CCl4INH ). Rats received saline or enoxaparin s.c. (40 IU/Kg/d or 180 IU/Kg/d) following various protocols. Blood biochemical parameters, liver fibrosis, endothelium- and fibrosis-related genes, portal pressure, splenomegaly, bacterial translocation, systemic inflammation, and survival were evaluated. Endothelial dysfunction was assessed by in-situ bivascular liver perfusions. Enoxaparin did not ameliorate liver function, liver fibrosis, pro-fibrogenic gene expression, portal hypertension, splenomegaly, ascites development and infection, serum IL-6 levels or survival in rats with CCl4ORAL or BDL-induced cirrhosis. Contrarily, enoxaparin worsened portal pressure in BDL rats and decreased survival in CCl4ORAL rats. In CCl4INH rats, enoxaparin had no effects on hepatic endothelial dysfunction, except for correcting the hepatic arterial dysfunction when enoxaparin was started with the CCl4 exposure. In these rats, however, enoxaparin increased liver fibrosis and the absolute values of portal venous and sinusoidal resistance. Our results do not support a role of enoxaparin for improving liver fibrosis, portal hypertension or endothelial dysfunction in active disease at advanced stages of cirrhosis. These disease-related factors and the possibility of a limited therapeutic window should be considered in future studies evaluating the use of anticoagulants in cirrhosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Doppler assessment of splanchnic arterial flow in patients with liver cirrhosis: correlation with ammonia plasma levels and MELD score.

    PubMed

    Glišić, Tijana M; Perišić, Mirjana D; Dimitrijevic, Sladjana; Jurišić, Vladimir

    2014-06-01

    To assess the clinical significance of blood flow velocity and resistance index (RI) in the visceral arteries of patients with liver cirrhosis with respect to plasma ammonia (NH3) level and liver function. We included 80 patients with liver cirrhosis (58 men) and 20 healthy controls (11 men). Duplex Doppler ultrasonography was used to assess flow velocity and RI in the hepatic (HA), right (RRA), and left renal (LRA), and splenic (SA) (LA) artery. Plasma NH3 was measured by biochemistry. Liver function was assessed by MELD score (model of end-stage liver disease). HA, LRA, and SA systolic flow velocities were greater, whereas RRA diastolic velocity was lower in patients with liver cirrhosis than in controls RI was higher in LRA, RRA, SA, and HA in patients with liver cirrhosis than in controls. NH3 levels were significantly elevated in all patients with liver cirrhosis (p < 0.05) and significantly correlated with RI of RRA, LRA, and SA. We found greater renal, hepatic, and LA RI in patients with liver cirrhosis than in healthy controls. The correlation we found between elevated renal artery RI (≥0.70) and MELD score emphasizes the risk of renal dysfunction during progression of liver cirrhosis. Copyright © 2014 Wiley Periodicals, Inc.

  9. Study of liver cirrhosis over ten consecutive years in Southern China

    PubMed Central

    Wang, Xing; Lin, Shang-Xiong; Tao, Jin; Wei, Xiu-Qing; Liu, Yuan-Ting; Chen, Yu-Ming; Wu, Bin

    2014-01-01

    AIM: To investigate the etiology and complications of liver cirrhosis (LC) in Southern China. METHODS: In this retrospective, cross-sectional study, we identified cases of liver cirrhosis admitted between January 2001 to December 2010 and reviewed the medical records. Patient demographics, etiologies and complications were collected, and etiological changes were illustrated by consecutive years and within two time periods (2001-2005 and 2006-2010). All results were expressed as the mean ± SD or as a percentage. The χ2 test or Student’s t-test was used to analyze the differences in age, gender, and etiological distribution, and one-way analysis of variance was applied to estimate the trends in etiological changes. We analyzed the relationship between the etiologies and complications using unconditioned logistic regression, and the risk of upper gastrointestinal bleeding (UGIB) and hepatocellular carcinoma (HCC) in the major etiological groups was evaluated as ORs. A P value less than 0.05 was considered significant. Statistical computation was performed using SPSS 17.0 software. RESULTS: In this study, we identified 6719 (83.16%) male patients and 1361 (16.84%) female patients. The average age of all of the patients was 50.5 years at the time of diagnosis. The distribution of etiological agents was as follows: viral hepatitis, 80.62% [hepatitis B virus (HBV) 77.22%, hepatitis C virus (HCV) 2.80%, (HBV + HCV) 0.58%]; alcohol, 5.68%; mixed etiology, 4.95%; cryptogenic, 2.93%; and autoimmune hepatitis, 2.03%; whereas the other included etiologies accounted for less than 4% of the total. Infantile hepatitis syndrome LC patients were the youngest (2.5 years of age), followed by the metabolic LC group (27.2 years of age). Viral hepatitis, alcohol, and mixed etiology were more prevalent in the male group, whereas autoimmune diseases, cryptogenic cirrhosis, and metabolic diseases were more prevalent in the female group. When comparing the etiological distribution in

  10. LIVER TRANSPLANTATION FOR ALCOHOLIC CIRRHOSIS: LONG TERM FOLLOW-UP AND IMPACT OF DISEASE RECURRENCE

    PubMed Central

    Bellamy, Christopher O.C.; DiMartini, Andrea M.; Ruppert, Kris; Jain, Ashok; Dodson, Forrest; Torbenson, Michael; Starzl, Thomas E.; Fung, John J.; Demetris, Anthony J.

    2010-01-01

    Background Alcoholic liver disease has emerged as a leading indication for hepatic transplantation, although it is a controversial use of resources. We aimed to examine all aspects of liver transplantation associated with alcohol abuse. Methods Retrospective cohort analysis of 123 alcoholic patients with a median of 7 years follow-up at one center. Results In addition to alcohol, 43 (35%) patients had another possible factor contributing to cirrhosis. Actuarial patient and graft survival rates were, respectively, 84% and 81% (1 year); 72% and 66% (5 years); and 63% and 59% (7 years). After transplantation, 18 patients (15%) manifested 21 noncutaneous de novo malignancies, which is significantly more than controls (P=0.0001); upper aerodigestive squamous carcinomas were overrepresented (P=0.03). Thirteen patients had definitely relapsed and three others were suspected to have relapsed. Relapse was predicted by daily ethanol consumption (P=0.0314), but not by duration of pretransplant sobriety or explant histology. No patient had alcoholic hepatitis after transplantation and neither late onset acute nor chronic rejection was significantly increased. Multiple regression analyses for predictors of graft failure identified major biliary/vascular complications (P=0.01), chronic bile duct injury on biopsy (P=0.002), and pericellular fibrosis on biopsy (P=0.05); graft viral hepatitis was marginally significant (P=0.07) on univariate analysis. Conclusions Alcoholic liver disease is an excellent indication for liver transplantation in those without coexistent conditions. Recurrent alcoholic liver disease alone is not an important cause of graft pathology or failure. Potential recipients should be heavily screened before transplantation for coexistent conditions (e.g., hepatitis C, metabolic diseases) and other target-organ damage, especially aerodigestive malignancy, which are greater causes of morbidity and mortality than is recurrent alcohol liver disease. PMID:11544420

  11. Impact of physical and psychological factors on health-related quality of life in adult patients with liver cirrhosis: a systematic review protocol.

    PubMed

    Polis, Suzanne; Fernandez, Ritin

    2015-01-01

    image and pitting edema.Psychological symptoms include stress, depression and anxiety.Living with liver cirrhosis has a marked impact on the quality of life of the individual. Health-related quality of life (HRQOL) is the individual's perception of their physical, cognitive, emotional and social functioning.Studies report that physical and psychological factors affect the quality of life of patients with cirrhosis which can be problematic and debilitating.There is strong evidence which indicates that disease severity is associated with an impairment of the patient's HRQOL.For example, gross ascites causes abdominal discomfort, breathlessness, increased stress and anxiety related to body image, immobility and an increased likelihood of falls. In addition, the management of ascites involves frequent invasive procedures, an increase in pill burden and implementation of dietary restrictions, all of which impact on HRQOL.Despite the clear relationship between HRQOL and severity of disease, there has been no systematic review undertaken to determine the physical, psychological and physiological factors that affect the HRQOL of patients with liver cirrhosis. This systematic review will therefore identify the best available evidence related to the impact of physical, psychological and physiological factors on the health-related quality of life of adult patients with liver cirrhosis. The results of the review will increase clinicians' knowledge and highlight areas of clinical management that may require additional strategies and treatment plans to improve symptom relief and HRQOL.

  12. Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V₂-receptor antagonist tolvaptan.

    PubMed

    Gaglio, Paul; Marfo, Kwaku; Chiodo, Joseph

    2012-11-01

    Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V(2)-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24 h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely.

  13. Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment

    PubMed Central

    Meikle, Peter J.; Mundra, Piyushkumar A.; Wong, Gerard; Rahman, Khairunnessa; Huynh, Kevin; Barlow, Christopher K.; Duly, Alastair M. P.; Haber, Paul S.; Whitfield, John B.; Seth, Devanshi

    2015-01-01

    Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease. PMID:26107182

  14. Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment.

    PubMed

    Meikle, Peter J; Mundra, Piyushkumar A; Wong, Gerard; Rahman, Khairunnessa; Huynh, Kevin; Barlow, Christopher K; Duly, Alastair M P; Haber, Paul S; Whitfield, John B; Seth, Devanshi

    2015-01-01

    Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.

  15. Enhanced expression of glucose-regulated protein 78 correlates with malondialdehyde levels during the formation of liver cirrhosis in rats

    PubMed Central

    ZHANG, YUN; ZHANG, HUIYING; ZHAO, ZHONGFU; LV, MINLI; JIA, JIANTAO; ZHANG, LILI; TIAN, XIAOXIA; CHEN, YUNXIA; LI, BAOHONG; LIU, MINGSHE; HAN, DEWU; JI, CHENG

    2015-01-01

    The aim of the present study was to explore the role of glucose-regulated protein 78 (GRP78) in the development of liver cirrhosis promoted by intestinal endotoxemia in rats. Fifty-one male Wistar rats were randomly divided into the liver cirrhosis 4-week, 6-week and 8-week groups and the normal control group at each time point. Liver cirrhosis was induced by employing multiple pathogenic factors in the rats. Blood and liver tissues were collected. The levels of alanine aminotransferase (ALT), homocysteine, endotoxin and tumor necrosis factor-α (TNF-α) in the plasma, and TNF-α, malondialdehyde (MDA) and procollagen type III peptide (PIIIP) in the liver tissues were determined. The mRNA and protein expression levels of GRP78 in the liver were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Morphological changes were observed through hematoxylin and eosin and van Gieson staining of the liver. Liver cirrhosis caused marked histopathological changes to the livers of the rats. Following significant increases in the levels of ALT, homocysteine, endotoxin and TNF-α in the plasma, and TNF-α, MDA and PIIIP in the liver tissues of all experimental groups with the progression of liver cirrhosis, the mRNA and protein expression levels of GRP78 also gradually increased. In addition, correlation analysis indicated that the enhanced expression of GRP78 correlated with the MDA levels of the rats during the formation of liver cirrhosis. PMID:26668603

  16. Genotyping diagnosis of alpha-1 antitrypsin deficiency in Saudi adults with liver cirrhosis

    PubMed Central

    Al-Jameil, Noura; Hassan, Amina A.; Buhairan, Ahlam; Hassanato, Rana; Isac, Sree R.; Al-Otaiby, Maram; Al-Maarik, Basmah; Al-Ajeyan, Iman

    2017-01-01

    Abstract The acute phase protein alpha-1 antitrypsin (AAT) is mainly produced in liver cells. AAT deficiency affects the lungs and liver. We conducted a case-control study to define a valuable method for the proper diagnosis of alpha-1 antitrypsin deficiency (AATD), as well as the association of liver cirrhosis with AATD in Saudi adults. Blood samples from 300 liver cirrhosis patients and 400 controls were analyzed according to serum AAT concentration, phenotyping, and genotyping. Nephelometry was used for AAT quantification, isoelectric focusing electrophoresis was used for phenotyping detection, and real-time PCR was used for genotyping to determine the Z and S deficiency alleles. This study highlights the accuracy of using genotyping in addition to AAT quantification, since this technique has proven to be successful in the diagnosis of AATD for 100% of our cases. A significant deviation in AAT genotypes frequencies from the Hardy–Weinberg equilibrium in the adult cirrhosis group occurred due to a higher observed frequency than expected for the Pi ZZ homozygous genotype. Pi ZZ in adults may be considered as the risk factor for liver cirrhosis. However, we could not establish this relationship for heterozygous AATD genotypes (such as Pi MZ and Pi SZ). PMID:28178162

  17. Alcoholic cirrhosis is a good indication for liver transplantation, even for cases of recidivism

    PubMed Central

    Pageaux, G; Michel, J; Coste, V; Perney, P; Possoz, P; Perrigault, P; Navarro, F; Fabre, J; Domergue, J; Blanc, P; Larrey, D

    1999-01-01

    BACKGROUND/AIMS—Alcoholic cirrhosis remains a controversial indication for liver transplantation, mainly because of ethical considerations related to the shortage of donor livers. The aim of this study was to review experience to date, focusing on survival rates and complications, and the effect of alcohol relapse on outcome and alterations in marital and socioprofessional status.
METHODS—The results for 53 patients transplanted for alcoholic cirrhosis between 1989 and 1994 were compared with those for 48 patients transplanted for non-alcoholic liver disease. The following variables were analysed: survival, rejection, infection, cancer, retransplantation, employment and marital status, alcoholic recurrence. The same variables were compared between alcohol relapsers and non-relapsers.
RESULTS—Recovery of employment was the only significantly different variable between alcoholic (30%) and non-alcoholic patients (60%). Two factors influenced survival in the absence of alcohol recidivism: age and abstinence before transplantation. For all other variables, there were no differences between alcoholic and non-alcoholic patients, and, within the alcoholic group, between relapsers and non-relapsers. The recidivism rate was 32%.
CONCLUSION—The data indicate that liver transplantation is justified for alcoholic cirrhosis, even in cases of recidivism, which did no affect survival and compliance with the immunosuppressive regimen. These good results should help in educating the general population about alcoholic disease.


Keywords: liver; transplantation; alcohol; cirrhosis PMID:10446113

  18.  High prevalence of undiagnosed liver cirrhosis and advanced fibrosis in type 2 diabetic patients.

    PubMed

    Arab, Juan P; Barrera, Francisco; Gallego, Consuelo; Valderas, Juan P; Uribe, Sergio; Tejos, Cristian; Serrano, Cristóbal; Serrano, Cristóbal; Huete, Álvaro; Liberona, Jessica; Labbé, Pilar; Quiroga, Teresa; Benítez, Carlos; Irarrázaval, Pablo; Riquelme, Arnoldo; Arrese, Marco

    2016-01-01

     Background. Patients with type 2 diabetes mellitus (T2DM) are at risk for developing end-stage liver disease due to nonalcoholic steatohepatitis (NASH), the aggressive form of non-alcoholic fatty liver disease (NAFLD). Data on prevalence of advanced fibrosis among T2DM patients is scarce. To evaluate prevalence of steatosis, advanced fibrosis and cirrhosis using non-invasive methods in T2DM patients. 145 consecutive T2DM patients (> 55 years-old) were prospectively recruited. Presence of cirrhosis and advanced fibrosis was evaluated by magnetic resonance imaging (MRI) and NAFLD fibrosis score (NFS) respectively. Exclusion criteria included significant alcohol consumption, markers of viral hepatitis infection or other liver diseases. Results are expressed in percentage or median (interquartile range). 52.6% of patients were women, the median age was 60 years old (57-64), mean BMI was 29.6 ± 4.7 kg/m2 and diabetes duration was 7.6 ± 6.9 years. A high prevalence of liver steatosis (63.9%), advanced fibrosis assessed by NFS (12.8%) and evidence of liver cirrhosis in MRI (6.0%) was observed. In a multivariate analysis GGT > 82 IU/L (P = 0.004) and no alcohol intake (P = 0.032) were independently associated to advanced fibrosis. A high frequency of undiagnosed advanced fibrosis and cirrhosis was observed in non-selected T2DM patients. Screening of these conditions may be warranted in this patient population.

  19. The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy

    PubMed Central

    Nandivada, Prathima; Chang, Melissa I.; Potemkin, Alexis K.; Carlson, Sarah J.; Cowan, Eileen; O’loughlin, Alison A.; Mitchell, Paul D.; Gura, Kathleen M.; Puder, Mark

    2014-01-01

    Objective To determine the natural history of cirrhosis from parenteral nutrition-associated liver disease (PNALD) after resolution of cholestasis with fish oil (FO) therapy Background Historically, cirrhosis from PNALD resulted in end-stage liver disease (ESLD), often requiring transplantation for survival. With FO therapy, most children now experience resolution of cholestasis and rarely progress to ESLD. However, outcomes for cirrhosis after resolution of cholestasis are unknown and patients continue to be considered for liver/multivisceral transplantation. Methods Prospectively collected data was reviewed for children with cirrhosis due to PNALD who had resolution of cholestasis after treatment with FO from 2004 to 2012. Outcomes evaluated included need for liver/multivisceral transplantation, mortality, and the clinical progression of liver disease. Results Fifty-one patients with cirrhosis from PNALD were identified, with 76% demonstrating resolution of cholestasis after FO therapy. The mean direct bilirubin decreased from 6.4 ± 4 mg/dL to 0.2 ± 0.1 mg/dL (p <0.001) 12 months after resolution of cholestasis, with a mean time to resolution of 74 days. None of the patients required transplantation or died from ESLD. Pediatric End-Stage Liver Disease (PELD) scores decreased from 16 ± 4.6 to −1.2 ± 4.6, 12 months after resolution of cholestasis (p <0.001). In children who remained PN-dependent, the PELD score remained normal throughout the follow-up period. Conclusions Cirrhosis from PNALD may be stable rather than progressive once cholestasis resolves with FO therapy. Furthermore, these patients may not require transplantation and show no clinical evidence of liver disease progression, even when persistently PN-dependent. PMID:24374535

  20. Biliary liver cirrhosis secondary to cystic fibrosis: a rare indication for liver transplantation.

    PubMed

    Sańko-Resmer, J; Paczek, L; Wyzgał, J; Ziółkowski, J; Ciszek, M; Alsharabi, A; Grzelak, I; Paluszkiewicz, R; Patkowski, W; Krawczyk, M

    2006-01-01

    As more effective therapies prolong the lives of patients with cystic fibrosis, there are now more patients in this population diagnosed with liver diseases. Secondary biliary cirrhosis is not a rare complication of mucoviscidosis. It is diagnosed in 20% of patients with mucoviscidosis; in 2% it is accompanied by portal hypertension. On average patients with portal hypertension and its complications are 12 years old. Liver transplantation is an accepted method of treatment for children with cystic fibrosis and portal hypertension. It eliminates the cause of the portal hypertension, decreases life-threatening medical conditions, and improves their nutritional status and quality of life. Despite immunosuppressive treatment they do not seem to beat increased risk of upper respiratory tract infections. On the contrary improved respiratory function and status are generally observed. We present our first case of orthotopic liver transplantation performed in a 29-year-old man with cystic fibrosis. The donor was a 42-year-old woman who died of a ruptured cerebral aneurysm. The surgery was performed in September 2004. The patient received immunosuppression based on steroids, basiliximab, tacrolimus, and mycophenolic acid due to renal insufficiency. Antibiotic (meropenem) and antiviral prophylaxis (gancyclovir) were used. A 6-month period of observation confirmed the clinical data from the pediatric population-a good prognosis with improved nutritional status, respiratory function, and quality of life.

  1. Laparoscopic hepatectomy in a morbidly obese patient with liver cirrhosis: A case report

    PubMed Central

    Machairas, Nikolaos; Kostakis, Ioannis D.; Mantas, Dimitrios; Sotiropoulos, Georgios C.

    2017-01-01

    Cirrhotic patients constitute a high-risk population, and present a major challenge for the performance of minimally invasive laparoscopic resections due to difficulties in parenchymal transection. The present study describes the case of a 71-year-old morbidly obese male patient who was referred to our department with a hepatic mass identified on routine abdominal ultrasound. Abdominal computer tomography and magnetic resonance imaging confirmed a mass in segments V–VI of the liver, highly suspicious for HCC. The patient's past medical history additionally included non-alcoholic steatohepatitis, diabetes mellitus and arterial hypertension and myocardial infarction. The patient's body mass index was 45 kg/m2, and the American Society of Anesthesiologists' classification of preoperative risk was 3. The patient underwent laparoscopic resection of segments V–VI and cholecystectomy. Two years postoperatively, the patient remains disease-free and in excellent condition. To the best of our knowledge, this is the first report on laparoscopic liver resection for such a morbidly obese patient in the context of advanced liver cirrhosis.

  2. Liver surgery in the presence of cirrhosis or steatosis: Is morbidity increased?

    PubMed Central

    McCormack, Lucas; Capitanich, Pablo; Quiñonez, Emilio

    2008-01-01

    Background data The prevalence of steatosis and hepatitis-related liver cirrhosis is dramatically increasing together worldwide. Cirrhosis and, more recently, steatosis are recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection when compared with patients with healthy liver. Objective To review present knowledge regarding how the presence of cirrhosis or steatosis can influence postoperative outcome after liver resection. Methods A critical review of the English literature was performed to provide data concerning postoperative outcome of patients presenting injured livers who required hepatectomy. Results In clinical studies, the presence of steatosis impaired postoperative outcome regardless the severity and quality of the hepatic fat. A great improvement in postoperative outcome has been achieved using modern and multidisciplinary preoperative workup in cirrhotic patients. Due to the lack of a proper classification for morbidity and a clear definition of hepatic failure in the literature, the comparison between different studies is very limited. Although, many surgical strategies have been developed to protect injured liver surgery, no one have gained worldwide acceptance. Conclusion Surgeons should take the presence of underlying injured livers into account when planning the extent and type of hepatic surgery. Preoperative and perioperative interventions should be considered to minimize the additional damage. Further randomized trials should focus on the evaluation of novel preoperative strategies to minimize risk in these patients. Each referral liver center should have the commitment to report all deaths related to postoperative hepatic failure and to use a common classification system for postoperative complications. PMID:18439273

  3. Endogenous carbon monoxide downregulates hepatic cystathionine-γ-lyase in rats with liver cirrhosis

    PubMed Central

    GUO, SHI-BIN; DUAN, ZHI-JUN; WANG, QIU-MING; ZHOU, QIN; LI, QING; SUN, XIAO-YU

    2015-01-01

    The aim of the present study was to investigate the effect of endogenous carbon monoxide (CO) on the hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) pathway in cirrhotic rat livers. The rats were allocated at random into four groups: Sham, cirrhosis, cobalt protoporphyrin (CoPP) and zinc protoporphyrin IX (ZnPP). The expression of hepatic CSE mRNA was evaluated using a quantitative polymerase chain reaction, while CSE protein expression was determined using immunohistochemical analysis. Hematoxylin and eosin staining was performed for the histological evaluation of liver fibrosis. The levels of H2S, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and carboxyhemoglobin (COHb) in the arterial blood were determined, in addition to the portal vein pressure. The mRNA and protein expression levels of hepatic CSE and the serum levels of H2S were significantly decreased in the cirrhosis group compared with those in the sham group (P<0.05). Compared with the cirrhosis group, rats in the ZnPP group had significantly lower levels of serum ALT, AST and TBIL, arterial COHb and hepatic fibrosis, while hepatic CSE expression and the production of H2S were significantly increased (P<0.05). The CoPP group exhibited decreased hepatic CSE expression and H2S production, but aggravated hepatic function and fibrosis (P<0.05). In conclusion, the H2S/CSE pathway is involved in the formation of liver cirrhosis and serves a crucial function in protecting liver cells against the progression of liver fibrosis. Endogenous CO downregulates hepatic CSE mRNA and protein expression and the production of H2S in rats with liver cirrhosis. PMID:26668593

  4. 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

  5. Microbiota and the gut-liver axis: bacterial translocation, inflammation and infection in cirrhosis.

    PubMed

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

    2014-12-07

    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.

  6. Optimizing the Clinical Use of Carvedilol in Liver Cirrhosis Using a Physiologically Based Pharmacokinetic Modeling Approach.

    PubMed

    Rasool, Muhammad Fawad; Khalil, Feras; Läer, Stephanie

    2017-06-01

    Liver cirrhosis is a complex pathophysiological condition that can affect the pharmacokinetics (PK) and hereby dosing of administered drugs. The physiologically based pharmacokinetic (PBPK) models are a valuable tool to explore PK of drugs in cirrhosis patients. The objective of this study was to develop and evaluate a PBPK-carvedilol-cirrhosis model with the available clinical data in liver cirrhosis patients and to recommend model-based drug dosing after exploring the underlying differences in unbound and total (bound and unbound) systemic carvedilol concentrations with the different disease stages. A whole body PBPK model was developed using the population-based PBPK simulator, Simcyp(®). After model development and evaluation in healthy adults, system parameters were modified according to the pathophysiological changes that occur in liver cirrhosis, and predictions were compared to available experimental data from liver cirrhosis Child-Pugh [CP]-C patients. A two-fold error range for the observed/predicted ratios (ratioObs/Pred) of the pharmacokinetic parameters was used for model evaluation. Simulations were then extended to cirrhosis CP-A and CP-B populations were no experimental data that are available to explore changes in drug disposition in these patients. Finally, drug unbound and total (bound and unbound) exposure were predicted in cirrhotic patients of different disease severity, and the results were compared to those of healthy adults. The developed model has successfully described carvedilol PK in healthy and cirrhosis CP-C patients. The model predictions showed that, there was an ~13-fold increase in unbound and ~7-fold increase in total (bound and unbound) systemic exposure of carvedilol between healthy and CP-C populations. To have comparable predicted unbound drug exposure in cirrhosis CP-A, CP-B, and CP-C populations as in healthy subjects receiving a dose of 25 mg, reductions of administered doses to 9.375 mg in CP-A, 4.68 mg in CP-B, and 2

  7. Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease

    PubMed Central

    Kessoku, Takaomi; Ogawa, Yuji; Yoneda, Masato; Imajo, Kento; Sumida, Yoshio; Eguchi, Yuichiro; Fujii, Hideki; Hyogo, Hideyuki; Ono, Masafumi; Suzuki, Yasuaki; Kawaguchi, Takumi; Chayama, Kazuaki; Tanaka, Saiyu; Fujimoto, Kazuma; Anzai, Keizo; Saibara, Toshiji; Sata, Michio; Itoh, Yoshito; Nakajima, Atsushi; (JSG-NAFLD), Takeshi Okanoue; Japan Study Group of NAFLD

    2014-01-01

    AIM: To investigate a simple noninvasive scoring system for predicting liver cirrhosis in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3, 190; stage 4, 38). The weight and height of the patients were measured using a calibrated scale after requesting the patients to remove their shoes and any heavy clothing. Venous blood samples were obtained in the morning after the patients had fasted overnight for 12 h. Laboratory evaluation was performed in all patients. Statistical analysis was conducted using SPSS version 12.0. Continuous variables were expressed as mean ± SD. RESULTS: The optimal cutoff value of platelet count, serum albumin, and aminotransferase/alanine aminotransferase ratio (AAR) was set at < 15.3 104/μL, < 4.0 g/dL, and > 0.9, respectively, by the receiver operating characteristic curve. These three variables were combined in an unweighted sum (platelet count = 1 point, serum albumin = 1 point, AAR = 1 point) to form an easily calculated composite score for predicting cirrhosis in NAFLD patients, called the PLALA (platelet, albumin, AAR) score. The diagnosis of PLALA ≥ 2 had sufficient accuracy for detecting liver cirrhosis in NAFLD patients. CONCLUSION: The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use. PMID:25110437

  8. Impact of muscle wasting on survival in patients with liver cirrhosis.

    PubMed

    Kalafateli, Maria; Konstantakis, Christos; Thomopoulos, Konstantinos; Triantos, Christos

    2015-06-28

    Muscle wasting is defined as the progressive and generalized loss of muscle mass. Muscle depletion is a common feature of chronic liver disease found in approximately 40% of patients with cirrhosis. Its etiology is multifactorial subsequent to liver failure and its prevalence increases along with disease severity. Cross-sectional analytic morphometry using computed tomography (CT) scan or magnetic resonance imaging are considered by consensus the gold standards to assess muscle size in cirrhosis for research purposes because they are not biased by fluid accumulation. Several studies have assessed the impact of muscle wasting on overall survival of patients in the waiting list for liver transplantation and there is a general agreement that decreased muscle size assessed by CT scan is an independent predictor for mortality in cirrhosis. It has been proposed that the addition of cross-sectional muscle area into the Model for End-stage Liver Disease can increase its prognostic performance. Nevertheless, the use of CT scan in assessing muscle size is inappropriate for routine clinical practice and an alternative cost-effective, easy to use and accurate tool should be developed. In conclusion, muscle wasting has a detrimental impact on survival of patients with cirrhosis and, thus, it remains to be elucidated if nutritional interventions and exercise could improve muscle wasting and, subsequently, survival in this setting.

  9. [Action of DDPH in the interventional treatment of portal hypertension induced by liver cirrhosis in rabbits].

    PubMed

    Qian, J; Feng, G; Liang, H

    1998-01-01

    To explore a new way of utilizing intervential treatment to effectively decrease the portal hypertension, the animal models of liver cirrhosis accompanying portal hypertension were set up by intraportal vein injection of suspensions of Bletilla striata to 10 rabbits by means of prospective investigational method. The catheter filled with heparin solution was remained in theportal vein for infusion of drugs. Three weeks later, DDPH solution was injected into the portal vein via the catheter to determine its effect of decreasing portal vein pressure and its influence of peripheral blood pressure and heart rate. At the same time, other 10 rabbits with liver cirrhosis associated with portal hypertension were subjected to the injection of DDPH solution via the ear vein served as control group. The results showed that administration of DDPH by portal vein could rapidly, safely and effectively decrease the portal hypertenive pressure without side effects and partially reverse liver cirrhosis, as compared with injection of DDPH via peripheral veins. It was concluded that DDPH exerted its alpha 1-adrenoceptor blocking and calcium antagonistic effects, thereby significantly reduce the portal hypertension. Injection of DDPH via portal vein is a completely new and relaible method for the treatment of liver cirrhosis with portal hypertension.

  10. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis.

    PubMed

    Moriwaki, Hisataka; Miwa, Yoshiyuki; Tajika, Masahiro; Kato, Masahiko; Fukushima, Hideki; Shiraki, Makoto

    2004-01-09

    Protein-energy malnutrition (PEM) is a common manifestation in cirrhotic patients with reported incidences as high as 65-90%. PEM affects largely the patients' quality of life and survival. Thus, diagnosis of and intervention for PEM is important in the clinical management of liver cirrhosis. Supplementation with branched-chain amino acids (BCAA) is indicated to improve protein malnutrition. As an intervention for energy malnutrition, frequent meal or late evening snack has been recently recommended. Plasma amino acid analysis characterizes the patients with liver cirrhosis to have decreased BCAA. Such reduction of BCAA is explained by enhanced consumption of BCAA for ammonia detoxication and for energy generation. Supplementation with BCAA raises in vitro the synthesis and secretion of albumin by cultured rat hepatocytes without affecting albumin mRNA expression. BCAA recover the impaired turnover kinetics of albumin both in rat cirrhotic model and in cirrhotic patients. Longer-term supplementation with BCAA raises plasma albumin, benefits quality of life issues, and finally improves survival in liver cirrhosis. Recent interests focused on the timing of administration of BCAA, since daytime BCAA are usually consumed by energy generation for physical exercise of skeletal muscles. Nocturnal BCAA seem to be more favorable as a source of protein synthesis by giving higher nitrogen balance. This minireview focuses on the basic and clinical aspects of BCAA as a pharmaco-nutritional source to control PEM in liver cirrhosis.

  11. [Cryoglobulinemia following liver transplantation for cirrhosis secondary to hepatitis C virus infection].

    PubMed

    Argüello Viúdez, L; Bustamante Balén, M; Prieto Castillo, M; Moll Guillén, J L; Ramírez Palanca, J J; Berenguer Lapuerta, J

    1999-02-01

    Hepatitis C virus (HCV) infection has been linked with some extrahepatic immunologic abnormalities. Cryoglobulinemia is one of the most frequently reported. Nevertheless, there are only a few reports of cryoglobulinemia in the setting of liver transplantation. More studies are needed to clarify the frequency of post-OLT cryoglobulinemia in patients with HCV-related cirrhosis and its impact on OLT outcome. A case of a patient who underwent liver transplantation because of HCV end-stage liver disease and in whom cryoglobulinemia appeared 3 years after transplantation is reported. Treatment with cyclophosphamide and steroids was attempted but patient died of septicemia 3 years after liver transplantation.

  12. The direct and indirect relationships between alcohol prevention measures and alcoholic liver cirrhosis mortality.

    PubMed

    Xie, X; Mann, R E; Smart, R G

    2000-07-01

    The objective of this article is to investigate direct and indirect relationships between prevention measures and alcoholic liver cirrhosis mortality in Canadian provinces from 1968 to 1986. The data base that was assembled included alcoholic cirrhosis mortality rates, alcohol availability measures (rate of licensed premises, year in which the legal drinking age was reduced), per capita consumption of alcohol, rates of AA members and groups, and economic and demographic measures. This article develops a two-equation analytic model based on the availability theory of alcohol problems and prevention (Single, 1988). The distinction between direct and indirect effects of prevention measures can be made explicitly with this model. Alcohol availability measures, but not AA measures, had a significant direct potential impact on alcohol consumption. AA measures had a significant direct relationship to cirrhosis mortality rates. Alcohol consumption also had a significant direct relationship to cirrhosis mortality, and alcohol availability measures had an important indirect relationship through their influence on per capita alcohol consumption. While these observations need to be interpreted cautiously, the two-equation model shows promise as an approach to understanding direct and indirect influences on alcohol problems. As expected, AA measures and per capita alcohol consumption demonstrated significant direct relationship to cirrhosis mortality. In addition, important indirect influences of drinking-age changes and rates of licensed premises on cirrhosis mortality were observed through their relationships to per capita alcohol consumption.

  13. Risk factors for hepatocellular carcinoma in cirrhosis due to nonalcoholic fatty liver disease: A multicenter, case-control study

    PubMed Central

    Corey, Kathleen E; Gawrieh, Samer; deLemos, Andrew S; Zheng, Hui; Scanga, Andrew E; Haglund, Jennifer W; Sanchez, Jorge; Danford, Christopher J; Comerford, Megan; Bossi, Krista; Munir, Samina; Chalasani, Naga; Wattacheril, Julia

    2017-01-01

    AIM To identify risk factors associated with hepatocellular carcinoma (HCC), describe tumor characteristics and treatments pursed for a cohort of individuals with nonalcoholic steatohepatitis (NASH) cirrhosis. METHODS We conducted a retrospective case-control study of a well-characterized cohort of patients among five liver transplant centers with NASH cirrhosis with (cases) and without HCC (controls). RESULTS Ninety-four cases and 150 controls were included. Cases were significantly more likely to be male than controls (67% vs 45%, P < 0.001) and of older age (61.9 years vs 58 years, P = 0.002). In addition, cases were more likely to have had complications of end stage liver disease (83% vs 71%, P = 0.032). On multivariate analysis, the strongest association with the presence of HCC were male gender (OR 4.3, 95%CI: 1.83-10.3, P = 0.001) and age (OR = 1.082, 95%CI: 1.03-1.13, P = 0.001). Hispanic ethnicity was associated with a decreased prevalence of HCC (OR = 0.3, 95%CI: 0.09-0.994, P = 0.048). HCC was predominantly in the form of a single lesion with regional lymph node(s) and distant metastasis in only 2.6% and 6.3%, respectively. Fifty-nine point three percent of individuals with HCC underwent locoregional therapy and 61.5% underwent liver transplantation for HCC. CONCLUSION Male gender, increased age and non-Hispanic ethnicity are associated with HCC in NASH cirrhosis. NASH cirrhosis associated HCC in this cohort was characterized by early stage disease at diagnosis and treatment with locoregional therapy and transplant. PMID:28321274

  14. Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

    PubMed Central

    2010-01-01

    Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls) were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD) and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%). One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease models is feasible and

  15. Elevated renin levels in patients with liver cirrhosis and hepatocellular carcinoma.

    PubMed

    Lotfy, Mahmoud; El-Kenawy, Ayman El-Meghawry; Abdel-Aziz, Mohamed M; El-Kady, Ibrahim; Talaat, Ayman

    2010-01-01

    Liver fibrosis is the common consequence of chronic liver injury of any etiology, disrupting the normal architecture,and causing hepatocellular dysfunction and portal hypertension. Since the renin-angiotensin system (RAS) may be involved in chronic liver diseases, in the present study we assayed renin levels using ELISA in groups of Egyptian patients with liver cirrhosis (N=32) and hepatocellular carcinoma (HCC) (N=67), for comparison with twenty five healthy controls. The results showed significant differences between the control and liver cirrhosis patients (P<0.001) and also the controls and HCC patients (P<0.001), without significant variation between the patient groups. Furthermore, in HCC patients, it was found that the renin levels negatively correlated with serum albumin and prothrombin time (P=0.003 for each) and positively with α-fetoprotein (P=0.04). Thus, it is concluded that renin levels are elevated in patients with liver cirrhosis and HCC and suitable medical intervention should be placed for management of such alteration. Moreover, further studies are warranted to explore its prognostic significance.

  16. 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

  17. Cell-Free and Concentrated Ascites Reinfusion Therapy for Decompensated Liver Cirrhosis.

    PubMed

    Kozaki, Koichi; IInuma, Masahiro; Takagi, Tomoyuki; Fukuda, Takanori; Sanpei, Takaya; Terunuma, Yusuke; Yatabe, Yoshiharu; Akano, Kazuhiro

    2016-08-01

    Cell-free and concentrated ascites reinfusion therapy (CART) is expected to improve symptoms associated with refractory ascites of the decompensated liver cirrhosis patients. The aim of this study was to evaluate the safety and efficacy of the CART system performed on the decompensated liver cirrhosis patients. In this retrospective observational study, we evaluated 24 CART processes performed on 11 patients with decompensated liver cirrhosis. We evaluated the effectiveness and adverse events during CART procedures. The amounts of collected and concentrated ascites were 4491.7 ± 2222.8 mL (mean ± SD), respectively, and the concentration ratio was 22.4 ± 15.3 times, respectively. The amount of collected protein in ascites was 2.3 ± 0.5 g/dL, and concentration ratio of protein was 8.2 ± 9.4 times. Serum protein level was not significantly different between before and after CART sessions. Thus, CART allowed for the reduction of doses of albumin preparations (Alb) to be administered. CART has been reported to cause two adverse reactions: elevation of body temperature and decrease in blood pressure. In our study, decreased blood pressure was not observed even in patients with > 5 L of ascites drained. Although a transient elevation in body temperature was seen in only one patient, this febrile patient immediately returned to normal body temperature with the use of NSAIDs. In patients with refractory ascites of decompensated liver cirrhosis in whom complete cure cannot be expected, CART improves their QOL and, in terms of medical economy, allows for the reduction of doses of Alb. CART can be effectively applied as a palliative procedure for refractory ascites of decompensated liver cirrhosis patients. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  18. Alcohol drinking pattern and risk of alcoholic liver cirrhosis: a prospective cohort study.

    PubMed

    Askgaard, Gro; Grønbæk, Morten; Kjær, Mette S; Tjønneland, Anne; Tolstrup, Janne S

    2015-05-01

    Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern. We investigated the risk of alcoholic cirrhosis among 55,917 participants (aged 50-64 years) in the Danish Cancer, Diet, and Health study (1993-2011). Baseline information on alcohol intake, drinking pattern, and confounders was obtained from a questionnaire. Follow-up information came from national registers. We calculated hazard ratios (HRs) for alcoholic cirrhosis in relation to drinking frequency, lifetime alcohol amount, and beverage type. We observed 257 and 85 incident cases of alcoholic cirrhosis among men and women, respectively, none among lifetime abstainers. In men, HR for alcoholic cirrhosis among daily drinkers was 3.65 (95% CI: 2.39; 5.55) compared to drinking 2-4 days/week. Alcohol amount in recent age periods (40-49 and 50-59 years) was associated with an increased risk, whereas the amount in 20-29 and 30-39 years was not. In men drinking 14-28 drinks/week, HR was 7.47 (95% CI: 1.68; 33.12), 3.12 (95% CI: 1.53; 6.39), and 1.69 (95% CI: 0.79; 3.65) in drinkers of little (<1% of weekly amount), some (1-15%), and mostly wine (50-100%), compared to drinking <14 drinks/week. In general, results were similar for women. In men, daily drinking was associated with an increased risk of alcoholic cirrhosis. Recent alcohol consumption rather than earlier in life was associated with risk of alcoholic cirrhosis. Compared to beer and liquor, wine might be associated with a lower risk of alcoholic cirrhosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Diagnosis of liver cirrhosis with contrast-enhanced ultrasound

    PubMed Central

    Liu, Guang-Jian; Lu, Ming-De

    2010-01-01

    The assessment of the extent of liver fibrosis is very important for the prognosis and clinical management of chronic liver diseases. Although liver biopsy is the gold standard for the assessment of liver fibrosis, new non-invasive diagnostic methods are urgently needed in clinical work due to certain limitations and complications of biopsy. Noninvasive imaging studies play an important role in the diagnosis of focal liver disease and diffuse liver diseases. Among them, ultrasonography is the first choice for study of the liver in clinical work. With the development of ultrasound contrast agents and contrast specific imaging techniques, contrast-enhanced ultrasound (CEUS) shows good performance and great potential in the evaluation of liver fibrosis. Researchers have tried different kinds of contrast agent and imaging method, such as arrival time of contrast agent in the hepatic vein, and quantitative analysis of the enhancement level of liver parenchyma, to evaluate the degree of liver fibrosis during the past 10 years. This review mainly summarizes the clinical studies concerning the assessment of liver fibrosis using CEUS. PMID:21160737

  20. Evaluation of serum anion gap in patients with liver cirrhosis of diverse etiologies.

    PubMed

    Hassan, Hatim; Joh, Jung H; Bacon, Bruce R; Bastani, Bahar

    2004-09-01

    The low serum anion gap (AG) in patients with hepatic cirrhosis is generally attributed to hypoalbuminemia. Serum immunoglobulin G (IgG) (elevated in chronic viral hepatitis) and IgA (elevated in alcoholic cirrhosis) have different isoelectric points, and thus may affect serum AG in opposite directions. To define the normal serum AG in patients with liver cirrhosis of diverse etiologies. We retrospectively compared serum AG of 144 stable cirrhotics and 286 control patients (consecutive hospital admissions with serum creatinine concentration < 2 mg/dL). Serum AG was significantly lower among the cirrhotics, compared to the controls (5.8 +/- 2.2 mEq/L vs. 7.0 +/- 2.2 mEq/L, respectively, p<0.005). However, when patients with serum albumin concentration < 3.5 g/dL were excluded, there was no significant difference between the cirrhotics vs. controls (6.7 +/- 1.8 mEq/L vs. 7.0 +/- 2.2 mEq/L, p=ns). Moreover, patients with liver cirrhosis secondary to chronic viral hepatitis had AG similar to that of the alcoholic cirrhotics (5.6 +/- 2.5 mEq/L vs. 6.0 +/- 1.9 mEq/L, p=ns). There was a positive correlation between serum albumin concentrations > 1.9 g/dL and serum AG, and a tendency toward an inverse correlation between serum globulin concentration and serum AG. Our results support the contention that hypoalbuminemia accounts for the decreased serum AG frequently observed in patients with liver cirrhosis. We found no difference in serum AG with different causes of cirrhosis. We also suggest a lower reference range for normal serum AG.

  1. Complications associated with instrumented lumbar surgery in patients with liver cirrhosis: a matched cohort analysis.

    PubMed

    Liao, Jen-Chung; Chen, Wen-Jer; Chen, Lih-Hui; Niu, Chi-Chien; Fu, Tsai-Shen; Lai, Po-Liang; Tsai, Tsung-Ting

    2013-08-01

    There is no information in the English literature on the outcome of liver cirrhotic patients who have undergone instrumented lumbar surgery. To review the results of instrumented lumbar surgery in patients with liver cirrhosis and determine the surgical risk factors in this group of patients. A retrospective study for comparison between two cohorts (liver cirrhosis vs. nonliver cirrhosis). Fifty-eight patients. Child-Turcotte-Pugh scale was used to assess the patients' hepatic functional reserve. The clinical outcomes were evaluated by the five-grade patient-centered general outcome assessment questionnaire. Any event that led to reoperation, requirement of intensive care, prolonging of the hospital stay (more than 14 days), or admission after discharge within 30 days of surgery was defined as a perioperative complication. Between 1997 and 2009, patients with liver cirrhosis who had undergone instrumented lumbar surgeries for degenerative lumbar disease were studied. All data were compared with those for gender-, age-, and diagnosis-matched nonliver cirrhosis patients. Liver cirrhotic patients had significantly lower preoperative hemoglobin, white blood cell counts, platelets, and albumin levels and higher prothrombin time and bilirubin level. Instrumented lumbar surgery was associated with significantly more blood loss, a longer hospital stay, and more complications in patients with liver cirrhosis compared with control patients. The final satisfactory rate was higher in the control group but without statistical difference (85% vs. 65%, p=.240). In the cirrhotic group, 22 patients (76%) were Child Class A and 7 patients (24%) were Child Class B; 12 patients developed one or more complications. Patients with Child Class B had a significantly higher incidence of complications than those with Child Class A (p=.006). In patients with Child Class A, those with a score of 6 also had a significantly higher incidence of complications than those with a score of 5 (p<.001

  2. Spontaneous Bacterial Peritonitis and Henoch-Schönlein Purpura in a Patient with Liver Cirrhosis.

    PubMed

    Gupta, Neil; Kim, Joyce; Njei, Basile

    2015-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel systemic vasculitis, predominantly affecting children, characterized by a tetrad of manifestations, specifically palpable purpura, arthralgia, abdominal pain, and renal disease. HSP in the adult population is rare, and no case has been described of HSP in liver cirrhosis with spontaneous bacterial peritonitis (SBP). We present the case of a 58-year-old male with liver cirrhosis, who was subsequently diagnosed with SBP and later HSP. In this patient, the diagnosis of HSP was demonstrated clinically by his palpable purpura, diarrhea, hematuria, and abdominal pain and confirmed pathologically by his renal and skin biopsies demonstrating leukocytoclastic vasculitis and IgA complexes. We believe that this is an example of altered IgA processing in cirrhosis leading to the development of IgA immune complexes and ultimately HSP. The patient additionally had SBP, which may have increased his risk for developing HSP given antigen processing by mucosa-associated lymphoid tissues leading to immune complex deposition, which may not have been effectively cleared in the context of his liver disease. The patient unfortunately died of gastrointestinal hemorrhage, which is unclear to be due to his underlying cirrhosis or a gastrointestinal manifestation of HSP itself.

  3. Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects.

    PubMed

    Vargas, Jose Ignacio; Arrese, Marco; Shah, Vijay H; Arab, Juan Pablo

    2017-09-01

    The purpose of this study is to analyze the current evidence regarding the use of statins in patients with chronic liver disease and cirrhosis. Chronic liver disease (CLD), cirrhosis, and its complications, including hepatocellular carcinoma (HCC), are significant public health problems. The use of statins in patients with CLD has been a matter of concern, and physicians are often reluctant to its prescription in these patients. This mainly relates to the potential occurrence of drug-induced liver injury. However, newer evidence from pre-clinical and clinical research has shown that statins are drugs with a potentially beneficial impact on the natural history of cirrhosis, on portal hypertension, and in HCC prevention. In this review, we summarize current evidence regarding the influence of statins in endothelial dysfunction in CLD, their ability to modulate hepatic fibrogenesis, and their vasoprotective effects in portal hypertension; we also focus on existing data about the impact of statins in cirrhosis development, progression, and complications and critically assess the current concerns about its use in patients with CLD.

  4. Dobutamine stress echocardiography for evaluating cirrhotic cardiomyopathy in liver cirrhosis

    PubMed Central

    Kim, Moon Young; Won, Chan Sik; Park, Hong Jun; Jeon, Hyo Keun; Hong, Hyun Il; Kim, Jae Woo; Kim, Hyun Soo; Kwon, Sang Ok; Kim, Jang Young; Yoo, Byung Su; Lee, Seung Hwan

    2010-01-01

    Background/Aims The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the β-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). Methods Seventy-one cirrhotic patients with normal left ventricular (LV) chamber size and ejection fraction were enrolled. The LV systolic and diastolic functions were evaluated by two-dimensional and Doppler echocardiography at rest and during peak dobutamine infusion (40 µg/kg/min). An abnormal response was defined as a decrease of less than 10% in LV end-diastolic volume, a decrease of less than 20% in end-systolic volume, and an increase of less than 10% in LV ejection fraction (EF) at peak dobutamine infusion, based on previously used criteria. The early/late diastolic flow (E/A) ratio and diastolic parameters were also measured. Results A blunted LV response to dobutamine was observed in 18 of 71 cirrhotic patients (25.4%). The baseline EF was significantly higher in 18 patients with a blunted DSE response than that of those with a normal DSE response (P<0.05). The baseline and peak E/A ratios, which are common diastolic dysfunction markers, were higher in the cirrhosis group than in the control group (P<0.001). No adverse events associated with DSE were observed. Conclusions Blunted cardiac responses to dobutamine stimulation, which are implicated in defects in the β-adrenergic signaling pathway, might contribute to the pathogenesis of CCM in patients with cirrhosis. PMID:21415581

  5. Survival Benefit of Locoregional Treatment for Hepatocellular Carcinoma with Advanced Liver Cirrhosis

    PubMed Central

    Kitai, Satoshi; Kudo, Masatoshi; Nishida, Naoshi; Izumi, Namiki; Sakamoto, Michiie; Matsuyama, Yutaka; Ichida, Takafumi; Nakashima, Osamu; Matsui, Osamu; Ku, Yonson; Kokudo, Norihiro; Makuuchi, Masatoshi

    2016-01-01

    Background & Aims Hepatocellular carcinoma (HCC) with decompensated liver cirrhosis (LC) is a life-threatening condition, which is amenable to liver transplantation (LT) as the standard first-line treatment. However, the application of LT can be limited due to a shortage of donor livers. This study aimed to clarify the effect of non-surgical therapy on the survival of patients with HCC and decompensated LC. Methods Of the 58,886 patients with HCC registered in the nationwide survey of the Liver Cancer Study Group of Japan (January 2000-December 2005), we included 1,344 patients with primary HCC and Child-Pugh (C-P) grade C for analysis in this retrospective study. Among the patients analyzed, 108 underwent LT, 273 were treated by local ablation therapy (LAT), 370 were treated by transarterial chemoembolization (TACE), and 593 received best supportive care (BSC). The effect of LT, LAT, and TACE on overall survival (OS) was analyzed using multivariate and propensity score analyses. Results Patient characteristics did not differ significantly between each treatment group and the BSC group, after propensity score matching. LAT (hazard ratio [HR]) =0.568; 95% confidence interval [CI], 0.40-0.80) and TACE (HR=0.691; 95% CI, 0.50-0.96) were identified as significant contributors to OS if the C-P score was less than 11 and tumor conditions met the Milan criteria. Conclusions For patients with HCC within the Milan criteria and with a C-P score of 10 or 11, locoregional treatment can be used as a salvage treatment if LT is not feasible. PMID:27493893

  6. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis

    PubMed Central

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  7. 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.

  8. Training sample selection based on self-training for liver cirrhosis classification using ultrasound images

    NASA Astrophysics Data System (ADS)

    Fujita, Yusuke; Mitani, Yoshihiro; Hamamoto, Yoshihiko; Segawa, Makoto; Terai, Shuji; Sakaida, Isao

    2017-03-01

    Ultrasound imaging is a popular and non-invasive tool used in the diagnoses of liver disease. Cirrhosis is a chronic liver disease and it can advance to liver cancer. Early detection and appropriate treatment are crucial to prevent liver cancer. However, ultrasound image analysis is very challenging, because of the low signal-to-noise ratio of ultrasound images. To achieve the higher classification performance, selection of training regions of interest (ROIs) is very important that effect to classification accuracy. The purpose of our study is cirrhosis detection with high accuracy using liver ultrasound images. In our previous works, training ROI selection by MILBoost and multiple-ROI classification based on the product rule had been proposed, to achieve high classification performance. In this article, we propose self-training method to select training ROIs effectively. Evaluation experiments were performed to evaluate effect of self-training, using manually selected ROIs and also automatically selected ROIs. Experimental results show that self-training for manually selected ROIs achieved higher classification performance than other approaches, including our conventional methods. The manually ROI definition and sample selection are important to improve classification accuracy in cirrhosis detection using ultrasound images.

  9. Genetic Diseases That Predispose to Early Liver Cirrhosis

    PubMed Central

    Liguori, Renato

    2014-01-01

    Inherited liver diseases are a group of metabolic and genetic defects that typically cause early chronic liver involvement. Most are due to a defect of an enzyme/transport protein that alters a metabolic pathway and exerts a pathogenic role mainly in the liver. The prevalence is variable, but most are rare pathologies. We review the pathophysiology of such diseases and the diagnostic contribution of laboratory tests, focusing on the role of molecular genetics. In fact, thanks to recent advances in genetics, molecular analysis permits early and specific diagnosis for most disorders and helps to reduce the invasive approach of liver biopsy. PMID:25132997

  10. Improvement in liver cirrhosis after treatment of HCV-related mixed cryoglobulinemia with rituximab.

    PubMed

    Petrarca, Antonio; Rigacci, Luigi; Monti, Monica; Giannini, Carlo; Bernardi, Franco; Caini, Patrizio; Colagrande, Stefano; Bosi, Alberto; Laffi, Giacomo; Zignego, Anna Linda

    2007-09-01

    Mixed cryoglobulinemia (MC) is the most strictly virus-related extrahepatic HCV disease. Antiviral therapy is considered the first therapeutic option; however, MC patients are frequently excluded from treatment due to contraindications. The effectiveness of B-cell depletion by anti-CD20 monoclonal antibody (rituximab) has recently been described, but the possibility of an immunodepression- related increase in viral replication and aminotransferase values limits its use in patients with advanced liver disease. Unfortunately, MC patients frequently also have cirrhosis. To our knowledge, no data are available regarding the effect of rituximab therapy in patients with decompensated cirrhosis. We report the successful treatment with rituximab (4 weekly infusions of 375 mg/m 2) of two patients (a 58-year-old man, and a 65-year-old woman) with HCV-related MC syndrome and decompensated liver cirrhosis. These patients underwent at least 6 months of post-treatment follow-up. In both cases a consistent improvement of MC syndrome was evident after treatment. In addition, improvement of liver protidosynthetic activity, increased prothrombin time, impressive reduction or disappearance of ascites and encephalopathy were also observed, in spite of some increase in viral titers or in ALT values. The Child-Pugh score improved from B8 to A6 and from Cll to B7, respectively. Pre- and post-treatment transjugular liver biopsies were available in 1 patient, showing disappearance of lymphocytic infiltration after treatment. These case reports show the effectiveness and safety of rituximab in patients with HCV-related MC and advanced cirrhosis, and strongly suggest that the depletion of CD20+ B-cells induced by rituximab treatment may be responsible for liver function improvement. The mechanisms involved are unknown. Interesting working hypotheses may implicate a role played by B-cell infiltrates in conditioning liver damage. The improvement of Kupffer cell function due to the cryocrit

  11. Bacterial translocation aggravates CCl4-induced liver cirrhosis by regulating CD4+ T cells in rats

    PubMed Central

    Shi, Haiyan; Lv, Longxian; Cao, Hongcui; Lu, Haifeng; Zhou, Ning; Yang, Jiezuan; Jiang, Haiyin; Dong, Huihui; Hu, Xinjun; Yu, Wei; Jiang, Xiawei; Zheng, Beiwen; Li, Lanjuan

    2017-01-01

    Bacterial translocation (BT) is thought to play an important role in the development of liver cirrhosis, but the mechanisms have not been fully explored. This study aims to investigate the distribution of Treg (CD3+CD4+CD25+Foxp3+), Th17 (CD3+CD4+IL-17+), and Th1 (CD3+CD4+IFN-γ+) cells in the intestinal lamina propria, liver and blood and to explore their relationships with BT. Cirrhotic rats with ascites were induced by CCl4. We found that there were lower levels of total protein and albumin, lower albumin/globulin ratio, lower body weight and higher spleen weight and ascites volume in cirrhotic rats with than without BT. We found that BT may cause increase of Treg cells in the proximal small intestine and decrease of Th17 cells in the whole intestine and blood in cirrhotic rats. It may also aggravate the CCl4-induced decrease in Th1 cells in the whole intestine, liver, caecum, and blood and the CCl4-induced increase in Th17 cells in the liver and Tregs in the distal small intestine, colon, and liver. Our data suggest that BT may aggravate liver injury and decrease liver function via an interaction with CD4+ T Cells. The results of this study may be helpful for the development of new treatments for liver cirrhosis. PMID:28134306

  12. Hepatic venography in noncirrhotic idiopathic portal hypertension: comparison with cirrhosis of the liver

    SciTech Connect

    Futagawa, S.; Fukazawa, M.; Musha, H.

    1981-11-01

    Free and wedged hepatic venography were carried out in 37 patients with idiopathic portal hypertension (IPH) and the findings compared with those in 88 patients with cirrhosis of the liver. Characteristic changes in IPH included frequent vein-to-vein anastomoses, narrower angles between large veins and their tributaries, smooth and wavy middle-sized to large branches (giving a general ''weeping willow'' appearance), homogeneous sinusoidal filling, and minimal to absent filling of the portal venous system on wedged retrograde portography. In cirrhosis, by contrast, changes included rare vein-to-vein anastomoses, wide angles between veins and tributaries, irregular stenoses of large veins and branches at various levels, spotty sinusoidal filling, and frequent retrograde flow in the portal venous system. Hepatic venography is helpful in differentiating IPH from cirrhosis.

  13. MDCT Imaging Findings of Liver Cirrhosis: Spectrum of Hepatic and Extrahepatic Abdominal Complications

    PubMed Central

    Sangster, Guillermo P.; Previgliano, Carlos H.; Nader, Mathieu; Chwoschtschinsky, Elisa; Heldmann, Maureen G.

    2013-01-01

    Hepatic cirrhosis is the clinical and pathologic result of a multifactorial chronic liver injury. It is well known that cirrhosis is the origin of multiple extrahepatic abdominal complications and a markedly increased risk of hepatocellular carcinoma (HCC). This tumor is the sixth most common malignancy worldwide and the third most common cause of cancer related death. With the rising incidence of HCC worldwide, awareness of the evolution of cirrhotic nodules into malignancy is critical for an early detection and treatment. Adequate imaging protocol selection with dynamic multiphase Multidetector Computed Tomography (MDCT) and reformatted images is crucial to differentiate and categorize the hepatic nodular dysplasia. Knowledge of the typical and less common extrahepatic abdominal manifestations is essential for accurately assessing patients with known or suspected hepatic disease. The objective of this paper is to illustrate the imaging spectrum of intra- and extrahepatic abdominal manifestations of hepatic cirrhosis seen on MDCT. PMID:23986608

  14. 1H Magnetic Resonance Spectroscopy Predicts Hepatocellular Carcinoma in a Subset of Patients With Liver Cirrhosis: A Randomized Trial.

    PubMed

    Wang, Dan; Li, Yuehua

    2015-07-01

    The goal of this study was to investigate the utility of H magnetic resonance spectroscopy (H-MRS) to quantify the differences in liver metabolites. Magnetic resonance spectroscopy was used as a means of predicting the probability of developing hepatocellular carcinoma (HCC) in patients with liver cirrhosis secondary to chronic hepatitis B.This study included 20 healthy volunteers, 20 patients with liver cirrhosis secondary to chronic hepatitis B (cirrhosis group), and 20 patients with small HCC secondary to cirrhosis liver parenchyma (HCC group). All patients underwent routine MRI and H-MRS scanning. LCModel software was used to quantify Cho (Choline), Lip (lipid), and Cho/Lip in the 3 groups, and a one-way ANOVA was used to compare the differences in these metabolites between groups.Choline levels were significantly different between the control and HCC group and between the cirrhosis group and the HCC group (all P < 0.001). There was also a significant difference in Lip levels between the control and cirrhosis group and the control and HCC groups (all P < 0.001). There were also differences in Cho/Lip between the control and cirrhosis groups, the control and HCC groups, and the cirrhosis and HCC groups (all P < 0.001).H-MRS followed by the analysis with LCModel can be used to measure changes in hepatic metabolite levels in patients with liver cirrhosis secondary to chronic hepatitis B and HCC. Thus, H-MRS may be helpful in monitoring HCC and liver cirrhosis development.

  15. The Triad of Lichen Planus, Thymoma and Liver Cirrhosis-Hepatoma. First Reported Case

    PubMed Central

    Hassan, J. A.; Saadiah, S; Roslina, A M; Atan, M; Masir, Noraidah; Hussein, S; Ganesapillai, T

    2000-01-01

    We describe a patient with liver cirrhosis who presented with erosive oral and cutaneous lichen planus (LP) and incidentally was found simultaneously to have thymoma and hepatoma. We support the notion forwarded earlier that LP and chronic liver disease is more than a mere coincidence and that there is a non-coincidental association between LP and thymoma. We believe this is also the first reported case in the English Literature of coexistence of the three condition LP, thymoma and hepatoma complicating liver disease. PMID:22977389

  16. S100 protein positive dendritic cells in primary biliary cirrhosis and other chronic inflammatory liver diseases. Relevance to pathogenesis?

    PubMed Central

    Demetris, A. J.; Sever, C.; Kakizoe, S.; Oguma, S.; Starzl, T. E.; Jaffe, R.

    1989-01-01

    A study to determine the location of dendritic cells, in chronic inflammatory liver disease was performed. S100 protein positivity and dendritic cytoplasmic morphology were used to identify dendritic cells. S100 protein positive dendritic cells (S100 + DC) were found inside the basement membrane between biliary epithelial cells of septal bile ducts of livers affected by early stage PBC, but were not present at later stages. S100 + DC also were seen in areas of piecemeal necrosis in chronic active hepatitis of various etiologies. In contrast, intra-epithelial S100 + DC were not found with any consistency in sclerosing cholangitis, secondary biliary cirrhosis, extrahepatic biliary atresia, or chronic liver allograft rejection, all of which are characterized by inflammatory bile duct damage. The possible relevance of DC in the pathogenesis of PBC is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2705505

  17. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

    PubMed

    Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

    2015-09-22

    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

  18. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

    PubMed Central

    Cordell, Heather J.; Han, Younghun; Mells, George F.; Li, Yafang; Hirschfield, Gideon M.; Greene, Casey S.; Xie, Gang; Juran, Brian D.; Zhu, Dakai; Qian, David C.; Floyd, James A. B.; Morley, Katherine I.; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Schlicht, Erik M; Lammert, Craig; Atkinson, Elizabeth J; Chan, Landon L; de Andrade, Mariza; Balschun, Tobias; Mason, Andrew L; Myers, Robert P; Zhang, Jinyi; Milkiewicz, Piotr; Qu, Jia; Odin, Joseph A; Luketic, Velimir A; Bacon, Bruce R; Bodenheimer Jr, Henry C; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Gregersen, Peter K; Almasio, Piero L; Alvaro, Domenico; Andreone, Pietro; Andriulli, Angelo; Barlassina, Cristina; Battezzati, Pier Maria; Benedetti, Antonio; Bernuzzi, Francesca; Bianchi, Ilaria; Bragazzi, Maria Consiglia; Brunetto, Maurizia; Bruno, Savino; Casella, Giovanni; Coco, Barbara; Colli, Agostino; Colombo, Massimo; Colombo, Silvia; Cursaro, Carmela; Crocè, Lory Saveria; Crosignani, Andrea; Donato, Maria Francesca; Elia, Gianfranco; Fabris, Luca; Ferrari, Carlo; Floreani, Annarosa; Foglieni, Barbara; Fontana, Rosanna; Galli, Andrea; Lazzari, Roberta; Macaluso, Fabio; Malinverno, Federica; Marra, Fabio; Marzioni, Marco; Mattalia, Alberto; Montanari, Renzo; Morini, Lorenzo; Morisco, Filomena; Hani S, Mousa; Muratori, Luigi; Muratori, Paolo; Niro, Grazia A; Palmieri, Vincenzo O; Picciotto, Antonio; Podda, Mauro; Portincasa, Piero; Ronca, Vincenzo; Rosina, Floriano; Rossi, Sonia; Sogno, Ilaria; Spinzi, Giancarlo; Spreafico, Marta; Strazzabosco, Mario; Tarallo, Sonia; Tarocchi, Mirko; Tiribelli, Claudio; Toniutto, Pierluigi; Vinci, Maria; Zuin, Massimo; Ch'ng, Chin Lye; Rahman, Mesbah; Yapp, Tom; Sturgess, Richard; Healey, Christopher; Czajkowski, Marek; Gunasekera, Anton; Gyawali, Pranab; Premchand, Purushothaman; Kapur, Kapil; Marley, Richard; Foster, Graham; Watson, Alan; Dias, Aruna; Subhani, Javaid; Harvey, Rory; McCorry, Roger; Ramanaden, David; Gasem, Jaber; Evans, Richard; Mathialahan, Thiriloganathan; Shorrock, Christopher; Lipscomb, George; Southern, Paul; Tibble, Jeremy; Gorard, David; Palegwala, Altaf; Jones, Susan; Carbone, Marco; Dawwas, Mohamed; Alexander, Graeme; Dolwani, Sunil; Prince, Martin; Foxton, Matthew; Elphick, David; Mitchison, Harriet; Gooding, Ian; Karmo, Mazn; Saksena, Sushma; Mendall, Mike; Patel, Minesh; Ede, Roland; Austin, Andrew; Sayer, Joanna; Hankey, Lorraine; Hovell, Christopher; Fisher, Neil; Carter, Martyn; Koss, Konrad; Piotrowicz, Andrzej; Grimley, Charles; Neal, David; Lim, Guan; Levi, Sass; Ala, Aftab; Broad, Andrea; Saeed, Athar; Wood, Gordon; Brown, Jonathan; Wilkinson, Mark; Gordon, Harriet; Ramage, John; Ridpath, Jo; Ngatchu, Theodore; Grover, Bob; Shaukat, Syed; Shidrawi, Ray; Abouda, George; Ali, Faiz; Rees, Ian; Salam, Imroz; Narain, Mark; Brown, Ashley; Taylor-Robinson, Simon; Williams, Simon; Grellier, Leonie; Banim, Paul; Das, Debashis; Chilton, Andrew; Heneghan, Michael; Curtis, Howard; Gess, Markus; Drake, Ian; Aldersley, Mark; Davies, Mervyn; Jones, Rebecca; McNair, Alastair; Srirajaskanthan, Raj; Pitcher, Maxton; Sen, Sambit; Bird, George; Barnardo, Adrian; Kitchen, Paul; Yoong, Kevin; Chirag, Oza; Sivaramakrishnan, Nurani; MacFaul, George; Jones, David; Shah, Amir; Evans, Chris; Saha, Subrata; Pollock, Katharine; Bramley, Peter; Mukhopadhya, Ashis; Fraser, Andrew; Mills, Peter; Shallcross, Christopher; Campbell, Stewart; Bathgate, Andrew; Shepherd, Alan; Dillon, John; Rushbrook, Simon; Przemioslo, Robert; Macdonald, Christopher; Metcalf, Jane; Shmueli, Udi; Davis, Andrew; Naqvi, Asifabbas; Lee, Tom; Ryder, Stephen D; Collier, Jane; Klass, Howard; Ninkovic, Mary; Cramp, Matthew; Sharer, Nicholas; Aspinall, Richard; Goggin, Patrick; Ghosh, Deb; Douds, Andrew; Hoeroldt, Barbara; Booth, Jonathan; Williams, Earl; Hussaini, Hyder; Stableforth, William; Ayres, Reuben; Thorburn, Douglas; Marshall, Eileen; Burroughs, Andrew; Mann, Steven; Lombard, Martin; Richardson, Paul; Patanwala, Imran; Maltby, Julia; Brookes, Matthew; Mathew, Ray; Vyas, Samir; Singhal, Saket; Gleeson, Dermot; Misra, Sharat; Butterworth, Jeff; George, Keith; Harding, Tim; Douglass, Andrew; Panter, Simon; Shearman, Jeremy; Bray, Gary; Butcher, Graham; Forton, Daniel; Mclindon, John; Cowan, Matthew; Whatley, Gregory; Mandal, Aditya; Gupta, Hemant; Sanghi, Pradeep; Jain, Sanjiv; Pereira, Steve; Prasad, Geeta; Watts, Gill; Wright, Mark; Neuberger, James; Gordon, Fiona; Unitt, Esther; Grant, Allister; Delahooke, Toby; Higham, Andrew; Brind, Alison; Cox, Mark; Ramakrishnan, Subramaniam; King, Alistair; Collins, Carole; Whalley, Simon; Li, Andy; Fraser, Jocelyn; Bell, Andrew; Wong, Voi Shim; Singhal, Amit; Gee, Ian; Ang, Yeng; Ransford, Rupert; Gotto, James; Millson, Charles; Bowles, Jane; Thomas, Caradog; Harrison, Melanie; Galaska, Roman; Kendall, Jennie; Whiteman, Jessica; Lawlor, Caroline; Gray, Catherine; Elliott, Keith; Mulvaney-Jones, Caroline; Hobson, Lucie; Van Duyvenvoorde, Greta; Loftus, Alison; Seward, Katie; Penn, Ruth; Maiden, Jane; Damant, Rose; Hails, Janeane; Cloudsdale, Rebecca; Silvestre, Valeria; Glenn, Sue; Dungca, Eleanor; Wheatley, Natalie; Doyle, Helen; Kent, Melanie; Hamilton, Caroline; Braim, Delyth; Wooldridge, Helen; Abrahams, Rachel; Paton, Alison; Lancaster, Nicola; Gibbins, Andrew; Hogben, Karen; Desousa, Phillipa; Muscariu, Florin; Musselwhite, Janine; McKay, Alexandra; Tan, LaiTing; Foale, Carole; Brighton, Jacqueline; Flahive, Kerry; Nambela, Estelle; Townshend, Paula; Ford, Chris; Holder, Sophie; Palmer, Caroline; Featherstone, James; Nasseri, Mariam; Sadeghian, Joy; Williams, Bronwen; Thomas, Carol; Rolls, Sally-Ann; Hynes, Abigail; Duggan, Claire; Jones, Sarah; Crossey, Mary; Stansfield, Glynis; MacNicol, Carolyn; Wilkins, Joy; Wilhelmsen, Elva; Raymode, Parizade; Lee, Hye-Jeong; Durant, Emma; Bishop, Rebecca; Ncube, Noma; Tripoli, Sherill; Casey, Rebecca; Cowley, Caroline; Miller, Richard; Houghton, Kathryn; Ducker, Samantha; Wright, Fiona; Bird, Bridget; Baxter, Gwen; Keggans, Janie; Hughes, Maggie; Grieve, Emma; Young, Karin; Williams, D; Ocker, Kate; Hines, Frances; Martin, Kirsty; Innes, Caron; Valliani, Talal; Fairlamb, Helen; Thornthwaite, Sarah; Eastick, Anne; Tanqueray, Elizabeth; Morrison, Jennifer; Holbrook, Becky; Browning, Julie; Walker, Kirsten; Congreave, Susan; Verheyden, Juliette; Slininger, Susan; Stafford, Lizzie; O'Donnell, Denise; Ainsworth, Mark; Lord, Susan; Kent, Linda; March, Linda; Dickson, Christine; Simpson, Diane; Longhurst, Beverley; Hayes, Maria; Shpuza, Ervin; White, Nikki; Besley, Sarah; Pearson, Sallyanne; Wright, Alice; Jones, Linda; Gunter, Emma; Dewhurst, Hannah; Fouracres, Anna; Farrington, Liz; Graves, Lyn; Marriott, Suzie; Leoni, Marina; Tyrer, David; Martin, Kate; Dali-kemmery, Lola; Lambourne, Victoria; Green, Marie; Sirdefield, Dawn; Amor, Kelly; Colley, Julie; Shinder, Bal; Jones, Jayne; Mills, Marisa; Carnahan, Mandy; Taylor, Natalie; Boulton, Kerenza; Tregonning, Julie; Brown, Carly; Clifford, Gayle; Archer, Emily; Hamilton, Maria; Curtis, Janette; Shewan, Tracey; Walsh, Sue; Warner, Karen; Netherton, Kimberley; Mupudzi, Mcdonald; Gunson, Bridget; Gitahi, Jane; Gocher, Denise; Batham, Sally; Pateman, Hilary; Desmennu, Senayon; Conder, Jill; Clement, Darren; Gallagher, Susan; Orpe, Jacky; Chan, PuiChing; Currie, Lynn; O'Donohoe, Lynn; Oblak, Metod; Morgan, Lisa; Quinn, Marie; Amey, Isobel; Baird, Yolanda; Cotterill, Donna; Cumlat, Lourdes; Winter, Louise; Greer, Sandra; Spurdle, Katie; Allison, Joanna; Dyer, Simon; Sweeting, Helen; Kordula, Jean; Gershwin, M. Eric; Anderson, Carl A.; Lazaridis, Konstantinos N.; Invernizzi, Pietro; Seldin, Michael F.; Sandford, Richard N.; Amos, Christopher I.; Siminovitch, Katherine A.

    2015-01-01

    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist. PMID:26394269

  19. Body Posture Angle Affects the Physiological Indices of Patients With Liver Cirrhosis Ascites.

    PubMed

    Hsu, Wen-chuan; Ho, Lun-hui; Lin, Mei-hsiang; Chiu, Hsiu-ling

    2016-01-01

    The study objective was to compare the effect of different angles of lying positions on the physiological indices of patients with cirrhosis ascites. Chronic liver disease and cirrhosis were ranked 9th among the top 10 causes of death. Ascites is the most common cirrhosis comorbidity. Body posture can affect pulmonary ventilation and arterial oxygen partial pressure, making it an important clinical nursing intervention significantly affecting patient recovery. This was a quasi-experimental study design. From a medical center in Taiwan, 252 patients with cirrhosis ascites were recruited. Subjects were randomly divided into three groups by bed angle: 15°, 30°, and 45°. Physiological indices were measured at 5, 10, 15, 20, 25, and 30 minutes to determine any changes in heart rate, respiration rate, and oxygenation saturation. Data analysis included descriptive statistics and the generalized estimating equation for statistical analysis with significance set at α= 0.05. After controlling for confounding variables, the three groups differed significantly in heart rate at 20, 25, and 30 minutes, oxygenation saturations at 15 and 20 minutes, and respiration rate at 5 and 10 minutes (α< 0.05). Body posture can affect pulmonary ventilation and arterial oxygen partial pressure and is thus an important clinical nursing intervention that significantly affects the recovery of patients. When caring for patients with cirrhosis ascites, nurses should help patients to choose the most comfortable angle for them with no particular restrictions. Our results can be used to guide nurses in making a plan for health education and nursing that improves the quality of care for patients with chronic liver disease and cirrhosis patients with ascites.

  20. Small RNA- and DNA-based gene therapy for the treatment of liver cirrhosis, where we are?

    PubMed

    Kim, Kyung-Hyun; Park, Kwan-Kyu

    2014-10-28

    Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure. Based on the underlying cellular and molecular mechanisms of a liver fibrosis, there has been proposed several kinds of approaches for the treatment of liver fibrosis. Recently, liver gene therapy has been developed as an alternative way to liver transplantation, which is the only effective therapy for chronic liver diseases. The activation of hepatic stellate cells, a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis. Several targeted strategies have been developed, such as antisense oligodeoxynucleotides, RNA interference and decoy oligodeoxynucleotides to overcome this barriers. With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis, and particularly, of the targeted gene therapy using short RNA and DNA segments.

  1. Small RNA- and DNA-based gene therapy for the treatment of liver cirrhosis, where we are?

    PubMed Central

    Kim, Kyung-Hyun; Park, Kwan-Kyu

    2014-01-01

    Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure. Based on the underlying cellular and molecular mechanisms of a liver fibrosis, there has been proposed several kinds of approaches for the treatment of liver fibrosis. Recently, liver gene therapy has been developed as an alternative way to liver transplantation, which is the only effective therapy for chronic liver diseases. The activation of hepatic stellate cells, a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis. Several targeted strategies have been developed, such as antisense oligodeoxynucleotides, RNA interference and decoy oligodeoxynucleotides to overcome this barriers. With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis, and particularly, of the targeted gene therapy using short RNA and DNA segments. PMID:25356032

  2. Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus.

    PubMed

    El-Eshmawy, Mervat M; Arafa, Mona M; Elzehery, Rasha R; Elhelaly, Rania M; Elrakhawy, Mohamed M; El-Baiomy, Azza A

    2016-09-01

    Vitamin A deficiency (VAD) and altered thyroid function are commonly encountered in patients with liver cirrhosis. The link between vitamin A metabolism and thyroid function has been previously identified. The aim of this study was to explore the association between VAD and the thyroid axis in clinically stable patients with cirrhosis related to hepatitis C virus (HCV). One hundred and twelve patients with clinically stable HCV-related cirrhosis and 56 healthy controls matched for age, sex, and socioeconomic status were recruited for this study. Vitamin A status, liver function, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse triiodothyronine (rT3), anti-thyroid peroxidase antibodies (anti-TPO), and thyroid volume were evaluated. The prevalence of VAD among patients with HCV-related cirrhosis was 62.5% compared with 5.4% among controls (P < 0.001). Patients with HCV-related cirrhosis had significantly higher FT4, FT3, TSH, and thyroid volume than did healthy controls. Of the 112 patients initially recruited, 18 were excluded (patients with subclinical hypothyroidism and/or anti-TPO positive), so a total of 94 patients with HCV-related cirrhosis were divided into 2 groups according to vitamin A status: VAD and normal vitamin A. Patients with VAD had significantly lower vitamin A intake and serum albumin and higher serum bilirubin, FT4, FT3, and TSH than patients with normal vitamin A status. Multiple logistic regression analysis revealed that VAD was associated with Child-Pugh score (β = 0.11, P = 0.05) and TSH (β = -1.63, P = 0.02) independently of confounding variables. We conclude that VAD may be linked to central hyperthyroidism in patients with clinically stable HCV-related liver cirrhosis.

  3. Epigenetic Effects of an Adenosine Derivative in a Wistar Rat Model of Liver Cirrhosis.

    PubMed

    Rodríguez-Aguilera, Jesús Rafael; Guerrero-Hernández, Carlos; Pérez-Molina, Rosario; Cadena-Del-Castillo, Carla Elizabeth; Pérez-Cabeza de Vaca, Rebeca; Guerrero-Celis, Nuria; Domínguez-López, Mariana; Murillo-de-Ozores, Adrián Rafael; Arzate-Mejía, Rodrigo; Recillas-Targa, Félix; Chagoya de Sánchez, Victoria

    2017-06-07

    The pathological characteristic of cirrhosis is scarring which results in a structurally distorted and dysfunctional liver. Previously, we demonstrated that Col1a1 and Pparg genes are deregulated in CCl4 -induced cirrhosis but their normal expression levels are recovered upon treatment with IFC-305, an adenosine derivative. We observed that adenosine was able to modulate S-adenosylmethionine-dependent trans-methylation reactions, and recently, we found that IFC-305 modulates HDAC3 expression. Here, we investigated whether epigenetic mechanisms, involving DNA methylation processes and histone acetylation, could explain the re-establishment of gene expression mediated by IFC-305 in cirrhosis. Therefore, Wistar rats were CCl4 treated and a sub-group received IFC-305 to reverse fibrosis. Global changes in DNA methylation, 5-hydroxymethylation, and histone H4 acetylation were observed after treatment with IFC-305. In particular, during cirrhosis, the Pparg gene promoter is depleted of histone H4 acetylation, whereas IFC-305 administration restores normal histone acetylation levels which correlates with an increase of Pparg transcript and protein levels. In contrast, the promoter of Col1a1 gene is hypomethylated during cirrhosis but gains DNA methylation upon treatment with IFC-305 which correlates with a reduction of Col1a1 transcript and protein levels. Our results suggest a model in which cirrhosis results in a general loss of permissive chromatin histone marks which triggers the repression of the Pparg gene and the upregulation of the Col1a1 gene. Treatment with IFC-305 restores epigenetic modifications globally and specifically at the promoters of Pparg and Col1a1 genes. These results reveal one of the mechanisms of action of IFC-305 and suggest a possible therapeutic function in cirrhosis. J. Cell. Biochem. 9999: 1-13, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. The End-Organ Impairment in Liver Cirrhosis: Appointments for Critical Care

    PubMed Central

    Figueiredo, Antonio; Romero-Bermejo, Francisco; Perdigoto, Rui; Marcelino, Paulo

    2012-01-01

    Liver cirrhosis (LC) can lead to a clinical state of liver failure, which can exacerbate through the course of the disease. New therapies aimed to control the diverse etiologies are now more effective, although the disease may result in advanced stages of liver failure, where liver transplantation (LT) remains the most effective treatment. The extended lifespan of these patients and the extended possibilities of liver support devices make their admission to an intensive care unit (ICU) more probable. In this paper the LC is approached from the point of view of the pathophysiological alterations present in LC patients previous to ICU admission, particularly cardiovascular, but also renal, coagulopathic, and encephalopathic. Infections and available liver detoxifications devices also deserve mentioning. We intend to contribute towards ICU physician readiness to the care for this particular type of patients, possibly in dedicated ICUs. PMID:22666568

  5. Autoimmune hepatitis-primary biliary cirrhosis concurrent with biliary stricture after liver transplantation.

    PubMed

    Kang, Yong-Zhen; Sun, Xiao-Ye; Liu, Yi-He; Shen, Zhong-Yang

    2015-02-21

    Although the development of de novo autoimmune liver disease after liver transplantation (LT) has been described in both children and adults, autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome has rarely been seen in liver transplant recipients. Here, we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic steatohepatitis. His liver function tests became markedly abnormal 8 years after LT. Standard autoimmune serological tests were positive for anti-nuclear and anti-mitochondrial antibodies, and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant tacrolimus. Liver biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis, which confirmed the diagnosis of AIH-PBC overlap syndrome. We believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome; a novel type of autoimmune overlap syndrome.

  6. The molecular basis of susceptibility to infection in liver cirrhosis.

    PubMed

    Chavez-Tapia, Norberto C; Torre-Delgadillo, Aldo; Tellez-Avila, Felix I; Uribe, Misael

    2007-01-01

    There is much clinical evidence of a relationship between infectious disease and chronic liver disease. The consequences of this adverse association have been described and advances in the treatment and prophylaxis of infectious disease have had an important effect on the management of patients with chronic liver disease. The association between infectious disease and chronic liver disease involves altered cytokine production, cellular immunity, and vascular response. However, there is little information on the mechanisms underlying these phenomena. In this report, we review the mechanistic basis of this common association.

  7. Platelet count increase following phlebotomy in iron overloaded patients with liver cirrhosis.

    PubMed

    Franchini, Massimo

    2003-08-01

    Thrombocytopenia is a frequent hematological complication in patients with liver cirrhosis, but its pathogenesis is not clearly understood. We evaluated the effect of iron depletion by phlebotomy on platelet count in 62 consecutive iron overloaded patients with liver cirrhosis and thrombocytopenia. After a median follow-up of 30.2 months we observed a significant increase of platelet count in all patients (from mean baseline levels of 110.1 up to 168.22109/l at the end of follow-up, P<0.001) with platelet count normalization in 42 of them (67.7%). In addition, we observed a significant improvement of serum ALT levels (from pretreatment mean values of 126.7 up to 59.7 U/l at the end of follow-up, P<0.001) along with the reduction of serum ferritin levels and transferrin saturation during phlebotomy. Different pathogenetic mechanisms involving both humoral (erythropoietin and thrombopoietin, TPO) and physical (portal hypertension and hypersplenism) factors are here discussed to explain the platelet count increase following phlebotomy. Our results show that phlebotomy is effective not only in lowering iron overload, but also in improving liver function and thrombocytopenia in patients with liver cirrhosis.

  8. Prevalence of cholelithiasis in patients subjected to liver transplantation for cirrhosis.

    PubMed

    Coelho, Julio Cu; Slongo, Julio; Dambroski Silva, Andrea; Dudeque Andriguetto, Leonardo; Ramos, Eduardo Jb; da Costa, Marco Ar; Matias, Jorge Ef

    2010-12-01

    The prevalence of cholelithiasis in patients subjected to liver transplantation has not been evaluated yet. This study examines the prevalence of cholelithiasis in patients subjected to liver transplantation due to cirrhosis compared to an age- and sex-matched control group. The electronic study protocols of 400 consecutive cirrhotic patients aged between 20 and 69 years who had undergone liver transplantation for cirrhosis were evaluated to determine the presence of gallstones. The overall prevalence of cholelithiasis was higher in transplant recipients (96 patients; 24%) than in controls (38 patients; 9.5%) (p<0.001). There was no increase in the prevalence of cholelithiasis with age in the transplant recipients (p=0.332). Conversely, the prevalence of cholelithiasis increased with age in the control group (p<0.001). There was no difference in the gallstone prevalence between sexes in the transplant recipient group (p=0.102). However, the gallstone prevalence was 2.2 times higher in females (14.8%) than in males (6.8%) in the control group (p=0.009). Prevalence of cholelithiasis is higher in patients subjected to liver transplantation for cirrhosis. In contrast with the general population, the prevalence of cholelithiasis in cirrhotic patients is similar in both sexes and does not increase with age.

  9. Portal-systemic encephalopathy in two patients without liver cirrhosis and portal hypertension.

    PubMed

    K C, Sudhamshu; Matsutani, Shoichi; Maruyama, Hitoshi; Fukamachi, Tadahiro; Nomoto, Hiromasa; Akiike, Taro; Ebara, Masaaki; Saisho, Hiromitsu

    2002-06-01

    The portal-systemic venous shunt is uncommon in patients without portal hypertension. We present two cases of portal-systemic encephalopathy due to extrahepatic shunt without liver cirrhosis and portal hypertension. Two women in their seventies were admitted to our hospital because of recurrent episodes of altered sensorium, drowsiness, slurred speech, disorientation, asterexis and high blood ammonia levels. There was no history of abdominal surgery or abdominal trauma. Clinical examination revealed no signs of portal hypertension or stigmata of chronic liver diseases. Brain CT and MRI scanning were unremarkable except for a high intensity signal in the basal ganglia on T1 weighted MRI images. Laboratory tests were almost normal except for the hyperammonemia occurring on several occasions. There was no evidence of liver cirrhosis by imaging. However, color Doppler showed an extra-hepatic shunt in both patients and pulsed Doppler showed decreased velocity and volume of the portal venous flow. These sonographic findings were confirmed during percutaneous transhepatic portography (PTP). Portal pressures measured during PTP were 9 and 11 mmHg. Needle biopsy ruled out idiopathic portal hypertension and liver cirrhosis. The diagnosis was portal systemic encephalopathy due to extra-hepatic portosystemic venous shunting. Both patients were treated by embolization of the shunting vessel with metallic coils.

  10. [Autoimmune hemolytic anemia and posthepatitis-C liver cirrhosis].

    PubMed

    Espinosa Berenguel, J L; Muñoz Sánchez, J A

    1997-11-01

    Here we are presenting the case of a 70-years-old woman who has hepatic cirrhosis anti-HCV and insulin-dependent diabetes mellitus, without relevant epidemiologic ascendants or previous transfusions and HBV, HIV negatives. On admission to our hospital she showed signs of autoimmune hemolytic anaemia (AHA) which was confirmed by positive direct Coombs test and an improvement in blood test after corticoid treatment. Having discarded other possible causes such as drugs infectious diseases or essential mixed cryoglobulinemia (CME), we put forward the possible association between AHA and infection by HCV, where AHA was an extrahepatic immunological manifestation of HCV. This fact has never been brought to light in previous medical literature.

  11. Hyperammonemia Is Associated with Increasing Severity of Both Liver Cirrhosis and Hepatic Encephalopathy

    PubMed Central

    Ayub, Maimoona; Khan, Wazir Mohammad

    2016-01-01

    Background. Hyperammonemia resulting from chronic liver disease (CLD) can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was 42.33 ± 7.60. The mean duration (years) of CLD was 10.15 ± 3.53 while the mean Child-Pugh (CP) score was 8.84 ± 3.30. Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE). The frequency of hyperammonemia was 67.3%, more frequent in males (N = 81, z-score = 2.4, and P < 0.05) than in females (N = 34, z-score = 2.4, and P < 0.05), and had a statistically significant relationship with increasing CP grade of cirrhosis (χ2(2) = 27.46, P < 0.001, Phi = 0.40, and P < 0.001). Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; P < 0.001. Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy. PMID:27847646

  12. Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

    PubMed Central

    Reichen, J; Egger, B; Ohara, N; Zeltner, T B; Zysset, T; Zimmermann, A

    1988-01-01

    We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCl4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrahepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver. PMID:3198765

  13. Systemic hemodynamics in advanced cirrhosis: Concerns during perioperative period of liver transplantation

    PubMed Central

    Hori, Tomohide; Ogura, Yasuhiro; Onishi, Yasuharu; Kamei, Hideya; Kurata, Nobuhiko; Kainuma, Motoshi; Takahashi, Hideo; Suzuki, Shogo; Ichikawa, Takashi; Mizuno, Shoko; Aoyama, Tadashi; Ishida, Yuki; Hirai, Takahiro; Hayashi, Tomoko; Hasegawa, Kazuko; Takeichi, Hiromu; Ota, Atsunobu; Kodera, Yasuhiro; Sugimoto, Hiroyuki; Iida, Taku; Yagi, Shintaro; Taniguchi, Kentaro; Uemoto, Shinji

    2016-01-01

    Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation (LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow (PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green (ICG) kinetics reflect the patient’s functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant (kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT. PMID:27660671

  14. Assessing current nutritional status of patients with HCV-related liver cirrhosis in the compensated stage.

    PubMed

    Yasutake, Kenichiro; Bekki, Machiko; Ichinose, Masako; Ikemoto, Michiko; Fujino, Tatsuya; Ryu, Tomoki; Wada, Yoshiyuki; Takami, Yuko; Saitsu, Hideki; Kohjima, Motoyuki; Fukuizumi, Kunitaka; Nakashima, Manabu; Nakamuta, Makoto; Enjoji, Munechika

    2012-01-01

    Nutritional states of Japanese patients with liver cirrhosis have recently shown great diversity, some show protein energy malnutrition and others excessive nutrition and obesity. For there to be adequate guidance regarding dietary treatment, it is important that a patient's current nutritional state be clarified. We assessed nutritive intake in Japanese cirrhotic patients and determined their nutritional problems. Subjects were non-hospitalized patients with hepatitis C virus (HCV)-related cirrhosis in the compensated stage (n=47), chronic hepatitis C (n=46) or healthy volunteers (n=32). A brief self-administered diet history questionnaire was conducted with assistance from a registered dietitian. We categorized patients with cirrhosis according to daily intake of energy and protein; 10.6% had an energy and protein intake within a normal range, 72.4% showed excessive intake, and 17.0% showed insufficient intake of energy or protein. In cirrhotic patients with diabetic complications, the intake levels of energy, proteins, fat and carbohydrates were significantly higher than in patients without diabetes. Moreover, cirrhotic patients had significantly higher intake levels of energy, protein and fat than did chronic hepatitis C patients and healthy individuals. In patients with HCV-related liver cirrhosis, insufficient intake of energy and protein was shown in some, while many, especially those with diabetes, showed excessive intake. For nutritive management of cirrhotic patients, the intake of various nutrients should be appropriately assessed and effective nutritional education systems established.

  15. Dynamic study of rectally absorbed ammonia in liver cirrhosis using (13N)ammonia and a positron camera

    SciTech Connect

    Koen, H.; Okuda, K.; Musha, H.; Tateno, Y.; Fukuda, N.; Matsumoto, T.; Shisido, F.; Rikitake, T,; Iinuma, T.; Kurisu, A.; Arimizu, N.

    1980-11-01

    (13N)Ammonia produced by the cyclotron was instilled intrarectally in patients with cirrhosis and other liver diseases to study the turnover of rectally absorbed (12N)ammonia. In the control, (13N)ammonia was absorbed quickly and visualized the liver, whereas in patients with cirrhosis, the lungs and heart were first visualized, and 13N activity over the head was also higher. It was suggested that a large proportion of absorbed (13N)ammonia bypassed hepatocytes and reached peripheral tissues in cirrhosis. The heart/liver ratio of 13N and 13N over the head were correlated with various indices of portal hypertension. The relative proportion of nonammonia 13N metabolites in blood was lower at 5 and 15 min after administration in cirrhosis, suggesting a reduced capacity of the liver to remove and metabolize ammonia.

  16. A liver cirrhosis classification on B-mode ultrasound images by the use of higher order local autocorrelation features

    NASA Astrophysics Data System (ADS)

    Sasaki, Kenya; Mitani, Yoshihiro; Fujita, Yusuke; Hamamoto, Yoshihiko; Sakaida, Isao

    2017-02-01

    In this paper, in order to classify liver cirrhosis on regions of interest (ROIs) images from B-mode ultrasound images, we have proposed to use the higher order local autocorrelation (HLAC) features. In a previous study, we tried to classify liver cirrhosis by using a Gabor filter based approach. However, the classification performance of the Gabor feature was poor from our preliminary experimental results. In order accurately to classify liver cirrhosis, we examined to use the HLAC features for liver cirrhosis classification. The experimental results show the effectiveness of HLAC features compared with the Gabor feature. Furthermore, by using a binary image made by an adaptive thresholding method, the classification performance of HLAC features has improved.

  17. Peribiliary Gland Dilatation in Cirrhosis: Relationship with Liver Failure and Stem Cell/Proliferation Markers.

    PubMed

    Goossens, Nicolas; Breguet, Romain; De Vito, Claudio; Terraz, Sylvain; Lin-Marq, Nathalie; Giostra, Emiliano; Rubbia-Brandt, Laura; Spahr, Laurent

    2017-03-01

    Dilated peribiliary glands (PBG) in patients with cirrhosis are often an incidental finding although their significance and physiopathology remain unclear. We aimed to identify clinical factors associated with dilated PBG and to perform a detailed morphometric assessment of dilated PBG in cirrhotic patients undergoing liver transplantation (LT). All consecutive cirrhotic patients undergoing LT at our institution between October 2006 and October 2011 were assessed for inclusion. Ten non-cirrhotic patients were included as controls. We performed morphometrical assessment of PBG, assessed baseline clinical factors associated with dilated PBG, immunohistochemistry staining with CK-19, MiB-1 and EpCAM, and radiological assessment of all available cases. Seventy-one patients met the inclusion criteria, 24% had PBG dilatation of >1000 µm. On multivariable analysis, MELD (OR 1.11 per unit increase in MELD, p = 0.004) was the only significant factor associated with dilated PBG. Compared to PBG < 1000 µm, large PBG had a higher proportion of EpCAM-positive (69 vs. 28%, p < 0.001) and MiB-1-positive lining cells (2.8 vs. 0.55%, p = 0.036). Computed tomography and magnetic resonance imaging had high specificity but low sensitivity for the diagnosis of dilated PBG > 1000 µm (specificity 90-100%, sensitivity 25-29%). Dilated PBGs are a common finding in explants of cirrhotic subjects undergoing LT and are associated with liver failure although diagnostic performance of cross-sectional imaging is inconstant. The high number of proliferative and EpCAM-positive cells lining the PBG may suggest a role of PBG in organ repair during liver failure.

  18. Expression of leptin and leptin receptor during the development of liver fibrosis and cirrhosis.

    PubMed

    Otte, C; Otte, J-M; Strodthoff, D; Bornstein, S R; Fölsch, U R; Mönig, H; Kloehn, S

    2004-01-01

    Leptin is involved in the regulation of food intake and is mainly secreted by adipocytes. Major secretagogues are cytokines such as TNF-alpha or IL-1. Leptin in turn upregulates inflammatory immune responses. Elevated leptin serum levels have been detected in patients with liver cirrhosis, a disease frequently associated with elevated levels of circulating cytokines as well as hypermetabolism and altered body weight. Recently, leptin has been detected in activated hepatic stellate cells in vitro and an involvement of leptin in liver fibrogenisis has been suggested. The current study was designed to further clarify the role of leptin in liver disease by characterizing leptin and leptin receptor expression in the development and onset of experimental liver fibrosis. Liver fibrosis and cirrhosis was induced in rats by use of phenobarbitone and increasing doses of CCl (4). Leptin and leptin receptor mRNA expression was determined by semiquantitative RT-PCR, protein expression by Western blot analysis and localization of leptin and its receptor by immunohistochemistry. Normal liver tissue does not express leptin, but leptin receptor mRNA. Increasing levels of leptin mRNA were detected in fibrotic and cirrhotic livers correlated to the degree of fibrosis. Leptin receptor mRNA expression was not significantly altered in damaged livers. Increasing levels of leptin were detected in fibrotic and cirrhotic livers, whereas protein expression of the receptor remained unchanged. Throughout different stages of liver fibrosis, leptin immunoreactivity was localized in activated hepatic stellate cells only, whereas immunoreactivity for the receptor was mainly seen on hepatocytes. In conclusion, leptin is expressed at increasing levels in activated hepatic stellate cells in vivo, which may therefore be a source of increased leptin tissue and serum levels contributing to the pathophysiology and morphological changes of chronic liver disease.

  19. Curcumin Protects Against Intestinal Origin Endotoxemia in Rat Liver Cirrhosis by Targeting PCSK9.

    PubMed

    Cai, Yu; Lu, Di; Zou, Yanting; Zhou, Chaohui; Liu, Hongchun; Tu, Chuantao; Li, Feng; Liu, Lili; Zhang, Shuncai

    2017-03-01

    Intestinal origin endotoxemia always occurs in severe liver injury. The aim of the current study was to test antiendotoxemia effect of curcumin on tetrachloride (CCl4 )-induced liver cirrhosis rats, and to elucidate the underlying molecular mechanism. Rat cirrhosis models were constructed with CCl4 subcutaneous injections with curcumin (200 mg/kg/d) administered via gavages for 12 wk until the rats were sacrificed. We found that the administration of curcumin improved the physiological condition pertaining to activity index and temperature, and ameliorated the liver injury in CCl4 -induced cirrhosis rats. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR) showed that curcumin could reduce c-reaction protein levels and inflammatory cytokine (TNF-α, IL-1β, IL-6, and CINC-1/IL-8) concentrations in peripheral serum and liver tissue. Furthermore, curcumin treatment decreased lipopolysaccharide (LPS) levels in peripheral vein, but not in portal vein. As low-density lipoprotein receptor (LDLR) is the important receptor on the surface of hepatocyte during LPS detoxification process, we used qRT-PCR, western blot, and immunohistochemistry (IHC), finding that curcumin significantly increased LDLR protein levels, but not gene levels in the liver tissues. We also tested proprotein convertase subtilisin/kexin type 9 (PCSK9), one negative regulator of LDLR, by qRT-PCR, western blot, and IHC. The results showed that PCSK9 significantly decreased both gene and protein levels in the rat liver tissues of curcumin treatment. Thus, we concluded that curcumin could function to protect against intestinal origin endotoxemia by inhibiting PCSK9 to promote LDLR expression, thereby enhancing LPS detoxification as one pathogen lipid through LDLR in the liver. © 2017 Institute of Food Technologists®.

  20. The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

    PubMed Central

    Arrieta, Oscar; Cacho, Bernardo; Morales-Espinosa, Daniela; Ruelas-Villavicencio, Ana; Flores-Estrada, Diana; Hernández-Pedro, Norma

    2007-01-01

    Background Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. Methods We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. Results For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. Conclusion The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng

  1. [MALT lymphoma of the left lacrimal and mammary glands, liver cirrhosis caused by HCV and type II cryoglobulinemia].

    PubMed

    Cirasino, L; Guatteri, A; Sandri, L; Baudo, F; Silvani, A; Morra, E

    1998-02-01

    We describe a case of MALT (mucosa-associated lymphoid tissue) lymphoma associated to post-hepatitis C liver cirrhosis, type II cryoglobulinaemia, gastrointestinal bleedings and thromboses. HCV infection justified the association between the first three pathologies, while gastrointestinal bleedings and thromboses were respectively attributed to portal hypertension secondary to liver cirrhosis and to some thrombophilic conditions. Among the latter there was also an antithrombin III deficiency. The singularity of the case and some difficulties met in its treatment, justify the report.

  2. Primary biliary cirrhosis.

    PubMed

    Carey, Elizabeth J; Ali, Ahmad H; Lindor, Keith D

    2015-10-17

    Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options.

  3. Primary biliary cirrhosis

    MedlinePlus

    ... medlineplus.gov/ency/article/000282.htm Primary biliary cirrhosis To use the sharing features on this page, ... and leads to scarring of the liver called cirrhosis. This is called biliary cirrhosis. Causes The cause ...

  4. Alcoholic chronic pancreatitis and alcoholic liver cirrhosis: differences in alcohol use habits and patterns in Indian subjects.

    PubMed

    Veena, Ambadiyil Balan; Rajesh, Gopalakrishna; Varghese, Joye; Sundaram, Karimassery Ramaiyer; Balakrishnan, Vallath

    2012-07-01

    Alcohol abuse is a risk factor for both liver cirrhosis and chronic pancreatitis. However, less than 15% of heavy drinkers develop these complications. Coexistence of cirrhosis and pancreatitis in the same patient is considered uncommon. We compared drinking patterns and related patient factors in patients with alcoholic liver cirrhosis and alcoholic chronic pancreatitis. A prospective evaluation of 307 patients (all men: 188 with alcoholic liver cirrhosis and 119 with alcoholic chronic pancreatitis) was conducted over a 7-year period using a detailed alcohol assessment proforma. Assessment of demographic features, diet, and other habits like tobacco smoking were recorded. Patients with alcoholic liver cirrhosis were older. The mean ± SD age in alcoholic liver cirrhosis was 52.4 ± 9.16 years and 47.1 ± 9.78 years (P < 0.001) in alcoholic chronic pancreatitis. The mean ± SD age when they started drinking was similar in both groups (22.8 ± 5.32 years and 24.3 ± 6.94; P > 0.05). The mean ± SD duration of drinking was higher in the cirrhosis group (29.5 ± 10.25 years) than in the pancreatitis group (21.5 ± 9.61 years) (P < 0.001). Fifty-nine percent of cirrhosis and 75% of pancreatitis were heavy tobacco smokers (P = 0.004). There are distinct differences in drinking patterns and related patient factors between alcoholic liver cirrhosis and alcoholic chronic pancreatitis, suggesting the need to orient different interventional strategies.

  5. [Gender difference of clinical features in Japanese patients with alcoholic liver cirrhosis].

    PubMed

    Kawashima, Osamu; Ohata, Mitsuru; Sakamoto, Kazuhiko; Hashimoto, Kenichi; Nakajima, Hisato; Yamauchi, Masayoshi

    2003-02-01

    Gender difference of alcohol intake and laboratory data was investigated in 165 Japanese patients with alcoholic liver cirrhosis. Mean age of first drinking and habitual drinking were higher in female. Duration of drinking was shorter in female. Although cumulative alcohol intake was larger in male, mean daily alcohol intake did not differ in both gender. Moreover, daily alcohol intake adjusted to body weight was significantly larger in female. Body mass index, serum levels of total protein, albumin and cholinesterase were significantly decreased in female. Platelet counts on admission did not differ in both gender. However, it was significantly increased in female after one month abstinence. C reactive protein, ammonia and serum levels of total bilirubin were significantly higher in female as compared to male. In conclusion, female alcoholics seems to progress to liver cirrhosis earlier because of high daily alcohol intake adjusted to body weight, poor nutritional condition and inflammation caused by endotoxin.

  6. Multiple Brain Abscesses Due to Aspergillus Fumigatus in a Patient With Liver Cirrhosis: A Case Report.

    PubMed

    Tang, Hung-Jen; Liu, Wei-Lun; Chang, Tsung Chain; Li, Ming-Chi; Ko, Wen-Chien; Wu, Chi-Jung; Chuang, Yin-Ching; Lai, Chih-Cheng

    2016-03-01

    Invasive cerebral aspergillosis always developed in immunocompromised host. Early diagnosis may save life in this critical condition; however, it is difficult to reach. Herein, we presented an unusual case of invasive cerebral aspergillosis in a cirrhotic patient. A 47-year-old man presented with progressive deterioration of consciousness for three days. The patient had a history of alcoholic liver cirrhosis, Child-Pugh class C. Magnetic resonance imaging (MRI) of brain showed multi-focal parenchymal lesions, which was consistent with multiple brain abscesses. The diagnosis of invasive cerebral aspergillosis was made by molecular based laboratory methods including Aspergillus galactomannan antigen assay and oligonucleotide array. Despite treatment with the antifungal agent, Amphotericin B, the patient died at the ninth day of hospitalization. Our findings suggest that liver cirrhosis can be one of risk factors of invasive cerebral aspergillosis, and support the diagnosing usefulness of MRI, Aspergillus galactomannan antigen assay, and oligonucleotide array.

  7. The relationship between aminopyrine breath test and severity of liver disease in cirrhosis

    SciTech Connect

    Morelli, A.; Narducci, F.; Pelli, M.A.; Farroni, F.; Vedovelli, A.

    1981-08-01

    Twenty-two patients with cirrhosis were evaluated by the 2 hr.-(C14)-aminopyrine breath test, the conventional liver tests and two systems for grading the severity of liver disease. Twenty-three patients with noncirrhotic liver disease and 15 controls were also studied. Reduced 14CO2 values were found in 21 of the 22 cirrhotic patients and seven of those had noncirrhotic liver disease associated with severe functional reserve impairment. The values in patients with minor liver diseases or cholestasis were normal. In the cirrhotic patients 2 hr.-(C14)-aminopyrine breath test scores correlated with prothrombin time, retention of bromosulfalein, fasting serum bile acid, albumin, bilirubin, serum aspartate aminotransferase and, above all, with the scores of the two clinical rating systems. The 2 hr.-(C14)-aminopyrine breath test was superior to conventional tests in quantifying the degree of hepatic functional reserve and forecasting the prognosis.

  8. Mössbauer studies of hemoglobin of the patients with liver cancer and cirrhosis

    NASA Astrophysics Data System (ADS)

    Ni, Xinlei; Hsia, Yuanfu; Liu, Rongchuan; Lu, Qingyou; Huang, Runsheng; Sun, Yunhan; Wang, Quanxing; Long, Jianxui

    1992-04-01

    Red blood cells (RBC) of the patients with primary liver cancer and with cirrhosis were investigated by using Mössbauer spectroscopy. Control measurements were carried out on RBC from normal adults. The Mössbauer spectra of normal RBC are composed of two doublets corresponding to deoxy-Hb and Oxy-Hb. Besides disappearance or a decrease of the doublets corresponding to deoxy-Hb, no additional peak was detected in the samples from the patients.

  9. Recumbent deoxygenation in mild/moderate liver cirrhosis: the "clinodeoxia". The ortho-clino paradigm.

    PubMed

    Polverino, Francesca; Santoriello, Carlo; Andò, Filippo; Girbino, Giuseppe; Cappetta, Donato; D'Agostino, Bruno; Vatrella, Alessandro; Polverino, Mario; Milic-Emili, Joseph

    2014-07-01

    While the effects of postural change on arterial oxygenation have been well documented in normal subjects, and attributed to the relationship of closing volume (CV) to the tidal volume, in liver cirrhosis such postural changes have been evaluated mainly in a rare, peculiar clinical end-stage condition which is characterized by increased dyspnea shifting from supine to upright position ("platypnea"). The latter is associated with worsening of PaO2 ("orthodeoxia"). We evaluated the effects of postural changes on arterial oxygenation in patients affected by mild/moderate liver cirrhosis. We performed pulmonary function tests and arterial blood gas evaluation in sitting and supine positions in 22 patients with mild/moderate liver cirrhosis, biopsy-proved, and 22 matched non-smokers control subjects. Recumbency elicited a decrease of PaO2 (Δ(sup-sit)PaO2) in 19 out of 22 controls and in all but one cirrhotics. The magnitude of this postural change was significantly (p = 0.04) greater in cirrhotics (9.6 ± 5.3%) compared to controls (6.7 ± 3.7%). In the subset of cirrhotics younger than 60 yrs and with PaO2 greater than 80 mmHg in sitting position, the Δ(sup-sit)PaO2 in recumbency further increased to 12 ± 5.8%, significantly (p = 0.014) greater than in same subgroup of controls (7.1 ± 3.8%). In mild/moderate liver cirrhosis the postural variations in PaO2 follow the normal trends, but are of greater magnitude probably as a consequence of hypoventilated units of lung for postural and disease-linked tidal airway closure, resulting in more pronounced recumbent hypoxemia ("clinodeoxia"). Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Contemporary concepts of the medical therapy of portal hypertension under liver cirrhosis

    PubMed Central

    Garbuzenko, Dmitry Victorovich

    2015-01-01

    Severe complications of liver cirrhosis are mostly related to portal hypertension. At the base of the pathogenesis of portal hypertension is the increase in hepatic vascular resistance to portal blood flow with subsequent development of hyperdynamic circulation, which, despite of the formation of collateral circulation, promotes progression of portal hypertension. An important role in its pathogenesis is played by the rearrangement of vascular bed and angiogenesis. As a result, strategic directions of the therapy of portal hypertension under liver cirrhosis include selectively decreasing hepatic vascular resistance with preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis, while striving to reduce the hepatic venous pressure gradient to less than 12 mmHg or 20% of the baseline. Over the last years, substantial progress in understanding the pathophysiological mechanisms of hemodynamic disorders under liver cirrhosis has resulted in the development of new drugs for their correction. Although the majority of them have so far been investigated only in animal experiments, as well as at the molecular and cellular level, it might be expected that the introduction of the new methods in clinical practice will increase the efficacy of the conservative approach to the prophylaxis and treatment of portal hypertension complications. The purpose of the review is to describe the known methods of portal hypertension pharmacotherapy and discuss the drugs that may affect the basic pathogenetic mechanisms of its development. PMID:26034348

  11. The Effect of Transjugular Intrahepatic Portosystemic Shunt on Platelet Counts in Patients With Liver Cirrhosis

    PubMed Central

    Zein, Nizar N.

    2017-01-01

    Thrombocytopenia is a well-known complication of liver cirrhosis. Although the pathogenesis of thrombocytopenia is not well understood, splenic congestion resulting from portal hypertension is considered the most significant underlying mechanism. Therapeutic measures that lower portal hypertension, such as transjugular intrahepatic portosystemic shunt (TIPS), are expected to improve thrombocytopenia associated with liver cirrhosis. At present, there are few studies on the effect of TIPS on platelet counts, and the results are conflicting. This article assesses the effect of TIPS on thrombocytopenia associated with liver cirrhosis. Methods: Seventy-four patients with liver cirrhosis who were referred for TIPS were included in this study. Platelet counts were measured on 3 different occasions over a 3-month period prior to and following placement of TIPS. Thrombocytopenia was defined as a platelet count of 150,000/mm3 or less. Moderate thrombocytopenia was defined as a platelet count of 100,000/mm3 or less. Severe thrombocytopenia was defined as a platelet count of 50,000/mm3 or less. A significant increase in platelet count was defined as a 20% or higher increase from pre-TIPS values. The portosystemic pressure gradient (PSPG) was measured before and after placement of TIPS. The patency of the shunt was checked using Doppler ultrasound 24 hours and 3 months after the procedure. Results: Thirty-four of the 74 patients (46%) who underwent TIPS showed a significant increase in platelet count, with an average increase of 22% (P<.0005). Twenty-five of 40 patients (62%) with moderate thrombocytopenia showed a significant increase in platelet count, with an average increase of 36% (P<.0005). Patients with severe thrombocytopenia showed the greatest response to TIPS; 8 of 11 patients (73%) had a significant increase in platelet count (average increase, 55%; P<.0005). No correlation was found between the response to TIPS and age, sex, etiology of liver disease, pre-TIPS PSPG

  12. A semi-mechanistic model to predict the effects of liver cirrhosis on drug clearance.

    PubMed

    Johnson, Trevor N; Boussery, Koen; Rowland-Yeo, Karen; Tucker, Geoffrey T; Rostami-Hodjegan, Amin

    2010-03-01

    Liver cirrhosis is characterized by a decrease in functional hepatocytes, lowered circulating levels of plasma proteins and alterations in blood flow due to the development of portacaval shunts. Depending on the interplay between these parameters and the characteristics of an administered drug, varying degrees of impaired systemic clearance and first-pass metabolism are anticipated. The Simcyp Population-based ADME Simulator has already been used successfully to incorporate genetic, physiological and demographic attributes of certain subgroups within healthy populations into in vitro-in vivo extrapolation (IVIVE) of xenobiotic clearance. The objective of this study was to extend population models to predict systemic and oral drug clearance in relation to the severity of liver cirrhosis. Information on demographics, changes in hepatic blood flow, cytochrome P450 enzymes, liver size, plasma protein binding and renal function was incorporated into three separate population libraries. The latter corresponded to Child-Pugh scores A (mild), B (moderate) and C (severe) liver cirrhosis. These libraries, together with mechanistic IVIVE within the Simcyp Simulator, were used to predict the clearance of intravenous and oral midazolam, oral caffeine, intravenous and oral theophylline, intravenous and oral metoprolol, oral nifedipine, oral quinidine, oral diclofenac, oral sildenafil, and intravenous and oral omeprazole. The simulated patients matched the clinical studies as closely as possible with regard to demographics and Child-Pugh scores. Predicted clearance values in both healthy control and liver cirrhosis populations were compared with observed values, as were the fold increases in clearance values between these populations. There was good agreement (lack of statistically significant difference, two-tailed paired t-test) between observed and predicted clearance ratios, with the exception of those for two studies of intravenous omeprazole. Predicted clearance ratios were

  13. Liver cirrhosis in Malaysia: peculiar epidemiology in a multiracial Asian country.

    PubMed

    Qua, Choon-Seng; Goh, Khean-Lee

    2011-08-01

    To determine the etiology of liver cirrhosis and risk factors for hepatocellular carcinoma (HCC) in a multiracial Asian population. Consecutive patients with liver cirrhosis presenting to outpatient clinics and inpatient service at the University of Malaya Medical Centre from 1 April 2006 to 31 May 2009 were included. A total of 460 patients were included in the study: 317 male patients (68.9%) and 143 female patients (31.1%), with a mean age of 58.8years (range: 15-87years). The major causes of cirrhosis were: chronic hepatitis B, n=212, 46.1%; chronic hepatitis C, n=85, 18.5%; cryptogenic, n=71, 15.4%; alcohol, n=58, 12.6% and autoimmune, n=9, 2.0%. Alcohol was the main etiology in Indians (51.1%) compared to Malay (0%) and Chinese (4.4%) (both P<0.001). Hepatitis B was the predominant etiology in Malay (47.9%) and Chinese (58.8%) compared to Indians (5.6%) (both P<0.001). Hepatitis C cirrhosis was highest in Malays (25.0%). 136 patients (29.6%) had concurrent HCC. Male sex (P<0.001), age>60years (P=0.014), hepatitis B (P<0.001), hepatitis C (P=0.006) and cryptogenic cause (P=0.002) were found to be independent risk factors for HCC. The etiology of cirrhosis has a peculiar pattern based on racial differences in alcohol intake and in the prevalence of hepatitis B. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  14. Comparison of measured and predicted energy expenditure in patients with liver cirrhosis.

    PubMed

    Teramoto, Arisa; Yamanaka-Okumura, Hisami; Urano, Eri; Nakamura-Kutsuzawa, Taki; Sugihara, Kohei; Katayama, Takafumi; Miyake, Hidenori; Imura, Satoru; Utsunomiya, Tohru; Shimada, Mitsuo; Takeda, Eiji

    2014-01-01

    Obesity is a risk factor for the onset of liver cancer in patients with cirrhosis. To prevent overfeeding and obesity, estimation of energy requirement is important, but energy expenditure in patients with liver cirrhosis has not been fully elucidated. This study aimed to investigate resting energy expenditure (REE) and energy intake in patients with cirrhosis and determine adequate energy intake criteria. In this cross-sectional study, indirect calorimetry measurement was conducted in 488 Japanese inpatients with cirrhosis. We compared REE measured by indirect calorimetry (M-REE) with basal energy expenditure (BEE) predicted by the Harris-Benedict equation (H-BEE) and Dietary Reference Intakes (DRI) for Japanese (D-BEE). Mean M-REE (1256 kcal) was significantly lower than H-BEE (1279 kcal); however, it was not significantly different from D-BEE (1254 kcal). Mean M-REE expressed in relation to body weight (BW; REE/kg BW) was 21.7 kcal/kg BW. H-BEE was significantly higher than M-REE in patients in the first and second quartiles of BMI, and D-BEE was significantly different from MREE in patients in the highest and lowest quartiles of BMI. Average energy intake was 30.5 kcal/kg BW, which was 1.4 times greater than REE/kg BW. Although DRI is a useful tool for the estimation of REE in patients in the second and third quartiles of BMI, M-REE is recommended to ensure the provision of adequate nutritional care to patients with cirrhosis, including those in the highest and lowest quartiles of BMI.

  15. Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis

    SciTech Connect

    Angelico, M.; Alvaro, D.; Cantafora, A.; Masella, R.; Gaudio, E.; Gandin, C.; Ginanni Corradini, S.; Ariosto, F.; Riggio, O.; Capocaccia, L. )

    1991-07-01

    Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1{sup 14}Cpalmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls.

  16. The effect of liver iron deposition on hepatic apparent diffusion coefficient values in cirrhosis.

    PubMed

    Chandarana, Hersh; Do, Richard K G; Mussi, Thais C; Jensen, Jens H; Hajdu, Cristina H; Babb, James S; Taouli, Bachir

    2012-10-01

    The purpose of this study was to assess the effect of hepatic iron deposition on apparent diffusion coefficient (ADC) values measured with single-shot echo-planar imaging (EPI) diffusion-weighted MRI (DWI) in patients with liver cirrhosis and in vitro. Fifty-two patients with liver cirrhosis who underwent breath-hold single-shot EPI DWI at 1.5 T before liver transplantation were retrospectively assessed. Estimated signal-to-noise ratio (SNRest) and ADC were measured in the right hepatic lobe (for b values of 50 and 500 s/mm2). SNRest and ADC were compared between patients stratified by pathologic iron grade using the Mann-Whitney test. Hepatic ADC values were correlated to T2* values using the Spearman correlation test in a subset of patients. In addition, a phantom consisting of solutions of varying iron concentrations was imaged with single-shot EPI DWI and T2* imaging, and iron concentration was correlated with ADC and T2*. In phantoms, there was a decrease in ADC and T2* with increasing iron concentration (r=-0.95 and -0.92, respectively; p<0.05). Patients with hepatic siderosis had significantly lower SNRest and ADC compared with patients without siderosis (p<0.0001). SNRest at b=50 s/mm2 and b=500 s/mm2 and ADC had a significant negative correlation with pathologic iron grade (r=-0.67 to 0.77, p<0.0001). There was a significant correlation between liver T2* and ADC (r=0.83, p<0.0001). Hepatic siderosis lowers liver ADC and should be taken into account when using ADC for diagnosing liver cirrhosis.

  17. The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis.

    PubMed

    Hong, Young Mi; Yoon, Ki Tae; Heo, Jeong; Woo, Hyun Young; Lim, Won; An, Dae Seong; Han, Jun Hee; Cho, Mong

    2016-10-01

    Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding the prescription of analgesics in these patients. Therefore, we aimed to evaluate the prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Assessment Service database between January 1, 2012 and December 31, 2012. A total of 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more prescribed than acetaminophen even in decompensated cirrhosis compared with compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference in prescription preference between acetaminophen and NSAIDs among physicians. Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more frequently prescribed although they should be avoided. The prescription pattern of analgesics were different significantly among physicians in patients with liver cirrhosis. The harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians prescribing analgesics.

  18. The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis

    PubMed Central

    2016-01-01

    Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding the prescription of analgesics in these patients. Therefore, we aimed to evaluate the prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Assessment Service database between January 1, 2012 and December 31, 2012. A total of 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more prescribed than acetaminophen even in decompensated cirrhosis compared with compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference in prescription preference between acetaminophen and NSAIDs among physicians. Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more frequently prescribed although they should be avoided. The prescription pattern of analgesics were different significantly among physicians in patients with liver cirrhosis. The harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians prescribing analgesics. PMID:27550489

  19. 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

  20. Nanoparticle Based Delivery of Quercetin for the Treatment of Carbon Tetrachloride Mediated Liver Cirrhosis in Rats.

    PubMed

    Verma, Shashi Kant; Rastogil, Shweta; Arora, Indu; Javed, Kalim; Akhtar, Mohd; Samim, Mohd

    2016-02-01

    Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-β-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl₄)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability.

  1. Serum Concentrations of Selected Heavy Metals in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland.

    PubMed

    Prystupa, Andrzej; Błażewicz, Anna; Kiciński, Paweł; Sak, Jarosław J; Niedziałek, Jarosław; Załuska, Wojciech

    2016-06-13

    According to the WHO report, alcohol is the third most significant health risk factor for the global population. There are contrary reports about heavy metals concentrations in patients with alcoholic liver cirrhosis. The aim of this study was to investigate serum concentrations of selected heavy metals in patients with alcoholic liver cirrhosis living in the eastern part of Poland according to cirrhosis stage. The participants came from various hospitals of the Lublin region were enrolled. The study group included 46 male and 16 female patients. The control group consisted of 18 healthy individuals without liver disease. High Performance Ion Chromatography was used to determine the concentrations of metal ions (Cd, Zn, Cu, Ni, Co, Mn, and Pb) in serum samples. The concentrations of copper, zinc, nickel, and cobalt were found to be significantly lower in patients with alcoholic liver cirrhosis compared to the control group. The serum concentration of cadmium was significantly higher in patients with advanced alcoholic liver cirrhosis compared to the control group. We hypothesize that disorders of metabolism of heavy metals seem to be the outcome of impaired digestion and absorption, which are common in cirrhosis, improper diet, environmental and occupational exposure.

  2. Serum Concentrations of Selected Heavy Metals in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland

    PubMed Central

    Prystupa, Andrzej; Błażewicz, Anna; Kiciński, Paweł; Sak, Jarosław J.; Niedziałek, Jarosław; Załuska, Wojciech

    2016-01-01

    According to the WHO report, alcohol is the third most significant health risk factor for the global population. There are contrary reports about heavy metals concentrations in patients with alcoholic liver cirrhosis. The aim of this study was to investigate serum concentrations of selected heavy metals in patients with alcoholic liver cirrhosis living in the eastern part of Poland according to cirrhosis stage. The participants came from various hospitals of the Lublin region were enrolled. The study group included 46 male and 16 female patients. The control group consisted of 18 healthy individuals without liver disease. High Performance Ion Chromatography was used to determine the concentrations of metal ions (Cd, Zn, Cu, Ni, Co, Mn, and Pb) in serum samples. The concentrations of copper, zinc, nickel, and cobalt were found to be significantly lower in patients with alcoholic liver cirrhosis compared to the control group. The serum concentration of cadmium was significantly higher in patients with advanced alcoholic liver cirrhosis compared to the control group. We hypothesize that disorders of metabolism of heavy metals seem to be the outcome of impaired digestion and absorption, which are common in cirrhosis, improper diet, environmental and occupational exposure. PMID:27304961

  3. The PNPLA3 rs738409 148M/M Genotype Is a Risk Factor for Liver Cancer in Alcoholic Cirrhosis but Shows No or Weak Association in Hepatitis C Cirrhosis

    PubMed Central

    Luda, Carolin; Berg, Thomas; Müller, Tobias; Grünhage, Frank; Lammert, Frank; Coenen, Martin; Krämer, Benjamin; Körner, Christian; Vidovic, Natascha; Oldenburg, Johannes; Nattermann, Jacob; Sauerbruch, Tilman; Spengler, Ulrich

    2011-01-01

    Background An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC). Methods We compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV)-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection. Results PNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (p<0.001) increased in alcoholic cirrhosis with (53.7%) and without HCC (36.2%) but was not different between healthy controls (22.9%) and patients with cirrhosis (25.3%; p = 0.545) and HCC (30.2%; p = 0.071) due to hepatitis C. HCC risk was highest in 148M/M homozygous patients with alcoholic liver disease (odds ratio (OR) 16.8 versus healthy controls; 95% confidence interval (CI) 6.68–42.43, p<0.001). Finally, multivariate regression confirmed 148M/M homozygosity (OR 2.8; 95%-CI: 1.24–6.42; p = 0.013) as HCC risk factor in alcoholic cirrhosis. In HCV-related cirrhosis only HCV genotype 1 was confirmed as a HCC risk factor (OR 4.2; 95%-CI: 1.50–11.52; p = 0.006). Conclusion The PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that should

  4. [Two cases of rapidly progressive nephritic syndrome complicated with alcoholic liver cirrhosis].

    PubMed

    Kaneko, Tomohiro; Arima, Ryuji; Arakawa, Yusuke; Aoki, Michiko; Fukuda, Kumiko; Fukui, Megumi; Hirama, Akio; Fujita, Emiko; Mii, Akiko; Utsumi, Koichi; Shimizu, Akira; Iino, Yasuhiko

    2011-01-01

    It has been reported that glomerulosclerosis with IgA deposition is likely to be complicated with alcoholic liver cirrhosis. On the other hand, it is said that complications of nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN) are relatively rare. We experienced two patients with alcoholic liver cirrhosis complicated with RPGN syndrome who had obtained favorable outcomes through the use of steroids and immune system suppressors. Case 1 was a 55-year-old male. He was being treated for alcoholic liver cirrhosis, but as bloody urine was noticed macroscopically, his renal function rapidly decreased. Specimens from a renal biopsy showed endocapillary proliferative lesions accompanying necrotic lesions. Granular deposition of IgA (IgA1) and C3 was seen along the capillary walls and in the mesangial areas. After the combined treatments of bilateral palatotonsillectomy, three courses of steroid semi-pulse therapy and post-therapy with steroids and mizoribin (MZR)were started, his hematuria and proteinuria disappeared and renal function improved markedly. Case 2 was a 37-year-old male with alcoholic liver cirrhosis complicated with hepatic encephalopathy. Although he was being treated at another hospital, nephritic syndrome occurred with rapidly worsening renal function and massive ascites. After continuous drainage of the ascites, we performed a renal biopsy. Mild proliferative lesions and notable wrinkling, thickening and doubling of the basal membrane were seen. Crescent formations were found in about half of the glomeruli. The fluorescent antibody technique showed positive pictures of IgA (IgA1) and C3. When three courses of steroid semi-pulse therapy and post therapy with steroids and MZR were combined, his proteinuria and serum Cre level decreased and stagnated ascites markedly decreased. The two cases were diagnosed as having secondary IgA nephropathy induced by the deposition of the IgA1 derived mainly from the intestinal tract, which had increased

  5. Association of serum level of growth differentiation factor 15 with liver cirrhosis and hepatocellular carcinoma.

    PubMed

    Liu, Xiuying; Chi, Xiumei; Gong, Qiaoling; Gao, Lei; Niu, Yuqiang; Chi, Xiaojing; Cheng, Min; Si, Youhui; Wang, Maorong; Zhong, Jin; Niu, Junqi; Yang, Wei

    2015-01-01

    Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide. Currently, alpha-fetoprotein (AFP) is used as a standard serum marker for the detection of HCC, but its sensitivity and specificity are unsatisfactory, and optimal diagnostic markers for cirrhosis are lacking. We previously reported that growth differentiation factor 15 (GDF15) was significantly induced in HCV-infected hepatocytes. This study aimed to investigate GDF15 expression and its correlation with hepatitis virus-related liver diseases. A total of 412 patients with various liver diseases were studied. Healthy and Mycobacterium tuberculosis-infected subjects were included as controls. Serum and tissue GDF15 levels were measured. Serum GDF15 levels were significantly increased in patients with HCC (6.66±0.67 ng/mL, p<0.0001) and cirrhosis (6.51±1.47 ng/mL, p<0.0001) compared with healthy controls (0.31±0.01 ng/mL), though the GDF15 levels in HBV and HCV carriers were moderately elevated (1.34±0.19 ng/mL and 2.13±0.53 ng/mL, respectively). Compared with HBV or HCV carriers, GDF15 had a sensitivity of 63.1% and a specificity of 86.6% at the optimal cut-off point of 2.463 ng/mL in patients with liver cirrhosis or HCC. In HCC patients, the area under the receiver operating curve was 0.84 for GDF15 and 0.76 for AFP, but 0.91 for the combined GDF15 and AFP. Serum GDF15 levels did not significantly differ between the high-AFP and low-AFP groups. GDF15 protein expression in HCC was significantly higher than that in the corresponding adjacent paracarcinomatous tissue and normal liver. Using a combination of GDF15 and AFP will improve the sensitivity and specificity of HCC diagnosis. Further research and the clinical implementation of serum GDF15 measurement as a biomarker for HCC and cirrhosis are recommended.

  6. Prevalence of Iron deficiency anemia in children with liver cirrhosis: A cross-sectional study

    PubMed Central

    Zareifar, Soheila; Dehghani, Seyed Mohsen; Rahanjam, Najmeh; Farahmand Far, Mohammad Reza

    2015-01-01

    Background: Among the many complications reported for cirrhosis, iron deficiency anemia (IDA) has attracted much attention. This type of anemia, in contrast to other types of anemia, is easy to treat prophylactically, but if left untreated can lead to a poor quality of life. The aim of this study was to estimate the hemoglobin and serum iron levels among patients with liver cirrhosis for the early diagnosis of IDA and to avoid unnecessary testing and iron supplementation. Subjects and Methods: In this cross-sectional study, 88 children diagnosed with cirrhosis were included, and the values of hemoglobin, serum iron levels and relationship between serum iron (SI), total iron-binding capacity (TIBC), prothrombine time (PT), international normalization ratio (INR), total and direct bilirubin and hepatic enzymes were estimated using paired t test, Mann-Whitney, Chi-square and Kruskal-Wallis tests. Results: Forty-six (52.3%) of 88 children were girls and 42 (47.7%) were boys. Forty-eight (54.5%) patients had anemia and 8 (9%) had iron deficiency anemia (5 boys, 5.6%, and 3 girls, 3.4%). No relationships were observed between iron deficiency anemia and the patient’s age or gender, whereas there was a relationship between iron deficiency and severity and duration of the disease, although the correlation was not statistically significant. Conclusion: The high frequency of iron deficiency anemia in children with cirrhosis (9%) suggests that timely screening should be used for early diagnosis and treatment. PMID:26261697

  7. Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients

    PubMed Central

    Zhang, Xin; Wang, Shu-Zhen; Zheng, Jun-Fu; Zhao, Wen-Min; Li, Peng; Fan, Chun-Lei; Li, Bing; Dong, Pei-Ling; Li, Lei; Ding, Hui-Guo

    2014-01-01

    AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular carcinoma. METHODS: Thirty-nine patients (mean age 55 years, males: 32) with decompensated liver cirrhosis and refractory ascites were enrolled. All patients received a combination of tolvaptan (15 mg/d for 5-14 d) and diuretics (40-80 mg/d of furosemide and 80-160 mg/d of spironolactone). The etiology of cirrhosis included hepatitis B (69.2%), hepatitis C (7.7%) and alcohol-induced (23.1%). Changes in the urine excretion volume, abdominal circumference and edema were assessed. The serum sodium levels were also measured, and adverse events were recorded. A follow-up assessment was conducted 1 mo after treatment with tolvaptan. RESULTS: Tolvaptan increased the mean urine excretion volume (1969.2 ± 355.55 mL vs 3410.3 ± 974.1 mL, P < 0.001), and 89.7% of patients showed improvements in their ascites, 46.2% of whom showed significant improvements. The overall efficacy of tolvaptan in all patients was 89.7%; the efficacies in patients with hepatocellular carcinoma and hepatorenal syndrome were 84.2% and 77.8%, respectively. The incidence of hyponatremia was 53.8%. In patients with hyponatremia, the serum sodium levels increased after tolvaptan treatment (from 128.1 ± 4.22 mEq/L vs 133.1 ± 3.8 mEq/L, P < 0.001). Only mild drug-related adverse events, including thirst and dry mouth, were observed. CONCLUSION: Tolvaptan is a promising aquaretic for the treatment of refractory ascites in patients with decompensated liver cirrhosis. PMID:25170228

  8. Circulating vascular endothelial growth factor and its soluble receptors in patients with liver cirrhosis: possible association with hepatic function impairment.

    PubMed

    Jaroszewicz, Jerzy; Januszkiewicz, Marcin; Flisiak, Robert; Rogalska, Magdalena; Kalinowska, Alicja; Wierzbicka, Iwona

    2008-10-01

    Recent studies provided in vivo evidences of an increased angiogenesis in animal model of portal hypertension and cirrhosis which was linked to increased expression of vascular endothelial growth factor. The aim of study was to evaluate the plasma concentration of VEGF and its receptors in liver cirrhosis and the possible association with the degree of liver insufficiency. Methods. Vascular endothelial growth factor (VEGF) and its soluble receptors: sVEGF-R1, sVEGF-R2 were measured in plasma of 78 patients with liver cirrhosis by ELISA. Results. The significant increase of plasma VEGF and sVEGF-R1 was observed in liver cirrhosis compared to healthy individuals (153.1+/-51.9 vs. 46.8+/-4.1pg/mL, P<0.05; 279.8+/-34.3 vs. 105.1+/-5.9pg/mL, P<0.001, respectively). Plasma VEGF and foremost sVEGF R1 showed significant associations with biochemical indices of liver function. Among clinical parameters, only ascites revealed significant association with plasma VEGR and sVEGF-R1. VEGF and sVEGF-R1 were increased respectively to the degree of liver insufficiency. It was demonstrated through a significant positive correlation with Child-Pugh score and MELD classification. In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms.

  9. Neutrophil Gelatinase Associated Lipocalin (NGAL) – a biomarker of renal dysfunction in patients with liver cirrhosis: Do we have enough proof?

    PubMed Central

    Firu, SG; Streba, CT; Firu, D; Tache, DE; Rogoveanu, I

    2015-01-01

    Rationale. Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. Objective. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. Methods and results. We have searched through current literature and analyzed all significant full text articles on this topic. Discussions. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed. Abbreviations: ADQI = Acute Dialysis Quality Initiative, AKI = acute kidney injury, AKIN = Acute Kidney Injury Network, ATN = acute tubular necrosis, CKD = chronic kidney disease, Cys C = cystatin C, GFR = glomerular filtration rate, HRS = hepatorenal syndrome, IAC = International Ascites Club, IL-18 = interleukin-18, KIM-1 = kidney injury molecule-1, L-FABP = liver-type fatty acid-binding protein, LT = liver transplantation, MDRD6 = Modification of Diet in Renal Disease 6, NAG = N-acetyl-β-D-glucosaminidase, NGAL = Neutrophil Gelatinase-Associated Lipocalin, pi-GST = pi-glutathione S-transferase, PRA = prerenal azotemia, RBP = retinol binding protein, RRT = renal replacement therapies, SCr = serum creatinine, SLKT = simultaneous liver and kidney transplant, UO = urine output, γ-GT = γ-glutamyl transpeptidase PMID:26361506

  10. Liver stiffness predicts clinical outcome in human immunodeficiency virus/hepatitis C virus-coinfected patients with compensated liver cirrhosis.

    PubMed

    Merchante, Nicolás; Rivero-Juárez, Antonio; Téllez, Francisco; Merino, Dolores; José Ríos-Villegas, Maria; Márquez-Solero, Manuel; Omar, Mohamed; Macías, Juan; Camacho, Angela; Pérez-Pérez, Montserrat; Gómez-Mateos, Jesús; Rivero, Antonio; Antonio Pineda, Juan

    2012-07-01

    Our aim was to assess the predictive value of liver stiffness (LS), measured by transient elastography (TE), for clinical outcome in human immunodeficiency virus / hepatitis C virus (HIV/HCV)-coinfected patients with compensated liver cirrhosis. This was a prospective cohort study of 239 consecutive HIV/HCV-coinfected patients with a new diagnosis of cirrhosis, done by TE, and no previous decompensation of liver disease. The time from diagnosis to the first liver decompensation and death from liver disease, as well as the predictors of these outcomes, were evaluated. After a median (Q1-Q3) follow-up of 20 (9-34) months, 31 (13%, 95% confidence interval [CI]: 9%-17%) patients developed a decompensation. The incidence of decompensation was 6.7 cases per 100 person-years (95% CI, 4.7-9-6). Fourteen (8%) out of 181 patients with a baseline LS < 40 kPa developed a decompensation versus 17 (29%) out of 58 with LS ≥ 40 kPa (P = 0.001). Factors independently associated with decompensation were Child-Turcotte-Pugh (CTP) class B versus A (hazard ratio [HR] 7.7; 95% CI 3.3-18.5; P < 0.0001), log-plasma HCV RNA load (HR 2.1; 95% CI 1.2-3.6; P = 0.01), hepatitis B virus coinfection (HR, 10.3; 95% CI, 2.1-50.4; P = 0.004) and baseline LS (HR 1.03; 95% CI 1.01-1.05; P = 0.02). Fifteen (6%, 95% CI: 3.5%-9.9%) patients died, 10 of them due to liver disease, and one underwent liver transplantation. CTP class B (HR 16.5; 95% CI 3.4-68.2; P < 0.0001) and previous exposure to HCV therapy (HR 7.4; 95% CI 1.7-32.4, P = 0.007) were independently associated with liver-related death; baseline LS (HR 1.03; 95% CI 0.98-1.07; P = 0.08) was of borderline significance. LS predicts the development of hepatic decompensations and liver-related mortality in HIV/HCV-coinfection with compensated cirrhosis and provides additional prognostic information to that provided by the CTP score. Copyright © 2012 American Association for the Study of Liver Diseases.

  11. Sparse reconstruction of liver cirrhosis from monocular mini-laparoscopic sequences

    NASA Astrophysics Data System (ADS)

    Marcinczak, Jan Marek; Painer, Sven; Grigat, Rolf-Rainer

    2015-03-01

    Mini-laparoscopy is a technique which is used by clinicians to inspect the liver surface with ultra-thin laparoscopes. However, so far no quantitative measures based on mini-laparoscopic sequences are possible. This paper presents a Structure from Motion (SfM) based methodology to do 3D reconstruction of liver cirrhosis from mini-laparoscopic videos. The approach combines state-of-the-art tracking, pose estimation, outlier rejection and global optimization to obtain a sparse reconstruction of the cirrhotic liver surface. Specular reflection segmentation is included into the reconstruction framework to increase the robustness of the reconstruction. The presented approach is evaluated on 15 endoscopic sequences using three cirrhotic liver phantoms. The median reconstruction accuracy ranges from 0.3 mm to 1 mm.

  12. Serum Catecholamines and Dysautonomia in Diabetic Gastroparesis and Liver Cirrhosis

    PubMed Central

    Aslam, Naeem; Kedar, Archana; Nagarajarao, Harsha S.; Reddy, Kartika; Rashed, Hani; Cutts, Teresa; Riely, Caroline; Abell, Thomas L.

    2016-01-01

    Background Plasma catecholamine influences autonomic function and control, but there are few reports correlating them. In this study, 47 individuals (mean age, 38 years) were studied: 19 diabetes mellitus (DM) patients with gastroparesis, 16 with liver disease and 12 control subjects. Methods Noninvasive autonomic function was assessed for sympathetic adrenergic functions as peripheral vasoconstriction in response to cold stress test and postural adjustment ratio (PAR) and cholinergic function as Valsalva ratio, represented by change in R-R intervals. Measurements were compared by analysis of variance and Spearman’s correlation, and results were reported as mean ± standard error. Results Plasma norepinephrine (1902.7 ± 263.3; P = 0.001) and epinephrine (224.5 ± 66.5; P = 0.008) levels, as well as plasma dopamine levels (861.3 ± 381.7), and total plasma catecholamine levels were highest for patients with liver disease, who also had significant negative correlation between norepinephrine level and vasoconstriction (P = 0.01; r = −0.5), PAR1 (P = 0.01; r = −0.5), sympathetic adrenergic functions (P = 0.005; r = −0.6), total autonomic index (P = 0.01–0.5) and total autonomic function (P = 0.01; r = −0.2) and also negative correlation between epinephrine plasma level and total autonomic function (P = 0.04; r = 0.4). DM patients were next highest in norepinephrine level (133.26 ± 7.43), but lowest for plasma catecholamine; a positive correlation between dopamine level and PAR1 (P = 0.008; r = 0.6) was also seen in this group. Plasma dopamine levels and spider score correlated negatively (P = 0.04; r = −0.5) and total plasma catecholamine positively with encephalopathy (P = 0.04; r = 0.5) in patients with liver disease. Conclusions Plasma catecholamine levels correlated with adrenergic functions in control subjects and patients with DM and liver disease, with no significant correlation seen for cholinergic function. PMID:26181082

  13. Antifibrotic effect of total flavonoids of Astmgali Radix on dimethylnitrosamine-induced liver cirrhosis in rats.

    PubMed

    Cheng, Yang; Mai, Jing-Yin; Wang, Mei-Feng; Chen, Gao-Feng; Ping, Jian

    2017-01-01

    To study the effect of total flavonoids of Astmgali Radix (TFA) on liver cirrhosis induced with dimethylnitrosamine (DMN) in rats, and the effect on peroxisome proliferator-activated receptor γ (PPARγ), uncoupling protein 2 (UCP2) and farnesoid X receptor (FXR). Fifty-three Sprague-Dawley rats were randomly divided into a control group (10 rats) and a DMN group (43 rats). Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group (14 rats), a low-dosage TFA group (14 rats) and a high-dosage TFA group (15 rats) in the 3rd week. Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low- and high-TFA groups, respectively. At the end of the experiment blood and liver samples were collected. Serum liver function and liver tissue hydroxyproline content were determined. hematoxylin-eosin (HE), Sirus red and immunohistochemical stainings of collagen I, smooth muscle actin (α-SMA) was conducted in paraffinembedded liver tissue slices. Real time polymerase chain reaction (PCR) was adopted to determine PPARγ, UCP2 and FXR mRNA levels. Western blot was adopted to determine protein levels of collagen I, α-SMA, PPARγ, UCP2 and FXR. Compared with the model group, TFA increased the ratio of liver/body weight (low-TFA group P<0.05, high-TFA group P<0.01), improved liver biochemical indices (P<0.01 for ALT, AST, GGT in both groups, P<0.05 for albumin and TBil in the high-TFA group) and reduced liver tissue hydroxproline content (P<0.01 in both groups) in treatment groups significantly. HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition, alleviated formation and extent of liver pseudolobule. Collagen I and α-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group. TFA could increase PPARγ, it regulated target UCP2, and FXR levels significantly compared with the

  14. Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications.

    PubMed

    Nahon, Pierre; Bourcier, Valérie; Layese, Richard; Audureau, Etienne; Cagnot, Carole; Marcellin, Patrick; Guyader, Dominique; Fontaine, Hélène; Larrey, Dominique; De Lédinghen, Victor; Ouzan, Denis; Zoulim, Fabien; Roulot, Dominique; Tran, Albert; Bronowicki, Jean-Pierre; Zarski, Jean-Pierre; Leroy, Vincent; Riachi, Ghassan; Calès, Paul; Péron, Jean-Marie; Alric, Laurent; Bourlière, Marc; Mathurin, Philippe; Dharancy, Sébastien; Blanc, Jean-Frédéric; Abergel, Armand; Serfaty, Lawrence; Mallat, Ariane; Grangé, Jean-Didier; Attali, Pierre; Bacq, Yannick; Wartelle, Claire; Dao, Thông; Benhamou, Yves; Pilette, Christophe; Silvain, Christine; Christidis, Christos; Capron, Dominique; Bernard-Chabert, Brigitte; Zucman, David; Di Martino, Vincent; Thibaut, Vincent; Salmon, Dominique; Ziol, Marianne; Sutton, Angela; Pol, Stanislas; Roudot-Thoraval, Françoise

    2017-01-01

    We performed a prospective study to investigate the effects of a sustained viral response (SVR) on outcomes of patients with hepatitis C virus (HCV) infection and compensated cirrhosis. We collected data from 1323 patients included in the prospective Agence Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS) viral cirrhosis (CirVir) cohort, recruited from 35 clinical centers in France from 2006 through 2012. All patients had HCV infection and biopsy-proven cirrhosis, were Child-Pugh class A, and had no prior liver complications. All patients received anti-HCV treatment before or after inclusion (with interferon then with direct antiviral agents) and underwent an ultrasound examination every 6 months, as well as endoscopic evaluations. SVR was considered as a time-dependent covariate; its effect on outcome was assessed by the Cox proportional hazard regression method. We used a propensity score to minimize confounding by indication of treatment and capacity to achieve SVR. After a median follow-up period of 58.2 months, 668 patients (50.5%) achieved SVR. SVR was associated with a decreased incidence of hepatocellular carcinoma (hazard ratio [HR] compared with patients without an SVR, 0.29; 95% confidence interval [CI], 0.19-0.43; P < .001) and hepatic decompensation (HR, 0.26; 95% CI, 0.17-0.39; P < .001). Patients with SVRs also had a lower risk of cardiovascular events (HR, 0.42; 95% CI, 0.25-0.69; P = .001) and bacterial infections (HR, 0.44; 95% CI, 0.29-0.68; P < .001). Metabolic features were associated with a higher risk of hepatocellular carcinoma in patients with SVRs, but not in patients with viremia. SVR affected overall mortality (HR, 0.27 compared with patients without SVR; 95% CI, 0.18-0.42; P < .001) and death from liver-related and non-liver-related causes. Similar results were obtained in a propensity score-matched population. We confirmed a reduction in critical events, liver-related or not, in a prospective study of

  15. Effect of artesunate supplementation on bacterial translocation and dysbiosis of gut microbiota in rats with liver cirrhosis.

    PubMed

    Chen, Yun-Xia; Lai, Li-Na; Zhang, Hui-Ying; Bi, Yang-Hui; Meng, Li; Li, Xu-Jiong; Tian, Xiao-Xia; Wang, Li-Min; Fan, Yi-Min; Zhao, Zhong-Fu; Han, De-Wu; Ji, Cheng

    2016-03-14

    To evaluate the effect of artesunate (AS) supplementation on bacterial translocation (BT) and gut microbiota in a rat model of liver cirrhosis. Fifty-four male Sprague-Dawley rats were randomly divided into a normal control group (N), a liver cirrhosis group (M) and a liver cirrhosis group intervened with AS (MA). Each group was sampled at 4, 6 and 8 wk. Liver cirrhosis was induced by injection of carbon tetrachloride (CCl4), intragastric administration of 10% ethanol, and feeding a high fat diet. Rats in the MA group were intragastrically administered with AS (25 mg/kg body weight, once daily). Injuries of the liver and intestinal mucosa were assessed by hematoxylin-eosin or Masson's trichrome staining. Liver index was calculated as a ratio of the organ weight (g) to body weight (g). The gut microbiota was examined by automated ribosomal intergenic-spacer analysis of fecal DNA. BT was assessed by standard microbiological techniques in the blood, mesenteric lymph nodes (MLNs), liver, spleen, and kidney. Compared to group N, the body weight was reduced significantly in groups M and MA due to the development of liver cirrhosis over the period of 8 wk. The body weight was higher in group MA than in group M. The liver indices were significantly elevated at 4, 6 and 8 wk in groups M and MA compared to group N. AS supplementation partially decreased the liver indices in group MA. Marked histopathologic changes in the liver and small intestinal mucosa in group M were observed, which were alleviated in group MA. Levels of pro-inflammatory interleukin-6 and tumor necrosis factor-α were significantly elevated at 8 wk in ileal homogenates in group M compared to group N, which were decreased after AS supplementation in group MA. The dysbiosis of gut microbiota indicated by the mean diversity (Shannon index) and mean similarity (Sorenson index) was severe as the liver cirrhosis developed, and AS supplementation had an apparent intervention effect on the dysbiosis of gut

  16. MicroRNA panels as disease biomarkers distinguishing hepatitis B virus infection caused hepatitis and liver cirrhosis.

    PubMed

    Jin, Bo-Xun; Zhang, Yong-Hong; Jin, Wen-Jing; Sun, Xiang-Ying; Qiao, Gui-Fang; Wei, Ying-Ying; Sun, Li-Bo; Zhang, Wei-Hong; Li, Ning

    2015-10-12

    An important unresolved clinical issue is to distinguish hepatitis B virus (HBV) infection caused chronic hepatitis and their corresponding liver cirrhosis (LC). Recent research suggests that circulating microRNAs are useful biomarkers for a wide array of diseases. We analyzed microRNA profiles in the plasmas of a total of 495 chronic hepatitis B (CHB) patients, LC patients and healthy donors and identified 10 miRNAs that were differentially expressed between CHB and LC patients. Our logistic models show that three panels of miRNAs have promising diagnostic performances in discriminating CHB from LC. Blinded tests were subsequently conducted to evaluate the diagnostic performances in clinical practice and a sensitivity of 85% and specificity of 70% have been achieved in separating CHB from LC pateints. The expression levels of some circulating miRNAs were significantly correlated with HBV DNA load and liver function, such as prothrombin activity (PTA) and levels of alanin aminotransferase (ALT), albumin (ALB) and cholinesterase (CHE). Our results provide important information for developing novel diagnostic tools for distinguishing chronic HBV hepatitis and their corresponding cirrhosis.

  17. Diagnostic accuracy of APRI, FIB-4 and Forns for the detection of liver cirrhosis in HIV/HCV-coinfected patients.

    PubMed

    Merli, Marco; Galli, Laura; Castagna, Antonella; Salpietro, Stefania; Gianotti, Nicola; Messina, Emanuela; Poli, Andrea; Morsica, Giulia; Bagaglio, Sabrina; Cernuschi, Massimo; Bigoloni, Alba; Uberti-Foppa, Caterina; Lazzarin, Adriano; Hasson, Hamid

    2016-04-01

    We determined the diagnostic accuracy and optimal cut off of three indirect fibrosis biomarkers (APRI, FIB-4, Forns) compared with liver stiffness (LS) for the detection of liver cirrhosis in HIV/HCV-coinfected patients. An observational retrospective study on HIV/HCV-coinfected patients with concomitant LS measurement and APRI, FIB-4 and Forns was performed. The presence of liver cirrhosis was defined as a LS ≥13 KPa. The diagnostic accuracy and optimal cut-off values, compared with LS categorization (<13 vs ≥13 KPa), were determined by receiver operating characteristics (ROC) curves. The study sample included 646 patients. The area-under-the ROC curve (95% confidence interval) for the detection of liver cirrhosis were 0.84 (0.81-0.88), 0.87 (0.84-0.91) and 0.87 (0.84-0.90) for APRI, FIB-4 and Forns, respectively. According to the optimal cut off values for liver cirrhosis (≥0.97 for APRI, ≥2.02 for FIB-4 and ≥7.8 for Forns), 80%, 80% and 82% of subjects were correctly classified by the three indirect fibrosis biomarkers, respectively. Misclassifications were mostly due to false positive cases. The study suggests that indirect fibrosis biomarkers can help clinicians to exclude liver cirrhosis in the management of HIV/HCV co-infected patients, reducing the frequency of more expensive or invasive assessments.

  18. Demonstrating alcoholic cirrhosis of the liver by Tc-99m BIDA scintigram

    SciTech Connect

    Shih, W.J.; DeLand, F.H.; Domstad, P.A.

    1984-08-01

    Six patients with decompensated cirrhosis of the liver underwent Tc-99m BIDA studies. All demonstrated 1) persistently high blood pool activity in the heart, lung, and soft tissue, 2) slow hepatic tracer uptake, 3) prolonged liver-to-bowel transit time, and 4) visualization of an enlarged spleen. Four of the six patients demonstrated evidence of ascites and in one patient there were visible collateral veins of the abdomen. These findings are due primarily to hepatic dysfunction and retaining Tc-99m BIDA in blood pool because of Tc-99m BIDA exclusively hepatic excretion and little or no alternative renal excretion. All six Tc-99m sulfur colloid studies were performed concomitantly. Except for bone marrow uptake and reversal of the normal liver-spleen ratio of radioactivity, the imaging abnormalities observed with Tc-99m BIDA were similar to those seen by Tc-99m SC. It is concluded that with Tc-99m BIDA studies, three of six abnormal findings, as described, suggest a decompensated stage of cirrhosis of the liver.

  19. An MLP classifier for prediction of HBV-induced liver cirrhosis using routinely available clinical parameters.

    PubMed

    Cao, Yuan; Hu, Zhi-De; Liu, Xiao-Fei; Deng, An-Mei; Hu, Cheng-Jin

    2013-01-01

    Liver cirrhosis (LC) is the final stage of most of chronic liver diseases and is almost caused by chronic hepatitis B (CHB) in China. Liver biopsy is the reference method for the evaluation of liver cirrhosis. However, it is an invasive procedure with inherent risk. The aim of this study was to construct a new classifier based on the routine clinical markers for the prediction of HBV-induced LC. We collected routine clinical parameters from 124 LC patients with CHB and 115 with CHB. Training set (n = 120) and test set (n = 119) were built for model construction and evaluation, respectively. We describe a new classifier, MLP, for prediction of LC with CHB. MLP was built with seven routinely available clinical parameters, including age, ALT, AST, PT, PLT, HGB, and RDW. With optimal cutoff, we obtained a sensitivity of 95.2%, a specificity of 84.2%, and an overall accuracy of 89.9% on an independent test set, which were superior to those of FIB-4 and APRI. Our study suggests that the MLP classifier can be implemented for discriminating LC and non-LC cohorts by using machine learning method based on the routine available clinical parameters. It could be used for clinical practice in HBV-induced LC assessment.

  20. An MLP Classifier for Prediction of HBV-Induced Liver Cirrhosis Using Routinely Available Clinical Parameters

    PubMed Central

    Hu, Zhi-De; Liu, Xiao-Fei; Deng, An-Mei

    2013-01-01

    Background. Liver cirrhosis (LC) is the final stage of most of chronic liver diseases and is almost caused by chronic hepatitis B (CHB) in China. Liver biopsy is the reference method for the evaluation of liver cirrhosis. However, it is an invasive procedure with inherent risk. The aim of this study was to construct a new classifier based on the routine clinical markers for the prediction of HBV-induced LC. Subjects and Methods. We collected routine clinical parameters from 124 LC patients with CHB and 115 with CHB. Training set (n = 120) and test set (n = 119) were built for model construction and evaluation, respectively. Results. We describe a new classifier, MLP, for prediction of LC with CHB. MLP was built with seven routinely available clinical parameters, including age, ALT, AST, PT, PLT, HGB, and RDW. With optimal cutoff, we obtained a sensitivity of 95.2%, a specificity of 84.2%, and an overall accuracy of 89.9% on an independent test set, which were superior to those of FIB-4 and APRI. Conclusions. Our study suggests that the MLP classifier can be implemented for discriminating LC and non-LC cohorts by using machine learning method based on the routine available clinical parameters. It could be used for clinical practice in HBV-induced LC assessment. PMID:24302810

  1. Influence of smoking on caffeine elimination in healthy volunteers and in patients with alcoholic liver cirrhosis.

    PubMed

    Joeres, R; Klinker, H; Heusler, H; Epping, J; Zilly, W; Richter, E

    1988-01-01

    The effect of smoking on caffeine elimination was measured in 7 healthy volunteers and in 18 smoking and in 30 nonsmoking patients with alcoholic liver cirrhosis following oral application of 366 mg caffeine. In an intraindividual experiment in smoking health probands, caffeine clearance decreased from 118 +/- 33 to 77 +/- 22 ml per min (p less than 0.05) after abstaining cigarette smoking for 3 weeks. In a control group without liver disease (8 smokers, 15 nonsmokers), we found a caffeine clearance of 114 +/- 40 ml per min in smokers and 64 +/- 20 in nonsmokers (p less than 0.05). Smoking and nonsmoking patients with alcoholic liver cirrhosis did not differ with respect to clinical and laboratory data and hexobarbitone elimination. However, caffeine clearance was 63 +/- 63 ml per min in smoking patients compared to 34 +/- 49 ml per min in nonsmokers (p less than 0.05). Fasting plasma concentrations of caffeine were higher in nonsmokers (5.1 +/- 6.2 micrograms per ml) than in smokers (2.1 +/- 4.5 micrograms per ml, p less than 0.05). We conclude that smoking habits have to be taken into account if caffeine is used as a model compound for measuring quantitative liver function.

  2. The endocannabinoid system in advanced liver cirrhosis: pathophysiological implication and future perspectives.

    PubMed

    Baldassarre, Maurizio; Giannone, Ferdinando A; Napoli, Lucia; Tovoli, Alessandra; Ricci, Carmen S; Tufoni, Manuel; Caraceni, Paolo

    2013-10-01

    Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules providing different central and peripheral effects that are mediated mostly by the specific receptors CB1 and CB2. The EC system is highly upregulated during chronic liver disease and consistent experimental and clinical findings indicate that it plays a role in the pathogenesis of liver fibrosis and fatty liver disease associated with obesity, alcohol abuse and hepatitis C. Furthermore, a considerable number of studies have shown that EC and their receptors contribute to the pathogenesis of the cardio-circulatory disturbances occurring in advanced cirrhosis, such as portal hypertension, hyperdynamic circulatory syndrome and cirrhotic cardiomyopathy. More recently, the EC system has been implicated in the development of ascites, hepatic encephalopathy and the inflammatory response related to bacterial infection. Rimonabant, a selective CB1 antagonist, was the first drug acting on the EC system approved for the treatment of obesity. Unfortunately, it has been withdrawn from the market because of its neuropsychiatric side effects. Compounds able to target selectively the peripheral CB1 receptors are under evaluation. In addition, molecules stimulating CB2 receptor or modulating the activity of enzymes implicated in EC metabolism are promising areas of pharmacological research. Liver cirrhosis and the related complications represent an important target for the clinical application of these compounds.

  3. Gallstones in patients with liver cirrhosis: incidence, etiology, clinical and therapeutical aspects.

    PubMed

    Acalovschi, Monica

    2014-06-21

    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.

  4. Effects of ondansetron on portal hemodynamics in liver cirrhosis.

    PubMed

    Tripkovic, M; Kozjek, F; Krizman, I; Jereb, J; Francetic, I; Grabnar, I; Mrhar, A

    2000-09-01

    The double-blind randomized pilot study was undertaken to compare the effects of a 10-day course of ondansetron 8 mg/day and propranolol 80 mg/day perorally in treating portal hypertension. SUBIECTS AND METHODS: 16 patients with liver disease were enrolled in the study. Measurements of portal vein diameter, portal blood flow velocity and portal blood flow volume were done at days 1, 5 and 10 of treatment using duplex Doppler sonography. The propranolol group demonstrated a decrease in portal venous diameter, while patients treated with ondansetron exhibited reduced portal blood flow velocity values. A decreased portal blood flow volume was found in both groups after 10 days of therapy. No statistically significant differences were found between the groups with the exception of portal venous diameter which is significantly lower at the end of the treatment in the case of propranolol.

  5. [Peptic ulcer disease in liver cirrhosis: role of Helicobacter pylori infection and therapeutic approach].

    PubMed

    Mitrică, Dana; Constantinescu, R; Drug, V L; Stanciu, C

    2011-01-01

    Peptic ulcer has frequently been associated with liver cirrhosis. The death rate for peptic ulcer in cirrhotics has been reported to be five times higher than in general population. The underlying mechanisms are poorly understood. Different factors have been claimed to be involved, such as alterations in serum gastrin level, gastric acid secretions, mucosal blood flow and decreased prostaglandin production in gastric mucosa. Moreover, Helicobacter pylori infection, when accurately assessed, is detectable in most peptic ulcer cirrhotics. Since the H. pylori infection strongly correlates with peptic ulcer in general population, it is necessary to clarify the role of H. pylori in the pathogenesis of peptic ulcer in cirrhosis before eradication can be proposed as a preventive measure.

  6. Acute-on-chronic liver failure: a new syndrome in cirrhosis.

    PubMed

    Moreau, Richard

    2016-03-01

    Patients with cirrhosis who are hospitalized for an acute decompensation (AD) and also have organ failure(s) are at high risk of short-term death. These patients have a syndrome called Acute-on-Chronic Liver Failure (ACLF). ACLF is now considered as a new syndrome that it is distinct from "mere" AD not only because of the presence of organ failure(s) and high short-term mortality but also because of younger age, higher prevalence of alcoholic etiology of cirrhosis, higher prevalence of some precipitants (such as bacterial infections, active alcoholism), and more intense systemic inflammatory response. ACLF is a new syndrome also because severe sepsis or severe alcoholic hepatitis do not account for 100% of the observed cases; in fact, almost 50% of the cases are of "unknown" origin. In other words, severe sepsis, severe alcoholic hepatitis and ACLF of "unknown origin" are subcategories of the syndrome.

  7. 3-Dimensional liver volume assessment in patients with hepatitis B virus-related liver cirrhosis during long-term oral nucleos(t)ide analogues therapy

    PubMed Central

    Lee, Chang Hun; Kim, In Hee; Moon, Jin Chang; Seo, Seung Young; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul

    2017-01-01

    AIM To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. METHODS We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. RESULTS A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis (P = 0.046) but also in those with decompensated cirrhosis (P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume (P = 0.002 and 0.005, respectively). CONCLUSION Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program. PMID:28127203

  8. 3-Dimensional liver volume assessment in patients with hepatitis B virus-related liver cirrhosis during long-term oral nucleos(t)ide analogues therapy.

    PubMed

    Lee, Chang Hun; Kim, In Hee; Moon, Jin Chang; Seo, Seung Young; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul

    2017-01-14

    To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis (P = 0.046) but also in those with decompensated cirrhosis (P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume (P = 0.002 and 0.005, respectively). Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program.

  9. Hepatitis C virus (HCV)-related cryoglobulinemia after liver transplantation for HCV cirrhosis.

    PubMed

    Duvoux, Christophe; Tran Ngoc, Anh; Intrator, Liliane; Hézode, Christophe; Germanidis, Georgios; Pawlotsky, Jean-Michel; Cherqui, Daniel; Dhumeaux, Daniel

    2002-01-01

    The aim of this study was to analyze the clinical impact of hepatitis C virus (HCV)-related cryoglobulinemia in patients that had received liver transplants after HCV cirrhosis. Thirty patients who had received transplants between 1990 and 1996 for HCV cirrhosis and who had a follow-up longer than 1 year were studied. Serum HCV RNA levels, HCV genotype, cryoglobulinemia, rheumatoid factor, serum C3 and C4, IgA, IgG, IgM levels, liver tests, and liver histology were studied 30 +/- 16 months post-transplant. Cryoglobulinemia was found in 9 of 30 patients (30.0%) and was symptomatic in 4 of the 9 cases (glomerulonephritis, 1 case; palpable purpura, 3 cases). Age, sex distribution, alanine aminotransferase (ALAT) activity, and Knodell score did not differ, whether cryoglobulinemia was present or not. Rheumatoid factor (209.5 +/- 70.4 IU/l vs 12.0 +/- 4.4 IU/l, P = 0.004) and IgM levels (3.2 +/- 0.5 g/l vs 1.6 +/- 0.9 g/l, P = 0.0001) were significantly higher, and C4 levels (0.16 +/- 0.16 g/l vs 0.30 +/- 0.10 g/l, P = 0.009) were significantly lower in patients with cryoglobulinemia. One patient died from cryoglobulin-related renal failure. We concluded that, after liver transplantation (LT) for HCV cirrhosis, cryoglobulinemia was frequent and often symptomatic. Cryoglobulinemia did not seem to be associated with more severe graft damage. Cryoglobulinemia-associated morbidity must be taken into account in the management of post-transplant HCV infection.

  10. 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

  11. 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

  12. Pigment epithelium-derived factor and matrix metalloproteinase-9 in liver cirrhosis.

    PubMed

    Kozlowska, Joanna; Mikula, Tomasz; Suchacz, Magdalena; Jabnonska, Joanna; Stanczak, Wojciech; Cianciara, Janusz; Wiercinska-Drapalo, Alicja

    2016-01-01

    The aim of this study was to assess the role of serum pigment epithelium-derived factor (PEDF) and matrix metalloproteinase-9 (MMP-9) in progression of liver cirrhosis and development of hepatocellular carcinoma (HCC). Serum levels of PEDF and MMP-9 were tested in 212 patients with liver cirrhosis and in a control group of 30 healthy volunteers. HCC was diagnosed in 45 of the 212 patients studied (21%). Serum PEDF and MMP-9 were higher in the study group than that in the control group (P < 0.001). In patients with alcoholic or mixed (alcoholic and viral hepatitis-related) cirrhosis, serum PEDF was higher than that in other patients (13970.2 ± 13406.9 ng/ml vs. 8563.5 ± 9602.7 ng/ml, P = 0.008). In patients with viral hepatitis-related cirrhosis, significantly higher PEDF levels were recorded in those with HCC (13429.1 ± 12045.8) than that in patients without HCC (6660.1 ± 7927.1; P = 0.04). There was a trend for higher serum MMP-9 in patients with HCC (5778.7 ± 12426.6 vs. 1389.8 ± 1944.7 in those without HCC; P = 0.07). Significant negative correlation between serum MMP-9 and serum alpha-fetoprotein in patients with HCC was observed (r = -0.54; P = 0.04). Serum PEDF and MMP-9 could be auxiliary markers in diagnosis of HCC, especially in patients with low alpha-fetoprotein level. Alcohol consumption can affect serum PEDF.

  13. 201Tl heart-liver radioactivity uptake ratio and prediction of decompensation in patients with cirrhosis.

    PubMed

    Lee, Min-Ho; Tae, Hae-Jin; Jun, Dae-Won; Ryu, Seong-Eon; Choi, Yun-Young; Kwak, Min-Jeong; Kang, Ju-Seop

    2013-03-01

    The present study aimed to determine the predictive value of the heart-liver uptake ratio (H/L ratio) of rectally administered (201)Tl scintigraphy for hepatic decompensation, which was conducted in 107 patients with cirrhosis. We retrospectively assessed the predictive value of a noninvasive parameter, H/L ratio, for decompensation during a median follow-up period of 45.4 months using follow-up data from 1996 through 2008 for 107 patients with compensated cirrhosis. Logistic regression analysis and odds ratio estimates were used to estimate independent value of the H/L ratio on the risk of decompensation with 95% confidence intervals. At first visit, all subjects were confirmed as patients with compensated cirrhosis, 39 by liver biopsy and 68 by standard laboratory and radiological criteria. At end of the evaluation time, 81 patients remained compensated, whereas 26 patients decompensated as evidenced by ascites in 23, hepatic encephalopathy in 8, and variceal bleeding in 1 patient. First-visit parameters except bilirubin level, alanine aminotransferase (ALT), and H/L ratio and last visit parameters except ALT and aspartate aminotransferase-ALT ratio were significantly different between the 2 groups as ascertained by Wilcoxon rank sum test (P < 0.05). Among those parameters, we found that the last visit H/L ratio was a strongly reliable predictor of decompensation with an odds ratio estimates of 14.443, area under the receiver operating characteristic curve of 0.825, cutoff of 0.4, sensitivity of 73.1 %, and specificity of 71.6%. This evidence indicates that in patients with compensated cirrhosis, an increased H/L ratio at follow-up may be a useful predictive parameter showing a high risk of progression to a decompensated state.

  14. Studies on the incidence of hepatocellular carcinoma in heavy drinkers with liver cirrhosis.

    PubMed

    Suzuki, M; Suzuki, H; Mizuno, H; Tominaga, T; Kono, M; Kato, Y; Sato, A; Okabe, K

    1993-01-01

    The incidence of hepatocellular carcinoma (HCC) in heavy drinkers who drank more than 130 g per day for more than 10 years, and non-drinkers with cirrhosis who were positive or negative hepatitis C virus (HCV) markers, was analyzed in order to evaluate the effect of a large amount of alcohol on the development of HCC. A parallel study was also conducted in some patients from the aspect of HCV genotypes. Among 57 heavy drinkers with liver cirrhosis, HCV marker was positive in 36 patients (C+Al group) and negative in 21 patients (Al-alone group). Eighty-one patients with liver cirrhosis of non-drinkers were positive for HCV markers (C-alone group). HCV infection was involved in 63% of heavy drinkers with cirrhosis and 44% of patients with HCC. The majority of HCC patients in the C+Al group was infected with HCV through routes other than blood transfusion. HCC developed at a younger age in patients of the C+Al group than in patients of the C-alone group without relation to history of blood transfusion. In more than a third of patients who had tattoos or used stimulants in the C+Al group, HCC developed without a history of blood transfusion. These results suggest that heavy drinking enhances the development of HCC. The HCV genotypes in patients with HCC were all type II, except for one case of type III and one unclassified. The mixed type of HCV was often found in patients who had a blood transfusion or tattoo, suggesting that there may be some correlation between the routes of HCV infection and the diversity of genotypes.

  15. Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis.

    PubMed

    Calderaro, Julien; Nault, Jean C; Balabaud, Charles; Couchy, Gabrielle; Saint-Paul, Marie-Christine; Azoulay, Daniel; Mehdaoui, Dalila; Luciani, Alain; Zafrani, Elie S; Bioulac-Sage, Paulette; Zucman-Rossi, Jessica

    2016-01-01

    Hepatocellular adenoma is considered to occur exclusively in non-fibrotic livers. It is a heterogeneous entity and a molecular classification is now widely accepted. The most frequent hepatocellular adenoma subtype, namely inflammatory adenoma, harbor somatic activating mutations of genes involved in the interleukin-6 pathway that lead to high C-reactive protein and serum amyloid A expression. The aim of our study was to investigate a series of benign hepatocellular neoplasms developed on cirrhotic livers and characterized by an unequivocal histological diagnosis. We performed a clinical, pathological, and molecular study of 10 benign hepatocellular neoplasms developed in three patients with cirrhosis. Markers allowing hepatocellular adenoma classification were assessed by quantitative real-time PCR and immunohistochemistry. Samples were sequenced for CTNNB1, HNF1A, IL6ST, GNAS, STAT3, and TERT (promoter) mutations. A control series of 32 classical macronodules developed in cirrhosis related to various etiologies was screened by immunohistochemistry and gene sequencing. The three patients had cirrhosis related to metabolic syndrome and/or alcohol intake; two had a single tumor, while the third developed more than 30 lesions. Microscopic examination showed well-differentiated neoplasms sharing features with inflammatory adenoma including inflammatory infiltrates, sinusoidal dilatation, and dystrophic vessels. Sequencing revealed classical hotspot somatic mutations (IL6ST, n=8; STAT3, n=1; and GNAS, n=1) known to be responsible for IL-6/JAK/STAT pathway activation. Two classical high-grade macronodules demonstrated high serum amyloid A and/or C-reactive protein expression, without gene mutations. Altogether, our findings support the existence of rare inflammatory adenoma developed in cirrhosis.

  16. Does an association exist between chronic pancreatitis and liver cirrhosis in alcoholic subjects?

    PubMed Central

    Aparisi, Luis; Sabater, Luis; Del-Olmo, Juan; Sastre, Juan; Serra, Miguel-Angel; Campello, Ricardo; Bautista, Daniel; Wassel, Abdalla; Rodrigo, José-Manuel

    2008-01-01

    AIM: To study the possible association between chronic pancreatitis (CP) and liver cirrhosis (LC) of alcoholic etiology, after excluding any other causes. METHODS: One hundred and forty consecutive alcoholic patients were subdivided into three groups: CP (n = 53), LC (n = 57), and asymptomatic alcoholic (n = 30). Clinical, biochemical and morphological characteristics, Child-Pugh index, indocyanine green test, and fecal pancreatic elastase-1 test were assessed. RESULTS: In patients with cirrhosis, major clinical manifestations of CP such as pancreatic pain and steatorrhea, as well as imaging alterations of CP such as calcifications, duct dilation and pseudocysts were absent; insulin-dependent diabetes was present in 5.3% of cases, and elastase-1 test was altered in only 7%, and severely altered in none. In patients with CP, clinical characteristics of cirrhosis such as ascites, encephalopathy and gastrointestinal hemorrhage were present in one case, Child-Pugh grade > A in 5.7%, and altered indocyanine green test in 1.9% cases. In asymptomatic alcoholism, there was only a non-coincident alteration of elastase-1 test and indocyanine test in 14.8% and 10%, respectively, but other characteristics of cirrhosis or CP were absent. An inverse correlation (r = -0.746) between elastase-1 test and indocyanine test was found in alcoholic patients. CONCLUSION: There is a scarce coincidence in clinical and morphological alterations among patients with CP or LC of alcoholic etiology, but an inverse correlation between pancreatic and liver function tests. These findings support that these alcoholic diseases evolve in a different manner and have different etiopathogenesis. PMID:18985807

  17. Modifications of human total serum N-glycome during liver fibrosis-cirrhosis, is it all about immunoglobulins?

    PubMed

    Klein, André; Michalski, Jean-Claude; Morelle, Willy

    2010-04-01

    The study of the total serum N-glycome during liver cirrhosis has demonstrated numerous alterations. The identification of the glycoproteins carrying these modifications and their relative contribution to the modification of the total serum N-glycome has shown the important role of IgA and IgG. The possible mechanisms of glycosylation alteration of the Igs and of liver secreted glycoproteins, the consequences in the pathophysiology of cirrhosis and their relation to the biomarkers of liver diseases are also discussed in the present review. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Nadolol reduces insulin sensitivity in liver cirrhosis: a randomized double-blind crossover trial.

    PubMed

    Lee, Wai Gin; Murphy, Rinki; McCall, John L; Gane, Edward J; Soop, Mattias; Tura, Andrea; Plank, Lindsay D

    2017-03-01

    Liver cirrhosis is frequently complicated by portal hypertension leading to increased mortality from variceal bleeding and hepatic decompensation. Noncardioselective β-blockers not only reduce portal hypertension and prevent variceal bleeding in cirrhosis but also impair glucose tolerance and insulin sensitivity in other settings. This study aimed to determine whether nonselective β-blockade with nadolol impairs glucose metabolism in liver cirrhosis. A randomized, double-blind, placebo-controlled crossover trial of nadolol in cirrhotic patients examined insulin sensitivity, disposition index, and glucose tolerance. Stable cirrhotic patients of mixed etiology underwent an intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp for the measurement of insulin secretion and insulin sensitivity (n = 16) and a 75-g oral glucose tolerance test (n = 17). These measurements were conducted twice (after 3 months of treatment with nadolol or placebo and, after a 1-month washout period, after 3 months on the alternative treatment). Total body fat and plasma catecholamines were measured at the end of each 3-month treatment. Compared with placebo, nadolol treatment reduced insulin sensitivity (79.7 ± 10.1 vs 99.6 ± 10.3 μL/kg fat-free mass·min(-1) ·(mU/L)(-1) , P = .005). Insulin secretion was unchanged (P = .24), yielding a lower disposition index with nadolol (6083 ± 2007 vs 8692 ± 2036, P = .050). There was no change in total body fat or plasma catecholamines. A 2-hour plasma glucose concentration from the oral glucose tolerance test was higher on nadolol than placebo (10.8 ± 0.9 vs 9.9 ± 0.9 mmol/L, P = .035). Nadolol significantly worsened insulin sensitivity, glycemia, and disposition index in patients with liver cirrhosis. These findings may have significant clinical implications because cirrhosis is already associated with an increased prevalence of diabetes. Copyright © 2016 John Wiley & Sons, Ltd.

  19. NT Pro BNP Plasma Level and Atrial Volume Are Linked to the Severity of Liver Cirrhosis

    PubMed Central

    Licata, Anna; Corrao, Salvatore; Petta, Salvatore; Genco, Chiara; Cardillo, Mauro; Calvaruso, Vincenza; Cabibbo, Giuseppe; Massenti, Fatima; Cammà, Calogero; Licata, Giuseppe; Craxì, Antonio

    2013-01-01

    Background and Aims Plasma levels of NT-pro-BNP, a natriuretic peptide precursor, are raised in the presence of fluid retention of cardiac origin and can be used as markers of cardiac dysfunction. Recent studies showed high levels of NT pro BNP in patients with cirrhosis. We assessed NT pro-BNP and other parameters of cardiac dysfunction in patients with cirrhosis, with or without ascites, in order to determine whether the behaviour of NT pro BNP is linked to the stage of liver disease or to secondary cardiac dysfunction. Methods Fifty eight consecutive hospitalized patients mostly with viral or NAFLD-related cirrhosis were studied. All underwent abdominal ultrasound and upper GI endoscopy. Cardiac morpho-functional changes were evaluated by echocardiography and NT-pro-BNP plasma levels determined upon admission. Twenty-eight hypertensive patients, without evidence of liver disease served as controls. Results Fifty eight cirrhotic patients (72% men) with a median age of 62 years (11% with mild arterial hypertension and 31% with type 2 diabetes) had a normal renal function (mean creatinine 0.9 mg/dl, range 0.7–1.06). As compared to controls, cirrhotic patients had higher NT pro-BNP plasma levels (365.2±365.2 vs 70.8±70.6 pg/ml; p<0.001). Left atrial volume (LAV) (61.8±26.3 vs 43.5±14.1 ml; p = 0.001), and left ventricular ejection fraction (62.7±6.9 vs. 65.5±4%,; p = 0.05) were also altered in cirrhotic patients that in controls. Patients with F2-F3 oesophageal varices as compared to F0/F1, showed higher e' velocity (0.91±0.23 vs 0.66±0.19 m/s, p<0.001), and accordingly a higher E/A ratio (1.21±0.46 vs 0.89±0.33 m/s., p = 0.006). Conclusion NT-pro-BNP plasma levels are increased proportionally to the stage of chronic liver disease. Advanced cirrhosis and high NT-pro-BNP levels are significantly associated to increased LAV and to signs of cardiac diastolic dysfunction. NT pro-BNP levels could hence be an useful prognostic indicators of early

  20. Portal vein omentin is increased in patients with liver cirrhosis but is not associated with complications of portal hypertension.

    PubMed

    Eisinger, Kristina; Krautbauer, Sabrina; Wiest, Reiner; Karrasch, Thomas; Hader, Yvonne; Scherer, Marcus N; Farkas, Stefan; Aslanidis, Charalampos; Buechler, Christa

    2013-09-01

    Omentin is a visceral fat-derived adipokine associated with endothelium-dependent vasodilation. Impaired endothelial function is a major cause of portal hypertension in liver cirrhosis. The aim was to assess associations of omentin with systemic markers of endothelial function, namely arginine and asymmetric dimethylarginine (ADMA) and complications of portal hypertension in liver cirrhosis. Systemic omentin was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous serum (HVS) of 40 patients with liver cirrhosis and 10 liver-healthy controls. ADMA and arginine were determined in SVS of the patients by ELISA. Omentin is elevated in PVS and tends to be increased in SVS and HVS of patients with liver cirrhosis compared with controls. Omentin is principally expressed in visceral fat, and PVS omentin tends to be higher than SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly removed from the circulation by the liver. Omentin in serum is not associated with stages of liver cirrhosis defined by CHILD-POUGH or MELD score and is not affected in patients with ascites. HVS omentin tends to be reduced in patients with large varices compared with patients without/with small varices. Arginine/ADMA ratio is reduced in patients with massive ascites but is not associated with variceal size. Further, Arginine/ADMA ratio does not correlate with omentin. Current data show that PVS omentin is increased in liver cirrhosis but is not associated with complications of portal hypertension. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  1. The role of exosomes in hepatitis, liver cirrhosis and hepatocellular carcinoma.

    PubMed

    Shen, Jiliang; Huang, Chiung-Kuei; Yu, Hong; Shen, Bo; Zhang, Yaping; Liang, Yuelong; Li, Zheyong; Feng, Xu; Zhao, Jie; Duan, Lian; Cai, Xiujun

    2017-02-22

    Exosomes are small vesicles that were initially thought to be a mechanism for discarding unneeded membrane proteins from reticulocytes. Their mediation of intercellular communication appears to be associated with several biological functions. Current studies have shown that most mammalian cells undergo the process of exosome formation and utilize exosome-mediated cell communication. Exosomes contain various microRNAs, mRNAs and proteins. They have been reported to mediate multiple functions, such as antigen presentation, immune escape and tumour progression. This concise review highlights the findings regarding the roles of exosomes in liver diseases, particularly hepatitis B, hepatitis C, liver cirrhosis and hepatocellular carcinoma. However, further elucidation of the contributions of exosomes to intercellular information transmission is needed. The potential medical applications of exosomes in liver diseases seem practical and will depend on the ingenuity of future investigators and their insights into exosome-mediated biological processes.

  2. A novel APOB mutation identified by exome sequencing cosegregates with steatosis, liver cancer and hypocholesterolemia

    PubMed Central

    Cefalù, Angelo B; Pirruccello, James P; Noto, Davide; Gabriel, Stacey; Valenti, Vincenza; Gupta, Namrata; Spina, Rossella; Tarugi, Patrizia; Kathiresan, Sekar; Averna, Maurizio R

    2013-01-01

    Objective In familial hypobetalipoproteinemia (FHBL), fatty liver is a characteristic feature, and there are several reports of associated cirrhosis and hepatocarcinoma. We investigated a large kindred in which low-density lipoprotein (LDL) cholesterol, fatty liver and hepatocarcinoma displayed an autosomal dominant pattern of inheritance. Approach and Results The proband was a 25 year-old female with low plasma cholesterol and hepatic steatosis. Low plasma levels of total cholesterol and fatty liver were observed in 10 more family members; 1 member was affected by liver cirrhosis and four more subjects died of either hepatocarcinoma or carcinoma on cirrhosis. To identify the causal mutation in this family, we performed exome sequencing in two participants with hypocholesterolemia and fatty liver. Approximately 22,400 single nucleotide variants were identified in each sample. After variant filtering, 300 novel shared variants remained. A nonsense variant, p.K2240X due to an A>T mutation in exon 26 of APOB (c.6718A>T) was identified and this variant was confirmed by Sanger sequencing. The gentotypic analysis of 16 family members in total showed that this mutation segregated with the low cholesterol trait. In addition, genotyping of the PNPLA3 p.I148M did not show significant frequency differences between carriers and non-carriers of the c.6718A>T APOB gene mutation. Conclusions We used exome sequencing to discover a novel nonsense mutation in exon 26 of APOB (p.K2240X) responsible for low cholesterol and fatty liver in a large kindred. This mutation may also be responsible for cirrhosis and liver cancer in this family. PMID:23723369

  3. 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.

  4. Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies.

    PubMed

    de Mesquita, Fernanda Cristina; Guixé-Muntet, Sergi; Fernández-Iglesias, Anabel; Maeso-Díaz, Raquel; Vila, Sergi; Hide, Diana; Ortega-Ribera, Martí; Rosa, José Luís; García-Pagán, Juan Carlos; Bosch, Jaime; de Oliveira, Jarbas Rodrigues; Gracia-Sancho, Jordi

    2017-06-12

    Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). Liraglutide, well-established in type 2 diabetes, showed anti-inflammatory and anti-oxidant properties. We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function using diverse pre-clinical models of CLD. Human and rat HSC were in vitro treated with liraglutide, or vehicle, and their phenotype, viability and proliferation were evaluated. In addition, liraglutide or vehicle was administered to rats with CLD. Liver microvascular function, fibrosis, HSC phenotype and sinusoidal endothelial phenotype were determined. Additionally, the effects of liraglutide on HSC phenotype were analysed in human precision-cut liver slices. Liraglutide markedly improved HSC phenotype and diminished cell proliferation. Cirrhotic rats receiving liraglutide exhibited significantly improved liver microvascular function, as evidenced by lower portal pressure, improved intrahepatic vascular resistance, and marked ameliorations in fibrosis, HSC phenotype and endothelial function. The anti-fibrotic effects of liraglutide were confirmed in human liver tissue and, although requiring further investigation, its underlying molecular mechanisms suggested a GLP1-R-independent and NF-κB-Sox9-dependent one. This study demonstrates for the first time that liraglutide improves the liver sinusoidal milieu in pre-clinical models of cirrhosis, encouraging its clinical evaluation in the treatment of chronic liver disease.

  5. [A case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis caused by chronic hepatitis C].

    PubMed

    Choi, Hye Mi; Jung, Gum Mo; Lee, Woong Ki; Lee, Hyeuk Soo; Kim, Byung Sun; Seong, Choong Sil; Yoon, So Hee; Cho, Yong Keun

    2014-11-01

    Cryptococcus neoformans, an encapsulated fungus, is an important opportunistic pathogen that can cause meningitis in im-munocompromised patients. Since patients with cryptococcemia have high mortality, it is essential to make an early diagnosis and promptly initiate antifungal therapy. However, it is often very difficult to differentiate between cryptococcal meningitis and hepatic encephalopathy in patients with liver cirrhosis, and there is delay in making the diagnosis. Therefore, these patients have a particularly grave prognosis and consequently many patients die before culture results become available. In one study, starting antifungal therapy within 48 hours of the blood culture was associated with improved survival, but patients with liver cirrhosis were significantly less likely to receive antifungal therapy within 48 hours compared to those without liver cirrhosis. Recently, the authors experience a case of a 68-year-old woman with liver cirrhosis who presented with fever and a drowsy mental status. She had a previous history of having been admitted for infection-associated hepatic encephlopathy. Cryptococcal meningitis and cryptococcemia were diagnosed by spinal puncture and culture of cerebrospinal fluid. In spite of adequate treatment, the patient developed multi-system organ failure and eventually expired. Herein, we report a case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis.

  6. 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.

  7. Antifibrotic effect of edaravone in rat liver cirrhosis induced by dimethylnitrosamine.

    PubMed

    Tanaka, Hiroto; Ueda, Hiroki; Fukuchi, Hiroko; Ichinose, Masakazu

    2009-09-01

    Edaravone (EDA), a newly synthesized free radical scavenger, has shown excellent results in the treatment of stroke. An overproduction of reactive oxygen species (ROS) causing oxidative DNA damage has been accounted as a major factor causing liver injury and fibrosis. Therefore, we examined its effect of EDA in rat model of liver cirrhosis induced by dimethylnitrosamine (DMN). Ten rats (DMN-group) were injected intraperitoneally with DMN (10 microg/g body weight) alone and another ten rats (EDA-group) were injected intraperitoneally with EDA (10 mg/kg body weight) 2 h after being injected with DMN. Both groups underwent their injection regimen three times a week for 4 weeks, after which the rats were sacrificed and their liver tissue sections were stained with Azan-Mallory for quantitative analyses of fibrosis development, using soft imaging and a previously published scoring system. Additionally, these sections were immunohistochemically stained using an antibody against alpha-smooth muscle actin (alpha-SMA). The total-bililubin in the EDA-group was found to be lower than that in the DMN-group. Quantitive analysis of liver fibrosis showed that the fibrotic area of the EDA-group was significantly smaller than that of the DMN-group. Additionally, the number of alpha-SMA positive cells in the EDA-group were significantly lower than that in the DMN-group. This study showed that EDA reduces liver fibrosis in a rat of cirrhosis induced by DMN. These data suggest that the reduction of liver fibrosis by EDA may be induced by the suppression of activated hepatic stellate cells.

  8. [Clinical features of liver cirrhosis complicated by portal vein thrombosis and related risk factors].

    PubMed

    Lin, G S; Xu, Q; Zhao, S Y; Zhang, Y X

    2016-07-20

    Objective: To investigate the clinical features of patients with liver cirrhosis complicated by portal vein thrombosis (PVT) and related risk factors. Methods: A total of 65 patients with liver cirrhosis complicated by PVT who were diagnosed and treated from June 2013 to June 2015 were enrolled as PVT group, and 70 cirrhotic patients without PVT were enrolled as controls (non-PVT group). The data collected included general information, results of laboratory examination, imaging findings, clinical manifestations, and complications. The clinical features were compared between the two groups, and related risk factors were screened out. Results: There were no significant differences between the PVT group and non-PVT group in age, sex, nation, etiology, white blood cell count, platelet count, international normalized ratio, activated partial thromboplastin time, fibrinogen, serum creatinine, total bilirubin, and the diameter of the splenic vein (all P > 0.05), while between these two groups, there were significant differences in D-dimer (1.87±1.45 mg/ml vs 0.55±0.58 mg/ml, P < 0.05), fibrinogen degradation product (FDP) level (18.57±19.46 μg/ml vs 5.45±6.00 μg/ml, P < 0.05), hemoglobin (99.32±26.73 g/L vs 112.64±25.03 g/L, P < 0.05), albumin (28.51±5.19 g/L vs 33.07±7.94 g/L, P < 0.05), the diameter of the portal vein (12.53±2.70 mm vs 11.17±1.79 mm, P < 0.05), spleen thickness (5.12±0.95 cm vs 4.56±0.83 cm, P < 0.05), spleen length (15.35±3.21 cm vs 13.86±2.82 cm, P < 0.05), and Child-Pugh score (7.66±2.06 vs 6.93±1.87, P < 0.05). The two groups showed no significant differences in diarrhea, ileus, hepatorenal syndrome, and hepatic encephalopathy (P > 0.05), but showed significant differences in abdominal pain (18 vs 7 cases, P < 0.05), fever (17 vs 4 cases, P < 0.05), esophageal variceal bleeding (22 vs 9 cases, P < 0.05), and spontaneous peritonitis (24 vs 12 cases, P < 0.05). D-dimer (OR = 4.290, P < 0.000) and mean platelet volume (OR = 1.294, P

  9. Diagnosis of liver cancer and cirrhosis by the fluorescence spectra of blood and urine.

    PubMed

    AlSalhi, M; Al Mehmadi, A M; Abdo, Ayman Assad; Prasad, S; Masilamani, V

    2012-08-01

    Liver cancer or hepato cellular carcinoma (HCC) is a serious malady with only 10% survival rate and is fatal next only to pancreatic cancer. This disease is conventionally detected and diagnosed by ultra sound, CT or MRI scans which are quite expensive. Also the discrimination between cirrhosis and HCC, by these imaging techniques, is poor. The conventional tissue biopsy is quite invasive and painful. In the new diagnostic procedure presented in this paper we have obtained fluorescence emission spectra with excitation at 400 nm and the synchronous emission spectra (Δλ = 10 nm) for a set of blood and urine samples (Normal control N = 25, Liver Malfunction N = 58). Based on the ratio fluorometric parameters, all the three liver maladies (minor inflammation like Hepatitis C, serious diseases like Cirrhosis and hepatoma) could be detected and discriminated with an accuracy of about 80%. Hence this inexpensive, non invasive, optical technique may have significant impact in screening, diagnosis and also prognosis of HCC in large segment of people in the populous Asian countries.

  10. Risk Factors for Portal Vein Thrombosis in Patients With Cirrhosis Awaiting Liver Transplantation in Shiraz, Iran

    PubMed Central

    Bagheri Lankarani, Kamran; Homayon, Katayon; Motevalli, Dorna; Heidari, Seyed Taghi; Alavian, Seyed Moayed; Malek-Hosseini, Seyed Ali

    2015-01-01

    Background: Portal vein thrombosis is a fairly common and potentially life-threatening complication in patients with liver cirrhosis. The risk factors for portal vein thrombosis in these patients are still not fully understood. Objectives: This study aimed to investigate the associations between various risk factors in cirrhotic patients and the development of portal vein thrombosis. Patients and Methods: In this case-control study performed at the Shiraz organ transplantation center, Iran, we studied 219 patients (> 18 years old) with liver cirrhosis, who were awaiting liver transplants in our unit, from November 2010 to May 2011. The patients were evaluated by history, physical examination, and laboratory tests, including factor V Leiden, prothrombin gene mutation, Janus Kinase 2 (JAK2) mutation, and serum levels of protein C, protein S, antithrombin III, homocysteine, factor VIII, and anticardiolipin antibodies. Results: There was no statistically significant difference in the assessed hypercoagulable states between patients with or without portal vein thrombosis. A history of previous variceal bleeding with subsequent endoscopic treatment in patients with portal vein thrombosis was significantly higher than in those without it (P = 0.013, OR: 2.526, 95% CI: 1.200 - 5.317). Conclusions: In our population of cirrhotic patients, treatment of variceal bleeding predisposed the patients to portal vein thrombosis, but hypercoagulable disorders by themselves were not associated with portal vein thrombosis. PMID:26977162

  11. Influence of olive and rosemary leaves extracts on chemically induced liver cirrhosis in male rats

    PubMed Central

    Al-Attar, Atef M.; Shawush, Nessreen A.

    2014-01-01

    The current study was undertaken to evaluate the protective activity of olive and rosemary leaves extracts on experimental liver cirrhosis induced by thioacetamide (TAA) in Wistar male rats. Highly significant decline in the values of body weight gain and highly statistically increase of liver/body weight ratio were noted in rats treated with TAA. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase and total bilirubin were statistically increased. Additionally, light microscopic examination of liver sections from rats treated with TAA showed a marked increase in the extracellular matrix collagen content and bridging fibrosis was prominent. There were bundles of collagen surrounding the lobules that resulted in large fibrous septa and distorted tissue architecture. Interestingly, the findings of this experimental study indicated that the extracts of olive and rosemary leaves and their combination possess hepatoprotective properties against TAA-induced hepatic cirrhosis by inhibiting the physiological and histopathological alterations. Moreover, these results suggest that the hepatoprotective effects of these extracts may be attributed to their antioxidant activities. PMID:25737646

  12. An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis

    PubMed Central

    Reiberger, Thomas; Chen, Yunching; Ramjiawan, Rakesh R; Hato, Tai; Fan, Christopher; Samuel, Rekha; Roberge, Sylvie; Huang, Peigen; Lauwers, Gregory Y; Zhu, Andrew X; Bardeesy, Nabeel; Jain, Rakesh K; Duda, Dan G

    2016-01-01

    Subcutaneous xenografts have been used for decades to study hepatocellular carcinoma (HCC). These models do not reproduce the specific pathophysiological features of HCCs, which occur in cirrhotic livers that show pronounced necroinflammation, abnormal angiogenesis and extensive fibrosis. As these features are crucial for studying the role of the pathologic host microenvironment in tumor initiation, progression and treatment response, alternative HCC models are desirable. Here we describe a syngeneic orthotopic HCC model in immunocompetent mice with liver cirrhosis induced by carbon tetrachloride (CCl4) that recapitulates key features of human HCC. Induction of substantial hepatic fibrosis requires 12 weeks of CCl4 administration. Intrahepatic implantation of mouse HCC cell lines requires 30 min per mouse. Tumor growth varies by tumor cell line and mouse strain used. Alternatively, tumors can be induced in a genetically engineered mouse model. In this setting, CCl4 is administered for 12 weeks after tail-vein injection of Cre-expressing adenovirus (adeno-Cre) in Stk4−/−Stk3F/− (also known as Mst1−/−Mst2F/−; F indicates a floxed allele) mice, and it results in the development of HCC tumors (hepatocarcinogenesis) concomitantly with liver cirrhosis. PMID:26203823

  13. Influence of olive and rosemary leaves extracts on chemically induced liver cirrhosis in male rats.

    PubMed

    Al-Attar, Atef M; Shawush, Nessreen A

    2015-03-01

    The current study was undertaken to evaluate the protective activity of olive and rosemary leaves extracts on experimental liver cirrhosis induced by thioacetamide (TAA) in Wistar male rats. Highly significant decline in the values of body weight gain and highly statistically increase of liver/body weight ratio were noted in rats treated with TAA. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase and total bilirubin were statistically increased. Additionally, light microscopic examination of liver sections from rats treated with TAA showed a marked increase in the extracellular matrix collagen content and bridging fibrosis was prominent. There were bundles of collagen surrounding the lobules that resulted in large fibrous septa and distorted tissue architecture. Interestingly, the findings of this experimental study indicated that the extracts of olive and rosemary leaves and their combination possess hepatoprotective properties against TAA-induced hepatic cirrhosis by inhibiting the physiological and histopathological alterations. Moreover, these results suggest that the hepatoprotective effects of these extracts may be attributed to their antioxidant activities.

  14. Progression of liver stiffness predicts clinical events in HIV/HCV-coinfected patients with compensated cirrhosis.

    PubMed

    Merchante, Nicolás; Téllez, Francisco; Rivero-Juárez, Antonio; Ríos-Villegas, Maria José; Merino, Dolores; Márquez-Solero, Manuel; Omar, Mohamed; Recio, Eva; Pérez-Pérez, Montserrat; Camacho, Ángela; Macías-Dorado, Sara; Macías, Juan; Lorenzo-Moncada, Sandra; Rivero, Antonio; Pineda, Juan A

    2015-12-07

    Our objective was to assess the predictive value of the changes of liver stiffness (LS) for clinical outcome in HIV/HCV-coinfected patients with compensated liver cirrhosis and a LS value < 40 kPa. Prospective cohort of 275 HIV/HCV-coinfected patients with cirrhosis, no previous liver decompensation (LD) and LS < 40 kPa. The time from diagnosis to LD and/or hepatocellular carcinoma (HCC) and the predictors of this outcome were evaluated. Significant progression of LS was defined as an increase ≥ 30 % over the baseline value at any time during the follow-up. After a median (Q1-Q3) follow-up of 32 (20-48) months, 19 (6.9 %, 95 % CI: 3.8 %-9.9 %) patients developed a first LD and/or HCC. At the end of the follow-up, 247 (90 %) patients had undergone a further LS examination. Of them, 77 (31 %) patients had a significant progression of LS. The mean (SD) survival time free of LD and/or HCC was 67 (3) and 77 (1) months in patients with or without significant progression of LS (p = 0.01). Significant progression of LS was an independent predictor of LD and/or HCC (Adjusted Hazard Ratio 4.63; 95 % confidence interval: 1.34-16.02; p = 0.015). Significant progression of LS is associated with a higher risk of clinical events in HIV/HCV-coinfected patients with compensated cirrhosis and LS < 40 kPa.

  15. AKI in patients with acute on chronic liver failure is different from acute decompensation of cirrhosis.

    PubMed

    Maiwall, Rakhi; Kumar, Suman; Chandel, Shivendra Singh; Kumar, Guresh; Rastogi, Archana; Bihari, Chhagan; Sharma, Manoj Kumar; Thakur, Bhaskar; Jamwal, K; Nayak, Suman; Mathur, R P; Sarin, S K

    2015-10-01

    The current definitions of acute kidney injury (AKI) including HRS have been derived from patients with decompensated cirrhosis. No studies have carefully addressed AKI in patients with acute on chronic liver failure (ACLF). We evaluated the prevalence, spectrum, natural history and mortality of AKI at admission and new-onset AKI in hospitalized patients with ACLF and compared the results with patients with acute decompensation of cirrhosis (ADC). Consecutive patients with ACLF (n = 382) and ADC (n = 451) were prospectively studied. Serial renal and liver functions were recorded and correlated with the disease course and outcome. AKI at admission and new onset AKI in the hospital were not different in patients with ACLF and ADC (p > 0.05). However, a significant difference in the spectrum of AKI was noted; functional volume-responsive AKI was more common (p < 0.05) in ADC, while patients with ACLF more frequently had the structural form of AKI (p < 0.05). Moreover, patients with ADC had significantly less AKI progression (p < 0.05) and prolonged duration (p < 0.05), a lower requirement of RRT (p < 0.05) and also less AKI resolution (p < 0.05) compared to ACLF patients. Patients with ACLF (versus ADC) had a significantly higher mortality on multivariate analysis. The kidneys are differentially affected in patients with cirrhosis with or without liver failure. Patients with ACLF with AKI have more structural AKI, greater potential for reversibility despite higher progression as well as higher mortality compared to patients with ADC. Prevention and early detection of AKI should be considered in patients with ACLF.

  16. Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity.

    PubMed

    Dionigi, Elena; Garcovich, Matteo; Borzio, Mauro; Leandro, Gioacchino; Majumdar, Avik; Tsami, Aikaterini; Arvaniti, Vasiliki; Roccarina, Davide; Pinzani, Massimo; Burroughs, Andrew K; O'Beirne, James; Tsochatzis, Emmanuel A

    2017-04-01

    We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis. We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria. We used competing risk analysis and propensity score matching for data analysis. 501 patients (63% male, 48% alcoholic liver disease, median Model of End-stage Liver Disease (MELD)=17) underwent 781 admissions over the study period. Portal hypertensive bleeding and complicated ascites were the commonest reasons of admission. The incidence of proven bacterial infection was 25.6% (60% community acquired and 40% nosocomial). Survival rates at 3, 6, 12, and 30 months were 83%, 77%, 71%, and 62% in patients without diagnosis of infection, vs. 50%, 46%, 41%, and 34% in patients with diagnosis of infection. Overall survival was independently associated with MELD score (hazards ratio (HR) 1.099), intensive care (ITU) stay (HR 1.967) and bacterial infection (HR 2.226). Bacterial infection was an independent predictor of survival even when patients who died within the first 30 days were excluded from the analysis in Cox regression (HR 2.013) and competing risk Cox models in all patients (HR 1.46) and propensity risk score-matched infected and non-infected patients (HR 1.67). Infection most likely represents a distinct prognostic stage of cirrhosis, which affects survival irrespective of disease severity, even after recovery from the infective episode.

  17. Does low-dose rifaximin ameliorate endotoxemia in patients with liver cirrhosis: a prospective study.

    PubMed

    Zeng, Xin; Tang, Xia Jiao; Sheng, Xia; Ni, Wu; Xin, Hai Guang; Chen, Wei Zhong; Jiang, Cai Feng; Lin, Yong; Shi, Jian; Shi, Bin; Chen, Yue Xiang; Yuan, Zong Li; Xie, Wei Fen

    2015-11-01

    To evaluate the efficacy, safety and tolerability of different doses of rifaximin in Chinese patients with liver cirrhosis. This random prospective study included a screening visit, a 2-week treatment period and a subsequent 4-week observation phase. Patients with liver cirrhosis were randomly assigned to a low-dose rifaximin group, a high-dose rifaximin group and the control group in a ratio of 1:1:1. The low-dose and high-dose groups received 400 mg or 600 mg rifaximin per 12 h for 2 weeks, respectively. All other therapeutic strategies remained unchanged in the three groups as long as possible. In total, 60 patients with liver cirrhosis were screened and 43 of them met the eligibility criteria. After 2-week treatment serum endotoxin levels in the low-dose (1.1 ± 0.8 EU/mL) and high-dose rifaximin groups (1.0 ± 0.8 EU/mL) were significantly lower than that in the control group (2.5 ± 1.8 EU/mL), while no significant difference was found between the two rifaximin-treated groups. The effect of high-dose rifaximin on endotoxemia lasted for at least 4 weeks after drug withdrawal. A significant reduction in the abundance of the Veillonellaceae taxa and an increase in the abundance of Bacteroidaceae were shown after 2 weeks of rifaximin therapy. The incidence of adverse events and severe adverse events was similar among the three groups. Low-dose (800 mg/day) rifaximin could be analogous to high-dose (1200 mg/day) rifaximin to reduce the serum endotoxin level after 2 weeks of treatment. © 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  18. Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a rat model of hereditary tyrosinemia type I

    PubMed Central

    Zhang, Ludi; Shao, Yanjiao; Li, Lu; Tian, Feng; Cen, Jin; Chen, Xiaotao; Hu, Dan; Zhou, Yan; Xie, Weifen; Zheng, Yunwen; Ji, Yuan; Liu, Mingyao; Li, Dali; Hui, Lijian

    2016-01-01

    Hereditary tyrosinemia type I (HT1) is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (Fah). Fah-deficient mice and pigs are phenotypically analogous to human HT1, but do not recapitulate all the chronic features of the human disorder, especially liver fibrosis and cirrhosis. Rats as an important model organism for biomedical research have many advantages over other animal models. Genome engineering in rats is limited till the availability of new gene editing technologies. Using the recently developed CRISPR/Cas9 technique, we generated Fah−/− rats. The Fah−/− rats faithfully represented major phenotypic and biochemical manifestations of human HT1, including hypertyrosinemia, liver failure, and renal tubular damage. More importantly, the Fah−/− rats developed remarkable liver fibrosis and cirrhosis, which have not been observed in Fah mutant mice or pigs. Transplantation of wild-type hepatocytes rescued the Fah−/− rats from impending death. Moreover, the highly efficient repopulation of hepatocytes in Fah−/− livers prevented the progression of liver fibrosis to cirrhosis and in turn restored liver architecture. These results indicate that Fah−/− rats may be used as an animal model of HT1 with liver cirrhosis. Furthermore, Fah−/− rats may be used as a tool in studying hepatocyte transplantation and a bioreactor for the expansion of hepatocytes. PMID:27510266

  19. Predictors of mortality among patients with compensated and decompensated liver cirrhosis: the role of bacterial infections and infection-related acute-on-chronic liver failure.

    PubMed

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

    2015-07-01

    Population-based data on the impact of bacterial infections on the course of compensated and decompensated cirrhosis as well as the occurrence, predictors of infection-related acute-on-chronic liver failure (ACLF) and its fatal outcome are limited. All patients with incident cirrhosis in the period 2001-2010, residing in an area of 600,000 inhabitants, were retrospectively identified. All serious bacterial infections (resulting in or occurring during an inpatient hospital episode) during this period were analyzed. Infection site and acquisition type, comorbid illness (Charlson comorbidity index) and infection severity features were analyzed. Patients were followed up until death, transplant, or the end of 2011. Overall, 398 serious bacterial infections occurred in 241/633 (38%) patients (106/332 diagnosed with compensated and 135/301 with decompensated disease; follow-up time was 2276 patient-years). ACLF occurred in 95/398 (24%) serious infections with an in-hospital mortality of 50%. In logistic regression analysis, the model for end-stage liver disease score, active alcohol misuse and healthcare-associated infections were predictors of infection-related ACLF (p < 0.05 for all). In-hospital mortality in infections with ACLF was related to albumin levels, Charlson comorbidity index >1 and occurrence of one or more organ failures (p > 0.05 for all). In Cox regression analysis, infection-related ACLF was an independent negative predictor of transplant-free survival in decompensated patients (p = 0.049). In a population-based cirrhotic cohort, infection-related ACLF was a negative predictor of survival in decompensated disease. Infection-related ACLF was frequent and related to cirrhosis severity and infection acquisition type, as well as to high inpatient mortality, in particular in patients with significant comorbidity.

  20. A novel fibrosis index comprising a non-cholesterol sterol accurately predicts HCV-related liver cirrhosis.

    PubMed

    Ydreborg, Magdalena; Lisovskaja, Vera; Lagging, Martin; Brehm Christensen, Peer; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Mørch, Kristine; Wejstål, Rune; Norkrans, Gunnar; Lindh, Magnus; Färkkilä, Martti; Westin, Johan

    2014-01-01

    Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV) infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5-6, as the outcome variable. A new index, referred to as Nordic Liver Index (NoLI) in the paper, was based on the model: Log-odds (predicting cirrhosis) = -12.17+ (age × 0.11) + (BMI (kg/m(2)) × 0.23) + (D7-lathosterol (μg/100 mg cholesterol)×(-0.013)) + (Platelet count (x10(9)/L) × (-0.018)) + (Prothrombin-INR × 3.69). The area under the ROC curve (AUROC) for prediction of cirrhosis was 0.91 (95% CI 0.86-0.96). The index was validated in a separate cohort of 83 patients and the AUROC for this cohort was similar (0.90; 95% CI: 0.82-0.98). In conclusion, the new index may complement other methods in diagnosing cirrhosis in patients with chronic HCV infection.

  1. An unusual cause of spontaneous bacterial peritonitis due to Campylobacter fetus with alcoholic liver cirrhosis

    PubMed Central

    Hadano, Yoshiro; Iwata, Hiroyoshi

    2013-01-01

    A 40-year-old man with severe alcoholic liver cirrhosis with a 2-day history of fatigue and abdominal pain was admitted. He reported eating sushi and sliced raw chicken a few days previously. His abdomen was distended, with shifting dullness. Based on the patient's history, physical examination and the results of abdominocentesis, he was diagnosed as having spontaneous bacterial peritonitis; blood and ascitic fluid cultures were positive for Campylobacter fetus. The patient was started on treatment with cefotaxime, which was switched after 1 week to ampicillin for an additional 3 weeks. The patient was successfully treated with the 4-week course of intravenous antibiotic therapy. PMID:23417384

  2. An unusual cause of spontaneous bacterial peritonitis due to Campylobacter fetus with alcoholic liver cirrhosis.

    PubMed

    Hadano, Yoshiro; Iwata, Hiroyoshi

    2013-02-14

    A 40-year-old man with severe alcoholic liver cirrhosis with a 2-day history of fatigue and abdominal pain was admitted. He reported eating sushi and sliced raw chicken a few days previously. His abdomen was distended, with shifting dullness. Based on the patient's history, physical examination and the results of abdominocentesis, he was diagnosed as having spontaneous bacterial peritonitis; blood and ascitic fluid cultures were positive for Campylobacter fetus. The patient was started on treatment with cefotaxime, which was switched after 1 week to ampicillin for an additional 3 weeks. The patient was successfully treated with the 4-week course of intravenous antibiotic therapy.

  3. [Multiple gangrene of the digits in a female patient with liver cirrhosis, diabetes mellitus and cryoglobulinemia].

    PubMed

    Lazarov, G; Tsanev, A

    1985-01-01

    A case is described with multiple gangrene of the fingers of a female, aged 55, with confirmed cirrhosis of liver and diabetes mellitus. Cryoglobulins were established in the serum. A disturbed immunological balance was present and the family loading with collagenosis raises the problem of genetic moments of the disturbed homeostasis. The existing diabetic microangiopathy, histologically confirmed by biopsy of skin and subcutaneous tissue, brings forward the question of the complex pathogenesis of gangrene. At the end of her stay in the clinic, the patient developed cerebral apoplexy.

  4. Small intestinal transit in patients with liver cirrhosis and portal hypertension: a descriptive study

    PubMed Central

    2012-01-01

    Background Gastrointestinal dysmotility may be involved in the development of bacterial translocation and infection in patients with liver cirrhosis. The aim of the present study was to describe gastric, small intestinal and colorectal motility and transit in patients with liver cirrhosis and portal hypertension using a magnet-based Motility Tracking System (MTS-1) and standard radiopaque markers. Methods We included 15 patients with liver cirrhosis (8 Child-Pugh A, 6 Child-Pugh B, and 1 Child-Pugh C) and portal hypertension (11 males, median age 54 years (range 38–73), median hepatic venous pressure gradient 18 mmHg (range 12–37)), and 18 healthy controls (8 males, median age 58 years (range 34–64)). The gastric emptying time and small intestinal motility were evaluated by MTS-1, and the total gastrointestinal transit time was assessed by radiopaque markers and abdominal radiographs. Results The velocity through the proximal small intestine was significantly higher in cirrhotic patients (median 1.27 metres (m)/hour, range 0.82–2.68) than in the healthy controls (median 1.00 m/hour, range 0.46–1.88) (p = 0.03). Likewise, the magnet travelled significantly longer in both fast (p = 0.04) and slow movements (p = 0.05) in the patient group. There was no significant difference in either gastric emptying time—23 minutes (range 5–131) in patients and 29 minutes (range 10.5–182) in healthy controls (p = 0.43)—or total gastrointestinal transit time—1.6 days (range 0.5–2.9) in patients and 2.0 days (range 1.0–3.9) in healthy controls (p = 0.33). No correlation was observed between the hepatic venous pressure gradient and the velocity of the magnet through the small intestine. Conclusion Patients with liver cirrhosis and portal hypertension demonstrated faster-than-normal transit through the proximal small intestine. This may be due to an overactive bowel, as suggested by previous studies. PMID:23216853

  5. [Acidifying therapy in the combined treatment of patients with liver cirrhosis].

    PubMed

    Chervak, I M

    1998-01-01

    Data are submitted of clinical and biochemical examination of patients with cirrhosis of the liver complicated by different type encephalopathy. Examined before treatment and after the course of therapy involving administration of the acidifying drugs normase, dufalak were patients presenting with manifestations of hepatodepressive syndrome, parenchymal, mixed-type portosystemic encephalopathy, with n = 27, 12, 23 and 38 respectively. Clinical, biochemical findings, time course of the ratio blood serum levels of anticerebrotoxic: cerebrotoxic amino acids (valin + leucine + isoleucine) allowed judgement about efficacies of the treatments administered. The results obtained showed high clinical benefit from treatment with normase and dufalak in patients with hepatodepressive syndrome and portal-systemic encephalopathy.

  6. Estimating the cost of treating patients with liver cirrhosis at the Mexican Social Security Institute.

    PubMed

    Quiroz, María Esther; Flores, Yvonne N; Aracena, Belkis; Granados-García, Víctor; Salmerón, Jorge; Pérez, Ruth; Cabrera, Guillermo; Bastani, Roshan

    2010-01-01

    To estimate the annual cost of treating patients with cirrhosis at the Mexican Institute of Social Security (IMSS per its abbreviation in Spanish). The annual cost of treating three stages of cirrhosis (Child-Pugh A, Child-Pugh B and Child-Pugh C) was estimated using micro-costing techniques and medical experts. These results were compared and contrasted with prices reported by IMSS. The annual cost of treatment, in USA dollars, by Child-Pugh stage was: a) micro-costing results: $1110.17 stage A, $549.55 stage B and $348.16 stage C; b) opinion of medical experts: $1 633.64, $6564.04 and $19660.35, respectively; and c) IMSS costs: $4269.00, $16949.63 and $30249.25, respectively. The cost of treating patients with cirrhosis is considerable, and costs increase as the disease worsens. Cost estimates vary depending on the source of information, and the methodology used. There are discrepancies between the procedures reported in medical records and treatment recommendations by IMSS liver experts.

  7. AISF-SIMTI position paper: the appropriate use of albumin in patients with liver cirrhosis

    PubMed Central

    Caraceni, Paolo; Angeli, Paolo; Prati, Daniele; Bernardi, Mauro; Liumbruno, Giancarlo M.; Bennardello, Francesco; Piccoli, Pierluigi; Velati, Claudio

    2016-01-01

    The use of human albumin is common in hepatology since international scientific societies support its administration to treat or prevent severe complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction after large-volume paracentesis and renal failure induced by spontaneous bacterial peritonitis, and the treatment of hepatorenal syndrome in association with vasoconstrictors. However, these indications are often disregarded, mainly because the high cost of human albumin leads health authorities and hospital administrations to restrict its use. On the other hand, physicians often prescribe human albumin in patients with advanced cirrhosis for indications that are not supported by solid scientific evidence and/or are still under investigation in clinical trials. In order to implement appropriate prescription of human albumin and to avoid its futile use, the Italian Association for the Study of the Liver (AISF) and the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) nominated a panel of experts, who reviewed the available clinical literature and produced practical clinical recommendations for the use of human albumin in patients with cirrhosis. PMID:26820615

  8. 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

  9. AISF-SIMTI position paper: the appropriate use of albumin in patients with liver cirrhosis.

    PubMed

    Caraceni, Paolo; Angeli, Paolo; Prati, Daniele; Bernardi, Mauro; Liumbruno, Giancarlo M; Bennardello, Francesco; Piccoli, Pierluigi; Velati, Claudio

    2016-01-01

    The use of human albumin is common in hepatology since international scientific societies support its administration to treat or prevent severe complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction after large-volume paracentesis and renal failure induced by spontaneous bacterial peritonitis, and the treatment of hepatorenal syndrome in association with vasoconstrictors. However, these indications are often disregarded, mainly because the high cost of human albumin leads health authorities and hospital administrations to restrict its use. On the other hand, physicians often prescribe human albumin in patients with advanced cirrhosis for indications that are not supported by solid scientific evidence and/or are still under investigation in clinical trials.In order to implement appropriate prescription of human albumin and to avoid its futile use, the Italian Association for the Study of the Liver (AISF) and the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) nominated a panel of experts, who reviewed the available clinical literature and produced practical clinical recommendations for the use of human albumin in patients with cirrhosis.

  10. Liver cirrhosis deaths within occupations and industries in the California occupational mortality study.

    PubMed

    Leigh, J P; Jiang, W Y

    1993-06-01

    Mortality rates were drawn from the California Occupational Mortality Study (COMS) to analyze liver cirrhosis deaths within occupations and industries from 1979 to 1981. Age-adjusted Standardized Mortality Rates (SMRs) were made available by the State of California for separate analyses of women, men, blacks and whites. Rankings of occupations with narrow confidence intervals were strikingly similar for blacks and whites. Within occupations, the highest female SMRs were for waitresses, telephone operators, cosmetologists, dress makers, hospital orderlies, textile workers, and laborers. The lowest female SMRs were for skilled crafts workers and teachers. High male occupations included water transportation workers, bartenders, loggers, laborers, roofers, construction workers, farm workers, iron workers, and painters. Low male occupations included teachers, physicians and dentists, managers, factory supervisors, business sales workers, heavy equipment operators, and other professionals. High female industries included eating and drinking places, laundry/dry cleaning, nursing and personal care facilities, aerospace, beauty shops, and entertainment. Low female industries included wholesale trades and education. High male industries included water transportation, military, guard services, eating and drinking places, iron and steel mills, and railroads. Low male industries included research/engineering labs, education, and computer manufacturing. This study was descriptive. It remains unknown whether certain jobs cause excessive drinking and cirrhosis, or whether people who are prone to develop cirrhosis select certain jobs.

  11. 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

  12. The role of hepatic myofibroblasts in liver cirrhosis in fallow deer (Dama dama) naturally infected with giant liver fluke (Fascioloides magna).

    PubMed

    Marinković, Darko; Kukolj, Vladimir; Aleksić-Kovačević, Sanja; Jovanović, Milijan; Knežević, Milijana

    2013-03-06

    This paper describes liver cirrhosis in 35 fallow deer infected with the giant liver fluke, as well as the distribution, origin, and role of myofibroblasts in its development. In liver of infected deer, stripes of connective tissue are wound around groups of degenerated and regenerated liver lobuli. In the connective tissue, lymphocytes and macrophages which often contain parasite hematin are also present. The walls of the bile ducts are thickened, the epithelium multiplied with mucous metaplasia, and desquamated cells, parasite eggs and brown pigment are present in their lumen.In the livers with cirrhosis, immunopositivity to α-SMA and desmin was observed in cells in portal and septal spaces, at the edge between fibrotic septa and the surrounding parenchyma and in perisinusoidal spaces. These cells vary in size, they are round, oval, spindle-shaped or irregular in shape, similar to vascular smooth muscle cells. The derangement of epithelial-mesenchymal interactions detected in chronic cholangiopathies is most probably the pro-fibrogenic mechanism in liver cirrhosis of fallow deer (Dama dama) infected with the giant liver fluke (Fascioloides magna). Myofibroblasts, especially hepatic stellate cells (HSCs), play an important role in the synthesis of extracellular matrix components in the development of parasitic fibrosis and cirrhosis in the liver of fallow deer.

  13. Transient elastography for diagnosis of stages of hepatic fibrosis and cirrhosis in people with alcoholic liver disease.

    PubMed

    Pavlov, Chavdar S; Casazza, Giovanni; Nikolova, Dimitrinka; Tsochatzis, Emmanuel; Burroughs, Andrew K; Ivashkin, Vladimir T; Gluud, Christian

    2015-01-22

    The presence and progression of hepatic (liver) fibrosis into cirrhosis is a prognostic variable having impact on survival in people with alcoholic liver disease. Liver biopsy, although an invasive method, is the recommended 'reference standard' for diagnosis and staging of hepatic fibrosis in people with liver diseases. Transient elastography is a non-invasive method for assessing and staging hepatic fibrosis. To determine the diagnostic accuracy of transient elastography for diagnosis and staging hepatic fibrosis in people with alcoholic liver disease when compared with liver biopsy. To identify the optimal cut-off values for differentiating the five stages of hepatic fibrosis. The Cochrane Hepato-Biliary Group Controlled and Diagnostic Test Accuracy Studies Registers, The Cochrane Library, MEDLINE (OvidSP), EMBASE (OvidSP), and the Science Citation Index Expanded (last search August 2014). Diagnostic cohort and diagnostic case-control study designs that assessed hepatic fibrosis in participants with alcoholic liver disease with transient elastography and liver biopsy, irrespective of language or publication status. The study participants could be of any sex and ethnic origin, above 16 years old, hospitalised or managed as outpatients. We excluded participants with viral hepatitis, autoimmunity, metabolic diseases, and toxins. We followed the guidelines in the draft Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. Five retrospective and nine prospective cohort studies with 834 participants provided data for the review analyses. Authors of seven of those studies sent us individual participant data. The risk of bias in the included studies was high in all but three studies. We could identify no serious concerns regarding the applicability of the studies in answering the main study question of our review, namely to use transient elastography to diagnose hepatic fibrosis. We could not identify the optimal cut-off values for the fibrosis stages

  14. Renal dysfunction in liver cirrhosis: renal duplex Doppler US vs. scintigraphy for early identification.

    PubMed

    Al-Kareemy, E A; Sobh, M A; Muhammad, A M; Mostafa, M M; Saber, R A

    1998-01-01

    A diagnostic tool to detect early renal dysfunction before it becomes irreversible would be useful in cirrhosis. This study was carried out to evaluate the role of Doppler sonography and Tc-99m DTPA renography in the detection of early renal dysfunction in patients with different grades of liver cirrhosis. Renal arteries of 43 patients with cirrhosis and normal renal function tests were compared with 15 age and gender matched normal subjects as a control group using colour Doppler sonography and Tc-99m DTPA scintigraphy. The patients were categorized into three groups, A (14), B (14) and C (15), according to a modified Child's classification that assesses the severity of liver cirrhosis. Doppler results revealed a highly significant increase in both the pulsatility and resistive indices in groups B and C compared with either group A patients or control subjects and in group C compared with group B (P < 0.001) in the main renal arteries as well as in the interlobar and arcuate arteries. Insignificant differences were observed between group A and controls (PI: control 0.96+/-0.08, group A 0.95+/-0.07, group B 1.26+/-0.06, group C 1.48+/-0.06; RI: control 0.57+/-0.02, group A 0.58+/-0.02, group B 0.66+/-0.01, group C 0.72+/-0.02). Abnormal renograms in the form of delayed appearance (34+/-14.6 s), diminished blood flow bilaterally with prolonged secretory (12+/-4.5 min) and excretory phases (> 30 min) and poor response to intravenous frusemide were only observed in group C patients. Radionuclide computed glomerular filtration rate was within the normal range in patients of group A (81+/-9.5 ml/min) and group B (78+/-8.4 ml/min) and reduced only in patients of group C (34+/-14.5 ml/min). Thus Doppler sonography can detect an increase in renal vascular resistance in patients with moderately severe cirrhosis (Child grade B) when renography was normal. We conclude that Doppler sonography can be used for earlier identification of cirrhotic patients with a higher risk of

  15. Safety of ERCP in patients with liver cirrhosis: a national database study

    PubMed Central

    Navaneethan, Udayakumar; Njei, Basile; Zhu, Xiang; Kommaraju, Kiran; Parsi, Mansour A.; Varadarajulu, Shyam

    2017-01-01

    Background and aims Given the limited data on the safety of endoscopic retrograde cholangiopancreatography (ERCP) in patients with liver cirrhosis, we attempted to evaluate this question using a large national database. Methods We conducted a matched case – control study using the 2010 National Inpatient Sample database in which four non-cirrhotic controls were matched randomly for every cirrhotic patient from the same 10-year age group. We compared adverse events and safety of inpatient ERCP between patients with (n = 3228) and without liver cirrhosis (controls, n = 12 912). Results Of the 3228 cirrhotic patients, 2603 (80.6 %) had decompensated and 625 (19.4 %) had compensated disease. Post-procedure bleeding (2.1 % vs. 1.2 %, P < 0.01) was higher in patients compared to controls. On multivariable analysis, decompensated cirrhosis (adjusted odds ratio [aOR], 2.7; 95 % confidence interval [CI], 2.2 – 3.2), compensated cirrhosis (aOR 2.2; 95 %CI 1.2 – 3.9), therapeutic ERCPs (aOR 1.4; 95 % CI 1.2 – 2.1), and biliary sphincterotomy (aOR 1.6; 95 %CI 1.1 – 2.1) were independently associated with increased risk of post-procedure bleeding. Performing ERCPs in large (aOR 0.5; 95 %CI 0.4 – 0.6) and medium (aOR 0.7; 95 %CI 0.6 – 0.9) sized hospitals was associated with a decreased risk of post-procedure bleeding. Biliary sphincterotomy (aOR 1.7; 95 %CI 1.2 – 2.3) and therapeutic ERCPs (aOR 1.1; 95 %CI 1.1 – 1.3) increased the risk of post-ERCP pancreatitis, and pancreatic stent placement was associated with a decreased risk of post-ERCP pancreatitis (aOR 0.8; 95 %CI 0.7 – 0.9). Conclusions Cirrhosis (both compensated and decompensated), performing therapeutic ERCPs and biliary sphincterotomy increase the risk of post-procedure bleeding. Performing ERCPs in large and medium sized hospitals may improve outcomes. PMID:28393104

  16. Heteropolymerization of S, I, and Z α1-antitrypsin and liver cirrhosis

    PubMed Central

    Mahadeva, Ravi; Chang, Wun-Shaing W.; Dafforn, Timothy R.; Oakley, Diana J.; Foreman, Richard C.; Calvin, Jacqueline; Wight, Derek G.D.; Lomas, David A.

    1999-01-01

    The association between Z α1-antitrypsin deficiency and juvenile cirrhosis is well-recognized, and there is now convincing evidence that the hepatic inclusions are the result of entangled polymers of mutant Z α1-antitrypsin. Four percent of the northern European Caucasian population are heterozygotes for the Z variant, but even more common is S α1-antitrypsin, which is found in up to 28% of southern Europeans. The S variant is known to have an increased susceptibility to polymerization, although this is marginal compared with the more conformationally unstable Z variant. There has been speculation that the two may interact to produce cirrhosis, but this has never been demonstrated experimentally. This hypothesis was raised again by the observation reported here of a mixed heterozygote for Z α1-antitrypsin and another conformationally unstable variant (I α1-antitrypsin; 39Arg→Cys) identified in a 34-year-old man with cirrhosis related to α1-antitrypsin deficiency. The conformational stability of the I variant has been characterized, and we have used fluorescence resonance energy transfer to demonstrate the formation of heteropolymers between S and Z α1-antitrypsin. Taken together, these results indicate that not only may mixed variants form heteropolymers, but that this can causally lead to the development of cirrhosis. PMID:10194472

  17. Effective control of relapsing disseminated intravascular coagulation in a patient with decompensated liver cirrhosis by recombinant soluble thrombomodulin.

    PubMed

    Hasebe, Takumu; Sawada, Koji; Nakajima, Shunsuke; Maeda, Shigeaki; Abe, Masami; Suzuki, Yasuaki; Ohtake, Takaaki; Hasebe, Chitomi; Fujiya, Mikihiro; Kohgo, Yutaka

    2014-01-01

    A 70-year-old Japanese man was hospitalized for expanding purpura and chronic disseminated intravascular coagulation (DIC) caused by decompensated liver cirrhosis. As there are no effective treatments for chronic DIC caused by liver cirrhosis, we decided to administer recombinant human soluble thrombomodulin (rhsTM) after he provided informed consent. The DIC was rapidly improved; however, the purpura and coagulopathy recurred after two months, and repeated rhsTM treatments were required. The rhsTM treatment sufficiently controlled the coagulopathy for two years, without any complications, including bleeding. This is the first report demonstrating that rhsTM can be administered safely and repeatedly to a patient with decompensated liver cirrhosis, and that it appears to be associated with a favorable outcome.

  18. Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats.

    PubMed

    Kusumoto, Kazunori; Ido, Akio; Moriuchi, Akihiro; Katsura, Toshiya; Kim, Ildeok; Takahama, Yuka; Numata, Masatsugu; Kodama, Mayumi; Hasuike, Satoru; Nagata, Kenji; Uto, Hirofumi; Inui, Ken-Ichi; Tsubouchi, Hirohito

    2006-03-01

    Hepatocyte growth factor (HGF) is a promising agent for the treatment of liver cirrhosis because of its mitogenic and anti-fibrotic effects. We investigated the effect of recombinant human HGF (rh-HGF) on cirrhosis development; its pharmacokinetics and nephrotoxicity in rats with liver cirrhosis induced by 4-week treatment with dimethylnitrosamine (DMN). rh-HGF (0.3 mg/kg) was intravenously administered to rats once a day for 4 weeks in parallel with DMN treatment or twice a day for the last 2 weeks of DMN treatment. Repeated doses of rh-HGF increased the liver weight and serum albumin, and reduced serum ALT. The development of hepatic fibrosis was inhibited more efficiently by extended low-dose treatment with rh-HGF. In cirrhotic rats, serum levels of rh-HGF increased and clearance was decreased, leading to an increase in the area under the plasma-concentration time curve and a decrease in the steady-state volume of distribution. Repeated doses of rh-HGF led to increased urinary albumin excretion, but no rh-HGF-treated animals developed increased serum creatinine levels. Urinary albumin excretion returned to baseline after the cessation of rh-HGF. These results suggest that extended treatment with rh-HGF is required for the attenuation of cirrhosis, and repeated doses of rh-HGF cause adverse effects in extra-hepatic organs. These issues must be resolved before the widespread application of rh-HGF in the treatment of liver cirrhosis.

  19. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues.

    PubMed

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health.Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper,we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameter scan provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  20. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues

    NASA Astrophysics Data System (ADS)

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health. Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper, we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameters can provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  1. Dynamics of liver stiffness values by means of transient elastography in patients with HCV liver cirrhosis undergoing interferon free treatment.

    PubMed

    Sporea, Ioan; Lupușoru, Raluca; Mare, Ruxandra; Popescu, Alina; Gheorghe, Liana; Iacob, Speranța; Șirli, Roxana

    2017-06-01

    Liver stiffness (LS) measurement by Transient Elastography (TE) has been widely accepted as a tool for fibrosis assessment. The aim of this study was to assess LS dynamics in a group of patients with HCV liver cirrhosis after interferon free treatment (IFT). This two-center clinical trial included 225 patients with compensated HCV cirrhosis (all genotype 1b), who received IFT for 12 weeks. All patients were evaluated by means of TE at the beginning and at the end of treatment (EOT), and a subgroup (170 patients) also 12 weeks after EOT; all of them had sustained viral response (SVR). Reliable LS measurements (LSM) were defined as a median value of 10 valid LSM, with IQR <30% and SR >/=60%. Both M and XL probes were used. For diagnosing cirrhosis we used a cut-off value of 12kPa as proposed by the Tsochatzis meta-analysis. We considered a decrease or increase of more than 10% in LSM as being significant. Out of 225 subjects, reliable measurements were obtained in 93.7%, so that the final analysis included 211 patients. The mean LS values decreased significantly after IFT: 26.4+/-11.7 vs. 23.5+/-13.3 kPa (p=0.01). Most patients, 59.2% (125/211) presented more than 10% decrease in LS values, 24.1% (51/211) had stable LS values, while in 16.4% (35/211) cases, the LS values increased. In the subgroup of 170 patients with LSM also performed 12 weeks after EOT (SVR), the mean LS values were significantly lower as compared to baseline: 21.3+/-11 kPa vs. 27.4+/-11.9 kPa (p<0.0001) and also as compared to EOT: 21.3+/-11 kPa vs. 23.7+/-13.3 kPa (p<0.0001). In our patients with HCV liver cirrhosis, the mean LS values evaluated by TE significantly decreased after antiviral treatment at EOT and also 12 weeks after EOT as compared to baseline. Overall, about 60% of patients had LS values at EOT lower than at baseline, while 12 weeks after EOT about 75% of patients had LS values lower than at baseline.

  2. Outcomes after liver transplantation for alcoholic hepatitis are similar to alcoholic cirrhosis: exploratory analysis from the UNOS database.

    PubMed

    Singal, Ashwani K; Bashar, Hmoud; Anand, Bhupinderjit S; Jampana, Sarat C; Singal, Vineet; Kuo, Yong-Fang

    2012-05-01

    Data on liver transplantation for patients with alcoholic hepatitis are limited. Using the United Network for Organ Sharing database (2004-2010), adults undergoing liver transplantation for a listing diagnosis of alcoholic hepatitis were matched for age, gender, ethnicity, and model for endstage disease (MELD) score, donor risk index, and year of transplantation with three patients transplanted for a listing diagnosis of alcoholic cirrhosis. Study outcomes of graft and patient survival on follow-up were also analyzed for cohorts based on the diagnosis of the explant (46 alcoholic hepatitis and 138 alcoholic cirrhosis) and diagnosis at both listing as well as of the explant (11 alcoholic hepatitis and 33 alcoholic cirrhosis). Five-year graft and patient survival of alcoholic hepatitis and alcoholic cirrhosis patients were 75% and 73% (P = 0.97) and 80% and 78% (P = 0.90), respectively. Five-year graft and patient survival rates were also similar for cohorts based on diagnosis of the explant and diagnosis at listing as well as explant. Cox proportional regression analysis adjusting for other variables showed no impact of the etiology of liver disease (alcoholic hepatitis versus alcoholic cirrhosis) on the graft and patient survival. The causes of graft loss and patient mortality were similar in the two groups, and were not alcohol-related in any patient. Compared with alcoholic cirrhosis, patients with alcoholic hepatitis have similar posttransplantation graft and patient survival. Based on these preliminary findings, liver transplantation may be considered in a select group of patients with alcoholic hepatitis who fail to improve with medical therapy. Prospective studies are needed to assess the long-term outcome after liver transplantation in patients with alcoholic hepatitis. Copyright © 2011 American Association for the Study of Liver Diseases.

  3. Prospective study of profile of hepatic osteodystrophy in patients with non-choleastatic liver cirrhosis and impact of bisphosphonate supplementation

    PubMed Central

    Bansal, Rinkesh Kumar; Kumar, Mandhir; Kumar, Ashish

    2015-01-01

    Background and objectives Patients with liver cirrhosis are more prone to develop reduced bone mineral density (BMD), i.e. hepatic osteodystrophy (HOD). There are few data on the prevalence of HOD in the Indian population and its treatment. We aimed to determine the prevalence of HOD, factors associated with it and the impact of bisphosphonates on BMD in patients with liver cirrhosis. Patients and methods Consecutive patients with liver cirrhosis admitted at Sir Ganga Ram Hospital, New Delhi, between August 2012 and July 2013 were enrolled. Patients with chronic kidney disease, hyperparathyroidism and those on steroids were excluded. BMD was measured by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine and femoral neck. Osteopenia and osteoporosis were defined according to WHO criteria. Ibandronic acid 150 mg per day orally for six months was given to patients with osteoporosis and DEXA scan repeated. Results A total of 215 patients (males 179, 83%) with a mean age of 50.9 ± 11 years were enrolled in this study. Prevalence of HOD was found to be 66% (142/215). On multivariate analysis BMI, TLC, total serum bilirubin and transient elastography values were found to be independently associated with HOD. All the patients with osteoporosis (n = 47) were treated with ibandronic acid as per protocol. Treated patients had significant improvement in DEXA scans after six months as compared to baseline. Conclusions HOD was seen in two-thirds of patients with liver cirrhosis. Higher liver stiffness as determined by transient elastography is significantly associated with HOD. Severity scores of liver disease (CTP and MELD) and etiology of liver cirrhosis did not determine HOD. Ibandronic acid is a safe drug that showed significant improvement in BMD in patients with liver disease along with osteoporosis. PMID:26966526

  4. [Dental and salivary alterations in patients with liver cirrhosis: a study of 100 cases].

    PubMed

    Bagán, J V; Alapont, L; Sanz, C; del Olmo, J A; Morcillo, E; Cortijo, J; Milián, M A; Rodrigo, J M

    1998-07-04

    The aim of the present study was to investigate the existence of differences in dental status and in quantitative and qualitative salivary values between 100 patients with liver cirrhosis (LC) and a group of controls. We analyzed the number of carious, missing and filled teeth. Also the unstimulated (UWS) and stimulated whole saliva flow rates (SWS) were determined, along with the stimulated parotid saliva flow rate (PSS) and the concentration in both UWS and SWS of sodium, potassium, total proteins and immunoglobulin A (IgA). A significantly higher number of carious and missing teeth was observed in the patients with cirrhosis (2.4 and 14.6, respectively) than in the control group (1.3 and 10.6, respectively), and a higher stimulated parotid flow rate with LC (0.64 and 0.44, respectively; p < 0.02) with a decrease in sodium and an increase in potassium, total proteins and IgA in patients with cirrhosis. In the LC group, caries were found to affect more teeth in those patients with alcohol-induced LC than in those with liver disease of other causes (3.9 and 1.7, respectively; p < 0.05), but in contrast, no differences were found in the saliva flow rate and the concentration in both UWS and SWS of sodium, potassium, total proteins and IgA. Finally, no relationship was observed between the dental status and functional hepatic tests. CH patients showed a worse dental status, a higher SPS rate and some electrolytes and proteins alterations.

  5. Free amino acids in plasma and skeletal muscle of patients with liver cirrhosis.

    PubMed

    Montanari, A; Simoni, I; Vallisa, D; Trifirò, A; Colla, R; Abbiati, R; Borghi, L; Novarini, A

    1988-01-01

    Free amino acids were measured under postabsorptive conditions in plasma and intracellular water of skeletal muscle obtained by needle biopsy in nine healthy controls and 14 subjects suffering from clinically stable liver cirrhosis. The aromatic amino acids phenylalanine and tyrosine in cirrhotics were elevated to the same extent in plasma and in muscle water. Branched-chain amino acids were uniformly reduced in plasma, but in muscle water only valine was significantly lower (222 +/- 92 mumoles per kg intracellular water vs. 368 +/- 82, p less than 0.001), while isoleucine (142 +/- 63 vs. 103 +/- 30), leucine (223 +/- 88 vs. 226 +/- 36) and branched-chain amino acids as a whole (589 +/- 186 vs. 681 +/- 88) were normal or elevated with an increased muscle:plasma ratio (3.12 +/- 2.03 vs. 1.41 +/- 0.37, p less than 0.05 for isoleucine; 3.00 +/- 1.28 vs. 1.85 +/- 0.27, p less than 0.025 for leucine; 2.24 +/- 0.64 vs. 1.69 +/- 0.13, p less than 0.05 for total branched-chain amino acids. Our data show that, in cirrhosis, plasma concentrations of branched-chain amino acids do not reflect their levels in muscle cellular water; only the intracellular pool of valine is severely depleted. This suggests that higher amounts of valine supplementation may be useful in nutritional treatment of liver cirrhosis. The elevated muscle:plasma gradients for branched-chain amino acids may result from abnormalities in their transport through muscle-plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Intestinal first pass metabolism of midazolam in liver cirrhosis – effect of grapefruit juice

    PubMed Central

    Andersen, Vibeke; Pedersen, Natalie; Larsen, Niels-Erik; Sonne, Jesper; Larsen, Steen

    2002-01-01

    Aims Grapefruit juice inhibits CYP3A4 in the intestinal wall leading to a reduced intestinal first pass metabolism and thereby an increased oral bioavailability of certain drugs. For example, it has been shown that the oral bioavailability of midazolam, a CYP3A4 substrate, increased by 52% in healthy subjects after ingestion of grapefruit juice. However, this interaction has not been studied in patients with impaired liver function. Accordingly, the effect of grapefruit juice on the AUC of midazolam and the metabolite α-hydroxymidazolam was studied in patients with cirrhosis of the liver. Methods An open randomized two-way crossover study was performed. Ten patients (3 females, 7 males) with liver cirrhosis based on biopsy or clinical criteria participated. Six patients had a Child-Pugh score of A, one B and three C. Tap water (200 ml) or grapefruit juice were consumed 60 and 15 min before midazolam (15 mg) was administered orally. Plasma samples were analysed for midazolam and α-hydroxymidazolam. Results Grapefruit juice increased the AUC of midazolam by 106% (16, 197%) (mean (95% confidence interval)) and the AUC of the metabolite α-hydroxymidazolam decreased to 25% (12, 37%) (P < 0.05 for both). The ratio of the AUCs of the metabolite α-hydroxymidazolam to midazolam decreased from 0.77 (0.46, 1.07) to 0.11 (0.05, 0.19) (P<0.05). t1/2 remained unaltered for both drug and metabolite. Midazolam Cmax, tmax, and α-hydroxymidazolam tmax increased, but these changes were not statistically significant, whereas Cmax of the metabolite decreased to 30% (14, 47%) (P<0.05). Conclusions A marked interaction between oral midazolam and grapefruit juice was found and the data are consistent with a reduced first-pass metabolism of midazolam. This is likely to occur at the intestinal wall inhibition of CYP3A4 activity by grapefruit juice. These results indicate that patients with liver cirrhosis are more dependent on the intestine for metabolism of CYP3A4 substrates than

  7. [Fulminant hepatitis induced by disulfiram in a patient with alcoholic cirrhosis. Survival after liver transplantation].

    PubMed

    Vanjak, D; Samuel, D; Gosset, F; Derrida, S; Moreau, R; Soupison, T; Soulier, A; Bismuth, H; Sicot, C

    1989-12-01

    Fulminant hepatitis was observed in a 44-year-old patient with cirrhosis, 38 days after the beginning of a treatment by disulfiram. Hepatitis was associated with fever and hypereosinophilia. Liver transplantation was performed with success. We reviewed 15 previously published cases of disulfiram-induced hepatitis. They occurred from 10 to 180 days after the beginning of the treatment by disulfiram, aminotransferases were increased whereas alkaline phosphatases were not markedly changed; there was either focal or widespread necrosis. Fulminant hepatitis was observed mainly in patients with alcoholic chronic liver disease or in patients who continued to ingest disulfiram while jaundice was already present. An immunoallergic mechanism is thought to be responsible for disulfiram-induced hepatitis.

  8. Treatment of patients with HBV-related decompensated cirrhosis and liver transplanted patients.

    PubMed

    Roche, Bruno; Samuel, Didier

    2013-08-01

    Antiviral therapy using newer nucleos(t)ide analogs with lower resistance rates could suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, delay or obviate liver transplantation in some patients, and reduce the risk of HBV recurrence. Some form of HBV prophylaxis needs to be continued indefinitely posttransplant. However, in patients with a low-risk of HBV recurrence it is possible to discontinue hepatitis B immunoglobulins and maintain long-term nucleos(t)ide analog therapy. Currently, treatment of posttransplantation hepatitis B is a less important clinical problem than it was historically because effective antiviral therapies exist to rescue patients who failed initial prophylaxis.

  9. Modulation of thioacetamide-induced liver fibrosis/cirrhosis by sildenafil treatment.

    PubMed

    Said, Eman; Said, Shehta A; Gameil, Nariman M; Ammar, Elsayed M

    2013-12-01

    Sildenafil citrate is a phosphodiesterase-5 inhibitor, approved for the treatment of erectile dysfunction. It enhances nitric-oxide-induced vasodilatation and it promotes angiogenesis. A relationship between angiogenesis and hepatic fibrosis has long been speculated, where the 2 are believed to progress together. In this study, the ability of sildenafil (10 mg·(kg body mass)(-1), orally, once daily) to prevent and also reverse liver fibrosis/cirrhosis experimentally induced by thioacetamide injection (200 mg·kg(-1), intraperitoneal (i.p.), 3 times·week(-1)) in male Sprague-Dawley rats has been investigated. Sildenafil administration, either to prevent or to reverse liver fibrosis/cirrhosis significantly improved the estimated hepatic functions, reduced hepatic hydroxyproline and, in turn, hepatic collagen content, as well as reducing serum levels of the pro-fibrogenic mediator transforming growth factor β1. In co-ordination with such improvement, fibrosis grades declined and fibrosis retracted. Herein, the observed results provide evidence for the potential therapeutic efficacy of sildenafil as an antifibrotic agent.

  10. [A case of Pasteurella multocida subsp. multocida septicemia due to cat bites in liver cirrhosis patient].

    PubMed

    Shimizu, T; Hasegawa, K; Mitsuhashi, Y; Kojima, S; Ishikawa, K; Hayashi, N; Sawada, T

    1995-11-01

    A 60-year-old male who had been suffering from liver cirrhosis was admitted to our hospital with high grade fever accompanied by right chest pain. Chest X-rays revealed a moderate amount of pleural fluid suggesting pleuritis. Multocida was isolated from the blood culture as well as the pleural fluid. Antibiotic therapy was initiated according to the drug susceptibility of the isolates. Ten days treatment was effective on the cessation of both septicemia and the clinical symptoms. Since the patient had been bitten several times by his own pet cats, their mouth swabs were taken for pathogenic investigations. Serotypes of the cats' isolates coincided with that of the patient's which consequently indicated the route of infection. P. multocida is a Gram negative coccobacillary organism that resides as normal flora in the oral cavity of animals, including dogs and cats. It has been originally known to be a causative agent for hemorrhagic septicemia in domestic animals. However, recently reports of P. multocida infections in man has been increasing due to the enlargement of pet populations. Although outbreaks of septicemia is rare, it occurs most often in immunologically compromised hosts, including patients with liver cirrhosis as in this case. Therefore, it is important to initiate an urgent antibiotic therapy in such cases. Overall, it is of utmost importance to instruct immunosuppressed patients to avoid excessive exposure to animals including pets.

  11. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico

    PubMed Central

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo

    2015-01-01

    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features. PMID:26556986

  12. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico.

    PubMed

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo

    2015-11-07

    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features.

  13. Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy.

    PubMed

    Lee, Soon Jae; Cho, Yoo-Kyung; Na, Soo-Young; Choi, Eun Kwang; Boo, Sun Jin; Jeong, Seung Uk; Song, Hyung Joo; Kim, Heung Up; Kim, Bong Soo; Song, Byung-Cheol

    2016-09-01

    Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.

  14. Platelet Count to Spleen Diameter Ratio for the Diagnosis of Gastroesophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Chen, Runhua; Deng, Han; Xie, Chune; Wang, Wei

    2017-01-01

    Platelet count to spleen diameter ratio (PSR) was studied extensively as a noninvasive method of diagnosis for varices. The present study aimed to systematically assess the performance of PSR in the diagnosis of varices. PubMed, EMBASE, and article references were searched. The summary receiver operating characteristic curves (AUSROCs), sensitivities, specificities, positive and negative likelihood ratio, and diagnostic odds ratio were calculated. The heterogeneity, quality, and publication bias of studies were evaluated. Subgroup and sensitivity analyses were performed. A total of 49 papers were included. The AUSROCs of PSR for any varices and high-risk varices were 0.8719 and 0.8132, respectively. The summary sensitivities of PSR for any varices and high-risk varices were 0.84 and 0.78, respectively. The summary specificities of PSR for any varices and high-risk varices were 0.78 and 0.67, respectively. The AUSROC of PSR for any varices at the threshold of 909 was 0.8867. The AUSROC of PSR for any varices in viral liver cirrhosis was 0.8675. The overall quality of studies was moderate. Significant heterogeneity and publication bias existed in the study. In conclusion, PSR can be used to identify varices in liver cirrhosis. PSR had a high sensitivity in viral liver cirrhosis. PMID:28270848

  15. [Liver cirrhosis and encephalopathy: clinical and metabolic consequences and nutritional support].

    PubMed

    Mesejo, A; Juan, M; Serrano, A

    2008-05-01

    Cirrhosis represents the final stage of many chronic liver diseases and is associated to more or less pronounced hyponutrition, independently of the etiology, particularly at advanced stages. Its origin is multifactorial, with three factors contributing to it: a) limitation or decrease of intake; b) impairment in nutrients digestion or absorption; and c) the interference with nutrients metabolism. A poor nutritional status is associated with a poor survival prognosis. Whether caloric-protein malnourishment (CPM) is an independent predictor of mortality or only a marker of the severity of liver failure is subject to controversy. There is no consensus on which are the best diagnostic criteria for CPM in cirrhosis. Assessment of hyponutrition is extremely difficult since both the disease itself and the triggering or etiologic factors affect many of the parameters used. Metabolic impairments mimic a hypercatabolic state. These patients have decreased carbohydrate utilization and storage capacity and increased protein and fat catabolism leading to depletion of protein and lipid reserves. These abnormalities together with decreased nutrients intake and absorption are the bases for CPM. The most important metabolic impairment in patients with advanced liver disease is the change in amino acids metabolism. The plasma levels of branched amino acids (BAA) are decreased and of aromatic amino acids (AAA) are increased, which has therapeutic implications. Among the consequences of the structural impairments taking place in cirrhosis, we may highlight hepatic encephalopathy, defined as impaired central nervous system functioning that manifests as a series of neuropsychiatric, neuromuscular, and behavioral symptoms. These are due to the inability of the diseased liver to metabolize neurotoxins that accumulate in the brain affecting neurotransmitters and are attributed to the toxic effect of ammonium on the brain tissue. Nutritional therapy brings benefits in the different stages

  16. Impaired Expression of Type I and Type II Interferon Receptors in HCV-Associated Chronic Liver Disease and Liver Cirrhosis

    PubMed Central

    Chandra, Partha K.; Gunduz, Feyza; Hazari, Sidhartha; Kurt, Ramazan; Panigrahi, Rajesh; Poat, Bret; Bruce, David; Cohen, Ari J.; Behorquez, Humberto E.; Carmody, Ian; Loss, George; Balart, Luis A.; Wu, Tong; Dash, Srikanta

    2014-01-01

    Purpose Chronic Hepatitis C Virus (HCV)-infected patients with liver cirrhosis (LC) respond poorly to interferon-alpha (IFN-α) and ribavirin (RBV) combination therapy, but the reason for this is unclear. We previously reported that HCV-infection induces endoplasmic reticulum (ER) stress and autophagy response that selectively down regulates the type I IFN-α receptor-1 (IFNAR1) and RBV transporters (CNT1 and ENT1), leading to IFN-α/RBV resistance. The goal of this study is to verify whether an increase in ER stress and autophagy response is also associated with the reduced expression of IFNAR1 and RBV transporters in chronic HCV-infected patients. Methods Primary human hepatocytes (PHH) were infected with cell culture grown HCV particles (JFH-ΔV3-Rluc). HCV replication was confirmed by the detection of viral RNA by RT-qPCR and HCV-core protein by Western blotting. The ER stress and autophagy response and expression of IFN receptors and RBV transporters in HCV infected PHH and liver tissues derived from patients were measured by Western blotting. Result HCV infection of PHH showed impaired expression of IFNAR1, IFNγR1 (Type II IFN receptor) and RBV transporters but not IL10Rβ (Type III IFN-λ receptor). ER stress markers (BiP, IRE1α and peIF2α) and autophagy response (LC3II, Beclin 1 and ATG5) were induced in HCV infected chronic liver disease (CLD) and LC patients. Liver biopsies (CLD) show a 50% reduced expression of IFNAR1 and RBV transporters. Furthermore, the expression of IFNAR1 and RBV transporters was impaired in almost all LC patients. Conclusion HCV infection induces ER stress and autophagy response in infected PHH and chronically infected liver tissues. The expression of IFNAR1, IFNγR1 and RBV transporters were significantly impaired in CLD and cirrhotic livers. Our study provides a potential explanation for the reduced response rate of IFN-α and RBV combination therapy in HCV infected patients with liver cirrhosis. PMID:25265476

  17. Primary liver carcinoma and liver cirrhosis in atomic bomb survivors, Hiroshima and Nagasaki, 1961-75, with special reference to hepatitis B surface antigen

    SciTech Connect

    Asano, M.; Kato, H.; Yoshimoto, K.; Seyama, S.; Itakura, H.; Hamada, T.; Iijima, S.

    1982-12-01

    During 1961-75, 128 cases of primary liver carcinoma (PLC) in the Radiation Effects Research Foundation life-span study extended sample and 301 cases of liver cirrhosis in the pathology study sample were observed. The presence of hepatitis B surface antigen (HBsAg) was assessed in all of the cases with the use of orcein and aldehyde fuchsin stains and was confirmed by the immunofluorescence technique. The incidence of PLC was two times higher in Nagasaki than in Hiroshima, which was statistically significant, but little difference was noted in the prevalence of cirrhosis in the two cities. Findings that might possibly explain the higher PLC incidence in Nagasaki were 1) the 2.3 times higher presence in Nagasaki than in Hiroshima of HBsAg in the livers of subjects without liver disease and 2) the two times higher prevalence in Nagasaki than in Hiroshima of cirrhosis with PLC. We believe that the higher incidence of PLC in Nagasaki is attributable to hepatitis B virus infection, although other factors (e.g., immunologic competence affected by radiation) cannot be excluded. In both cities, a suggestive relationship of radiation dose to cirrhosis prevalence, but not to PCL prevalence, was noted. To clarify possible radiation effects on cirrhosis prevalence, further follow-up of the populations of these two cities is necessary.

  18. Correlation of circulating TLR2/4 expression with CD3+/4+/8+ T cells and Treg cells in HBV-related liver cirrhosis.

    PubMed

    Lian, Jian-Qi; Wang, Xiao-Qin; Zhang, Ye; Huang, Chang-Xing; Bai, Xue-Fan

    2009-10-01

    Toll-like receptors (TLRs) 2 and 4 play a key role in chronic hepatitis B virus (HBV) infection. However, the role of TLRs in the pathogenesis of HBV-related liver cirrhosis and their regulation of the innate immune response of patients with liver cirrhosis remain unknown. To assess the contribution of TLR2/4 in HBV-related liver cirrhosis, we examined the expression of circulating TLR2 and TLR4 on peripheral blood mononuclear cells (PBMCs), CD4(+)CD25(+)CD127(low/-) Treg proportions, and CD3(+)/CD4(+)/CD8(+) T-cell counts in 30 liver cirrhosis patients, 21 chronic hepatitis B (CHB) patients, and 16 normal controls (NC). Furthermore, we analyzed the relationship between TLR2/4 expression and Treg proportions and T-cell counts. We show that the expression of TLR2 and TLR4 was significantly upregulated in patients with liver cirrhosis compared to NC. TLR4 expression was significantly increased in patients with liver cirrhosis compared to patients with CHB, and for TLR2 expression there were no differences between them. TLR4 expression showed a significant positive correlation with the frequency of Tregs in liver cirrhosis patients. TLR2 expression negatively correlated with CD3(+)/CD4(+)/CD8(+) T-cell counts and HBV viral load in patients with liver cirrhosis. These findings indicate that TLR may be involved in the pathogenesis of HBV-related liver cirrhosis, and may interact with Tregs and CD3(+)/CD4(+)/CD8(+) T cells in the immune response during HBV-related liver cirrhosis.

  19. Eugenol-rich Fraction of Syzygium aromaticum (Clove) Reverses Biochemical and Histopathological Changes in Liver Cirrhosis and Inhibits Hepatic Cell Proliferation.

    PubMed

    Ali, Shakir; Prasad, Ram; Mahmood, Amena; Routray, Indusmita; Shinkafi, Tijjani Salihu; Sahin, Kazim; Kucuk, Omer

    2014-12-01

    Dried flower bud of Syzygium aromaticum (clove) is rich in eugenol, an antioxidant and antiinflammatory compound that can protect liver against injury. Clove, besides eugenol, also contains other pharmacologically active phytochemicals such as β-sitosterol and ascorbic acid. This study reports the effect of eugenol-rich fraction (ERF) of clove on liver cirrhosis induced by thioacetamide. Cirrhosis of the liver, which predisposes to hepatocellular carcinoma, was induced by administering thioacetamide (0.03%) in drinking water for 16 weeks. Cirrhotic animals were divided into two groups; the treated group was administered ERF for 9 weeks, one week after discontinuation of thioacetamide, while the other group received normal saline for a similar duration of time. The treatment with ERF, as determined by histopathology and through a battery of biochemical markers of hepatic injury, oxidative stress and drug metabolizing enzymes, significantly ameliorated the signs of liver cirrhosis. It lowered the elevated levels of alkaline phosphatase, γ-glutamyl transferase and other biochemical changes in liver cirrhosis. Histopathology of the liver corroborated the effect of ERF with biochemical findings. ERF treatment further inhibited cell proliferation, as demonstrated by reduced [(3)H]-thymidine uptake. Data provide evidence supporting the protective action of ERF on liver cirrhosis. The study assumes significance because cirrhosis predisposes the liver to cancer, which is characterized by abnormal cell proliferation. ERF in this study is reported to inhibit hepatic cell proliferation and at the same time decrease oxidative stress, which might be the mechanism of protection against liver cirrhosis.

  20. Identification of a liver cirrhosis signature in plasma for predicting hepatocellular carcinoma risk in a population-based cohort of hepatitis B carriers.

    PubMed

    Liu, Chia-Chi; Wang, Ya-Hui; Chuang, Eric Y; Tsai, Mong-Hsun; Chuang, Ya-Hui; Lin, Chih-Lin; Liu, Chun-Jen; Hsiao, Bo-Yu; Lin, Shi-Ming; Liu, Li-Yu; Yu, Ming-Whei

    2014-01-01

    Liver cirrhosis is a critical state in the natural course of hepatocellular carcinoma (HCC). We sought to investigate the potential of in-depth proteomics to reveal plasma protein signatures that reflect common networks/pathways of liver cirrhosis, and to determine whether the cirrhosis-related signature in plasma is linked to the development of HCC among hepatitis B virus (HBV) carriers. We first compared plasma protein profiles using a 174-antibody microarray system between three groups of HBV carriers with different Child's grades of cirrhosis, which revealed a panel of 45 differentially expressed proteins with a high accuracy for discriminating Child's B/C. Ingenuity Pathway Analysis identified two main up-regulated networks connecting the 45 proteins that were most enriched for genes in the pathway of hepatic stellate cell activation. A parsimonious subset of 11 pathway-based proteins was then selected for quantification to correlate with HCC risk among 49 HCC cases and 50 controls in a nested case-control study within a 16-yr follow-up cohort of HBV carriers. A high risk score derived from a principal component analysis, which was used to extract the cluster structure of the 11 proteins, was associated with HCC (odds ratio = 4.83, 95% confidence interval: 1.26-18.56) even after adjustment for viral and clinical variables, implying the involvement of a pattern of coordinated proteins. Stepwise logistic regression on the 11 proteins revealed ICAM-2 as an independent predictor for HCC. These findings may give further insight into the pathobiology of hepatocarcinogenesis, allow testing of the cirrhosis-related plasma protein signature as a potential predictive biomarker for HCC.

  1. Tyrosine kinase inhibitors improve parenchymal findings of liver cirrhosis in a patient exhibiting concomitant hepatocellular carcinoma and renal cell cancer

    PubMed Central

    KUS, TULAY; AKTAS, GOKMEN; SEVINC, ALPER; OKTAY, CEMIL; KALENDER, MEHMET EMIN; CAMCI, CELALETDIN

    2016-01-01

    Hepatocellular carcinoma (HCC) and renal cell cancer (RCC) are malignancies, which are chemotherapy resistant and fatal at the advanced stages. Previously developed tyrosine kinase inhibitors are used in the treatment of advanced stage disease. In the present case study, a patient using sunitinib for stage IV RCC presented with HCC following 2 years of treatment. A patient who exhibited Child-Pugh class C cirrhosis initially, exhibited a marked improvement of hepatocellular parenchyma findings following treatment with sunitinib. Sunitinib is suggested to have preventive effects on the pathogenesis of liver fibrosis and cirrhosis in vitro, via an anti-vascular endothelial growth factor and anti-platelet-derived growth factor mechanism. However, no clinical supportive study has been performed until now. Improvement of liver functions may be explained in this manner. Therefore, investigations are required with different doses of sunitinib and other tyrosine kinase inhibitors in order to evaluate the efficacy on treatment of cirrhosis progression. PMID:26893877

  2. Ex vivo expansion of circulating CD34+ cells enhances the regenerative effect on rat liver cirrhosis

    PubMed Central

    Nakamura, Toru; Koga, Hironori; Iwamoto, Hideki; Tsutsumi, Victor; Imamura, Yasuko; Naitou, Masako; Masuda, Atsutaka; Ikezono, Yu; Abe, Mitsuhiko; Wada, Fumitaka; Sakaue, Takahiko; Ueno, Takato; Ii, Masaaki; Alev, Cantas; Kawamoto, Atsuhiko; Asahara, Takayuki; Torimura, Takuji

    2016-01-01

    Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34+ cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34+ cells. CCl4 was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34+ cells were injected via the spleen. After 7 days, CD34+ cells were effectively expanded in a serum-free culture medium. Expanded CD34+ cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34+ cells increased compared with nonexpanded CD34+ cells. Expanded CD34+ cell transplantation reduced liver fibrosis, with a decrease of αSMA+ cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34+ cells over non-expanded CD34+ cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34+ cells and aggravated liver fibrosis. These findings suggest that expanded CD34+ cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model. PMID:27162932

  3. Ultrasound-guided percutaneous portal transplantation of peripheral blood monocytes in patients with liver cirrhosis

    PubMed Central

    Yu, Su Jong; Yoon, Jung-Hwan; Kim, Won; Lee, Jeong Min; Lee, Yun Bin; Cho, Yuri; Lee, Dong Hyeon; Lee, Minjong; Yoo, Jeong-Ju; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Kim, Chung Yong

    2017-01-01

    Background/Aims Liver transplantation offers the only definite cure for cirrhosis but lacking donors is problem. Stem cell therapy is attractive in this setting. In this study, we aimed to explore the safety and efficacy of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell (PBMC) in cirrhotic patients. Methods A total of nine decompensated cirrhotic patients were randomized into three groups: group 1 (n = 3) was control group, group 2 (n = 3) received granulocyte-colony stimulating factor (G-CSF) mobilization for 3 days, and group 3 (n = 3) received G-CSF mobilized PBMCs by leukapheresis and PBMC transplantation through ultrasound-guided percutaneous portal vein puncture. Liver function and clinical features were evaluated. Results At baseline, the Child-Turcotte-Pugh and the model for end-stage liver disease scores were comparable in study groups. Compared with group 1, there was a tendency to improve liver function in group 3 at 6 months after treatment. Treatment was tolerable and no complications were encountered related to the G-CSF mobilization or percutaneous portal administration of PBMCs. Imaging studies showed patent portal veins at the end of the study period. Conclusions Autologous PBMC transplantation through ultrasound-guided percutaneous portal vein puncture could be considered as a safe alternative treatment for decompensated cirrhotic patients. PMID:27044856

  4. Liver Allograft Its Use in Chronic Active Hepatitis With Macronodular Cirrhosis, Hepatitis B Surface Antigen

    PubMed Central

    Corman, Jarques L.; Putnam, Charles W.; Iwatsuki, Shunzaburo; Redeker, Allan G.; Porter, K. A.; Peters, Robert L.; Schröter, Gerhard; Starzl, Thomas E.

    2010-01-01

    A patient suffering from chronic active hepatitis with macronodular cirrhosis, positive for hepatitis B surface antigen (HB,Ag), was treated with an orthoiopic liver allograft. The HB, antigenemia, as measured with several precipltation tests and by complement fixation, became negati