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Sample records for stage liver disease

  1. Questions and Answers for Transplant Candidates about Model for End-Stage Liver Disease (MELD) and Pediatric End-Stage ....

    MedlinePlus

    ... needs a liver transplant most urgently. The MELD (Model for End Stage Liver Disease) is used for ... and the PELD (Pediatric End Stage Liver Disease Model) is used for patients age 11 and younger. ...

  2. Palliative care for patients with end-stage liver disease.

    PubMed

    Larson, Anne M

    2015-05-01

    Liver disease results in over four million physician visits and over 750,000 hospitalizations per year in the USA. Those with chronic liver disease frequently progress to cirrhosis, end-stage liver disease (ESLD), and death. Patients with ESLD experience numerous complications, including muscle cramps, confusion (hepatic encephalopathy), protein calorie malnutrition, muscle wasting, fluid overload (ascites, edema), bleeding (esophagogastric variceal hemorrhage), infection (spontaneous bacterial peritonitis), fatigue, anxiety, and depression. Despite significant improvements in palliation of these complications, patients still suffer reduced quality of life and must confront the fact that their disease will often inexorably progress to death. Liver transplantation is a valid option in this setting, increasing the duration of survival and palliating many of the symptoms. However, many patients die waiting for an organ or are not candidates for transplantation due to comorbid illness. Others receive a transplant but succumb to complications of the transplant itself. Patients and families must struggle with simultaneously hoping for a cure while facing a life-threatening illness. Ideally, the combination of palliative care with life-sustaining therapy can maximize the patients' quality and quantity of life. If it becomes clear that life-sustaining therapy is no longer an option, these patients are then already in a system to help them with end-of-life care.

  3. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.

  4. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

    PubMed Central

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-01-01

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  5. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  6. Markers of bacterial translocation in end-stage liver disease

    PubMed Central

    Koutsounas, Ioannis; Kaltsa, Garyfallia; Siakavellas, Spyros I; Bamias, Giorgos

    2015-01-01

    Bacterial translocation (BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence. BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT. PMID:26380651

  7. Integration of Palliative Care in End-Stage Liver Disease and Liver Transplantation

    PubMed Central

    Curry, Michael; Buss, Mary; Chittenden, Eva

    2014-01-01

    Abstract Background: Patients with end-stage liver disease (ESLD) have a life-limiting illness that causes multiple distressing symptoms and negatively affects quality of life (QOL). This population traditionally has not had much attention within the palliative care community. Discussion: This article provides an evidence-based review of palliative care issues that patients with ESLD and those awaiting liver transplant face, including approaches to prognosis, symptom management, advance care planning, and end-of-life care. Conclusion: Tremendous opportunity exists to integrate palliative medicine into the care of these patients. PMID:25390468

  8. The nature of malnutrition in children with end-stage liver disease awaiting orthotopic liver transplantation.

    PubMed

    Chin, S E; Shepherd, R W; Thomas, B J; Cleghorn, G J; Patrick, M K; Wilcox, J A; Ong, T H; Lynch, S V; Strong, R

    1992-07-01

    To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction, 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 +/- 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.

  9. The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation.

    PubMed

    Zhang, Qi-Kun; Wang, Meng-Long

    2015-10-01

    Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT.

  10. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  11. Liver disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the liver ...

  12. Beyond the Pediatric end-stage liver disease system: solutions for infants with biliary atresia requiring liver transplant.

    PubMed

    Tessier, Mary Elizabeth M; Harpavat, Sanjiv; Shepherd, Ross W; Hiremath, Girish S; Brandt, Mary L; Fisher, Amy; Goss, John A

    2014-08-28

    Biliary atresia (BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches: (1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and (2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant. PMID:25170195

  13. Assessment of Liver Viscoelasticity for the Diagnosis of Early Stage Fatty Liver Disease Using Transient Elastography

    NASA Astrophysics Data System (ADS)

    Remenieras, Jean-Pierre; Dejobert, Maelle; Bastard, Cécile; Miette, Véronique; Perarnau, Jean-Marc; Patat, Frédéric

    Nonalcoholic fatty liver disease (NAFLD) is characterized by accumulation of fat within the Liver. The main objective of this work is (1) to evaluate the feasibility of measuring in vivo in the liver the shear wave phase velocity dispersion cs(ω) between 20 Hz and 90 Hz using vibration-controlled transient elastography (VCTE); (2) to estimate through the rheological Kelvin-Voigt model the shear elastic μ and shear viscosity η modulus; (3) to correlate the evolution of these viscoelastic parameters on two patients at Tours Hospital with the hepatic fat percentage measured with T1-weighted gradient-echo in-and out-phase MRI sequence. For the first volunteer who has 2% of fat in the liver, we obtained μ = 1233 ± 133 Pa and η = 0.5 ± 0.4 Pa.s. For the patient with 22% of fat, we measure μ = 964 ± 91 Pa and η = 1.77 ± 0.3 Pa.s. In conclusion, this novel method showed to be sensitive in characterizing the visco-elastic properties of fatty liver.

  14. Liver pathology of hepatitis C, beyond grading and staging of the disease

    PubMed Central

    Dhingra, Sadhna; Ward, Stephen C; Thung, Swan N

    2016-01-01

    Liver biopsy evaluation plays a critical role in management of patients with viral hepatitis C. In patients with acute viral hepatitis, a liver biopsy, though uncommonly performed, helps to rule out other non-viral causes of deranged liver function. In chronic viral hepatitis C, it is considered the gold standard in assessment of the degree of necroinflammation and the stage of fibrosis, to help guide treatment and determine prognosis. It also helps rule out any concomitant diseases such as steatohepatitis, hemochromatosis or others. In patients with chronic progressive liver disease with cirrhosis and dominant nodules, a targeted liver biopsy is helpful in differentiating a regenerative nodule from dysplastic nodule or hepatocellular carcinoma. In the setting of transplantation, the liver biopsy helps distinguish recurrent hepatitis C from acute rejection and also is invaluable in the diagnosis of fibrosing cholestatic hepatitis, a rare variant of recurrent hepatitis C. This comprehensive review discusses the entire spectrum of pathologic findings in the course of hepatitis C infection. PMID:26819505

  15. Risk of Bleeding in End-Stage Liver Disease Patients Undergoing Cardiac Catheterization.

    PubMed

    Mahmoud, Ahmed M; Elgendy, Islam Y; Choi, Calvin Y; Bavry, Anthony A

    2015-10-01

    Patients with end-stage liver disease frequently have baseline coagulopathies. The international normalized ratio is in common use for the estimation of bleeding tendency in such patients, especially those undergoing an invasive procedure like cardiac catheterization. The practice of international normalized ratio measurement-followed by pharmacologic (for example, vitamin K or fresh frozen plasma) or nonpharmacologic intervention-is still debatable. The results of multiple randomized trials have shown the superiority of the radial approach over femoral access in reducing catheterization bleeding. This reduction in bleeding in turn decreases the risk and cost of blood-product transfusion. However, there is little evidence regarding the use of the radial approach in the end-stage liver disease patient population specifically. In this review, we summarize the studies that have dealt with cardiac catheterization in patients who have end-stage liver disease. We also discuss the role of the current measurements that are used to reduce the risk of bleeding in these same patients.

  16. Diagnostic Accuracy of Serum Procalcitonin for Spontaneous Bacterial Peritonitis Due to End-stage Liver Disease

    PubMed Central

    Yang, Yongtao; Li, Lianyong; Qu, Changmin; Zeng, Bolun; Liang, Shuwen; Luo, Zhiwen; Wang, Xiaoying; Zhong, Changqing

    2015-01-01

    Abstract Early diagnosis and prompt treatment of spontaneous bacterial peritonitis (SBP) due to end-stage liver disease is vital to shorten hospital stays and reduce mortality. Many studies have explored the potential usefulness of serum procalcitonin (PCT) in predicting SBP. The aim of this study is to evaluate the overall diagnostic accuracy of PCT levels for identifying SBP due to end-stage liver disease. After performing a systematic search of the Medline, Embase, and Cochrane databases for studies that evaluated the diagnostic role of PCT for SBP, sensitivity, specificity, and other measures of accuracy of PCT concentrations in serum for SBP diagnosis were pooled using random-effects models. A summary receiver operating characteristic curve was used to summarize overall test performance. Seven publications met the inclusion criteria covering 742 episodes of suspected SBP along with 339 confirmed cases. The summary estimates for serum PCT in the diagnosis of SBP attributable to end-stage liver disease were: sensitivity 0.82 (95% CI 0.79–0.87), specificity 0.86 (95% CI 0.82–0.89), positive likelihood ratio 4.94 (95% CI 2.28–10.70), negative likelihood ratio 0.22 (95% CI 0.10–0.52), and diagnostic OR 22.55 (95% CI 7.01–108.30). The area under the curve was 0.92. There was evidence of significant heterogeneity but no evidence of publication bias. Serum PCT is a relatively sensitive and specific test for the identification of SBP. However, due to the limited high-quality studies available, medical decisions should be carefully made in the context of both PCT test results and other clinical findings. PMID:26656333

  17. Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease

    PubMed Central

    Kinny-Köster, Benedict; Bartels, Michael; Becker, Susen; Scholz, Markus; Thiery, Joachim

    2016-01-01

    Background The liver plays a key role in amino acid metabolism. In former studies, a ratio between branched-chain and aromatic amino acids (Fischer’s ratio) revealed associations with hepatic encephalopathy. Furthermore, low concentrations of branched-chain amino acids were linked to sarcopenia in literature. Encephalopathy and sarcopenia are known to dramatically worsen the prognosis. Aim of this study was to investigate a complex panel of plasma amino acids in the context of mortality in patients with end-stage liver disease. Methods 166 patients evaluated for orthotopic liver transplantation were included. 19 amino acids were measured from citrated plasma samples using mass spectrometry. We performed survival analysis for plasma amino acid constellations and examined the relationship to established mortality predictors. Results 33/166 (19.9%) patients died during follow-up. Lower values of valine (p<0.001), Fischer’s ratio (p<0.001) and valine to phenylalanine ratio (p<0.001) and higher values of phenylalanine (p<0.05) and tyrosine (p<0.05) were significantly associated with mortality. When divided in three groups, the tertiles discriminated cumulative survival for valine (p = 0.016), phenylalanine (p = 0.024) and in particular for valine to phenylalanine ratio (p = 0.003) and Fischer’s ratio (p = 0.005). Parameters were also significantly correlated with MELD and MELD-Na score. Conclusions Amino acids in plasma are valuable biomarkers to determine increased risk of mortality in patients with end-stage liver disease. In particular, valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis. Due to their pathophysiological importance, the identified amino acids could be used to examine individual dietary recommendations to serve as potential therapeutic targets. PMID:27410482

  18. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease

    PubMed Central

    An, Chansik; Choi, Youn Ah; Choi, Dongil; Paik, Yong Han; Ahn, Sang Hoon; Kim, Myeong-Jin; Paik, Seung Woon; Han, Kwang-Hyub

    2015-01-01

    Background/Aims The goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate. Methods Patients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients. Results The median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234). Conclusions The etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC. PMID:26523271

  19. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells.

    PubMed

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has little effect on endoderm development from iPSCs, it reduces formation of hepatic progenitor cells during early hepatic specification. The proliferative activities of early and mature hepatocyte-like cells are significantly decreased after alcohol exposure. Importantly, at a mature stage of hepatocyte-like cells, alcohol treatment increases two liver progenitor subsets, causes oxidative mitochondrial injury and results in liver disease phenotypes (i.e., steatosis and hepatocellular carcinoma associated markers) in a dose dependent manner. Some of the phenotypes were significantly improved by antioxidant treatment. This report suggests that fetal alcohol exposure may impair generation of hepatic progenitors at early stage of hepatic specification and decrease proliferation of fetal hepatocytes; meanwhile alcohol injury in post-natal or mature stage human liver may contribute to disease phenotypes. This human iPSC model of alcohol-induced liver injury can be highly valuable for investigating alcoholic injury in the fetus as well as understanding the pathogenesis and ultimately developing effective treatment for alcoholic liver disease in adults. PMID:27570479

  20. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells

    PubMed Central

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has little effect on endoderm development from iPSCs, it reduces formation of hepatic progenitor cells during early hepatic specification. The proliferative activities of early and mature hepatocyte-like cells are significantly decreased after alcohol exposure. Importantly, at a mature stage of hepatocyte-like cells, alcohol treatment increases two liver progenitor subsets, causes oxidative mitochondrial injury and results in liver disease phenotypes (i.e., steatosis and hepatocellular carcinoma associated markers) in a dose dependent manner. Some of the phenotypes were significantly improved by antioxidant treatment. This report suggests that fetal alcohol exposure may impair generation of hepatic progenitors at early stage of hepatic specification and decrease proliferation of fetal hepatocytes; meanwhile alcohol injury in post-natal or mature stage human liver may contribute to disease phenotypes. This human iPSC model of alcohol-induced liver injury can be highly valuable for investigating alcoholic injury in the fetus as well as understanding the pathogenesis and ultimately developing effective treatment for alcoholic liver disease in adults. PMID:27570479

  1. Living donor liver transplantation for high model for end-stage liver disease score: What have we learned?

    PubMed Central

    Dabbous, Hany; Sakr, Mohammad; Abdelhakam, Sara; Montasser, Iman; Bahaa, Mohamed; Said, Hany; El-Meteini, Mahmoud

    2016-01-01

    AIM To assess the impact of model for end-stage liver disease (MELD) score on patient survival and morbidity post living donor liver transplantation (LDLT). METHODS A retrospective study was performed on 80 adult patients who had LDLT from 2011-2013. Nine patients were excluded and 71 patients were divided into two groups; Group 1 included 38 patients with a MELD score < 20, and Group 2 included 33 patients with a MELD score > 20. Comparison between both groups was done regarding operative time, intra-operative blood requirement, intensive care unit (ICU) and hospital stay, infection, and patient survival. RESULTS Eleven patients died (15.5%); 3/38 (7.9%) patients in Group 1 and 8/33 (24.2%) in Group 2 with significant difference (P = 0.02). Mean operative time, duration of hospital stay, and ICU stay were similar in both groups. Mean volume of blood transfusion and cell saver re-transfusion were 8 ± 4 units and 1668 ± 202 mL, respectively, in Group 1 in comparison to 10 ± 6 units and 1910 ± 679 mL, respectively, in Group 2 with no significant difference (P = 0.09 and 0.167, respectively). The rates of infection and systemic complications (renal, respiratory, cardiovascular and neurological complications) were similar in both groups. CONCLUSION A MELD score > 20 may predict mortality after LDLT. PMID:27574548

  2. The utility of the model for end-stage liver disease score: a reliable guide for liver transplant candidacy and, for select patients, simultaneous hospice referral.

    PubMed

    Medici, Valentina; Rossaro, Lorenzo; Wegelin, Jacob A; Kamboj, Amit; Nakai, Junko; Fisher, Kelli; Meyers, Frederick J

    2008-08-01

    Patients with chronic liver disease are referred late to hospice or never referred. There are several barriers to timely referral. First, liver transplantation (LT) and hospice care have always been perceived as mutually exclusive. Yet the criteria for hospice referral and for LT are more similar than different (for example, advanced liver disease and imminent death). Second, physicians, patients, and families have not had a reliable metric to guide referral. However, many patients wait for transplantation but never receive an organ. We hypothesized that the Model for End-Stage Liver Disease (MELD) score already in use to prioritize LT could be used in selected patients for concurrent hospice referral. Furthermore, we hypothesized that patients awaiting LT can receive hospice care and remain eligible for transplantation. Patients with advanced or end-stage liver disease were referred to the University of California Davis Health System hospice program. We correlated the MELD score at admission to length of stay (LOS) in hospice. A total of 157 end-stage liver disease patients were admitted to the hospice service. At the time of hospice admission the mean MELD score was 21 (range, 6-45). The mean length of hospice stay was 38 days (range, 1-329 days). A significant correlation was observed between hospice LOS and MELD score at hospice admission (P < 0.01). Six patients were offered a liver graft while on the combined (LT and hospice) program. MELD can be used to guide clinician recommendation to families about hospice care, achieving one of the national benchmark goals of increasing hospice care duration beyond the current median of 2-3 weeks. A higher MELD score might augment physician judgment as to hospice referral. Hospice care for selected patients may be an effective strategy to improve the care of end-stage liver disease patients waiting for LT. PMID:18668666

  3. Risk Factors for End-Stage Kidney Disease after Pediatric Liver Transplantation

    PubMed Central

    Ruebner, RL; Reese, PP; Denburg, MR; Rand, EB; Abt, PL; Furth, SL

    2015-01-01

    Adult liver transplant (LT) recipients commonly develop advanced kidney disease. However, burden of end-stage kidney disease (ESKD) after pediatric LT has not been well-described. We performed a retrospective cohort study of pediatric LTs in the US from 1990–2010. Multivariable Cox regression models were fit to determine risk factors for ESKD and death. 8976 children received LTs. During median follow-up of 7.8 years, 2005 (22%) subjects died (mortality rate 26.1 cases/1000 person-years); 167 (2%) developed ESKD (incidence rate 2.2 cases/1000 person-years). Risk factors for ESKD included older age at LT (highest risk age>15 vs <5 years, HR=4.94, p<0.001), hepatitis C (HR 2.79, p=0.004), liver re-transplant (HR 2.67, p<0.001), eGFR pre-LT <60 vs ≥60 (HR 2.37, p<0.001), hepatitis B (HR 2.25, p=0.027), black race (HR 1.46, p=0.046), and male sex (HR 1.44, p=0.022). LT recipients with ESKD had increased risk of mortality (HR 2.37, p<0.001). Among pediatric LT recipients, rate of ESKD was lower than among adults and far exceeded by rate of death, however follow-up time in this study may underestimate lifetime burden of ESKD. Although uncommon, ESKD was highly associated with mortality. Pediatric LT recipients should be routinely monitored for kidney disease, particularly those at highest risk of ESKD. PMID:22994862

  4. Vasopressin deficiency and vasodilatory state in end-stage liver disease

    PubMed Central

    Wagener, Gebhard; Kovalevskaya, Galina; Minhaz, Moury; Mattis, Fallon; Emond, Jean C.; Landry, Donald W.

    2010-01-01

    1. Objectives Relative vasopressin deficiency, a contributor to vasodilatory septic shock may also be a cause of the vasodilatory state in liver disease. This study assesses endogenous vasopressin levels in patients with liver disease and their hemodynamic response to exogenous vasopressin. 2. Design Prospective, observational study 3. Setting Single center, tertiary hospital 4. Participants Human subjects undergoing liver transplantation or major surgery 5. Interventions Vasopressin levels were measured in 28 patients with liver disease undergoing liver transplantation and 7 control patients with normal liver function. Additionally intravenous vasopressin was given to 20 liver transplant recipients and the hemodynamic response was observed. 6. Measurements and Main Results Patients with liver disease had significantly lower baseline vasopressin levels than controls (19.3 +/− 27.1 pg/mL versus 50.9 +/− 36.7 pg/mL, p=0.015). Patients with low vasopressin levels (• 20 pg/mL) were more likely to have low baseline mean blood pressure (• 80 mm Hg) than patients with high vasopressin levels (11 of 16 vs. 0 of 4, p=0.013). Systemic vascular resistance increased by 33% three minutes after intravenous vasopressin. Thirteen of 16 patients with low vasopressin levels compared to one of four patients with high vasopressin levels responded to exogenous vasopressin with an increase of mean blood pressure by more than 20% (p=0.028). 7. Conclusions Patients with liver disease have lower vasopressin levels than controls and respond with a brisk vasoconstrictor response to exogenous vasopressin. Relative endogenous vasopressin deficiency may therefore contribute to vasodilatory shock in liver disease similar to what has been observed in septic shock PMID:21126886

  5. Successful staged kidney and liver transplantation for glycogen storage disease type Ib: A case report.

    PubMed

    Martin, A P; Bartels, M; Schreiber, S; Buehrdel, P; Hauss, J; Fangmann, J

    2006-12-01

    Glycogen storage disease type Ib is a rare metabolic disease caused by a defect of the G6P transporter. Patients suffer from hypoglycemic episodes; growth and developmental delay; osteoporosis; neutropenia; and tendency to infections, ovarian cysts, and liver adenomas. Terminal kidney disease is a rare complication. Liver transplantation has been performed to prevent malignant transformation of hepatic adenomas. We present the case of a female patient with glycogenosis type Ib who had severe hypoglycemic episodes and recurrent infections since early childhood. She became dialysis dependent at the age of 24 years. Kidney transplantation was performed at age 30, and liver transplantation 2 years later. The main indication for liver transplantation were the persistent, therapy-refractory hypoglycemic episodes. The transplanted kidney function is stable. The liver transplantation resulted in the disappearance of hypoglycemic episodes, with the patient leading a normal life and eating a normal diet. The neutropenia did not recover, but there were no more significant infectious episodes after liver transplantation. This is, to the best of our knowledge, the first communication of a dual kidney and liver transplant performed in a patient with glycogenosis type Ib. It confirmed the beneficial effect of liver transplantation on the quality of life of patients with severe hypoglycemia. The transplantation should be attempted earlier in the course of the disease to reduce complications and allow catch-up growth. Hepatocyte transplantation may be considered; however, long-term results seem to be rather poor in the few documented cases. PMID:17175348

  6. End-Stage Liver Disease Is a Strong Predictor of Early Mortality in Cryptococcosis.

    PubMed

    Spec, Andrej; Raval, Krunal; Powderly, William G

    2016-01-01

    Background.  Cryptococcosis in the setting of end-stage liver disease (ESLD) has been associated with high mortality. We sought to compare the outcome of cryptococcal disease in patients with ESLD to that of human immunodeficiency virus (HIV)-positive patients and to those patients without HIV or ESLD. Methods.  We assembled a retrospective cohort of 232 consecutive cases of cryptococcosis in our institution, from 2002 to 2014, inclusively. We analyzed the cases for comorbidities, type of infection, and survival. Data were analyzed with t tests, Fishers Exact test, and Kaplan-Meyer analysis. Results.  Twenty-five (10.8%) patients with cryptococcal infection had concomitant ESLD; of these, 5 (20%) presented with peritonitis. Most (17 of 25, 68%) did not have any other cause of immunocompromise that has been more classically associated with cryptococcosis. Patients with ESLD had a significantly higher mortality than HIV-positive patients and HIV-negative patients without ESLD (HIVNE) (80% vs 13.6% and 22.7%, respectively; P < .001). In addition, fatal outcome in ESLD patients occurred more rapidly than in HIVNE patients, with a median survival of 6 days (vs 17), despite a comparable time to diagnosis (6.2 vs 6.6 days). Conclusions.  Cryptococcosis is an important morbidity in patients with ESLD. Patients with ESLD who are infected with Cryptococcus have a high and rapid mortality. This suggests that a high level of vigilance for cryptococcal infection should be kept in patients with ESLD. PMID:26835475

  7. Objective Radiological Assessment of Body Composition in Patients with End-Stage Liver Disease: Going Beyond the BMI

    PubMed Central

    Cruz, Ruy J.; Dew, Mary Amanda; Myaskovsky, Larissa; Goodpaster, Bret; Fox, Kristen; Fontes, Paulo; DiMartini, Andrea

    2015-01-01

    Body Mass Index is a commonly used but likely inexact measure of body composition for patients with end-stage liver disease. For this reason, we examined whether body composition measurements from direct visualization on computerized tomography (CT) scans provide new insights both into the degree of malnutrition and also discordant combinations such as obesity with muscle mass loss. This technology is widely used in other medically ill populations but not yet in liver transplantation. Methods We examined actual body composition using abdominal CT scan data and software designed to measure fat and muscle compartments. Results In 234 liver transplant candidates we found BMI was highly and significantly correlated to subcutaneous and visceral fat. However we additionally found that even among obese patients, cachexia, as defined by muscle mass, was common with 56% of those with BMIs over 30 being cachexic. We also found that patients with non-alcoholic steatohepatitis, compared to other types of liver diseases, were significantly more likely to have larger amounts of visceral fat while also having less muscle. In an exploratory analysis muscle mass corrected for height was a significant predictor of post-transplant survival. Conclusions Body composition by CT scan data provides a specific method to identify obesity and muscle wasting for end-stage liver disease patients. Whether these data can aid in the prognostication of outcomes and survival requires further investigation. PMID:23348896

  8. Ascertainment and Verification of End-Stage Renal Disease and End-Stage Liver Disease in the North American AIDS Cohort Collaboration on Research and Design

    PubMed Central

    Kitahata, Mari M.; Drozd, Daniel R.; Crane, Heidi M.; Van Rompaey, Stephen E.; Althoff, Keri N.; Gange, Stephen J.; Klein, Marina B.; Lucas, Gregory M.; Abraham, Alison G.; Lo Re, Vincent; McReynolds, Justin; Lober, William B.; Mendes, Adell; Modur, Sharada P.; Jing, Yuezhou; Morton, Elizabeth J.; Griffith, Margaret A.; Freeman, Aimee M.; Moore, Richard D.

    2015-01-01

    The burden of HIV disease has shifted from traditional AIDS-defining illnesses to serious non-AIDS-defining comorbid conditions. Research aimed at improving HIV-related comorbid disease outcomes requires well-defined, verified clinical endpoints. We developed methods to ascertain and verify end-stage renal disease (ESRD) and end-stage liver disease (ESLD) and validated screening algorithms within the largest HIV cohort collaboration in North America (NA-ACCORD). Individuals who screened positive among all participants in twelve cohorts enrolled between January 1996 and December 2009 underwent medical record review to verify incident ESRD or ESLD using standardized protocols. We randomly sampled 6% of contributing cohorts to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ESLD and ESRD screening algorithms in a validation subcohort. Among 43,433 patients screened for ESRD, 822 screened positive of which 620 met clinical criteria for ESRD. The algorithm had 100% sensitivity, 99% specificity, 82% PPV, and 100% NPV for ESRD. Among 41,463 patients screened for ESLD, 2,024 screened positive of which 645 met diagnostic criteria for ESLD. The algorithm had 100% sensitivity, 95% specificity, 27% PPV, and 100% NPV for ESLD. Our methods proved robust for ascertainment of ESRD and ESLD in persons infected with HIV. PMID:25789171

  9. Does the model for end-stage liver disease score predict transfusion amount, acid-base imbalance, haemodynamic and oxidative abnormalities during living donor liver transplantation?

    PubMed

    Lee, J; Chung, M Y

    2011-01-01

    The model for end-stage liver disease (MELD) score is associated with the severity of liver failure in transplant patients. This study examined whether life-threatening stress factors during liver transplantation differed according to the patients' preoperative MELD scores. Forty-four patients who underwent living donor liver transplantation were divided into a high MELD group (MELD score ≥ 20) (n = 25) and a low MELD group (MELD score < 20) (n = 19). The volume of blood components transfused, acid-base homeostasis variables, and haemodynamic and oxidative variables were measured at each stage of the surgery. The systemic vascular resistance index was significantly lower in the high MELD group than in the low MELD group at all time points. The oxygen utility index and the oxygen extraction ratio were all significantly lower in the high MELD group than in the low MELD group only at the preanhepatic stage and not at later stages of surgery. Intraoperative transfusion volume and the severity of metabolic acidosis were not associated with the preoperative MELD score.

  10. Liver disease - resources

    MedlinePlus

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  11. Predictors of Disease Recurrence Post Living Donor Liver Transplantation in End Stage Chronic HCV Patients

    PubMed Central

    El Awady, Mostafa K.; Bader El Din, Noha G.; Abdel Aziz Riad, Mahmoud; Omran, Moataza H.; Abdelhafez, Tawfeek H.; Elbaz, Tamer Mahmoud; Hunter, Shereen Shoukry; Dawood, Reham M.; Abdel Aziz, Ashraf O.

    2014-01-01

    HCV recurrence represents a universal phenomenon after liver transplantation. In this study Fifty HCV patients who underwent living donor liver transplantation were enrolled and factors that may accelerate HCV reinfection of the allograft such as donor's age and degree of liver steatosis, recipient's age, gender, BMI, MELD score, liver functions, HCV viral load, type of immunosuppressive drug, and genetic polymorphisms of IL28B, OAS, and IL1B were studied. The results of disease-free survival (DFS) rates showed inverse correlation with the recipient's postoperative levels of ALT, AST, ALP (P < 0.001, <0.001, and 0.006 resp.) as well as pre- and postoperative titers of HCV RNA (P < 0.003 and <0.001 resp.). Recipient's IL28B SNP was a significant factor in predicting postoperative DFS (P < 0.025). However, SNPs in OAS and IL1B genes had no apparent correlation with DFS. Cox proportional hazards model revealed that patients with elevated levels of ALT, preoperative viral titers, IL28B CT, and IL28B TT were 8.28, 4.22, 3.35, and 1.36 times, respectively, more likely to develop recurrence. In conclusion IL28B SNP, ALT level, and preoperative HCV titer besides proper choice of immunosuppressant are helpful for predicting posttransplant HCV recurrence and DFS. PMID:24695489

  12. Etiology and Viral Genotype in Patients with End-Stage Liver Diseases admitted to a Hepatology Unit in Colombia

    PubMed Central

    Cortes-Mancera, Fabian; Loureiro, Carmen Luisa; Hoyos, Sergio; Restrepo, Juan-Carlos; Correa, Gonzalo; Jaramillo, Sergio; Norder, Helene; Pujol, Flor Helene; Navas, Maria-Cristina

    2011-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the principal risk factor associated to end-stage liver diseases in the world. A study was carried out on end-stage liver disease cases admitted to an important hepatology unit in Medellin, the second largest city in Colombia. From 131 patients recruited in this prospective study, 71% of cases were diagnosed as cirrhosis, 12.2% as HCC, and 16.8% as cirrhosis and HCC. Regarding the risk factors of these patients, alcohol consumption was the most frequent (37.4%), followed by viral etiology (17.6%). Blood and/or hepatic tissue samples from patients with serological markers for HCV or HBV infection were characterized; on the basis of the phylogenetic analysis of HCV 5′ UTR and HBV S gene, isolates belonged to HCV/1 and HBV/F3, respectively. These results confirm the presence of strains associated with poor clinical outcome, in patients with liver disease in Colombia; additionally, HBV basal core promoter double mutant was identified in HCC cases. Here we show the first study of cirrhosis and/or HCC in Colombian and HBV and HCV molecular characterization of these patients. Viral aetiology was not the main risk factor in this cohort but alcohol consumption. PMID:21941645

  13. The Model for End-stage Liver Disease accurately predicts 90-day liver transplant wait-list mortality in Atlantic Canada

    PubMed Central

    Renfrew, Paul Douglas; Quan, Hude; Doig, Christopher James; Dixon, Elijah; Molinari, Michele

    2011-01-01

    OBJECTIVE: To determine the generalizability of the predictions for 90-day mortality generated by Model for End-stage Liver Disease (MELD) and the serum sodium augmented MELD (MELDNa) to Atlantic Canadian adults with end-stage liver disease awaiting liver transplantation (LT). METHODS: The predictive accuracy of the MELD and the MELDNa was evaluated by measurement of the discrimination and calibration of the respective models’ estimates for the occurrence of 90-day mortality in a consecutive cohort of LT candidates accrued over a five-year period. Accuracy of discrimination was measured by the area under the ROC curves. Calibration accuracy was evaluated by comparing the observed and model-estimated incidences of 90-day wait-list failure for the total cohort and within quantiles of risk. RESULTS: The area under the ROC curve for the MELD was 0.887 (95% CI 0.705 to 0.978) – consistent with very good accuracy of discrimination. The area under the ROC curve for the MELDNa was 0.848 (95% CI 0.681 to 0.965). The observed incidence of 90-day wait-list mortality in the validation cohort was 7.9%, which was not significantly different from the MELD estimate of 6.6% (95% CI 4.9% to 8.4%; P=0.177) or the MELDNa estimate of 5.8% (95% CI 3.5% to 8.0%; P=0.065). Global goodness-of-fit testing found no evidence of significant lack of fit for either model (Hosmer-Lemeshow χ2 [df=3] for MELD 2.941, P=0.401; for MELDNa 2.895, P=0.414). CONCLUSION: Both the MELD and the MELDNa accurately predicted the occurrence of 90-day wait-list mortality in the study cohort and, therefore, are generalizable to Atlantic Canadians with end-stage liver disease awaiting LT. PMID:21876856

  14. From Child-Pugh to Model for End-Stage Liver Disease: Deciding Who Needs a Liver Transplant.

    PubMed

    Reddy, Sheela S; Civan, Jesse M

    2016-05-01

    This article reviews the historical evolution of the liver transplant organ allocation policy and the indications/contraindications for liver transplant, and provides an overview of the liver transplant evaluation process. The article is intended to help internists determine whether and when referral to a liver transplant center is indicated, and to help internists to counsel patients whose initial evaluation at a transplant center is pending. PMID:27095638

  15. Diagnostic Accuracy of Serum Procalcitonin for Spontaneous Bacterial Peritonitis Due to End-stage Liver Disease: A Meta-analysis.

    PubMed

    Yang, Yongtao; Li, Lianyong; Qu, Changmin; Zeng, Bolun; Liang, Shuwen; Luo, Zhiwen; Wang, Xiaoying; Zhong, Changqing

    2015-12-01

    Early diagnosis and prompt treatment of spontaneous bacterial peritonitis (SBP) due to end-stage liver disease is vital to shorten hospital stays and reduce mortality. Many studies have explored the potential usefulness of serum procalcitonin (PCT) in predicting SBP. The aim of this study is to evaluate the overall diagnostic accuracy of PCT levels for identifying SBP due to end-stage liver disease.After performing a systematic search of the Medline, Embase, and Cochrane databases for studies that evaluated the diagnostic role of PCT for SBP, sensitivity, specificity, and other measures of accuracy of PCT concentrations in serum for SBP diagnosis were pooled using random-effects models. A summary receiver operating characteristic curve was used to summarize overall test performance.Seven publications met the inclusion criteria covering 742 episodes of suspected SBP along with 339 confirmed cases. The summary estimates for serum PCT in the diagnosis of SBP attributable to end-stage liver disease were: sensitivity 0.82 (95% CI 0.79-0.87), specificity 0.86 (95% CI 0.82-0.89), positive likelihood ratio 4.94 (95% CI 2.28-10.70), negative likelihood ratio 0.22 (95% CI 0.10-0.52), and diagnostic OR 22.55 (95% CI 7.01-108.30). The area under the curve was 0.92. There was evidence of significant heterogeneity but no evidence of publication bias.Serum PCT is a relatively sensitive and specific test for the identification of SBP. However, due to the limited high-quality studies available, medical decisions should be carefully made in the context of both PCT test results and other clinical findings.

  16. Alcoholic liver disease: Treatment

    PubMed Central

    Suk, Ki Tae; Kim, Moon Young; Baik, Soon Koo

    2014-01-01

    The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation. PMID:25278689

  17. Cost of a quality-adjusted life year in liver transplantation: the influence of the indication and the model for end-stage liver disease score.

    PubMed

    Åberg, Fredrik; Mäklin, Suvi; Räsänen, Pirjo; Roine, Risto P; Sintonen, Harri; Koivusalo, Anna-Maria; Höckerstedt, Krister; Isoniemi, Helena

    2011-11-01

    Cost issues in liver transplantation (LT) have received increasing attention, but the cost-utility is rarely calculated. We compared costs per quality-adjusted life year (QALY) from the time of placement on the LT waiting list to 1 year after transplantation for 252 LT patients and to 5 years after transplantation for 81 patients. We performed separate calculations for chronic liver disease (CLD), acute liver failure (ALF), and different Model for End-Stage Liver Disease (MELD) scores. For the estimation of QALYs, the health-related quality of life was measured with the 15D instrument. The median costs and QALYs after LT were €141,768 and 0.895 for 1 year and €177,618 and 3.960 for 5 years, respectively. The costs of the first year were 80% of the 5-year costs. The main cost during years 2 to 5 was immunosuppression drugs (59% of the annual costs). The cost/QALY ratio improved from €158,400/QALY at 1 year to €44,854/QALY at 5 years, and the ratio was more beneficial for CLD patients (€42,500/QALY) versus ALF patients (€63,957/QALY) and for patients with low MELD scores versus patients with high MELD scores. Although patients with CLD and MELD scores > 25 demonstrated markedly higher 5-year costs (€228,434) than patients with MELD scores < 15 (€169,541), the cost/QALY difference was less pronounced (€59,894/QALY and €41,769/QALY, respectively). The cost/QALY ratio for LT appears favorable, but it is dependent on the assessed time period and the severity of the liver disease.

  18. United Network for Organ Sharing regional variations in appeal denial rates with non-standard Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exceptions: support for a national review board.

    PubMed

    Gish, Robert G; Wong, Robert J; Honerkamp-Smith, Gordon; Xu, Ronghui; Osorio, Robert W

    2015-06-01

    Although it has been generally recognized that there are inconsistencies among Regional Review Boards in the assignment of points for model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) exception patients with resulting considerable variation in appeal denial rates, data to actually prove this have been limited. We reviewed 6533 MELD/PELD exception applications submitted between 2005 and 2008, calculated the variation in approval/denial rates, and followed these cases through mid-2013 to assess the effects on patient outcomes. We found highly significant regional variations in denial rates for appeals by exception patients and in transplantation rates. The odds of transplant for patients whose appeals are approved is 2.45 times that of patients not approved; that this effect does not vary by region suggests that the variation in transplant rates is driven, at least in part, by the variation in appeal denial rates. Health deterioration or death accounts for more than two-thirds of wait list removals among patients removed for reasons other than transplant. Our findings add to the weight of evidence that a national review board that uses current clinical expertise, peer review literature, and data to consistently assign priority could reduce regional inequities and move toward equitable allocation of organs and compliance with the United States Department of Health & Human Services Final Rule.

  19. Liver fibrosis markers in alcoholic liver disease.

    PubMed

    Chrostek, Lech; Panasiuk, Anatol

    2014-07-01

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients. PMID:25009372

  20. Autoimmune liver disease panel

    MedlinePlus

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  1. Alcohol-Related Liver Disease

    MedlinePlus

    ... to run events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community ... Liver > Liver Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn ...

  2. Validation of the Model of End-Stage Liver Disease for Liver Transplant Allocation in Alberta: Implications for Future Directions in Canada

    PubMed Central

    Burak, Kelly W.; Meeberg, Glenda A.; Myers, Robert P.; Fick, Gordon H.; Swain, Mark G.; Bain, Vincent G.; Kneteman, Norman M.; Hilsden, Robert J.

    2016-01-01

    Background. Since 2002, the Model of End-Stage Liver Disease (MELD) has been used for allocation of liver transplants (LT) in the USA. In Canada, livers were allocated by the CanWAIT algorithm. The aim of this study was to compare the abilities of MELD, Child-Pugh (CP), and CanWAIT status to predict 3-month and 1-year mortality before LT in Canadian patients and to describe the use of MELD in Canada. Methods. Validation of MELD was performed in 320 patients listed for LT in Alberta (1998–2002). In October 2014, a survey of MELD use by Canadian LT centers was conducted. Results. Within 1 year of listing, 47 patients were removed from the waiting list (29 deaths, 18 too ill for LT). Using logistic regression, the MELD and CP were better than the CanWAIT at predicting 3-month (AUROC: 0.79, 0.78, and 0.59; p = 0.0002) and 1-year waitlist mortality (AUROC: 0.70, 0.70, and 0.55; p = 0.0023). Beginning in 2004, MELD began to be adopted by Canadian LT programs but its use was not standardized. Conclusions. Compared with the CanWAIT system, the MELD score was significantly better at predicting LT waitlist mortality. MELD-sodium (MELD-Na) has now been adopted for LT allocation in Canada. PMID:27446823

  3. Based on surface-enhanced Raman spectroscopy analysis of serum albumin in different stages of liver disease for early screening primary liver cancer

    NASA Astrophysics Data System (ADS)

    Liao, Fadian; Ruan, Qiuyong; Lin, Juqiang; Lin, Jinyong; Zeng, Yongyi; Li, Ling; Huang, Zufang; Liu, Nenrong; Chen, Rong

    2014-09-01

    Despite the introduction of high-technology methods of detection and diagnosis, screening of primary liver cancer (PLC) remains imperfect. To diagnosis PLC earlier, Surface-enhanced Raman spectroscopy (SERS) coupled with cellulose-acetate membrane electrophoresis were introduced to separate human serum albumin and SERS spectra. Three groups (15 normal persons' samples, 17 hepatitis/cirrhosis samples, 15 cases of PLC) of serum albumin were tested. Silver colloid was used to obtain SERS spectra of human serum albumin. Principal component analysis (PCA) and linear discriminant analysis (LDA) were also employed for statistical analysis. The mean Raman spectra of three groups and the difference spectra of any two suggested that the albumin has changed in liver patients. Compared to normal groups, some Raman peaks have shifted or even disappeared in hepatitis/cirrhosis and PLCs groups. The sensitivity and specificity between PLCs and normal groups is 80% and 93.3%. Among hepatitis/cirrhosis and normal groups, the sensitivity is 88.2% and specificity is also 93.3%. Besides, the sensitivity and specificity between PLCs and hepatitis/cirrhosis groups is 86.7% and 76.5%. All the above data and results indicated that early screening of PLC is potential by SERS in different stages of liver disease before cancer occurs.

  4. Peribiliary hepatic cysts presenting as hilar cholangiocarcinoma in a patient with end-stage liver disease

    PubMed Central

    Lim, Jane; Nissen, Nicholas N.; McPhaul, Christopher; Annamalai, Alagappan; Klein, Andrew S.; Sundaram, Vinay

    2016-01-01

    Peribiliary cysts are cystic dilatations of peribiliary glands in the liver. They are present in ~50% of cirrhotic patients, but are underrecognized because they are usually asymptomatic and rarely present as obstructive jaundice. A 63-year-old male with hepatitis C cirrhosis, awaiting liver transplantation, had a new finding of intrahepatic dilatation on magnetic resonance imaging. This was initially concerning for cholangiocarcinoma, but was ultimately diagnosed as peribiliary cysts. Peribiliary cysts can imitate cholangiocarcinoma on imaging. Therefore, awareness of this condition is essential because misdiagnosis may lead to inappropriate delay or denial for liver transplantation. The ideal imaging modalities to identify peribiliary cysts are magnetic resonance cholangiography and drip infusion cholangiographic computed tomography, though hepatic dysfunction may limit the usefulness of the latter. Peribiliary cysts should be considered in cirrhotic patients with cholestasis, biliary dilatations and negative biopsy of the biliary system for malignancy. PMID:27511912

  5. Liver transplantation for Wilson's disease.

    PubMed

    Schilsky, Michael L

    2014-05-01

    Although Wilsons's disease (WD) may be treated with copper chelation (to remove copper) or zinc salts (to prevent absorption) to alleviate or prevent symptom development in most patients, there are WD patients for whom medical therapy is inadequate and survival would be unlikely without liver transplantation. Liver transplantation is indicated for the ∼5% of WD patients with acute liver failure as the first presentation of disease, most commonly in the second decade of life, or those who present with end-stage liver disease and severe hepatic insufficiency, most commonly in the third and fourth decades. Liver transplantation restores normal biliary copper excretion (thereby preventing disease recurrence) and promotes removal of copper from extrahepatic sites. Outcomes of liver transplantation for WD are excellent, including both cadaveric and living donors.

  6. Improved waiting-list outcomes in Argentina after the adoption of a model for end-stage liver disease-based liver allocation policy.

    PubMed

    Cejas, Nora Gabriela; Villamil, Federico G; Lendoire, Javier C; Tagliafichi, Viviana; Lopez, Arturo; Krogh, Daniela Hansen; Soratti, Carlos A; Bisigniano, Liliana

    2013-07-01

    In July 2005, Argentina became the first country after the United States to introduce the Model for End-Stage Liver Disease (MELD) for organ allocation. In this study, we investigated waiting-list (WL) outcomes (n = 3272) and post-liver transplantation (LT) survival in 2 consecutive periods of 5 years before and after the implementation of a MELD-based allocation policy. Data were obtained from the database of the national institute for organ allocation in Argentina. After the adoption of the MELD system, there were significant reductions in WL mortality [28.5% versus 21.9%, P < 0.001, hazard ratio (HR) = 1.57, 95% confidence interval (CI) = 1.37-1.81] and total dropout rates (38.6% versus 29.1%, P < 0.001, HR = 1.31, 95% CI = 1.16-1.48) despite significantly less LT accessibility (57.4% versus 50.7%, P < 0.001, HR = 1.53, 95% CI = 1.39-1.68). The annual number of deaths per 1000 patient-years at risk decreased from 273 in 2005 to 173 in 2010, and the number of LT procedures per 1000 patient-years at risk decreased from 564 to 422. MELD and Model for End-Stage Liver Disease-Sodium scores were excellent predictors of 3-month WL mortality with c statistics of 0.828 and 0.857, respectively (P < 0.001). No difference was observed in 1-year posttransplant survival between the 2 periods (81.1% versus 81.3%). Although patients with a MELD score > 30 had lower posttransplant survival, the global accuracy of the score for predicting outcomes was poor, as indicated by a c statistic of only 0.523. Patients with granted MELD exceptions (158 for hepatocellular carcinoma and 52 for other reasons) had significantly higher access to LT (80.4%) in comparison with nonexception patients with equivalent listing priority (MELD score = 18-25; 54.6%, P < 0.001, HR = 0.49, 95% CI = 0.40-0.61). In conclusion, the adoption of the MELD model in Argentina has resulted in improved liver organ allocation without compromising

  7. Model for end-stage liver disease predicts right ventricular failure in patients with left ventricular assist devices.

    PubMed

    Yost, Gardner L; Coyle, Laura; Bhat, Geetha; Tatooles, Antone J

    2016-03-01

    High rates of right ventricular failure continue to affect postoperative outcomes in patients implanted with left ventricular assist devices (LVADs). Development of right ventricular failure and implantation with right ventricular assist devices is known to be associated with significantly increased mortality. The model for end-stage liver disease (MELD) score is an effective means of evaluating liver dysfunction. We investigated the prognostic utility of postoperative MELD on post-LVAD implantation outcomes. MELD scores, demographic data, and outcomes including length of stay, survival, and postoperative right ventricular failure were collected for 256 patients implanted with continuous flow LVADs. Regression and Kaplan-Meier analyses were used to investigate the relationship between MELD and all outcomes. Increased MELD score was found to be an independent predictor of both right heart failure and necessity for RVAD implantation (OR 1.097, CI 1.040-1.158, p = 0.001; OR 1.121, CI 1.015, p = 0.024, respectively). Patients with RV failure and who underwent RVAD implantation had reduced postoperative survival compared to patients with RV dysfunction (no RV failure = 651.4 ± 609.8 days, RV failure = 392.6 ± 444.8 days, RVAD = 89.3 ± 72.8 days; p < 0.001). In conclusion, MELD can be used to reliably predict postoperative right heart failure and the necessity for RVAD implantation. Those patients with RV failure and RVADs experience significantly increased postoperative mortality compared to those without RV dysfunction. PMID:26187243

  8. Reestablishment of Active Immunity against HBV Graft Reinfection after Liver Transplantation for HBV-Related End Stage Liver Disease

    PubMed Central

    Lai, Wei; Liu, Yuan; Zhang, Jing; Zeng, Dao-Bing; Li, Chuan-Yun; Wang, Meng-Long; Lin, Dong-Dong; Zhu, Yue; Li, You-Ping; Li, Ning

    2014-01-01

    Background. The aim of this study was to establish a hepatitis B virus (HBV) vaccination protocol among orthotopic liver transplantation (OLT) recipients under the coverage of a low-dose hepatitis B immunoglobulin (HBIG) combined with an antiviral agent prophylaxis protocol. Method. Two hundred OLT recipients were included in this study. The vaccine was injected at months 0, 1, 2, and 6. Low-dose HBIG combined with antiviral agent prophylaxis protocol was continued before reestablishment of active immunity against HBV in order to maintain a steady anti-HBs titer. Results. Active immunity against HBV was reestablished in 50 patients, for an overall response rate of 25%. Of the 50 patients, 24 discontinued HBIG without any HBV graft reinfection during a follow-up period of 26.13 ± 7.05 months. 21 patients discontinued both HBIG and antiviral agents during a follow-up period of 39.86 ± 15.47 months, and 4 patients among them appeared to be HBsAg positive. There was no recipient death or graft loss because of HBV reinfection. Conclusions. Vaccination preventing HBV reinfection for OLT recipients is feasible. The strategy withdrawal of HBIG with induction of active immunity against hepatitis B is reasonable for long-term survivors of OLT; however, discontinuation nucleoside analogues should be cautious. PMID:25759834

  9. Model for end-stage liver disease-Na score or Maddrey discrimination function index, which score is best?

    PubMed Central

    Amieva-Balmori, Mercedes; Mejia-Loza, Scherezada María Isabel; Ramos-González, Roberto; Zamarripa-Dorsey, Felipe; García-Ruiz, Eli; Pérez y López, Nuria; Juárez-Valdés, Eumir I; López-Luria, Adriana; Remes-Troche, José María

    2015-01-01

    AIM: To compare the ability of model for end-stage liver disease (MELD)-Na and Maddrey discrimination function index (DFI) to predict mortality at 30 and 90 d in patients with alcoholic hepatitis (AH). METHODS: We prospectively assessed 52 patients with AH. Demographic, clinical and laboratory parameters were obtained. MELD-Na and Maddrey DFI were calculated on admission. Short-term mortality was assessed at 30 and 90 d. Receiver operating characteristic curve analysis was performed. RESULTS: Thirty-day and 90-d mortality was 44% and 58%, respectively. In the univariate analysis, sodium levels was associated with mortality at 30 and 90 d (P = 0.001 and P = 0.03). Child stage, encephalopathy, ascites, or types of treatment were not associated with mortality. MELD-Na was the only predictive factor for mortality at 90 d. For 30-d mortality area under the curve (AUC) was 0.763 (95%CI: 0.63-0.89) for Maddrey DFI and 0.784 for MELD-Na (95%CI: 0.65-0.91, P = 0.82). For 90-d mortality AUC was 0.685 (95%CI: 0.54-0.83) for Maddrey DFI and 0.8710 for MELD-Na (95%CI: 0.76-0.97, P = 0.041). CONCLUSION: AH is associated with high short-term mortality. Our results show that MELD-Na is a more valuable model than DFI to predict short-term mortality. PMID:26301054

  10. Coffee and Liver Disease.

    PubMed

    Wadhawan, Manav; Anand, Anil C

    2016-03-01

    Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality. PMID:27194895

  11. Ultrasound Shear Wave Elastography for Liver Disease. A Critical Appraisal of the Many Actors on the Stage.

    PubMed

    Piscaglia, F; Salvatore, V; Mulazzani, L; Cantisani, V; Schiavone, C

    2016-02-01

    In the last 12 - 18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(®) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by

  12. Ultrasound Shear Wave Elastography for Liver Disease. A Critical Appraisal of the Many Actors on the Stage.

    PubMed

    Piscaglia, F; Salvatore, V; Mulazzani, L; Cantisani, V; Schiavone, C

    2016-02-01

    In the last 12 - 18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(®) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by

  13. Aging and liver disease

    PubMed Central

    Kim, Hee; Kisseleva, Tatiana; Brenner, David A.

    2016-01-01

    Purpose of review Aging is a condition in which a person gradually loses the ability to maintain homeostasis, due to structural alteration or dysfunction. Aging is a major risk factor for most chronic diseases. As the liver has a remarkable ability to regenerate, this review assessed the effect of aging on clinical liver disease with references to preclinical models when relevant to pathogenesis. Recent findings Aging has been shown to not only enhance vulnerability to acute liver injury but also increase susceptibility of the fibrotic response. Aging is associated with the severity and poor prognosis of various liver diseases including nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis C, and liver transplantation. Summary Treatment of older patients with liver disease may require different or longer interventions. Transplantation of an older liver will be less tolerant of subsequent injury. Future studies are needed to understand more about the molecular mechanism of aging and contribute to the development of a noble treatment strategy that can block the progression of aging-induced liver diseases. PMID:25850346

  14. Projected outcomes of 6-month delay in exception points versus an equivalent Model for End-Stage Liver Disease score for hepatocellular carcinoma liver transplant candidates.

    PubMed

    Alver, Sarah K; Lorenz, Douglas J; Marvin, Michael R; Brock, Guy N

    2016-10-01

    The United Network for Organ Sharing (UNOS) recently implemented a 6-month delay before granting exception points to liver transplantation candidates with hepatocellular carcinoma (HCC) to address disparity in transplantation access between HCC and non-HCC patients. An HCC-specific scoring scheme, the Model for End-Stage Liver Disease equivalent (MELDEQ ), has also been developed. We compared projected dropout and transplant probabilities and posttransplant survival for HCC and non-HCC patients under the 6-month delay and the MELDEQ using UNOS data from October 1, 2009, to June 30, 2014, and multistate modeling. Overall (combined HCC and non-HCC) wait-list dropout was similar under both schemes and slightly improved (though not statistically significant) compared to actual data. Projected HCC wait-list dropout was similar between the MELDEQ and 6-month delay at 6 months but thereafter started to differ, with the 6-month delay eventually favoring HCC patients (3-year dropout 10.0% [9.0%-11.0%] for HCC versus 14.1% [13.6%-14.6%]) for non-HCC) and the MELDEQ favoring non-HCC patients (3-year dropout 16.0% [13.2%-18.8%] for HCC versus 12.3% [11.9%-12.7%] for non-HCC). Projected transplant probabilities for HCC patients were substantially lower under the MELDEQ compared to the 6-month delay (26.6% versus 83.8% by 3 years, respectively). Projected HCC posttransplant survival under the 6-month delay was similar to actual, but slightly worse under the MELDEQ (2-year survival 82.9% [81.7%-84.2%] versus actual of 85.5% [84.3%-86.7%]). In conclusion, although the 6-month delay improves equity in transplant and dropout between HCC and non-HCC candidates, disparity between the 2 groups may still exist after 6 months of wait-list time. Projections under the MELDEQ , however, appear to disadvantage HCC patients. Therefore, modification to the exception point progression or refinement of an HCC prioritization score may be warranted. Liver Transplantation 22 1343-1355 2016 AASLD.

  15. Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

    PubMed

    Hong, Geun; Yi, Nam-Joon; Suh, Suk-won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Lee, Kyungbun; Lee, Kwang-Woong; Park, Myoung Hee; Suh, Kyung-Suk

    2014-05-01

    Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe. PMID:24851018

  16. Pattern of microRNA expression associated with different stages of alcoholic liver disease in rat models

    PubMed Central

    CHEN, YI-PENG; JIN, XI; KONG, MEI; LI, YOU-MING

    2014-01-01

    Emerging evidence has suggested that aberrant expression of micro (mi)RNAs contributes to the development of alcoholic liver injury (ALD). However, miRNA profiles distinguishing different stages of ALD have not yet been reported. The present study was designed to investigate the unique miRNA expression patterns at different stages of ALD in a rat model and analyze the gene functions and pathways of dysregulated miRNA-targeted genes. Using microarray and stem-loop quantitative polymerase chain reaction analyses, 16 miRNAs were identified as upregulated and 13 were identified as downregulated in an alcoholic steatohepatitis (ASH) group compared with the control group, while five miRNAs were identified to be upregulated and eight were identified to be downregulated in the alcoholic fatty liver (AFL) group as compared with the control group. Following further confirmation by Significance Analysis of Microarray and prediction by Prediction Analysis of Microarray, 8 and 12 types of miRNA were screened as molecular signatures in distinguishing AFL and ASH, respectively, from normal rat liver. In addition, several miRNA-target pairs were predicted by computer-aided algorithms (Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery platform) and these genes may be involved in cancer signaling pathways, the Wnt signaling pathway and other signaling pathways. These results may provide novel miRNA targets for diagnosis and therapeutic intervention at different stages of ALD. PMID:25017766

  17. Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis, End-Stage Renal Disease and Transplant Medicine

    PubMed Central

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H.; Heinzow, Hauke S.

    2015-01-01

    Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts. PMID:26251895

  18. Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis, End-Stage Renal Disease and Transplant Medicine.

    PubMed

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H; Heinzow, Hauke S

    2015-01-01

    Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts. PMID:26251895

  19. Nutrition and liver diseases.

    PubMed

    Teran, J C

    1999-08-01

    Malnutrition and micronutrient deficiencies are common in patients with liver diseases. The pathogenesis of protein-energy malnutrition in cirrhosis involves many factors, including poor oral intake, malabsorption, and metabolic abnormalities similar to stress. Encephalopathy may complicate cirrhosis but is usually not caused by diet. Protein restriction is only necessary in rare patients with refractory encephalopathy. The use of branched-chain amino-acid solutions is not supported by the literature. Chronic liver diseases without cirrhosis are not usually associated with protein-energy malnutrition, but vitamin and mineral deficiencies are common, especially with significant cholestasis. Fatty liver may result from excessive triglyceride uptake and production by the liver or by a secretory defect. Therapy for fatty liver depends on its cause. Chronic total parenteral nutrition may induce fatty liver and inflammation especially in patients with short-bowel syndrome. Deficiency of choline in parenteral nutrition has been proposed as the mechanism for liver disease. Acute liver diseases such as fulminant hepatic failure or alcoholic hepatitis are considered hypercatabolic diseases and thus require prompt nutritional intervention with a high-calorie enteral or parenteral formula. In fulminant hepatic failure, low-protein, fluid-restricted formulas are recommended. PMID:10980970

  20. Magnetic Resonance Elastography for Staging Liver Fibrosis in Non-alcoholic Fatty Liver Disease: A Diagnostic Accuracy Systematic Review and Individual Participant Data Pooled Analysis

    PubMed Central

    Singh, Siddharth; Venkatesh, Sudhakar K.; Loomba, Rohit; Wang, Zhen; Sirlin, Claude; Chen, Jun; Yin, Meng; Miller, Frank H.; Low, Russell N.; Hassanein, Tarek; Godfrey, Edmund M.; Asbach, Patrick; Murad, Mohammad Hassan; Lomas, David J.; Talwalkar, Jayant A.; Ehman, Richard L.

    2016-01-01

    Objectives We conducted an individual participant data (IPD) pooled analysis on the diagnostic accuracy of magnetic resonance elastography (MRE) to detect fibrosis stage in patients with NAFLD. Methods Through a systematic literature search, we identified studies of MRE (at 60–62.5Hz) for staging fibrosis in patients with NAFLD, using liver biopsy as gold standard and contacted study authors for IPD. Through pooled analysis, we calculated the cluster-adjusted AUROC, sensitivity and specificity of MRE for any (≥stage 1), significant (≥stage 2) and advanced fibrosis (≥stage 3) and cirrhosis (stage 4). Results We included 9 studies reporting on 232 patients with NAFLD (mean age, 51±13y; 37.5% males; mean BMI, 33.5±6.7 kg/m2; interval between MRE and biopsy <1 year, 98.3%). Fibrosis stage distribution (stage 0/1/2/3/4) was 33.6%, 32.3%, 10.8%, 12.9% and 10.4%, respectively. Mean AUROC (and 95% confidence intervals) for diagnosis of any (≥stage 1), significant (≥stage 2) or advanced fibrosis (≥stage 3) and cirrhosis was 0.86 (0.82–0.90), 0.87 (0.82–0.93), 0.90 (0.84–0.94) and 0.91 (0.76–0.95), respectively. Similar diagnostic performance was observed in stratified analysis based on sex, obesity, and degree of inflammation. Conclusions Based on pooled IPD analysis, MRE has high diagnostic accuracy for detection of fibrosis in NAFLD, independent of BMI and degree of inflammation. PMID:26314479

  1. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

    Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT. PMID:26689244

  2. Staging Liver Fibrosis with Statistical Observers

    NASA Astrophysics Data System (ADS)

    Brand, Jonathan Frieman

    Chronic liver disease is a worldwide health problem, and hepatic fibrosis (HF) is one of the hallmarks of the disease. Pathology diagnosis of HF is based on textural change in the liver as a lobular collagen network that develops within portal triads. The scale of collagen lobules is characteristically on order of 1mm, which close to the resolution limit of in vivo Gd-enhanced MRI. In this work the methods to collect training and testing images for a Hotelling observer are covered. An observer based on local texture analysis is trained and tested using wet-tissue phantoms. The technique is used to optimize the MRI sequence based on task performance. The final method developed is a two stage model observer to classify fibrotic and healthy tissue in both phantoms and in vivo MRI images. The first stage observer tests for the presence of local texture. Test statistics from the first observer are used to train the second stage observer to globally sample the local observer results. A decision of the disease class is made for an entire MRI image slice using test statistics collected from the second observer. The techniques are tested on wet-tissue phantoms and in vivo clinical patient data.

  3. Fibrosis in Autoimmune and Cholestatic Liver Disease

    PubMed Central

    Penz-Österreicher, Melitta; Österreicher, Christoph H.; Trauner, Michael

    2011-01-01

    Autoimmune and cholestatic liver disease account for a significant part of end-stage liver disease and are leading indications for liver transplantation. Especially cholestatic liver diseases (primary biliary cirrhosis and primary sclerosing cholangitis) appear to be different from other chronic liver diseases with regards to pathogenesis. Portal fibroblasts located in the connective tissue surrounding bile ducts appear to be different from hepatic stellate cells with regards to expression of marker proteins and response the profibrogenic and mitogenic stimuli. In addition there is increasing evidence for a cross talk between activated cholangiocytes and portal myofibroblasts. Several animal models have improved our understanding of the mechanisms underlying these chronic liver diseases. In the present review, we discuss the current concepts and ideas with regards to myofibroblastic cell populations, mechanisms of fibrosis, summarize characteristic histological findings and currently employed animal models of autoimmune and cholestatic liver disease. PMID:21497742

  4. Genetic diversity of hepatitis B virus and mutations associated to hepatocellular carcinoma in patients from Venezuela, with different stages of liver disease.

    PubMed

    Puche, Mary L; Kay-Valero, Sharon; Michelli, Pedro; Oropeza, Maria D; Loureiro, Carmen L; Devesa, Marisol; Dagher, Lucy; Puol, Flor H

    2016-03-01

    Globally, about 50% of liver cancer originates as a result of long term infection with hepatitis B virus (HBV), and some genotypes and mutations have been associated with an increased severity of infection. The aim of this study was to evaluate the genetic diversity of HBV in patients from Venezuela, with chronic infection, cirrhosis and hepatocellular carcinoma (HCC) and to compare the occurrence of mutations in all patient groups. Samples from patients with different pathologies of the liver, associated with HBV infection, were collected. The HBV S region was analyzed for genotype determination and, when available, the whole genome sequence was examined for mutations analysis. Genotype F was the most common genotype (87%). While the HBV subgenotype F3 was the most frequent genotype in the whole group of samples (44%), the subgenotype F2 predominated in HCC patients (56%). Mutations were more common in HCC and cirrhosis cases (p=0.01). The A1762T mutation was significantly associated with the advanced stage of liver disease (p=0.008). Additionally, mutations were more common in early stages of liver disease in HBV subgenotype F2-infected patients, and a significant association between this subgenotype and the emergence of T 1753C, A1762T, A1762T/G1764A (p=0.04) and C1773T (p=0.001) mutations in chronic patients was found, when compared to the HBV subgenotype F3. By comparing F2 with all other HBV subgenotypes, a positive association for the three basal core promoter (BCP) mutants (A1762T, A1762T/G1764A p=0.01, G1764A p=0.04) was found. These results suggest that the HBV subgenotype F2 might be associated to more severe forms of liver disease in comparison with the HBV subgenotype F3. PMID:27382800

  5. [Liver diseases in the elderly].

    PubMed

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. PMID:24951302

  6. [Liver diseases in the elderly].

    PubMed

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice.

  7. [Probiotics in liver diseases].

    PubMed

    Soriano, Germán; Sánchez, Elisabet; Guarner, Carlos

    2013-01-01

    Alterations in intestinal microbiota and inflammatory response play a key role in disease progression and development of complications in liver diseases, mainly in cirrhosis and non-alcoholic steatohepatitis. Probiotics can be useful to delay disease progression and to prevent development of complications due to their ability to modulate intestinal flora, intestinal permeability and inflammatory response. Several studies have shown the efficacy of probiotics in the treatment of minimal hepatic encephalopathy and the prevention of episodes of overt hepatic encephalopathy. Probiotics have also been observed to prevent postoperative bacterial infections and to improve liver damage in non-alcoholic steatohepatitis. However, more studies are needed in order to confirm the efficacy and safety of probiotics in patients with liver diseases, and to better understanding of the mechanisms implicated in their effects.

  8. Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients.

    PubMed

    Patel, Viren; Rink, Cameron; Gordillo, Gayle M; Khanna, Savita; Gnyawali, Urmila; Roy, Sashwati; Shneker, Bassel; Ganesh, Kasturi; Phillips, Gary; More, J Layne; Sarkar, Atom; Kirkpatrick, Robert; Elkhammas, Elmahdi A; Klatte, Emily; Miller, Michael; Firstenberg, Michael S; Chiocca, E Antonio; Nesaretnam, Kalanithi; Sen, Chandan K

    2012-03-01

    The natural vitamin E family is composed of 8 members equally divided into 2 classes: tocopherols (TCP) and tocotrienols (TE). A growing body of evidence suggests TE possess potent biological activity not shared by TCP. The primary objective of this work was to determine the concentrations of TE (200 mg mixed TE, b.i.d.) and TCP [200 mg α-TCP, b.i.d.)] in vital tissues and organs of adults receiving oral supplementation. Eighty participants were studied. Skin and blood vitamin E concentrations were determined from healthy participants following 12 wk of oral supplementation of TE or TCP. Vital organ vitamin E levels were determined by HPLC in adipose, brain, cardiac muscle, and liver of surgical patients following oral TE or TCP supplementation (mean duration, 20 wk; range, 1-96 wk). Oral supplementation of TE significantly increased the TE tissue concentrations in blood, skin, adipose, brain, cardiac muscle, and liver over time. α-TE was delivered to human brain at a concentration reported to be neuroprotective in experimental models of stroke. In prospective liver transplantation patients, oral TE lowered the model for end-stage liver disease (MELD) score in 50% of patients supplemented, whereas only 20% of TCP-supplemented patients demonstrated a reduction in MELD score. This work provides, to our knowledge, the first evidence demonstrating that orally supplemented TE are transported to vital organs of adult humans. The findings of this study, in the context of the current literature, lay the foundation for Phase II clinical trials testing the efficacy of TE against stroke and end-stage liver disease in humans.

  9. Usefulness of international normalized ratio to predict bleeding complications in patients with end-stage liver disease who undergo cardiac catheterization.

    PubMed

    Townsend, Jacob C; Heard, Richard; Powers, Eric R; Reuben, Adrian

    2012-10-01

    Patients with end-stage liver disease frequently require invasive cardiac procedures in preparation for liver transplantation. Because of the impaired hepatic function, these patients often have a prolonged prothrombin time and elevated international normalized ratio (INR). To determine whether an abnormal prothrombin time/INR is predictive of bleeding complications from invasive cardiac procedures, we retrospectively reviewed, for bleeding complications, the databases and case records of our series of patients with advanced cirrhosis who underwent cardiac catheterization. A total of 157 patients underwent isolated right-sided heart catheterization, and 83 underwent left-sided heart catheterization or combined left- and right-sided heart catheterization. The INR ranged from 0.93 to 2.35. No major procedure-related complications occurred. Several patients in each group required a blood transfusion for gastrointestinal bleeding but not for procedure-related bleeding. No significant change was found in the hemoglobin after right-sided or left-sided heart catheterization, and no correlation was found between the preprocedure INR and the change in postprocedure hemoglobin. When comparing patients with a normal (≤1.5) and elevated (>1.5) INR, no significant difference in hemoglobin after the procedure was found in either group. In conclusion, despite an elevated INR, patients with end-stage liver disease can safely undergo invasive cardiac procedures. An elevated INR does not predict catheterization-related bleeding complications in this patient population.

  10. Liver disease and malnutrition.

    PubMed

    Purnak, Tugrul; Yilmaz, Yusuf

    2013-08-01

    Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.

  11. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  12. Metabolic therapy: lessons from liver diseases.

    PubMed

    Garcia-Ruiz, Carmen; Marí, Montserrat; Colell, Anna; Morales, Albert; Fernandez-Checa, Jose C

    2011-12-01

    Fatty liver disease is one of most prevalent metabolic liver diseases, which includes alcoholic (ASH) and nonalcoholic steatohepatitis (NASH). Its initial stage is characterized by fat accumulation in the liver, that can progress to steatohepatitis, a stage of the disease in which steatosis is accompanied by inflammation, hepatocellular death, oxidative stress and fibrosis. Recent evidence in experimental models as well as in patients with steatohepatitis have uncovered a role for cholesterol and sphingolipids, particularly ceramide, in the transition from steatosis to steatohepatitis, insulin resistance and hence disease progression. Cholesterol accumulation and its trafficking to mitochondria sensitizes fatty liver to subsequent hits including inflammatory cytokines, such as TNF/Fas, in a pathway involving ceramide generation by acidic sphingomyelinase (ASMase). Thus, targeting both cholesterol and/or ASMase may represent a novel therapeutic approach of relevance in ASH and NASH, two of the most common forms of liver diseases worldwide. PMID:21933146

  13. Arsenic and liver disease.

    PubMed

    Guha Mazumder, D N

    2001-06-01

    The hepatotoxic action of arsenic, when used as a therapeutic agent, has long been recognised. Data on liver involvement following chronic exposure to arsenic-contaminated water are scanty. The nature and degree of liver involvement are reported on the basis of hospital based studies in patients who consumed arsenic contaminated drinking water for one to 15 years. Two hundred forty-eight patients with evidence of chronic arsenic toxicity underwent clinical and laboratory examination including liver function tests and hepatitis B surface antigen (HBsAg) status. Liver biopsy was done in 69 cases; in 29 patients, liver arsenic content was estimated by neutron activation analysis. Hepatomegaly was present in 190 of 248 patients (76.6%). Non-cirrhotic portal fibrosis was the predominant lesion (91.3%) in liver histology. The maximum arsenic content in liver was 6 mg/kg (mean 1.46 [0.42], control value 0.16 [0.04]; p <0.001); it was undetected in 6 of 29 samples studied. The largest number of patients with liver disease due to chronic arsenicosis from drinking arsenic contaminated water are reported. Non-cirrhotic portal fibrosis is the predominant lesion in this population. Hepatic fibrosis has also been demonstrated due to long term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferases elevated at 12 months and hepatic fibrosis at 15 months.

  14. End-stage renal disease and African American race are independent predictors of mild liver fibrosis in patients with chronic hepatitis C infection.

    PubMed

    Aslinia, F M; Wasan, S K; Mindikoglu, A L; Adeyemo, O A; Philosophe, B; Drachenberg, C; Howell, C D

    2012-05-01

    Recipients of haemodialysis for end-stage renal disease (ESRD) have a higher prevalence of hepatitis C virus (HCV) infection relative to the general US population. However, the natural course of HCV infection in patients with renal failure, including African Americans (AAs) and Caucasian Americans (CAs), is not well known. We compared the degree of liver inflammation and fibrosis in AA and CA patients with HCV infection, with and without ESRD. This was a cross-sectional study of 156 HCV patients with ESRD (130 AAs and 26 CAs) with a liver biopsy between 1992 and 2005. The control group consisted of 138 patients (50 AAs; 88 CAs) with HCV infections and a serum creatinine <1.5 mg/dL with a liver biopsy between 1995 and 1998. Specimens were graded for inflammation and fibrosis using Knodell histological activity index. Compared to patients without renal impairment, HCV patients with renal failure were older and more likely to be AA. Patients with renal impairment had lower mean serum transaminases, a higher mean serum alkaline phosphatase levels (all P < 0.0001) and less hepatic necro-inflammation (Knodell histological activity index -I, II and III; P < 0.05) and fibrosis (Knodell histological activity index -IV; P < 0.0001). There were no racial differences in serum liver chemistry and histology scores among patients with renal failure. In a multivariate analysis, younger age, ESRD, AA race and a lower serum alkaline phosphatase were associated with lower odds for advanced liver fibrosis. Thus, HCV patients with ESRD had a lower degree of hepatic inflammation and fibrosis compared to those without renal disease, independent of race.

  15. Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy

    PubMed Central

    Moris, Demetrios; Vernadakis, Spyridon; Papalampros, Alexandros; Vailas, Michail; Dimitrokallis, Nikolaos; Petrou, Athanasios; Dimitroulis, Dimitrios

    2016-01-01

    AIM To highlight the potential mechanisms of regeneration in the Associating Liver Partition and Portal vein ligation for Stage hepatectomy models (clinical and experimental) that could unlock the myth behind the extraordinary capability of the liver for regeneration, which would help in designing new therapeutic options for the regenerative drive in difficult setup, such as chronic liver diseases. Associating Liver Partition and Portal vein ligation for Stage hepatectomy has been recently advocated to induce rapid future liver remnant hypertrophy that significantly shortens the time for the second stage hepatectomy. The introduction of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in the surgical armamentarium of therapeutic tools for liver surgeons represented a real breakthrough in the history of liver surgery. METHODS A comprehensive literature review of Associating Liver Partition and Portal vein ligation for Stage hepatectomy and its utility in liver regeneration is performed. RESULTS Liver regeneration after Associating Liver Partition and Portal vein ligation for Stage hepatectomy is a combination of portal flow changes and parenchymal transection that generate a systematic response inducing hepatocyte proliferation and remodeling. CONCLUSION Associating Liver Partition and Portal vein ligation for Stage hepatectomy represents a real breakthrough in the history of liver surgery because it offers rapid liver regeneration potential that facilitate resection of liver tumors that were previously though unresectable. The jury is still out though in terms of safety, efficacy and oncological outcomes. As far as Associating Liver Partition and Portal vein ligation for Stage hepatectomy -induced liver regeneration is concerned, further research on the field should focus on the role of non-parenchymal cells in liver regeneration as well as on the effect of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in liver

  16. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  17. Liver Transplantation After Bone Marrow Transplantation for End Stage Liver Disease with Severe Hepatopulmonary Syndrome in Dyskeratosis Congenita: A Literature First.

    PubMed

    Mahansaria, Shyam Sunder; Kumar, Senthil; Bharathy, Kishore G S; Kumar, Sachin; Pamecha, Viniyendra

    2015-12-01

    Dyskeratosis congenita is a multisystem genetic disorder. Although hepatic involvement is reported in about 7% of patients with dyskeratosis congenita, it is not well characterized and often attributed to hemochromatosis from frequent blood transfusions. A few case reports describe cirrhosis and hepatic cell necrosis in affected individuals in autosomal dominant pedigrees. Bone marrow failure and malignancies are the principal causes of death in dyskeratosis congenita. We describe the first case of living donor liver transplantation, in dyskeratosis congenita for decompensated cirrhosis with portal hypertension. The patient also had associated severe hepatopulmonary syndrome, interstitial lung disease, bilateral hip replacement for avascular necrosis of the head of femur, and a past history of bone marrow transplantation for bone marrow failure. PMID:26900277

  18. Animal models of chronic liver diseases.

    PubMed

    Liu, Yan; Meyer, Christoph; Xu, Chengfu; Weng, Honglei; Hellerbrand, Claus; ten Dijke, Peter; Dooley, Steven

    2013-03-01

    Chronic liver diseases are frequent and potentially life threatening for humans. The underlying etiologies are diverse, ranging from viral infections, autoimmune disorders, and intoxications (including alcohol abuse) to imbalanced diets. Although at early stages of disease the liver regenerates in the absence of the insult, advanced stages cannot be healed and may require organ transplantation. A better understanding of underlying mechanisms is mandatory for the design of new drugs to be used in clinic. Therefore, rodent models are being developed to mimic human liver disease. However, no model to date can completely recapitulate the "corresponding" human disorder. Limiting factors are the time frame required in humans to establish a certain liver disease and the fact that rodents possess a distinct immune system compared with humans and have different metabolic rates affecting liver homeostasis. These features account for the difficulties in developing adequate rodent models for studying disease progression and for testing new pharmaceuticals to be translated into the clinic. Nevertheless, traditional and new promising animal models that mimic certain attributes of chronic liver diseases are established and being used to deepen our understanding in the underlying mechanisms of distinct liver diseases. This review aims at providing a comprehensive overview of recent advances in animal models recapitulating different features and etiologies of human liver diseases. PMID:23275613

  19. 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

  20. Coagulation factors in chronic liver disease.

    PubMed

    Donaldson, G W; Davies, S H; Darg, A; Richmond, J

    1969-03-01

    Coagulation studies were carried out on 30 patients with chronic liver disease. The clotting defect was complex and involved factors V, VII, IX (Christmas factor), and prothrombin. Some patients showed a significant depression of factor IX in the presence of a normal one-stage prothrombin time. Thrombotest was found to be a good indicator of factor IX deficiency in this group of patients and may be of use as an additional liver function test. The screening of patients with liver disease for surgery or liver biopsy should assess the coagulation factors involved in both intrinsic and extrinsic thromboplastin generation.

  1. TGF-β signalling and liver disease.

    PubMed

    Fabregat, Isabel; Moreno-Càceres, Joaquim; Sánchez, Aránzazu; Dooley, Steven; Dewidar, Bedair; Giannelli, Gianluigi; Ten Dijke, Peter

    2016-06-01

    The transforming growth factor-beta (TGF-β) family signalling pathways play essential roles in the regulation of different cellular processes, including proliferation, differentiation, migration or cell death, which are essential for the homeostasis of tissues and organs. Because of the diverse and pleiotropic TGF-β functions, deregulation of its pathways contributes to human disease. In the case of the liver, TGF-β signalling participates in all stages of disease progression, from initial liver injury through inflammation and fibrosis, to cirrhosis and cancer. TGF-β has cytostatic and apoptotic effects in hepatocytes, promoting liver differentiation during embryogenesis and physiological liver regeneration. However, high levels of TGF-β, as a consequence of chronic liver damage, result in activation of stellate cells to myofibroblasts and massive hepatocyte cell death, which contributes to the promotion of liver fibrosis and later cirrhosis. During liver tumorigenesis, TGF-β may behave as a suppressor factor at early stages; however, there is strong evidence that overactivation of TGF-β signalling might contribute to later tumour progression, once cells escape from its cytostatic effects. For these reasons, targeting the TGF-β signalling pathway is being explored to counteract liver disease progression. In this review, we aim to shed light on the state-of-the-art in the signalling pathways induced by TGF-β that are involved in different stages of liver physiology and pathology.

  2. Endocannabinoids in Liver Disease

    PubMed Central

    Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George

    2010-01-01

    Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists. PMID:21254182

  3. Therapy for alcoholic liver disease

    PubMed Central

    Jaurigue, Maryconi M; Cappell, Mitchell S

    2014-01-01

    Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and

  4. Biopsy-Controlled Liver Fibrosis Staging Using the Enhanced Liver Fibrosis (ELF) Score Compared to Transient Elastography

    PubMed Central

    Wahl, Kristin; Rosenberg, William; Vaske, Bernhard; Manns, Michael P.; Schulze-Osthoff, Klaus; Bahr, Matthias J.; Bantel, Heike

    2012-01-01

    Background and Aims Chronic liver diseases are characterized by inflammatory and fibrotic liver injuries that often result in liver cirrhosis with its associated complications such as portal hypertension and hepatocellular carcinoma. Liver biopsy still represents the reference standard for fibrosis staging, although transient elastography is increasingly used for non-invasive monitoring of fibrosis progression. However, this method is not generally available and is associated with technical limitations emphasizing the need for serological biomarkers staging of liver fibrosis. The enhanced liver fibrosis (ELF) score was shown to accurately predict significant liver fibrosis in different liver diseases, although extracellular matrix components detected by this score may not only mirror the extent of liver fibrosis but also inflammatory processes. Methods In this prospective biopsy-controlled study we evaluated the utility of the ELF score in comparison to transient elastography to predict different stages of fibrosis in 102 patients with chronic liver diseases. Results Both techniques revealed similar area under receiver operating characteristic curve values for prediction of advanced fibrosis stages. Compared to transient elastography, the ELF score showed a broader overlap between low and moderate fibrosis stages and a stronger correlation with inflammatory liver injury. Conclusions Both the ELF score as well as transient elastography allowed for high quality fibrosis staging. However, the ELF score was less discriminative in low and moderate fibrosis stages and appeared more strongly influenced by inflammatory liver injury. This should be considered when making clinical interpretations on the basis of ELF score values. PMID:23284811

  5. [Iron and liver disease].

    PubMed

    Miyanishi, Koji; Kato, Junji

    2016-07-01

    Free iron in the liver is believed to facilitate the formation of reactive oxygen species (ROS), including hydroxyl radicals (*OH), which cause oxidative damage of numerous cellular components such as lipids, proteins, and nucleic acids, and also upregulate collagen synthesis. The *OH radical is known to generate promutagenic bases such as 8-hydroxy-2-deoxyguanosine (8-OHdG). In cases with chronic hepatitis C, long-term iron reduction therapy reduced the activity of hepatitis, suppressed fibrosis, and prevented hepatocarcinogenesis. In nonalcoholic steatohepatitis (NASH) livers, hepatic iron accumulation as well as oxidative DNA damage significantly increased. Humoral factor(s) in NASH serum may upregulate DMT1 expression in small intestine. Iron reduction therapy for NASH patients has a potential to reduce disease activity as well as hepatic oxidative damage. PMID:27455806

  6. Interventional Treatments for Liver Disease

    MedlinePlus

    ... Search Patient information Membership Directory (SIR login) Interventional Radiology Interventional Treatments for Liver Disease There are a ... liver that can be treated with nonsurgical, interventional radiology techniques. Portal Hypertension Seen most frequently in patients ...

  7. A toolbox to study liver stage malaria.

    PubMed

    Prudêncio, Miguel; Mota, Maria M; Mendes, António M

    2011-12-01

    The first obligatory phase of mammalian infection by Plasmodium parasites, the causative agents of malaria, occurs in the liver of the host. This stage of Plasmodium infection bears enormous potential for anti-malarial intervention. Recent technological progress has strongly contributed to overcoming some of the long-standing difficulties in experimentally assessing hepatic infection by Plasmodium. Here, we review appropriate infection models and infection assessment tools, and provide a comprehensive description of recent advances in experimental strategies to investigate the liver stage of malaria. These issues are discussed in the context of current challenges in the field to provide researchers with the technical tools that enable effective experimental approaches to study liver stage malaria.

  8. Treatment of alcoholic liver disease.

    PubMed

    Barve, Ashutosh; Khan, Rehan; Marsano, Luis; Ravindra, Kadiyala V; McClain, Craig

    2008-01-01

    Alcoholic Liver Disease (ALD) is a major cause of morbidity and mortality both in the United States and worldwide. In the United States, it is projected that over 2,000,000 persons have ALD, and the mortality for cirrhosis with superimposed alcoholic hepatitis is much worse than that of many common types of cancer. Unfortunately, there is no FDA approved therapy for ALD. We have made major strides in the last decade in identifying mechanisms for the development of liver injury in ALD, and therapies are evolving directed at specific mechanisms. It is clear that life style modification with abstinence, cessation of smoking and weight loss (if overweight) are beneficial. It is also clear that most patients with advanced liver disease have some form of malnutrition, and nutritional supplementation is of benefit. Patients with alcoholic hepatitis that is relatively severe in nature, but not complicated by issues such as infection or GI bleeding, appear to benefit from steroids. A drop in bilirubin should be monitored in steroid treated patients. Pentoxifylline appears to be beneficial in patients with alcoholic hepatitis, especially those with early hepatorenal syndrome. A variety of other agents such as PTU, lecithin, colchicine, and anabolic steroids are probably not effective. Complementary and alternative medicine agents such as zinc, milk thistle, and SAM have great therapeutic rationale. Results of ongoing NIH studies evaluating agents such as specific anti-TNF's, SAM and Milk Thistle are eagerly awaited. Transplantation is clearly an option for end stage ALD in patients who are abstinent.

  9. Malaria Blood Stage Suppression of Liver Stage Immunity by Dendritic Cells

    PubMed Central

    Ocaña-Morgner, Carlos; Mota, Maria M.; Rodriguez, Ana

    2003-01-01

    Malaria starts with Plasmodium sporozoites infection of the host's liver, where development into blood stage parasites occurs. It is not clear why natural infections do not induce protection against the initial liver stage and generate low CD8+ T cell responses. Using a rodent malaria model, we show that Plasmodium blood stage infection suppresses CD8+ T cell immune responses that were induced against the initial liver stage. Blood stage Plasmodium affects dendritic cell (DC) functions, inhibiting maturation and the capacity to initiate immune responses and inverting the interleukin (IL)-12/IL-10 secretion pattern. The interaction of blood stage parasites with DCs induces the secretion of soluble factors that inhibit the activation of CD8+ T cells in vitro and the suppression of protective CD8+ T cell responses against the liver stage in vivo. We propose that blood stage infection induces DCs to suppress CD8+ T cell responses in natural malaria infections. This evasion mechanism leaves the host unprotected against reinfection by inhibiting the immune response against the initial liver stage of the disease. PMID:12538654

  10. Progression of Liver Disease

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  11. Screening in liver disease

    PubMed Central

    Poggio, Paolo Del; Mazzoleni, Marzio

    2006-01-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines, although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors, such as transfusion before 1992 and drug addiction, is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation. PMID:16981254

  12. Screening in liver disease.

    PubMed

    Del Poggio, Paolo; Mazzoleni, Marzio

    2006-09-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines, although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors, such as transfusion before 1992 and drug addiction, is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation. PMID:16981254

  13. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease

    PubMed Central

    Lucero, Catherine; Brown, Robert S.

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  14. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease.

    PubMed

    Lucero, Catherine; Brown, Robert S

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  15. Folate, Alcohol, and Liver Disease

    PubMed Central

    Medici, Valentina; Halsted, Charles H.

    2013-01-01

    Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of alcoholic liver disease with particular focus on ethanol-induced alterations in methionine metabolism which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

  16. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  17. Telomeres, NAFLD and Chronic Liver Disease.

    PubMed

    Donati, Benedetta; Valenti, Luca

    2016-01-01

    Telomeres consist of repeat DNA sequences located at the terminal portion of chromosomes that shorten during mitosis, protecting the tips of chromosomes. During chronic degenerative conditions associated with high cell replication rate, progressive telomere attrition is accentuated, favoring senescence and genomic instability. Several lines of evidence suggest that this process is involved in liver disease progression: (a) telomere shortening and alterations in the expression of proteins protecting the telomere are associated with cirrhosis and hepatocellular carcinoma; (b) advanced liver damage is a feature of a spectrum of genetic diseases impairing telomere function, and inactivating germline mutations in the telomerase complex (including human Telomerase Reverse Transcriptase (hTERT) and human Telomerase RNA Component (hTERC)) are enriched in cirrhotic patients independently of the etiology; and (c) experimental models suggest that telomerase protects from liver fibrosis progression. Conversely, reactivation of telomerase occurs during hepatocarcinogenesis, allowing the immortalization of the neoplastic clone. The role of telomere attrition may be particularly relevant in the progression of nonalcoholic fatty liver, an emerging cause of advanced liver disease. Modulation of telomerase or shelterins may be exploited to prevent liver disease progression, and to define specific treatments for different stages of liver disease. PMID:26999107

  18. [Wilson's disease: clinical spectrum of liver disease].

    PubMed

    Ochoa Palominos, Alejandra; Ibáñez Samaniego, Luis; Catalina Rodríguez, María-Vega; Pajares Díaz, José; Clemente Ricote, Gerardo

    2013-02-01

    Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism,characterized by copper accumulation in the liver and brain. This rare entity, which has a broad clinical spectrum, is often difficult to diagnose and should therefore always be suspected in patients with liver disease of unclear cause. We describe two types of manifestation of liver disease in two patients; the first developed fulminant hepatic failure requiring urgent liver transplantation and the second showed advanced chronic liver disease and received standard medical treatment. The objective of this clinical observation is to analyze the diagnosis of Wilson's disease in two patients with distinct onset, illustrating the broad clinical spectrum of the disease, and its treatment.

  19. Transcending chronic liver disease: a qualitative study.

    PubMed

    Wainwright, S P

    1997-01-01

    This study explores and describes experiences of chronic liver disease from the patient's perspective. No qualitative research studies appear to have examined the experiences of these patients. In-depth focused interviews and grounded theory data collection and data analysis methods were used. A two-stage theoretical framework (becoming ill, and not living) of the experience of transcending chronic liver disease is presented. Sociological and psychological literature on common sense models of health and illness are briefly reviewed. Several suggestions for further research are made. The way in which this qualitative research study is leading to a quantitative and qualitative appraisal of the psychological adjustment in end-stage chronic liver disease patients is outlined.

  20. Intestinal microbiota in liver disease.

    PubMed

    Haque, Tanvir R; Barritt, A Sidney

    2016-02-01

    The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation.

  1. How to Diagnose Nonalcoholic Fatty Liver Disease.

    PubMed

    de Alwis, Nimantha M W; Anstee, Quentin M; Day, Christopher P

    2016-01-01

    Patients with nonalcoholic fatty liver disease (NAFLD) are asymptomatic and present with either unexplained abnormal liver blood tests or a bright liver on ultrasonography. Some patients will have normal liver blood tests raising the issue of whether patients with risk factors for NAFLD (diabetes and/or metabolic syndrome [MS]) should be screened for its presence with biomarkers, such as the fatty liver index (FLI). The diagnosis of NAFLD requires the exclusion of other causes of chronic liver disease and steatosis, especially heavy alcohol consumption and viral hepatitis particularly HCV genotype 3. Diagnostic work-up should include evaluation of family and personal history of components of the MS and assessment of liver tests, fasting blood glucose, triglycerides and HDL levels. A drug history is important due to a number being associated with steatosis. To confirm the diagnosis of NAFLD and quantify steatosis, ultrasound (US) and MRI-based techniques are available but none are in routine use outside clinical trials. Standard US is no more accurate than biomarkers such as FLI. The accurate staging of NAFLD requires liver biopsy; however, this is clearly impractical for such a prevalent disease. Accordingly, a number of imaging and blood-based biomarker tests have been evaluated. While none have proved reliable for the diagnosis of nonalcoholic steatohepatitis, several have proved accurate in diagnosing the presence of stage 3 or 4 fibrosis, including the NAFLD fibrosis score, fibrosis-4 and the enhanced liver fibrosis test. Of the imaging techniques, elastography has received the most attention and is being used in routine clinical practice. US acoustic radiation force impulse imaging, and MR-based elastography have recently been described but none are sufficiently accurate to replace liver biopsy for clinical trials as yet or are cost effective for use in routine clinical settings. PMID:27547937

  2. Chronic Liver Disease and Hispanic Americans

    MedlinePlus

    ... Population Profiles > Hispanic/Latino > Chronic Liver Disease Chronic Liver Disease and Hispanic Americans Among the Hispanic/Latino population, chronic liver disease is a leading cause of death. While the ...

  3. [Treatment of alcoholic liver diseases. Abstinence, nutritional support, drug therapy, liver transplantation].

    PubMed

    Pár, A

    2000-04-16

    The review summarizes clinically established treatment forms of alcoholic liver disease in four main chapters: abstinence, nutritional supportation, drug therapy and liver transplantation are discussed. Drug therapy is described according to the three types of alcoholic hepatopathies (fatty liver, hepatitis and cirrhosis). Early diagnosis and treatment depending on the severity and stage of alcoholic liver disease are of importance for the attempts to retard progression and improve prognosis. PMID:10817009

  4. Hepatocyte cell therapy in liver disease.

    PubMed

    Bartlett, David Christopher; Newsome, Philip N

    2015-01-01

    Liver disease is a leading cause of morbidity and mortality. Liver transplantation remains the only proven treatment for end-stage liver failure but is limited by the availability of donor organs. Hepatocyte cell therapy, either with bioartificial liver devices or hepatocyte transplantation, may help address this by delaying or preventing liver transplantation. Early clinical studies have shown promising results, however in most cases, the benefit has been short lived and so further research into these therapies is required. Alternative sources of hepatocytes, including stem cell-derived hepatocytes, are being investigated as the isolation of primary human hepatocytes is limited by the same shortage of donor organs. This review summarises the current clinical experience of hepatocyte cell therapy together with an overview of possible alternative sources of hepatocytes. Current and future areas for research that might lead towards the realisation of the full potential of hepatocyte cell therapy are discussed. PMID:26212798

  5. Biomarkers in Pediatric Liver Disease.

    PubMed

    Kyrana, Eirini; Fitzpatrick, Emer; Dhawan, Anil

    2016-01-01

    The chronic nature of liver diseases in children and adults merits close follow-up for disease progression and/or treatment evaluation. Disease progression involves injury to liver cells resulting in cell death, varying degrees of inflammation, steatosis depending on the insult, oxidative stress, and eventually fibrosis and cirrhosis unless the process is modified with treatment or spontaneous recovery. Inflammation, cell death, and fibrosis are the three major processes that determine the outcome of liver disease irrespective of the etiology. Markers to measure the activity or status of these parameters in a dynamic way, particularly via noninvasive methods, are urgently required. In this chapter, we summarize recent advances in the identification of biomarkers of liver diseases: biomarkers corresponding to inflammation, cell death, fibrosis, and the development of malignancy.

  6. Nitric oxide in liver diseases.

    PubMed

    Iwakiri, Yasuko; Kim, Moon Young

    2015-08-01

    Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling - nitrated fatty acids (NO2-FAs) and S-guanylation - and conclude with suggestions for future directions in NO-related studies on the liver. PMID:26027855

  7. NITRIC OXIDE IN LIVER DISEASES

    PubMed Central

    Iwakiri, Yasuko; Kim, Moon Young

    2015-01-01

    Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling, nitrated fatty acids and S-guanylation, and conclude with suggestions on future directions of NO-related studies on the liver. PMID:26027855

  8. Increased accumulation of 4-hydroxynonenal adducts in male GSTA4/PPAR alpha double knockout mice enhances injury during early stages of alcoholic liver disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hepatic lipid peroxidation and accumulation of aldehyde-adducted proteins occur early in alcohol-mediated injury and are postulated to mediate the subsequent pro-inflammatory and fibrotic responses observed in alcoholic liver disease. To test the significance of lipid peroxidation formation in the ...

  9. Research Areas: Liver Disease

    MedlinePlus

    ... 900 drugs and supplements.​​ Recent discoveries from NIDDK research include: New medication shows promise against liver fibrosis ... linked to biliary atresia in newborn animals Support Research NIDDK invests in basic, clinical and translational research ...

  10. Alcoholic liver disease

    MedlinePlus

    ... weight loss Nausea or belly pain Small, red spider-like blood vessels on the skin As liver ... result of too much fluid Reddened palms Red spider-like blood vessels on the skin Small testicles ...

  11. Autoantibodies in autoimmune liver diseases.

    PubMed

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  12. Breath Tests to Assess Alcoholic Liver Disease.

    PubMed

    Furnari, Manuele; Ahmed, Iftikhar; Erpecum, Karel J van; Savarino, Vincenzo; Giannini, Edoardo G

    2016-01-01

    The prevalence of Alcohol related Liver Disease (ALD) continues to rise all over the world due to changing drinking behaviour of the population. Liver disease due to excessive alcohol consumption causes significant morbidity and mortality, and poses a substantial economic burden to the health care resources. Early diagnosis and treatment of ALD may help prevent progression to cirrhosis and hepatocellular carcinoma. The last decade has seen a rising interest in potential use of non-invasive tests in clinical practice, including diagnosis and monitoring of chronic liver diseases. Over the past few decades, breath testing has been investigated extensively in the diagnosis of ALD, and has shown promising results in predicting the early stages of ALD. A variety of breath tests have been utilised in this regard including the13Clabelled breath tests, aminopyrine breath test , galactose breath test , methacetin breath test, and keto-isocaproic acid breath test. These tests have demonstrated good results in identification of both significant and severe liver disease among patients with ALD. Volatile Organic Compounds (VOC) are chemicals, which can be quantified in breath and other biological fluids, and represent physio-pathological activities within an individual. Alteration in the pattern of breath VOCs can be correlated with a number of diseases including ALD. Early stages of ALD can be detected using these breath tests, which can lead to adoption of preventive measures to reduce the progression of liver disease. This review focuses on the clinical utility of current and future breath tests, including breath VOC, as a non-invasive means of predicting early stages of ALD. PMID:27515960

  13. Coagulation in Liver Disease.

    PubMed

    Hoffman, Maureane

    2015-07-01

    The liver plays a key role in hemostasis as the site of synthesis of many of the proteins involved in the coagulation, antithrombotic and fibrinolytic systems that interact to both establish hemostasis, and preventing thrombosis. The common laboratory tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), evolved from studies of plasma clotting in test tubes. Such studies laid the basis for the coagulation cascade model of hemostasis. However, thought has evolved to place a greater emphasis on the active roles of cells in localizing and regulating hemostasis. The PT and aPTT do not reflect the roles of cellular elements in hemostasis, nor do they reflect the crucial roles of antithrombotic and fibrinolytic systems. Thus, though the PT may indeed reflect the synthetic capacity of the liver, it does not accurately reflect the risk of bleeding or thrombosis in patients with liver failure.

  14. Nonmedicinal interventions in nonalcoholic fatty liver disease

    PubMed Central

    Neuman, Manuela G; Nanau, Radu M; Cohen, Lawrence B

    2015-01-01

    Unhealthy diet and lack of physical exercise are responsible for fat accumulation in the liver, which may lead to liver disease. Histologically, the severity of the disease has two stages: nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD is defined by the presence of steatosis with no evidence of cellular injury such as hepatocyte ballooning. NASH is a distinct entity from NAFLD, and is characterized by the presence of inflammation with hepatocytes damage, with or without fibrosis. While several therapeutic strategies have been proposed to improve this condition, the present review aims to discuss nonmedicinal interventions used to reduce liver involvement or to prevent the disease altogether. The authors investigated dietary patterns and vitamin deficiencies associated with NAFLD, and their role in enhancing disease severity. Additionally, they reviewed the role of exercise and the use of interventions, such as as intragastric balloon and bariatric surgery, for improving disease progression. The authors propose monitoring disease progression or repair by following changes in cytoadipokine levels. PMID:26076224

  15. Lipoprotein metabolism in nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Zhenghui Gordon; Robson, Simon C.; Yao, Zemin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide, covers a spectrum of pathologies characterized by fatty accumulation in hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellular role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metabolism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD. PMID:23554788

  16. EGFR Signaling in Liver Diseases

    PubMed Central

    Komposch, Karin; Sibilia, Maria

    2015-01-01

    The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase that is activated by several ligands leading to the activation of diverse signaling pathways controlling mainly proliferation, differentiation, and survival. The EGFR signaling axis has been shown to play a key role during liver regeneration following acute and chronic liver damage, as well as in cirrhosis and hepatocellular carcinoma (HCC) highlighting the importance of the EGFR in the development of liver diseases. Despite the frequent overexpression of EGFR in human HCC, clinical studies with EGFR inhibitors have so far shown only modest results. Interestingly, a recent study has shown that in human HCC and in mouse HCC models the EGFR is upregulated in liver macrophages where it plays a tumor-promoting function. Thus, the role of EGFR in liver diseases appears to be more complex than what anticipated. Further studies are needed to improve the molecular understanding of the cell-specific signaling pathways that control disease development and progression to be able to develop better therapies targeting major components of the EGFR signaling network in selected cell types. In this review, we compiled the current knowledge of EGFR signaling in different models of liver damage and diseases, mainly derived from the analysis of HCC cell lines and genetically engineered mouse models (GEMMs). PMID:26729094

  17. Liver disease in vineyard sprayers.

    PubMed

    Pimentel, J C; Menezes, A P

    1977-02-01

    Liver disease with inclusions of copper was recognized among 30 rural workers with "vineyard sprayer's lung." The pathological findings were varied: focal or diffuse swelling and proliferation of Kupffer cells; histiocytic and sarcoid-like granulomata; fibrosis of variable degree in the perisinusoidal, portal, and subcapsular areas, accompanied by atypical proliferation of the sinusoidal lining cells; micronodular cirrhosis; angiosarcoma of the liver; idiopathic portal hypertension. Abundant deposits of copper were revealed by histochemical techniques within hepatic and pulmonary lesions in these patients. The observations on the human and experimental material suggest an etiological relationship between exposure to copper sulfate and the lesions described. A morphological resemblance was noted between the "liver disease of vineyard sprayers" and the hepatic lesions reported in workers exposed to inorganic arsenic and to vinyl chloride. The identification of the inhaled foreign material within the liver lesions raises important etiological considerations.

  18. Folate, alcohol, and liver disease.

    PubMed

    Medici, Valentina; Halsted, Charles H

    2013-04-01

    Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of ALD with particular focus on ethanol-induced alterations in methionine metabolism, which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of ALD based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

  19. Extracellular Matrix and Liver Disease

    PubMed Central

    Arriazu, Elena; Ruiz de Galarreta, Marina; Cubero, Francisco Javier; Varela-Rey, Marta; Pérez de Obanos, María Pilar; Leung, Tung Ming; Lopategi, Aritz; Benedicto, Aitor; Abraham-Enachescu, Ioana

    2014-01-01

    Abstract Significance: The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage. Critical Issues: This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs. Recent Advances: Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF’ apoptosis, senescence, and reversal to quiescence. Future Directions: We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new “omics” tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs. Antioxid. Redox Signal. 21, 1078–1097. PMID:24219114

  20. Relationship of factor VIII-like antigen (VIII AGN) and clot promoting acitivty (VIII AHF) as measured by one- and two-stage assays in patients with liver disease.

    PubMed

    Rogers, J S; Eyster, E

    1976-12-01

    We recently observed a increase in factor-VIII clot promoting activity as measured by a one-stage assay (VIII AHF) in a haemophiliac with hepatitis. However, VIII AHF as measured by a two-stage assay (VIII AHF) was 0.013 u/ml at a time when VIII AHF measured 0.38 u/ml. We then studied seven non-haemophiliacs with liver disease, and attempted to correlate the lvels of VIII AHF and VIII AHF with factor VIII-like antigen (VIII AGN) as measured by quantitative immunoelectrophoresis. In four of the seven patients, disproportionate elevations of VIII AHF compared to VIII AHF were found. Furthermore, VIII AHF values correlated well with VIII AGN vales . No such discrepancy was apparent in four normal control subjects. These findings emphasize the necessity for performing two-stage assays in haemophiliacs as well as non-haemophiliacs with liver disease to assess factor-VIII levels. In addition, they suggest that confirmation of the diagnosis of haemophilia may not be possible in the haemophiliac with hepatitis unless VIII AHF determinations are performed. The reason for the disparity between VIII ahf and VIII AHF levels is not apparent. However, the correlation of VIII AGN and VIII AHF levels in the non-haemophiliacs with liver disease provides further support for the concept that VIII AGN and VIII AHF are closely related or identical molecular entities.

  1. Liver Disease and IBD

    MedlinePlus

    ... 34% of Crohn’s patients with disease of the terminal ileum (the last segment of the small intestine). ... increased risk for developing gallstones because the diseased terminal ileum cannot absorb bile salts, which are necessary ...

  2. Non-Alcoholic Fatty Liver Disease (NAFLD)

    MedlinePlus

    Non-Alcoholic Fatty Liver Disease What is Non-alcoholic fatty liver disease (NAFLD)? FAT N AFLD is a name that is given to a ... and under “Liver Health Information view ‘Nonalcoholic fatty liver Disease (NAFLD/NASH)’ IMPORTANT REMINDER: This information from the ...

  3. Novel approaches to assessing renal function in cirrhotic liver disease.

    PubMed

    Portal, Andrew J; Austin, Mark; Heneghan, Michael A

    2007-09-01

    Renal dysfunction is common in patients with end-stage liver disease. Etiological factors include conditions as diverse as acute tubular necrosis, immunoglobulin A nephropathy and hepatorenal syndrome. Current standard tests of renal function, such as measurement of serum urea and creatinine levels, are inaccurate as the synthesis of these markers is affected by the native liver pathology. This article reviews novel markers of renal function and their potential use in patients with liver disease.

  4. Malaria vaccines: identifying Plasmodium falciparum liver-stage targets.

    PubMed

    Longley, Rhea J; Hill, Adrian V S; Spencer, Alexandra J

    2015-01-01

    The development of a highly efficacious and durable vaccine for malaria remains a top priority for global health researchers. Despite the huge rise in recognition of malaria as a global health problem and the concurrent rise in funding over the past 10-15 years, malaria continues to remain a widespread burden. The evidence of increasing resistance to anti-malarial drugs and insecticides is a growing concern. Hence, an efficacious and durable preventative vaccine for malaria is urgently needed. Vaccines are one of the most cost-effective tools and have successfully been used in the prevention and control of many diseases, however, the development of a vaccine for the Plasmodium parasite has proved difficult. Given the early success of whole sporozoite mosquito-bite delivered vaccination strategies, we know that a vaccine for malaria is an achievable goal, with sub-unit vaccines holding great promise as they are simple and cheap to both manufacture and deploy. However a major difficulty in development of sub-unit vaccines lies within choosing the appropriate antigenic target from the 5000 or so genes expressed by the parasite. Given the liver-stage of malaria represents a bottle-neck in the parasite's life cycle, there is widespread agreement that a multi-component sub-unit malaria vaccine should preferably contain a liver-stage target. In this article we review progress in identifying and screening Plasmodium falciparum liver-stage targets for use in a malaria vaccine. PMID:26441899

  5. Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice.

    PubMed

    Mikolajczak, Sebastian A; Vaughan, Ashley M; Kangwanrangsan, Niwat; Roobsoong, Wanlapa; Fishbaugher, Matthew; Yimamnuaychok, Narathatai; Rezakhani, Nastaran; Lakshmanan, Viswanathan; Singh, Naresh; Kaushansky, Alexis; Camargo, Nelly; Baldwin, Michael; Lindner, Scott E; Adams, John H; Sattabongkot, Jetsumon; Prachumsri, Jetsumon; Kappe, Stefan H I

    2015-04-01

    Plasmodium vivax malaria is characterized by periodic relapses of symptomatic blood stage parasite infections likely initiated by activation of dormant liver stage parasites-hypnozoites. The lack of tractable P. vivax animal models constitutes an obstacle in examining P. vivax liver stage infection and drug efficacy. To overcome this obstacle, we have used human liver-chimeric (huHep) FRG KO mice as a model for P. vivax infection. FRG KO huHep mice support P. vivax sporozoite infection, liver stage development, and hypnozoite formation. We show complete P. vivax liver stage development, including maturation into infectious exo-erythrocytic merozoites as well as the formation and persistence of hypnozoites. Prophylaxis or treatment with the antimalarial primaquine can prevent and eliminate liver stage infection, respectively. Thus, P. vivax-infected FRG KO huHep mice are a model to investigate liver stage development and dormancy and may facilitate the discovery of drugs targeting relapsing malaria.

  6. New insights into the coagulopathy of liver disease and liver transplantation

    PubMed Central

    Senzolo, M; Burra, P; Cholongitas, E; Burroughs, AK

    2006-01-01

    The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery. PMID:17203512

  7. Liver transplantation for chronic liver disease: advances and controversies in an era of organ shortages

    PubMed Central

    Prince, M; Hudson, M

    2002-01-01

    Since liver transplantation was first performed in 1968 by Starzl et al, advances in case selection, liver surgery, anaesthetics, and immunotherapy have significantly increased the indications for and success of this operation. Liver transplantation is now a standard therapy for many end stage liver disorders as well as acute liver failure. However, while demand for cadaveric organ grafts has increased, in recent years the supply of organs has fallen. This review addresses current controversies resulting from this mismatch. In particular, methods for increasing graft availability and difficulties arising from transplantation in the context of alcohol related cirrhosis, primary liver tumours, and hepatitis C are reviewed. Together these three indications accounted for 42% of liver transplants performed for chronic liver disease in the UK in 2000. Ethical frameworks for making decisions on patients' suitability for liver transplantation have been developed in both the USA and the UK and these are also reviewed. PMID:11884694

  8. Liver transplantation for Wilson disease

    PubMed Central

    Catana, Andreea M; Medici, Valentina

    2012-01-01

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  9. Liver transplantation for Wilson disease.

    PubMed

    Catana, Andreea M; Medici, Valentina

    2012-01-27

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  10. Pharmacotherapy of cholestatic liver diseases.

    PubMed

    Paumgartner, Gustav

    2010-06-01

    New insights into the molecular mechanisms of bile formation and cholestasis have provided new concepts for pharmacotherapy of cholestatic liver diseases. The major aim in all forms of cholestasis is the reduction of hepatocellular retention of bile acids and other potentially toxic constituents of bile. Reduction of hepatocellular retention may be achieved by drugs that stimulate hepatocellular secretion via the canalicular route into the bile or via the alternative route across the basolateral membrane into the blood, and by drugs that stimulate the hepatocellular metabolism of hydrophobic bile acids to hydrophilic, less toxic metabolites. In cholestatic liver diseases that start with an injury of the biliary epithelium (e.g., primary biliary cirrhosis; PBC), protection of the cholangiocytes against the toxic effects of hydrophobic bile acids is most important. When hepatocellular retention of bile acids has occurred, the inhibition of bile acid-induced apoptosis becomes another target of therapy. Ursodeoxycholic acid protects the biliary epithelium by reducing the toxicity of bile, stimulates hepatobiliary secretion by upregulating transporters and inhibits apoptosis. It is the mainstay of therapy in PBC but of benefit also in a number of other cholestatic liver diseases. New drugs such as 6-ethyl-chenodeoxycholic acid and 24-nor-ursodeoxycholic acid are being evaluated for the treatment of cholestatic liver diseases.

  11. Cholestatic liver disease masquerading as Wilson disease.

    PubMed

    Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev; Alam, Seema

    2015-03-01

    Wilson disease and cholestatic liver diseases may present as a diagnostic dilemma if standard guidelines incorporating markers of copper overload are followed. We hereby present a series of four cases of sclerosing cholangitis masquerading as Wilson disease. True Wilson disease cases had significantly lower ceruloplasmin (6 vs. 16 mg/dL) and higher 24-hour urinary copper (322.3 vs. 74.5 μg/day) as compared to mimickers. Initial low serum ceruloplasmin levels normalized in mimickers on follow up, and this may used as a diagnostic indicator. Standard Wilson disease diagnostic criteria thus need further modification especially in developing countries to help avoid mismanagement.

  12. Application of Induced Pluripotent Stem Cells in Liver Diseases

    PubMed Central

    Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

    2014-01-01

    Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

  13. Teen Obesity May Mean Liver Disease Later

    MedlinePlus

    ... news/fullstory_159416.html Teen Obesity May Mean Liver Disease Later Study found risk increased as weight went ... obese could be at increased risk for severe liver disease later in life, a new study suggests. The ...

  14. Gut microbiota and liver disease.

    PubMed

    Goel, Amit; Gupta, Mahesh; Aggarwal, Rakesh

    2014-06-01

    Microbes are present in large numbers in each human being, in particularly in the gastrointestinal (GI) tract, and have long been believed to have some beneficial effects for their hosts. Till recently, however, we lacked tools for studying these organisms. Rapid technological advances in recent years have markedly improved our understanding of their role both in health and disease. Recent literature suggests that organisms in the GI tract, referred to collectively as gut microbiota, play an indispensable role in the maintenance of host's homeostasis. Alterations in the gut microbiota, that is in the nature and relative density of various constituent bacterial species, appear to have a role in pathogenesis and progression of several GI and hepatic diseases. This has also opened the vista for tinkering with gut flora in an attempt to treat or prevent such diseases. In this review, we have tried to summarize information on normal gut microbiota, laboratory techniques and animal models used to study it, and the role of its perturbations in some of the common hepatic disorders, such as non-alcoholic fatty liver disease (including obesity), non-alcoholic steatohepatitis, alcoholic liver disease, and liver cirrhosis and its complications.

  15. [Liver ultrasound: focal lesions and diffuse diseases].

    PubMed

    Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

    2016-01-01

    Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed.

  16. Diagnosis of alcoholic liver disease.

    PubMed

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-09-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  17. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  18. Osteoporosis in liver disease: pathogenesis and management

    PubMed Central

    Handzlik-Orlik, Gabriela; Holecki, Michał; Wilczyński, Krzysztof; Duława, Jan

    2016-01-01

    Osteoporosis affects a substantial proportion of patients with chronic liver disease. Pathologic fracture in osteoporosis significantly affects quality of life and life expectancy. By some estimates, 40% of patients with chronic liver disease may experience osteoporotic fracture. In this study we review the pathogenesis, diagnosis and treatment of specific liver disease entities and their relation to osteoporosis. PMID:27293541

  19. Kidneys in chronic liver diseases

    PubMed Central

    Hartleb, Marek; Gutkowski, Krzysztof

    2012-01-01

    Acute kidney injury (AKI), defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL, occurs in about 20% of patients hospitalized for decompensating liver cirrhosis. Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state, reduced effective blood volume and stimulation of vasoconstrictor hormones. The most common causes of AKI in cirrhosis are pre-renal azotemia, hepatorenal syndrome and acute tubular necrosis. Differential diagnosis is based on analysis of circumstances of AKI development, natriuresis, urine osmolality, response to withdrawal of diuretics and volume repletion, and rarely on renal biopsy. Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients. AKI is one of the last events in the natural history of chronic liver disease, therefore, such patients should have an expedited referral for liver transplantation. Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension, and may be prematurely triggered by bacterial infections, nonbacterial systemic inflammatory reactions, excessive diuresis, gastrointestinal hemorrhage, diarrhea or nephrotoxic agents. Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy. The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion, which is effective in about 50% of patients. The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt, renal vasoprotection or systems of artificial liver support. PMID:22791939

  20. Pregnancy and Vascular Liver Disease

    PubMed Central

    Bissonnette, Julien; Durand, François; de Raucourt, Emmanuelle; Ceccaldi, Pierre-François; Plessier, Aurélie; Valla, Dominique; Rautou, Pierre-Emmanuel

    2015-01-01

    Vascular disorders of the liver frequently affect women of childbearing age. Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a trigger for Budd–Chiari syndrome in patients with an underlying prothrombotic disorder. Whether pregnancy is a risk factor for other vascular liver disorders is unknown. In women with a known vascular liver disorder and a desire for pregnancy, stabilisation of the liver disease, including the use of a portal decompressive procedure when indicated, should be reached prior to conception. The presence of esophageal varices should be screened and adequate prophylaxis of bleeding applied in a manner similar to what is recommended for patients with cirrhosis. Most women likely benefit from anticoagulation during pregnancy and the postpartum. Labor and delivery are best managed by a multidisciplinary team with experience in this situation. Assisted vaginal delivery is the preferred mode of delivery. Although the risk of miscarriage and premature birth is heightened, current management of these diseases makes it very likely to see the birth of a live baby when pregnancy reaches 20 weeks of gestation. PMID:25941432

  1. Challenges in transplantation for alcoholic liver disease.

    PubMed

    Berlakovich, Gabriela A

    2014-07-01

    Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist's assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient's pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key

  2. Alcoholic Liver Disease and Malnutrition

    PubMed Central

    McClain, Craig J.; Barve, Shirish S.; Barve, Ashutosh; Marsano, Luis

    2013-01-01

    Malnutrition, both protein energy malnutrition (PEM) and deficiencies in individual nutrients, is a frequent complication of alcoholic liver disease (ALD). Severity of malnutrition correlates with severity of ALD. Malnutrition also occurs in patients with cirrhosis due to etiologies other than alcohol. The mechanisms for malnutrition are multifactorial, and malnutrition frequently worsens in the hospital due to fasting for procedures and metabolic complications of liver disease, such as hepatic encephalopathy. Aggressive nutritional support is indicated in inpatients with ALD, and patients often need to be fed through an enteral feeding tube to achieve protein and calorie goals. Enteral nutritional support clearly improves nutrition status and may improve clinical outcome. Moreover, late-night snacks in outpatient cirrhotics improve nutritional status and lean body mass. Thus, with no FDA-approved therapy for ALD, careful nutritional intervention should be considered as frontline therapy. PMID:21284673

  3. Liver-stage malaria parasites vulnerable to diverse chemical scaffolds

    PubMed Central

    Derbyshire, Emily R.; Prudêncio, Miguel; Mota, Maria M.; Clardy, Jon

    2012-01-01

    Human malaria infection begins with a one-time asymptomatic liver stage followed by a cyclic symptomatic blood stage. All high-throughput malaria drug discovery efforts have focused on the cyclic blood stage, which has limited potential for the prophylaxis, transmission blocking, and eradication efforts that will be needed in the future. To address these unmet needs, a high-throughput phenotypic liver-stage Plasmodium parasite screen was developed to systematically identify molecules with liver-stage efficacy. The screen recapitulates liver-stage infection by isolating luciferase-expressing Plasmodium berghei parasites directly from the salivary glands of infected mosquitoes, adding them to confluent human liver cells in 384-well plates, and measuring luciferase activity after a suitable incubation period. Screening 5,375 known bioactive compounds identified 37 liver-stage malaria inhibitors with diverse modes of action, as shown by inhibition time course experiments. Further analysis of the hits in the Food and Drug Administration-approved drug subset revealed compounds that seem to act specifically on the liver stage of infection, suggesting that this phase of the parasite’s life cycle presents a promising area for new drug discovery. Notably, many active compounds in this screen have molecular structures and putative targets distinctly different from those of known antimalarial agents. PMID:22586124

  4. Respiratory Complication in Liver Disease.

    PubMed

    Ramalingam, Vijaya S; Ansari, Sikandar; Fisher, Micah

    2016-07-01

    Cirrhosis, the twelfth leading cause of death, accounts for 1.1% of all deaths in the United States. Although there are multiple pulmonary complications associated with liver disease, the most important complications that cause significant morbidity and mortality are hepatopulmonary syndrome, hepatic hydrothorax, and portopulmonary hypertension. Patients with cirrhosis who complain of dyspnea should be evaluated for these complications. This article reviews these complications. PMID:27339676

  5. [Polycystic liver disease without autosomal dominant polycystic kidney disease].

    PubMed

    Peces, R; González, P; Venegas, J L

    2003-01-01

    Polycystic liver disease is characterized by the presence of multiple bile duct-derived epithelial cysts scattered in the liver parenchyma. The natural history and clinical manifestations of polycystic liver disease are based on the disease as it manifests in patients with autosomal dominant polycystic kidney disease (ADPKD). The occurrence of polycystic liver disease independently from polycystic kidney disease has been known for a long time. More recently, a gene for autosomal dominant polycystic liver disease has been identified on chromosome 19p 13.2-13.1. Isolated polycystic liver disease is underdiagnosed and genetically distinct from polycystic liver disease associated with ADPKD but with similar pathogenesis and clinical manifestations. We report here two men with polycystic liver disease no associated with ADPKD. Ultrasound and computed tomography imaging were effective in documenting the underlying lesions non-invasively.

  6. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance

    PubMed Central

    Stål, Per

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD. PMID:26494963

  7. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

    PubMed

    Stål, Per

    2015-10-21

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

  8. Distinctly altered gut microbiota in the progression of liver disease.

    PubMed

    Xie, Guoxiang; Wang, Xiaoning; Liu, Ping; Wei, Runmin; Chen, Wenlian; Rajani, Cynthia; Hernandez, Brenda Y; Alegado, Rosanna; Dong, Bing; Li, Defa; Jia, Wei

    2016-04-12

    Recent studies underscore important roles of intestinal microbiota and the bacterial lipopolysaccharides (LPS) production in the pathogenesis of liver disease. However, how gut microbiota alters in response to the development of steatosis and subsequent progression to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remains unclear. We aimed to study the gut microbial changes over liver disease progression using a streptozotocin-high fat diet (STZ-HFD) induced NASH-HCC C57BL/6J mouse model that is highly relevant to human liver disease. The fecal microbiota at various liver pathological stages was analyzed by 16S rDNA gene pyrosequencing. Both UniFrac analysis and partial least squares-discriminant analysis showed significant structural alterations in gut microbiota during the development of liver disease. Co-abundance network analysis highlighted relationships between genera. Spearman correlation analysis revealed that the bacterial species, Atopobium spp., Bacteroides spp., Bacteroides vulgatus, Bacteroides acidifaciens, Bacteroides uniformis, Clostridium cocleatum, Clostridium xylanolyticum and Desulfovibrio spp., markedly increased in model mice, were positively correlated with LPS levels and pathophysiological features. Taken together, the results showed that the gut microbiota was altered significantly in the progression of liver disease. The connection between the gut microbial ecology and the liver pathology may represent potential targets for the prevention and treatment of chronic liver disease and HCC. PMID:27036035

  9. Distinctly altered gut microbiota in the progression of liver disease

    PubMed Central

    Xie, Guoxiang; Wang, Xiaoning; Liu, Ping; Wei, Runmin; Chen, Wenlian; Rajani, Cynthia; Hernandez, Brenda Y.; Alegado, Rosanna; Dong, Bing; Li, Defa; Jia, Wei

    2016-01-01

    Recent studies underscore important roles of intestinal microbiota and the bacterial lipopolysaccharides (LPS) production in the pathogenesis of liver disease. However, how gut microbiota alters in response to the development of steatosis and subsequent progression to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remains unclear. We aimed to study the gut microbial changes over liver disease progression using a streptozotocin-high fat diet (STZ-HFD) induced NASH-HCC C57BL/6J mouse model that is highly relevant to human liver disease. The fecal microbiota at various liver pathological stages was analyzed by 16S rDNA gene pyrosequencing. Both UniFrac analysis and partial least squares-discriminant analysis showed significant structural alterations in gut microbiota during the development of liver disease. Co-abundance network analysis highlighted relationships between genera. Spearman correlation analysis revealed that the bacterial species, Atopobium spp., Bacteroides spp., Bacteroides vulgatus, Bacteroides acidifaciens, Bacteroides uniformis, Clostridium cocleatum, Clostridium xylanolyticum and Desulfovibrio spp., markedly increased in model mice, were positively correlated with LPS levels and pathophysiological features. Taken together, the results showed that the gut microbiota was altered significantly in the progression of liver disease. The connection between the gut microbial ecology and the liver pathology may represent potential targets for the prevention and treatment of chronic liver disease and HCC. PMID:27036035

  10. Nonalcoholic fatty liver disease and cardiovascular disease.

    PubMed

    Liu, Hong; Lu, Hong-Yun

    2014-07-14

    Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are two diseases that are common in the general population. To date, many studies have been conducted and demonstrate a direct link between NAFLD and CVD, but the exact mechanisms for this complex relationship are not well established. A systematic search of the PubMed database revealed that several common mechanisms are involved in many of the local and systemic manifestations of NAFLD and lead to an increased cardiovascular risk. The possible mechanisms linking NAFLD and CVD include inflammation, oxidative stress, insulin resistance, ectopic adipose tissue distribution, dyslipidemia, endothelial dysfunction, and adiponectin, among others. The clinical implication is that patients with NAFLD are at an increased risk of CVD and should undergo periodic cardiovascular risk assessment. PMID:25024598

  11. Defining Normal Liver Stiffness Range in a Normal Healthy Chinese Population without Liver Disease

    PubMed Central

    Fung, James; Lee, Cheuk-kwong; Chan, Monica; Seto, Wai-kay; Wong, Danny Ka-ho; Lai, Ching-lung; Yuen, Man-fung

    2013-01-01

    Background For patients with chronic liver disease, different optimal liver stiffness cut-off values correspond to different stages of fibrosis, which are specific for the underlying liver disease and population. Aims To establish the normal ranges of liver stiffness in the healthy Chinese population without underlying liver disease. Methods This is a prospective cross sectional study of 2,528 healthy volunteers recruited from the general population and the Red Cross Transfusion Center in Hong Kong. All participants underwent a comprehensive questionnaire survey, measurement of weight, height, and blood pressure. Fasting liver function tests, glucose and cholesterol was performed. Abdominal ultrasound and transient elastography were performed on all participants. Results Of the 2,528 subjects, 1,998 were excluded with either abnormal liver parenchyma on ultrasound, chronic medical condition, abnormal blood tests including liver enzymes, fasting glucose, fasting cholesterol, high body mass index, high blood pressure, or invalid liver stiffness scan. The reference range for the 530 subjects without known liver disease was 2.3 to 5.9 kPa (mean 4.1, SD 0.89). The median liver stiffness was higher in males compared with females (4.3 vs 4.0 kPa respectively, p<0.001). There was also a decline in median Lliver stiffness in the older age group, from 4.2 kPa in those <25 years to 3.4 kPa for those >55 years (p=0.001). Conclusions The healthy reference range for liver stiffness in the Chinese population is 2.3 to 5.9 kPa. Female gender and older age group was associated with a lower median liver stiffness. PMID:24386446

  12. Paediatric cholestatic liver disease: Diagnosis, assessment of disease progression and mechanisms of fibrogenesis

    PubMed Central

    Pereira, Tamara N; Walsh, Meagan J; Lewindon, Peter J; Ramm, Grant A

    2010-01-01

    Cholestatic liver disease causes significant morbidity and mortality in children. The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy. There is no single gold standard test that accurately reflects the presence of liver disease, or that can be used to monitor fibrosis progression, particularly in conditions such as cystic fibrosis. This has lead to controversy over how suspected liver disease in children is detected and diagnosed. This review discusses the challenges in using commonly available methods to diagnose hepatic fibrosis and monitor disease progression in children with cholestatic liver disease. In addition, the review examines the mechanisms hypothesised to be involved in the development of hepatic fibrogenesis in paediatric cholestatic liver injury which may ultimately aid in identifying new modalities to assist in both disease detection and therapeutic intervention. PMID:21607144

  13. Non-alcoholic fatty liver disease.

    PubMed

    Pearce, Lynne

    2016-08-24

    Essential facts Non-alcoholic fatty liver disease (NAFLD) is an excess of fat in the liver that is not the result of excessive alcohol consumption or other secondary causes, such as hepatitis C. According to the National Institute for Health and Care Excellence, fatty liver - steatosis - affects between 20% and 30% of the population and its prevalence is increasing. PMID:27641564

  14. Zebrafish: an important tool for liver disease research.

    PubMed

    Goessling, Wolfram; Sadler, Kirsten C

    2015-11-01

    As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration.

  15. Zebrafish: An Important Tool for Liver Disease Research

    PubMed Central

    Goessling, Wolfram; Sadler, Kirsten C.

    2016-01-01

    As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. PMID:26319012

  16. Current Status of Therapy in Autoimmune Liver Disease

    PubMed Central

    Al-Harthi, Nadya; Heathcote, E. Jenny

    2009-01-01

    Therapeutic strategies for autoimmune liver diseases are increasingly established. Although proportionately uncommon, specialist centers have with time refined the best approaches for each disease, based on an improved understanding of the spectrum of presentation. The major treatment aims are to prevent end-stage liver disease and its associated complications. As a result of drugs such as ursodeoxycholic acid, predniso(lo)ne and azathioprine, both primary biliary cirrhosis and autoimmune hepatitis are now less commonly indications for liver transplantation. Unfortunately, the same inroads in treatment efficacy have as yet not been made for primary sclerosing cholangitis, although the recognition that a subset of patients may have a treatable secondary sclerosing cholangitis (IgG4 related) is helping a proportion. With better biological understanding, more specific interventions are expected that will benefit all those with autoimmune liver diseases. PMID:21180531

  17. Cell and tissue engineering for liver disease.

    PubMed

    Bhatia, Sangeeta N; Underhill, Gregory H; Zaret, Kenneth S; Fox, Ira J

    2014-07-16

    Despite the tremendous hurdles presented by the complexity of the liver's structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near- and long-term prospects for such cell-based therapies and the unique challenges for clinical translation.

  18. Staging of biliary atresia at diagnosis by molecular profiling of the liver

    PubMed Central

    2010-01-01

    Background Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis. Methods We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years. Results Fourteen of 47 livers displayed predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival. Conclusions Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes. PMID:20465800

  19. Transfemoral Transcatheter Aortic Valve Replacement for Mixed Aortic Valve Disease in Child's Class C Liver Disease Prior to Orthotopic Liver Transplantation: A Case Report.

    PubMed

    Wilkey, Barbara J; Hanson, Ross; Reece, T Brett; Forman, Lisa; Burton, James R; Messenger, John C; Kim, Michael S; Cleveland, Joseph C; Fiegel, Matt J; Nydam, Trevor L; Mandell, M Susan

    2016-06-01

    The American Association for the Study of Liver Diseases practice guidelines list severe cardiac disease as a contraindication to liver transplantation. Transcatheter aortic valve replacement has been shown to decrease all-cause mortality in patients with severe aortic stenosis who are not considered candidates for surgical aortic valve replacement. We report our experience of liver transplantation in a patient with severe aortic stenosis and moderate aortic insufficiency who underwent transcatheter aortic valve replacement with Child-Pugh Class C disease at a Model For End-Stage Liver Disease score of 29. The patient had a difficult post procedure course that was successfully medically managed. After liver transplantation the patient was discharged to home on postoperative day 11. The combination of cardiac disease and end stage liver disease is challenging but these patients can have a successful outcome despite very severe illness.

  20. Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

    PubMed

    Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

    2015-10-21

    Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

  1. Non-alcoholic fatty liver disease in 2015

    PubMed Central

    Ahmed, Monjur

    2015-01-01

    There is worldwide epidemic of non-alcoholic fatty liver disease (NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase. PMID:26085906

  2. The Natural Course of Non-Alcoholic Fatty Liver Disease.

    PubMed

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from "bland steatosis" to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death.

  3. The Natural Course of Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death. PMID:27213358

  4. The Natural Course of Non-Alcoholic Fatty Liver Disease.

    PubMed

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from "bland steatosis" to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death. PMID:27213358

  5. Interaction between periodontitis and liver diseases

    PubMed Central

    Han, Pengyu; Sun, Dianxing; Yang, Jie

    2016-01-01

    Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30–50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue. PMID:27588170

  6. Increased 4-hydroxynonenal protein adducts in male GSTA4–4/PPAR-alpha double knockout mice enhance injury during early stages of alcoholic liver disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To test the significance of lipid peroxidation in the development of alcoholic liver injury, an ethanol (EtOH) liquid diet was fed to male wild type 129/SvJ mice, and glutathione S-transferase A4-4 null (GSTA4-/-) mice for 40 d. GSTA4-/- mice were also crossed with peroxisome proliferator-activated ...

  7. Management of coagulation abnormalities in liver disease.

    PubMed

    Potze, Wilma; Porte, Robert J; Lisman, Ton

    2015-01-01

    Liver disease is characterized by changes in all phases of hemostasis. These hemostatic alterations were long considered to predispose patients with liver disease towards a bleeding tendency, as they are associated with prolonged conventional coagulation tests. However, these patients may also suffer from thrombotic complications, and we now know that the hemostatic system in patient with liver disease is, in fact, in a rebalanced state. In this review we discuss the concept of rebalanced hemostasis and its implications for clinical management of patients with liver disease. For instance, there is no evidence that the use of prophylactic blood product transfusion prior to invasive procedures reduces bleeding risk. Clinicians should also be aware of the possibility of thrombosis occurring in patients with a liver disease, and regular thrombosis prophylaxis should not be withheld in these patients.

  8. Role of spleen elastography in patients with chronic liver diseases

    PubMed Central

    Giunta, Mariangela; Conte, Dario; Fraquelli, Mirella

    2016-01-01

    The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations. PMID:27672283

  9. Role of spleen elastography in patients with chronic liver diseases.

    PubMed

    Giunta, Mariangela; Conte, Dario; Fraquelli, Mirella

    2016-09-21

    The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations. PMID:27672283

  10. Role of spleen elastography in patients with chronic liver diseases

    PubMed Central

    Giunta, Mariangela; Conte, Dario; Fraquelli, Mirella

    2016-01-01

    The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations.

  11. Role of spleen elastography in patients with chronic liver diseases.

    PubMed

    Giunta, Mariangela; Conte, Dario; Fraquelli, Mirella

    2016-09-21

    The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations.

  12. Chronic Liver Disease and Asian Americans/Pacific Islanders

    MedlinePlus

    ... Liver Disease Chronic Liver Disease and Asian Americans/Pacific Islanders Among Asian Americans, chronic liver disease is ... women. At a glance – Cancer Rates for Asian/Pacific Islanders (2008-2012) Cancer Incidence Rates per 100, ...

  13. Usefulness of Cardiac MetaIodobenzylguanidine Imaging to Improve Prognostic Power of the Model for End-Stage Liver Disease Scoring System in Patients With Mild-to-Moderate Chronic Heart Failure.

    PubMed

    Hakui, Hideyuki; Yamada, Takahisa; Tamaki, Shunsuke; Morita, Takashi; Furukawa, Yoshio; Iwasaki, Yusuke; Kawasaki, Masato; Kikuchi, Atsushi; Kondo, Takumi; Ishimi, Masashi; Sato, Yoshihiro; Seo, Masahiro; Ozaki, Tatsuhisa; Ikeda, Iyo; Fukuhara, Eiji; Sakata, Yasushi; Fukunami, Masatake

    2016-06-15

    Liver dysfunction has a prognostic impact on the outcomes of patients with advanced heart failure (HF). The model for end-stage liver disease (MELD) score is a robust system for rating liver dysfunction, and a high score has been shown to be associated with a poor prognosis in ambulatory patients with HF. In addition, cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with chronic HF (CHF). However, the long-term predictive value of combining the MELD score and cardiac MIBG imaging in patients with CHF has not been elucidated. To prospectively investigate whether cardiac MIBG imaging provides additional prognostic value to the MELD score in patients with mild-to-moderate CHF, we studied 109 CHF outpatients (New York Heart Association: 2.0 ± 0.6) with left ventricular ejection fraction <40%. At enrollment, an MELD score was obtained, and the heart-to-mediastinal ratio on delayed imaging and MIBG washout rate (WR) were measured using cardiac MIBG scintigraphy. During a follow-up period of 7.5 ± 4.2 years, 36 of 109 patients experienced cardiac death (CD). On multivariate Cox analysis, MELD score and WR were significantly independently associated with CD, although heart-to-mediastinal ratio showed an association with CD only on univariate Cox analysis. Patients with abnormal WR (>27%) had a significantly greater risk of CD than those with normal WR in both those with high MELD scores (≥10; hazard ratio 4.0 [1.2 to 13.6]) and with low MELD scores (<10; hazard ratio 6.4 [1.7 to 23.2]). In conclusion, cardiac MIBG imaging would provide additional prognostic information to the MELD score in patients with mild-to-moderate CHF. PMID:27237625

  14. [Rare case of cystic disease of the liver - alveolar echinococcosis of the liver].

    PubMed

    Kupka, Tomáš; Baľa, Peter; Hozáková, Lubomíra; Havelka, Jaroslav; Bojková, Martina; Břegová, Bohdana; Martínek, Arnošt; Dítě, Petr

    2015-06-01

    Alveolar echinococcosis is a rare parasitic disease, especially of liver, caused by larval stage of tapeworm Echinococcus multilocularis. At the end of the last century France, Germany, Austria and Switzerland were the most often regions with this disease, these days is this infection diagnosed also in our territory. We describe the case of the disease of the twenty-five years old male with nonspecific signs and hepatomegaly, who was diagnosed on the basis of imaging and laboratory sampling. Due to inoperability the patient is now in infectologist follow-up on a long-term treatment with albendazole. He is clinically stable, included in waiting list for liver transplantation.Key words: alveolar echinococcosis - benzimidazols - Echinococcus multilocularis - parasitic disease of liver. PMID:26258967

  15. Cutaneous Manifestations of Common Liver Diseases

    PubMed Central

    Dogra, Sunil; Jindal, Rashmi

    2012-01-01

    Skin functions as a window to our overall health and a number of systemic diseases result in various cutaneous changes. Knowledge of these manifestations helps in suspecting an underlying systemic illness. Cutaneous abnormalities are quite common in patients with liver diseases and this article aims to focus on these dermatoses. Cutaneous manifestations seen in patients with liver disease though common are nonspecific. They can also be seen in patients without liver diseases and generally do not indicate about a specific underlying hepatic disorder. The presence of a constellation of signs and symptoms is more useful in pointing toward an underlying hepatobiliary condition. The commonest symptom in patients with liver disease is pruritus which is often protracted and disabling. Other common features include spider angiomas, palmar erythema, paper money skin, xanthelasmas, pigmentary changes, and nutritional deficiencies. In this article, first the common cutaneous manifestations that may be associated with liver disorders are discussed and then common liver diseases with their specific cutaneous findings are discussed. Cutaneous abnormalities may be the first clue to the underlying liver disease. Identifying them is crucial for early diagnosis and better management. PMID:25755383

  16. GFR Estimating Equations and Liver Disease.

    PubMed

    Beben, Tomasz; Rifkin, Dena E

    2015-09-01

    It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver disease to deliver care and allocate organs for transplantation in a way that improves outcomes. The most commonly used methods to estimate GFR in this population are based on creatinine, which is biased by these patients' low creatinine production and potentially by elevated serum bilirubin and decreased albumin levels. None of the creatinine-based estimated glomerular filtration rate (eGFR) equations have been specifically modified for a population with liver disease, and even measurement of a 24-hour creatinine clearance has limitations. In liver disease, all creatinine-based estimates of GFR overestimate gold standard-measured GFR, and the degree of overestimation is highest at lower measured GFR values and in more severe liver disease. Cystatin C-based eGFR has shown promise in general population studies by demonstrating less bias than creatinine-based eGFR and improved association with clinically important outcomes, but results in the liver disease population have been mixed, and further studies are necessary. Ultimately, specific eGFR equations for liver disease or novel methods for estimating GFR may be necessary. However, for now, the limitations of currently available methods need to be appreciated to understand kidney function in liver disease.

  17. GFR Estimating Equations and Liver Disease

    PubMed Central

    Beben, Tomasz; Rifkin, Dena E.

    2015-01-01

    It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver disease in order to deliver care and allocate organs for transplantation in a way that improves outcomes. The most commonly used methods to estimate GFR in this population are based on creatinine, which is biased by these patients’ low creatinine production and potentially by elevated serum bilirubin and decreased albumin levels. None of the creatinine based estimated GFR (eGFR) equations have been specifically modified for a population with liver disease, and even measurement of a 24 hour creatinine clearance has limitations. In liver disease, all creatinine based estimates of GFR overestimate gold standard measured GFR (mGFR), and the degree of overestimation is highest at lower mGFR values and in more severe liver disease. Cystatin C based eGFR has shown promise in general population studies by demonstrating less bias than creatinine based eGFR and improved association with clinically important outcomes, but results in the liver disease population have been mixed and further studies are necessary. Ultimately, specific eGFR equations for liver disease or novel methods for estimating GFR may be necessary. However, for now, the limitations of currently available methods need to be appreciated to understand renal function in liver disease. PMID:26311594

  18. Diagnosis and management of polycystic liver disease.

    PubMed

    Gevers, Tom J G; Drenth, Joost P H

    2013-02-01

    Polycystic liver disease (PLD) is arbitrarily defined as a liver that contains >20 cysts. The condition is associated with two genetically distinct diseases: as a primary phenotype in isolated polycystic liver disease (PCLD) and as an extrarenal manifestation in autosomal dominant polycystic kidney disease (ADPKD). Processes involved in hepatic cystogenesis include ductal plate malformation with concomitant abnormal fluid secretion, altered cell-matrix interaction and cholangiocyte hyperproliferation. PLD is usually a benign disease, but can cause debilitating abdominal symptoms in some patients. The main risk factors for growth of liver cysts are female sex, exogenous oestrogen use and multiple pregnancies. Ultrasonography is very useful for achieving a correct diagnosis of a polycystic liver and to differentiate between ADPKD and PCLD. Current radiological and surgical therapies for symptomatic patients include aspiration-sclerotherapy, fenestration, segmental hepatic resection and liver transplantation. Medical therapies that interact with regulatory mechanisms controlling expansion and growth of liver cysts are under investigation. Somatostatin analogues are promising; several clinical trials have shown that these drugs can reduce the volume of polycystic livers. The purpose of this Review is to provide an update on the diagnosis and management of PLD with a focus on literature published in the past 4 years.

  19. Optical spectroscopy for differentiation of liver tissue under distinct stages of fibrosis: an ex vivo study

    NASA Astrophysics Data System (ADS)

    Fabila, D. A.; Hernández, L. F.; de la Rosa, J.; Stolik, S.; Arroyo-Camarena, U. D.; López-Vancell, M. D.; Escobedo, G.

    2013-11-01

    Liver fibrosis is the decisive step towards the development of cirrhosis; its early detection affects crucially the diagnosis of liver disease, its prognosis and therapeutic decision making. Nowadays, several techniques are employed to this task. However, they have the limitation in estimating different stages of the pathology. In this paper we present a preliminary study to evaluate if optical spectroscopy can be employed as an auxiliary tool of diagnosis of biopsies of human liver tissue to differentiate the fibrosis stages. Ex vivo fluorescence and diffuse reflectance spectra were acquired from biopsies using a portable fiber-optic system. Empirical discrimination algorithms based on fluorescence intensity ratio at 500 nm and 680 nm as well as diffuse reflectance intensity at 650 nm were developed. Sensitivity and specificity of around 80% and 85% were respectively achieved. The obtained results show that combined use of fluorescence and diffuse reflectance spectroscopy could represent a novel and useful tool in the early evaluation of liver fibrosis.

  20. Cell and Tissue Engineering for Liver Disease

    PubMed Central

    Bhatia, Sangeeta N.; Underhill, Gregory H.; Zaret, Kenneth S.; Fox, Ira J.

    2015-01-01

    Despite the tremendous hurdles presented by the complexity of the liver’s structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near and long-term prospects for such cell-based therapies and the unique challenges for clinical translation. PMID:25031271

  1. Clinical presentation of metabolic liver disease.

    PubMed

    Odievre, M

    1991-01-01

    Some clinical clues should alert paediatricians to the possibility of metabolic liver diseases. They can be classified into three categories: (i) Manifestations due to hepatocellular necrosis, acute or subacute, which can reveal galactosaemia, hereditary fructose intolerance, tyrosinaemia type I, Wilson disease and alpha 1-antitrypsin deficiency. Symptoms and signs suggestive of Reye syndrome should lead to a study of fatty acid oxidation and urea cycle enzymes. All these manifestations may necessitate a rapid diagnosis and treatment when liver dysfunction is severe. (ii) Cholestatic jaundice can reveal alpha 1-antitrypsin deficiency, Byler's disease, cystic fibrosis, Niemann-Pick disease and some disorders of peroxisome biogenesis. (iii) Hepatomegaly can reveal disorders with liver damage but also storage diseases such as glycogen storage diseases, cholesteryl ester storage disease and, when associated with splenomegaly, lysosomal storage diseases. Appropriate investigations for recognizing all these entities are proposed.

  2. Liver abnormalities in connective tissue diseases.

    PubMed

    De Santis, Maria; Crotti, Chiara; Selmi, Carlo

    2013-08-01

    The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.

  3. Managing non-alcoholic fatty liver disease

    PubMed Central

    Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

    2016-01-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment. PMID:27439352

  4. Gut-Liver Axis in Alcoholic Liver Disease

    PubMed Central

    Szabo, Gyongyi

    2014-01-01

    Alcoholic liver disease (ALD) has been amongst the leading causes of liver cirrhosis and liver-related death worldwide for decades. Early discoveries in alcoholic liver disease identified increased levels of bacterial endotoxin in the portal circulation suggesting a role for gut-derived “toxins” in ALD. Indeed, alcohol consumption can disrupt the intestinal epithelial barrier and result in increased gut permeability that is increasingly recognized as a major factor in ALD. Bacterial endotoxin, LPS, is a prototypic microbe-derived inflammatory signal that contributes to inflammation in ALD through activation of the Toll-like receptor 4 (TLR4). Recent studies also demonstrated that alcohol consumption is associated with alterations in the gut microbiome and the dysbalance of pathogenic and commensal organisms in the intestinal microbiome may contribute to the abnormal gut-liver axis in ALD. Indeed, bacterial decontamination improves ALD both in human and animal models. This short review summarizes recent findings and highlights emerging trends in the gut-liver axis relevant to ALD. PMID:25447847

  5. Managing systemic symptoms in chronic liver disease.

    PubMed

    Newton, Julia L; Jones, David E J

    2012-01-01

    Improved medical management and the changing disease demographic mean that the majority of patients with chronic liver disease are living with the disease rather than dying from it. Historically, the perception has been that the impact of chronic liver disease is related entirely to the consequences of endstage liver disease; however, more recently a number of systemic symptoms have been recognised that can occur at any point in the natural history of chronic liver disease and which can be associated with functional impairment and reduced quality of life. The most characteristic of these systemic symptoms is fatigue, which frequently associates with sleep disturbance and autonomic dysfunction, particularly manifest as abnormality of blood pressure regulation. Cognitive symptoms can occur even in non-cirrhotic patients. Falls can present in patients with autonomic dysfunction, complicated by the presence of peripheral muscle strength problems. Importantly for clinicians managing chronic liver disease, the severity of these systemic symptoms is typically not related to liver disease severity, and therefore despite optimal liver disease management, patients can often continue to experience debilitating symptoms. The similarity in systemic symptoms between different chronic liver diseases (and indeed chronic inflammatory conditions affecting other organs) suggests the possibility of shared pathogenetic processes and raises the possibility of common management strategies, although further research is urgently needed to confirm this. In primary biliary cirrhosis, where our understanding of systemic symptoms is arguably most developed, structured management strategies have been shown to improve the quality of life of patients. It is highly likely that similar approaches will have comparable benefits for other chronic liver disease groups. Here, we review the current understanding of systemic symptoms in chronic liver disease and offer recommendations regarding the

  6. Hepatocellular Carcinoma Management in Nonalcoholic Fatty Liver Disease Patients

    PubMed Central

    Oliveira, Claudia P.; Alvares-da-Silva, Mario R.; Tani, Claudia M.; Diniz, Marcio A.; Stefano, Jose T.; Chagas, Aline L.; Alencar, Regiane S.S.M.; Vezozzo, Denise C.P.; Santos, Gilmar R.; Campos, Priscila B.; Alves, Venancio AF.; Ratziu, Vlad; Carrilho, Flair J.

    2016-01-01

    Background/Aims: Nonalcoholic fatty liver disease (NAFLD) has emerged as an important cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) system is the preferred staging system to evaluate patients with HCC and links prognosis assessment with treatment recommendation. The aim of this retrospective study was to evaluate whether the BCLC staging system and its treatment algorithm are suitable for patients with HCC arising from NAFLD. Methods: Forty-two patients with HCC related to either to NAFLD or cryptogenic cirrhosis were retrieved retrospectively from 2 centers in Brazil. Patients were classified according to BCLC staging system. If the proposed HCC therapy could not be applied, the case was considered to represent deviations from the recommended BCLC guideline. Causes of treatment deviations were investigated. Results: There were 4 patients without evidence of cirrhosis according to liver biopsy and/or clinical evaluation. One (2%), 21 (50%), 10 (24%), 5 (12%), and 5 patients (12%) were classified initially to the very early (0), early (A), intermediate (B), advanced (C), and terminal (D) BCLC stages, respectively. Thirty-five patients (83%) were treated according to BCLC recommendations. There were 3 cases (of 5) of protocol deviation in BCLC C patients. The 1- and 2-year overall survival rates were 81% and 66%, respectively. Conclusions: The BCLC system is applied in most cases of NAFLD-related HCC cases. Deviation of BCLC is found more frequently in BCLC C stage patients. PMID:25268068

  7. Exercise manual for liver disease patients

    PubMed Central

    Limongi, Vivian; Dos Santos, Daniele Costa; de Oliveira da Silva, Aurea Maria; Boin, Ilka de Fátima Santana Ferreira; Stucchi, Raquel Silveira Bello

    2016-01-01

    AIM: To increase inspiratory muscle strength and improve the quality of life of candidates for liver transplantation. METHODS: Twenty-three candidates for liver transplantation participated in the control group and 14 made up the intervention group. The control group consisted of 18 men and 5 women, body mass index (BMI) 27.3 ± 4.5 kg/m2 and Model for End-Stage Liver Disease (MELD) 18.2 ± 6.1. The intervention group consisted of 11 men and 3 women, BMI 28.6 ± 5.4 kg/m2 and MELD 18 ± 4.5. The presence or absence of ascites was identified in the first patient evaluation and after three months. We evaluated maximal inspiratory pressure (MIP) and maximal expiratory pressure, spirometry, root mean square (RMS) of diaphragm and rectus abdominis, and the quality of life. The exercises were performed daily by patients at home for three months and were supervised at distance monthly. The manual consisted of diaphragmatic breathing exercises, diaphragmatic isometric exercise, Threshold IMT®, lifting upper limbs with a bat and strengthening the abdomen. RESULTS: There was significant difference (P = 0.01) between the first (initial) and the third month (final) MIP in the control group and in the intervention group, but there was no difference (P = 0.45) between the groups. The RMS of the diaphragm was lower (P = 0.001) and the functional capacity was higher (P = 0.006) in the intervention group compared to the control. The general health and mental health domains received higher scores after three months in the control group (P = 0.01) and the intervention group (P = 0.004), but there was no significant difference between them. The comparison between the presence of initial ascites with the presence of ascites was performed after three months in the control group (P = 0.083) and intervention group (P = 0.31). There was no significant difference, in relation to the presence of ascites after three months between groups (P = 0.21). In the intervention group, patients with

  8. [Occupational liver diseases: (author's transl)].

    PubMed

    Kuntz, H D; May, B

    1980-07-18

    A large number of exogenous substances with potential liver toxicity are to be found in work places and in the environment. Decisive importance is ascribed to regular supervision of exposed persons and adhering to the appropriate safety provisions without being able to ensure reliable prevention of toxic liver damage thereby. The prognosis of occupational toxic liver damage is good if recognition is timely and the causal noxae are eliminated. The aim of all diagnostic and prophylactic efforts must be rehabilitation, in addition to specific occupational medical and hygienic measures.

  9. Vitamin D deficiency in chronic liver disease

    PubMed Central

    Iruzubieta, Paula; Terán, Álvaro; Crespo, Javier; Fábrega, Emilio

    2014-01-01

    Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis, but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation, has immunomodulatory and anti-inflammatory properties. Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) virus infection. The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known, but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases. Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease. Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required. PMID:25544877

  10. Chronic liver disease in Aboriginal North Americans

    PubMed Central

    Scott, John D; Garland, Naomi

    2008-01-01

    A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLD) in Aboriginal North Americans. CLD affects Aboriginal North Americans disproportionately and is now one of the most common causes of death. Alcoholic liver disease is the leading etiology of CLD, but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLD. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLD. Future research should monitor the incidence and etiology of CLD and should be geographically inclusive. In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholic fatty liver disease (NAFLD) in this population. PMID:18698674

  11. Role of Gut Microbiota in Liver Disease.

    PubMed

    Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

    2015-01-01

    Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism. PMID:26447960

  12. Role of Gut Microbiota in Liver Disease.

    PubMed

    Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

    2015-01-01

    Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.

  13. Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease.

    PubMed

    Toshikuni, Nobuyuki; Tsutsumi, Mikihiro; Arisawa, Tomiyasu

    2014-07-14

    Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple hepatic steatosis to steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis, a small percentage of individuals will develop progressive liver disease. Notably, both ALD and NAFLD are frequently accompanied by extrahepatic complications, including cardiovascular disease and malignancy. The survival of patients with ALD and NAFLD depends on various disease-associated conditions. This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology, the factors associated with disease susceptibility and progression, and the predictors and characteristics of outcomes. A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases. PMID:25024597

  14. Protective efficacy and safety of liver stage attenuated malaria parasites

    PubMed Central

    Kumar, Hirdesh; Sattler, Julia Magdalena; Singer, Mirko; Heiss, Kirsten; Reinig, Miriam; Hammerschmidt-Kamper, Christiane; Heussler, Volker; Mueller, Ann-Kristin; Frischknecht, Friedrich

    2016-01-01

    During the clinically silent liver stage of a Plasmodium infection the parasite replicates from a single sporozoite into thousands of merozoites. Infection of humans and rodents with large numbers of sporozoites that arrest their development within the liver can cause sterile protection from subsequent infections. Disruption of genes essential for liver stage development of rodent malaria parasites has yielded a number of attenuated parasite strains. A key question to this end is how increased attenuation relates to vaccine efficacy. Here, we generated rodent malaria parasite lines that arrest during liver stage development and probed the impact of multiple gene deletions on attenuation and protective efficacy. In contrast to P. berghei strain ANKA LISP2(–) or uis3(–) single knockout parasites, which occasionally caused breakthrough infections, the double mutant lacking both genes was completely attenuated even when high numbers of sporozoites were administered. However, different vaccination protocols showed that LISP2(–) parasites protected better than uis3(–) and double mutants. Hence, deletion of several genes can yield increased safety but might come at the cost of protective efficacy. PMID:27241521

  15. Dame Sheila Sherlock: pioneer in liver diseases.

    PubMed

    Ellis, Harold

    2009-04-01

    Within living memory of some of us, liver disease was a Cinderella subject. If you look up the first edition of the standard medical textbook of the time, Sir William Osler's 'Principles and Practice of Medicine', published in 1892, you will find a mere 24 of its 1079 pages devoted to the liver, compared with 38 pages on typhoid fever alone; and matters hardly changed throughout the first half of the 20th century. Although 'cirrhosis' and 'hepatitis' were well recognised conditions when I was a house surgeon in 1948, their classification, aetiologies, detailed pathology and management were little understood, while laboratory investigations of the liver diseases were few and non-specific.

  16. Chronic Liver Disease and Native Hawaiian/Pacific Islanders

    MedlinePlus

    ... Liver Disease Chronic Liver Disease and Native Hawaiian/Pacific Islander Native Hawaiian/Pacific Islanders were seven times ... At a glance – Cancer Rates for Native Hawaiian/Pacific Islander Liver & IBD Cancer Incidence Rates per 100, ...

  17. A totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy assisted with radiofrequency (radiofrequency assisted liver partition with portal vein ligation) for staged liver resection

    PubMed Central

    Hakim, David N.; Gall, Tamara M. H.; Fajardo, Ana; Pencavel, Tim D.; Fan, Ruifang; Sodergren, Mikael H.

    2016-01-01

    In order to induce liver hypertrophy to enable liver resection in patients with a small future liver remnant (FLR), various methods have been proposed in addition to portal vein embolisation (PVE). Most recently, the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique has gained significant international interest. This technique is limited by the high morbidity associated with an in situ liver splitting and the patient undergoing two open operations. We present the case of a variant ALPPS technique performed entirely laparoscopically with no major morbidity or mortality. An increased liver volume of 57.9% was seen after 14 days. This technique is feasible to perform and compares favourably to other ALPPS methods whilst gaining the advantages of laparoscopic surgery. PMID:27500150

  18. Study of Hepatic Osteodystrophy in Patients with Chronic Liver Disease

    PubMed Central

    Karoli, Yogesh; Fatima, Jalees; Manhar, Mohammad

    2016-01-01

    Introduction Chronic Liver Disease (CLD) is a major cause of morbidity and mortality worldwide. It involves haemodynamic and metabolic complications. Hepatic Osteodystrophy is a metabolic bone disease that may occur in individuals with chronic liver disease. It can significantly affect morbidity and quality of life of these patients. Fractures are also associated with an excess mortality. It has been an under recognized and inadequately studied complication among Indian population. An early diagnosis is essential to correct reversible risk factors which predispose to bone mass loss. Aim To assess the prevalence of metabolic bone disease and identify the risk factors associated with hepatic osteodystrophy in patients with cirrhosis. Materials and Methods This was an observational, cross-sectional, hospital based study conducted at a medical college hospital. All patients more than 20-year-old, diagnosed with chronic liver disease/Cirrhosis were enrolled. They were subjected to haematological, biochemical investigations, evaluation of Vitamin D and other hormonal parameters. Bone Mineral Density (BMD) was estimated by Dual Energy X-ray Absorptiometry (DEXA). Results A total of 72 patients with mean age 50.04±11.24 years were included in the study. Amongst causes of chronic liver disease were alcoholic liver disease 22 (30.6%), CLD due to hepatitis B 24 (33.3%) and chronic hepatitis C 26 (36.1%). Twenty one (29.2%) patients had normal BMD while 51 (70.8%) had a low BMD. Out of these 51 patients, 36 (70.6%) were diagnosed of osteopenia and 15 (29.4%) others were found to have osteoporosis. Vitamin D levels and severity of liver disease had correlation with low BMD. Conclusion Low BMD is highly prevalent in patients with chronic liver disease of variable aetiologies. We advocate more randomised and prospective studies to be conducted on homogeneous groups with chronic liver disease in its various stages. In view of numerous therapeutic options available both for liver

  19. Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Chen, Guanliang; Ni, Yinhua; Nagata, Naoto; Xu, Liang; Ota, Tsuguhito

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin. PMID:27563875

  20. Probiotics and Nonalcoholic Fatty liver Disease

    PubMed Central

    Eslamparast, Tannaz; Eghtesad, Sareh; Hekmatdoost, Azita; Poustchi, Hossein

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, both in adults and in children. NAFLD represents a spectrum of liver diseases that range from hepatic steatosis to steatohepatitis and cirrhosis. However, NAFLD is more prevalent in overweight and obese individuals. Evidences thus far suggest that hepatic triglyceride accumulation is not always derived from obesity; gut microbiota can also play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. On the other hand, probiotics can strengthen the intestinal wall, reducing its permeability, bacterial translocation, and endotoxemia according to animal and human studies. They can also reduce oxidative and inflammatory liver damage, while improving the histological state in certain situations. This review article focuses on research that has been conducted on probiotics and NAFLD, highlighting their efficacy as a novel therapeutic option for the treatment of this condition. PMID:24829682

  1. Hepatic inflammation and progressive liver fibrosis in chronic liver disease

    PubMed Central

    Czaja, Albert J

    2014-01-01

    Chronic liver inflammation drives hepatic fibrosis, and current immunosuppressive, anti-inflammatory, and anti-viral therapies can weaken this driver. Hepatic fibrosis is reversed, stabilized, or prevented in 57%-79% of patients by conventional treatment regimens, mainly by their anti-inflammatory actions. Responses, however, are commonly incomplete and inconsistently achieved. The fibrotic mechanisms associated with liver inflammation have been clarified, and anti-fibrotic agents promise to improve outcomes as adjunctive therapies. Hepatitis C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within hepatocytes. Angiotensin can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen species. Anti-oxidants (N-acetylcysteine, S-adenosyl-L-methionine, and vitamin E) and angiotensin inhibitors (losartin) have had anti-fibrotic actions in preliminary human studies, and they may emerge as supplemental therapies. Anti-fibrotic agents presage a new era of supplemental treatment for chronic liver disease. PMID:24627588

  2. The gut microbiota and liver disease

    PubMed Central

    Llorente, Cristina; Schnabl, Bernd

    2015-01-01

    The leaky gut hypothesis links translocating microbial products with the onset and progression of liver disease, and for a long time was considered one of its major contributors. However, a more detailed picture of the intestinal microbiota contributing to liver disease started to evolve. The gut is colonized by trillions of microbes that aid in digestion, modulate immune response, and generate a variety of products that result from microbial metabolic activities. These products together with host-bacteria interactions influence both normal physiology and disease susceptibility. A disruption of the symbiosis between microbiota and host is known as dysbiosis and can have profound effects on health. Qualitative changes such as increased proportions of harmful bacteria and reduced levels of beneficial bacteria, and also quantitative changes in the total amount of bacteria (overgrowth) have been associated with liver disease. Understanding the link between the pathophysiology of liver diseases and compositional and functional changes of the microbiota will help in the design of innovative therapies. In this review, we focus on factors resulting in dysbiosis, and discuss how dysbiosis can disrupt intestinal homeostasis and contribute to liver disease. PMID:26090511

  3. [Function of zinc in liver disease].

    PubMed

    Katayama, Kazuhiro

    2016-07-01

    Zinc deficiency is highly prevalent in cirrhotic patients, and contributes to several clinical symptoms such as hepatic encephalopathy and liver fibrosis. Ammonia is detoxified in liver to urea through urea cycle, and is also detoxified in extrahepatic tissue to glutamine through glutamine synthetase. The reduced ability of ammonia detoxification in liver cirrhosis is ascribed to zinc deficiency, because a member of urea cycle, ornithine transcarbamylase is a zinc enzyme. In this condition, glutamine synthesis is enhanced, which enables the body, at least temporarily, to suppress the increase of ammonia. However, the glutamine is metabolized predominantly in enterocyte to ammomia and glutamate, indicating that a vicious cycle in glutamine synthesis and glutamine breakdown occurs in liver cirrhosis. Attention should be given to the clinical significance of zinc in liver diseases. PMID:27455801

  4. Managing antiretroviral-associated liver disease.

    PubMed

    Dieterich, Douglas

    2003-09-01

    The use of all potent drugs is associated with toxicities and antiretroviral (ARV) drugs are no exception. Antiretroviral therapy-associated hepatic toxicity is of increasing concern in the management of patients with HIV/AIDS. Liver toxicity has been reported in some HIV-infected patients being treated with drugs from all of these classes of ARV drugs: protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although the majority of cases involve asymptomatic elevations of liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), severe, and, in a minority of cases, life threatening, liver disease has been reported in patients treated with ARV drugs. The exact causes of elevated plasma levels of AST and ALT are complex and, in many cases, obscure. The combination of viral hepatic disease, drugs that act adversely directly on the liver and drugs that act on other systems of the body which in turn, adversely affect the liver, can result in hepatic toxicity. Such toxicity may be inappropriately attributed solely to the direct effect of a drug. Knowledge of the possible causes of liver toxicity, and ways to avoid it, should reduce the risk of developing hepatotoxicity. The physician's task is to prevent the development of liver toxicity, e.g., by choosing appropriate therapeutic regimens and by careful management of the patient. This involves frequent monitoring of the patient, both clinically and by utilizing liver function tests on a regular basis. If signs and symptoms of liver disease do develop, prompt and expert management is essential. This review discusses the influence of a number of factors on hepatic toxicity including viral hepatitis, insulin resistance and the specific ARV drugs used in the treatment of patients with HIV/AIDS.

  5. [Nonalcoholic fatty liver disease in children].

    PubMed

    Bojórquez-Ramos, María del Carmen

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in children and adolescents in the United States of America (USA) and probably in the entire western hemisphere, due to the increase in the prevalence of overweight and obesity. Steatosis can progress to inflammation, fibrosis and even cirrhosis, which increases the morbidity and mortality associated to liver disease. In every overweight and obese child a thorough analysis should be performed including liver function tests and liver ultrasound, in order to establish a timely diagnosis. The liver biopsy is the most specific study to rule out other potentially treatable entities. It is necessary to count on non-invasive methods to detect children with NAFLD and identify those in risk of progression. Biomarkers related to inflammation, oxidative stress, apoptosis and fibrosis have been reported. The main goal of the treatment is to modify the life style, starting with a healthy diet and an increase of physical activity. Regarding pharmacological treatment, there is evidence of histological improvement with vitamin E use, as opposed to metformin, but more conclusive studies regarding this subject are needed.

  6. Assessment of thyroid and gonadal function in liver diseases

    PubMed Central

    Kharb, Sandeep; Garg, M. K.; Puri, Pankaj; Brar, Karninder S.; Pandit, Aditi; Srivastava, Sharad

    2015-01-01

    Introduction: Liver is involved with the synthesis of carrier proteins and metabolism of various hormones and liver diseases may, therefore, be associated with various endocrine disturbances. This study was conducted to assess thyroid and gonadal function in subjects with acute hepatitis (AH), chronic liver disease (CLD), and those who had undergone liver transplantation (LT). Materials and Methods: Patients with AH, CLD with Child-Pugh stage A (CLD-1) and Child-Pugh stage B or C (CLD-2), and LT seen at our tertiary level hospital were assessed clinically, biochemically, and for thyroid and gonadal functions besides 25 healthy controls. Results: Thyroid dysfunction and hypogonadism were present in 14 (16%) and 24 (28%) patients with liver diseases respectively. Among thyroid dysfunction, the commonest was sick euthyroid syndrome six (7%), followed by subclinical hypothyroidism in three patients (3.5%), subclinical hyperthyroidism and thyrotoxicosis in two patients each (2.3%) and overt hypothyroidism in one patient. Among patients with LT and AH groups, the only abnormality was significantly lower total T3 compared with healthy controls. The CLD2 group had significantly lower levels of all thyroid hormones compared with controls and CLD1 group. Hypogonadism was commonest in patients with CLD-2 (14; 50%) followed by LT (3; 33%), CLD-1 (4; 20%), and AH (3; 14%). Hypogonadism was predicted by older age, lower levels of serum albumin, total cholesterol, and triglycerides and higher levels of plasma glucose, serum bilirubin, aspartate transaminases, and international normalized ratio. Gonadal functions showed recovery following LT. Conclusions: Thyroid dysfunction and hypogonadism form an important part of the spectrum of acute and CLD, and patients with LT. Deterioration of synthetic functions of liver disease predicts presence of hypogonadism. PMID:25593833

  7. Review article: Nutritional therapy in alcoholic liver disease.

    PubMed

    Stickel, F; Hoehn, B; Schuppan, D; Seitz, H K

    2003-08-15

    Chronic alcohol consumption may lead to primary and secondary malnutrition. In particular, protein energy malnutrition not only aggravates alcoholic liver disease but also correlates with impaired liver function and increased mortality. Therefore, in these patients, adequate nutritional support should be implemented in order to improve their prognosis. Clinical trials addressing this issue have shown that nutritional therapy either enterally or parenterally improves various aspects of malnutrition, and there is increasing evidence that it may also improve survival. Therefore, malnourished alcoholics should be administered a diet rich in carbohydrate- and protein-derived calories preferentially via the oral or enteral route. Micronutrient deficiencies typically encountered in alcoholics, such as for thiamine and folate, require specific supplementation. Patients with hepatic encephalopathy may be treated with branched-chain amino acids in order to achieve a positive nitrogen balance. Fatty liver represents the early stage of alcoholic liver disease, which is usually reversible with abstinence. Metadoxine appears to improve fatty liver but confirmatory studies are necessary. S-adenosyl-L-methionine may be helpful for patients with severe alcoholic liver damage, since various mechanisms of alcohol-related hepatotoxicity are counteracted with this essential methyl group donor, while a recent large trial showed that the use of polyenylphosphatidylcholine is of limited efficacy. PMID:12940921

  8. Treatment of Non-Alcoholic Fatty Liver Disease.

    PubMed

    Scherer, Antonia; Dufour, Jean-François

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions from steatosis to cirrhosis and hepatocellular carcinoma. Steatosis is a benign reversible condition, which does not need treatment. Cirrhosis and hepatocellular carcinoma are the end stages of any chronic liver disease and do not have etiology-specific treatments. In this chapter, we will review treatment options for non-alcoholic steatohepatitis, which is the progressive form of NAFLD. Basically there are 2 strategies, the first of which is to address lifestyle and the second to use medication. The first approach is the most physiologic, the least expensive, but is also the most difficult to implement. The second approach, which should help patients who failed the first approach, is at the advanced clinical research stage. PMID:27548081

  9. Diagnosis and Management of Alcoholic Liver Disease

    PubMed Central

    Dugum, Mohannad; McCullough, Arthur

    2015-01-01

    Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials. PMID:26356792

  10. Complement activation in chronic liver disease.

    PubMed Central

    Munoz, L E; De Villiers, D; Markham, D; Whaley, K; Thomas, H C

    1982-01-01

    Patients with HBsAg positive chronic active liver disease (CALD) and primary biliary cirrhosis (PBC) exhibit increased C3d concentrations and changes in the serum concentrations of the complement components consistent with activation of the classical and alternative pathways. In these patients the concentrations of the regulatory proteins, C3b inactivator (C3bINA) and beta IH globulin, are normal. Patients with HBsAg negative CALD and alcohol induced liver disease (ALD) exhibit no evidence of an increased level of complement system activation. In these patients diminished serum concentrations of complement components appear to be related to diminished hepatic synthetic function. C4 synthesis may be specifically reduced in autoimmune chronic active liver disease. PMID:7083631

  11. Toll-like receptors and liver disease.

    PubMed

    Kesar, Vivek; Odin, Joseph A

    2014-02-01

    Toll-like receptors (TLRs) are pattern recognition receptors that play an important role in host defence by recognizing pathogen-associated molecular patterns (PAMP). Recent studies indicate that TLR signalling plays an important role in progression of chronic liver diseases. Ongoing clinical trials suggest that therapeutic manipulation of TLR pathways may offer novel means of reversing chronic liver diseases. Upon activation by their respective ligands, TLRs initiate an intracellular pro-inflammatory/anti-inflammatory signalling cascade via recruitment of various adaptor proteins. TLR associated signalling pathways are tightly regulated to keep a check on inappropriate production of pro-inflammatory cytokines and interferons thereby preventing various autoimmune and inflammatory processes. Herein, we review the current state of knowledge of hepatic distribution, signalling pathways and therapeutic modulation of TLRs in chronic liver diseases. PMID:24118797

  12. Susceptibility of L-FABP-/- mice to oxidative stress in early-stage alcoholic liver.

    PubMed

    Smathers, Rebecca L; Galligan, James J; Shearn, Colin T; Fritz, Kristofer S; Mercer, Kelly; Ronis, Martin; Orlicky, David J; Davidson, Nicholas O; Petersen, Dennis R

    2013-05-01

    Chronic ethanol consumption is a prominent cause of liver disease worldwide. Dysregulation of an important lipid uptake and trafficking gene, liver-fatty acid binding protein (L-FABP), may contribute to alterations in lipid homeostasis during early-stage alcoholic liver. We have reported the detrimental effects of ethanol on the expression of L-FABP and hypothesize this may deleteriously impact metabolic networks regulating fatty acids. Male wild-type (WT) and L-FABP(-/-) mice were fed a modified Lieber-DeCarli liquid diet for six weeks. To assess the response to chronic ethanol ingestion, standard biochemical indicators for alcoholic liver disease (ALD) and oxidative stress were measured. Ethanol ingestion resulted in attenuation of hepatic triglyceride accumulation and elevation of cholesterol in L-FABP(-/-) mice. Lipidomics analysis validated multiple alterations in hepatic lipids resulting from ethanol treatment. Increased immunohistochemical staining for the reactive aldehydes 4-hydroxynonenal and malondialdehyde were observed in WT mice ingesting ethanol; however, L-FABP(-/-) mice displayed prominent protein adducts in liver sections evaluated from pair-fed and ethanol-fed mice. Likewise, alterations in glutathione, thiobarbituric acid reactive substances (TBARS), 8-isoprostanes, and protein carbonyl content all indicated L-FABP(-/-) mice exhibit high sustained oxidative stress in the liver. These data establish that L-FABP is an indirect antioxidant protein essential for sequestering FFA and that its impairment could contribute to in the pathogenesis of ALD.

  13. Acute Kidney Disease After Liver and Heart Transplantation.

    PubMed

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

  14. Non-alcoholic fatty liver disease and liver transplantation.

    PubMed

    Khan, Reenam S; Newsome, Philip N

    2016-08-01

    Cirrhosis secondary to non-alcoholic steatohepatitis (NASH) is a common indication for liver transplant. In comparison to other cirrhotic patients, patients with NASH cirrhosis are more likely to be older and have the metabolic syndrome. Pre-transplant, patients require careful evaluation of cardiovascular risk. As the incidence of non-alcoholic fatty liver disease (NAFLD) is rising, a greater proportion of donor grafts have steatosis greater than 30%, which is associated with poor outcomes. Grafts with steatosis greater than 60% are unsuitable for transplant. Overall, post-transplant survival outcomes for patients with NASH cirrhosis are similar to those with cirrhosis without NASH. However, NASH cirrhosis is associated with a higher 30-day mortality, predominantly from an increase in cardiovascular events and infections. Following liver transplant, there is a significant risk of NASH recurrence, although this seldom results in allograft loss. Furthermore, a significant number of patients who had a liver transplant for other reasons develop NASH de novo. When patients with NASH cirrhosis are considered for transplant, one of the major challenges lies in identifying which patients are too high risk for surgery. This review aims to provide information to aid this decision making process, and to provide guidance on the peri-operative care strategies that can modify risk. PMID:26997540

  15. Liver transplantation for alcoholic liver disease: selection and outcome.

    PubMed

    Maldonado, J R; Keeffe, E B

    1997-08-01

    There is clear consensus that patients with alcoholic cirrhosis should be considerated for liver transplantation, barring complicating medical or psychosocial problems. Short-term and long-term survival rates are comparable to patients receiving transplants for other conditions, and the relapse rate to alcohol use averages 15%, with troublesome drinking seen uncommonly. To date, no nationally accepted selection criteria have been established and proved effective in predicting long-term sobriety and compliance. To maximize the outcome of liver transplantation in patients with alcoholic liver disease, an approach to the selection of candidates is outlined herewith. 1. Minimum pretransplant sobriety period of 6 months. 2. Assessment of overall psychosocial support and stress. 3. Assessment of comorbid psychiatric conditions that may impair ability to comply with the transplant protocol during and after transplantation. 4. Assessment of past and present compliance with medical treatment. 5. Acceptance of problem with alcohol and willingness to sign an alcohol contract. 6. Willingness to participate in alcohol rehabilitation treatment program. 7. Willingness to participate in liver support groups to improve understanding of the condition and obtain social support. 8. Willingness to undergo random toxicology screening to assess compliance with sobriety. PMID:15562571

  16. Candidates for liver transplantation with alcoholic liver disease: Psychosocial aspects

    PubMed Central

    Telles-Correia, Diogo; Mega, Inês

    2015-01-01

    In Europe, 30% to 50% of liver transplantations are currently due to alcoholic liver disease (ALD). In the United States, this percentage is 17.2%. Post-transplant survival and other predictors of clinical course do not differ significantly from those in other types of transplanted patients, as long as there is no relapse of drinking. However, 20%-25% of these patients lapse or relapse to heavy drinking post-operatively, which has been associated with an increased risk of liver damage and mortality. It is therefore crucial to design specific selection and follow-up strategies aimed at this particular type of patient. Several good and poor prognosis factors that could help to predict a relapse have been suggested, among them the duration of abstinence, social support, a family history of alcoholism, abuse diagnosis versus alcohol dependence, non-acceptance of diagnosis related to alcohol use, presence of severe mental illness, non-adherence in a broad sense, number of years of alcoholism, and daily quantity of alcohol consumption. In this article, we discuss these and other, more controversial factors in selecting ALD patients for liver transplantation. Abstinence should be the main goal after transplantation in an ALD patient. In this article, we review the several definitions of post-transplant relapse, its monitoring and the psychopharmacological and psychotherapeutic treatment. PMID:26494959

  17. Testosterone in men with advanced liver disease: abnormalities and implications.

    PubMed

    Sinclair, Marie; Grossmann, Mathis; Gow, Paul J; Angus, Peter W

    2015-02-01

    Serum testosterone is reduced in up to 90% of men with cirrhosis, with levels falling as liver disease advances. Testosterone is an important anabolic hormone, with effects on muscle, bone, and hematopoiesis. Many of the features of advanced liver disease are similar to those seen in hypogonadal men, including sarcopenia, osteoporosis, gynecomastia, and low libido. However, the relative contribution of testosterone deficiency to the symptomatology of advanced liver disease has not been well established. More recently, it has been demonstrated that low testosterone in men with cirrhosis is associated with increased mortality, independent of the classically recognized prognostic factors, such as the Model for End-Stage Liver Disease score. Only several small clinical trials have examined the role of testosterone therapy in men with cirrhosis, none of which have resolved the issue of whether or not testosterone is beneficial. However, in men with organic hypogonadism due to structural hypothalamic-pituitary-testicular axis disease, testosterone therapy has been shown to improve muscle mass and bone mineral density, increase hemoglobin, and reduce insulin resistance. Despite initial concerns linking testosterone with hepatocellular carcinoma, more recent data suggest that this risk has been overstated. There is, therefore, now a strong rationale to assess the efficacy and safety of testosterone therapy in cirrhosis in well-designed randomized controlled trials. PMID:25087838

  18. Non-alcoholic fatty liver disease: The diagnosis and management

    PubMed Central

    Abd El-Kader, Shehab M; El-Den Ashmawy, Eman M Salah

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease. PMID:25937862

  19. Vinyl chloride-associated liver disease.

    PubMed

    Berk, P D; Martin, J F; Young, R S; Creech, J; Selikoff, I J; Falk, H; Watanabe, P; Popper, H; Thomas, L

    1976-06-01

    Although polyvinyl chloride has been produced from vinyl chlride monomer for more than 40 years, recognition of toxicity among vinyl chloride polymerization workers is more recent. In the mid 1960s, workers involved in cleaning polymerization tanks were found to have acro-osteolysis. In 1974, the same population of workers was found to be at risk for an unusual type of hepatic fibrosis and angiosarcoma of the liver. We describe two cases of vinyl chloride-associated liver injury, one of hepatic fibrosis and one of angiosarcoma. Histologic features of these lesions are similar to the hepatic fibrosis and angiosarcomas resulting from chronic exposure to inorganic arsenicals. Preliminary studies suggest that the toxicity of vinyl chloride may result from formation, during high-dose exposure, of active metabolites by mixed function oxidases of the liver. Epidemiologic studies indicate an increased incidence not only of liver disease, but also of cancers of the brain, lung, and possibly other organs.

  20. Histopathology of nonalcoholic fatty liver disease

    PubMed Central

    Brunt, Elizabeth M; Tiniakos, Dina G

    2010-01-01

    Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease (NAFLD) are measured. Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD, i.e. nonalcoholic steatohepatitis (NASH) and fibrosis. Included in the lesions of NAFLD are steatosis, lobular and portal inflammation, hepatocyte injury in the forms of ballooning and apoptosis, and fibrosis. However, patterns of these lesions are as distinguishing as the lesions themselves. Liver injury in adults and children due to NAFLD may have different histological patterns. In this review, the rationale for liver biopsy, as well as the histopathological lesions, the microscopically observable patterns of injury, and the differential diagnoses of NAFLD and NASH are discussed. PMID:21072891

  1. Antioxidants as Therapeutic Agents for Liver Disease

    PubMed Central

    Singal, Ashwani K.; Jampana, Sarat C.; Weinman, Steven A.

    2011-01-01

    Oxidative stress is commonly associated with a number of liver diseases and is thought to play a role in the pathogenesis of chronic hepatitis C, alcoholic liver disease, nonalcoholic steatohepatitis (NASH), hemochromatosis and Wilson’s disease. Antioxidant therapy has thus been considered to have the possibility of beneficial effects in the management of these liver diseases. In spite of this promise, antioxidants have produced mixed results in a number of clinical trials of efficacy. This review summarizes the results of clinical trials of antioxidants as sole or adjuvant therapy of chronic hepatitis C, alcoholic liver disease and NASH. Overall, the most promising results to date are for vitamin E therapy of NASH but some encouraging results have been obtained with antioxidant therapy of acute alcoholic hepatitis as well. In spite of evidence for small reductions of serum ALT, there is as yet no convincing evidence that antioxidant therapy itself is beneficial to patients with chronic hepatitis C. Problems such as small sample size, short follow up duration, inadequate end points, failure to demonstrate tissue delivery and antioxidant efficacy, and heterogeneous nature of the “antioxidant” compounds used have complicated interpretation of results of the clinical studies. These limitations and their implications for future trial design are discussed. PMID:22093324

  2. Role of Osteopontin in Liver Diseases

    PubMed Central

    Wen, Yankai; Jeong, Seogsong; Xia, Qiang; Kong, Xiaoni

    2016-01-01

    Osteopontin (OPN), a multifunctional protein, is involved in numerous pathological conditions including inflammation, immunity, angiogenesis, fibrogenesis and carcinogenesis in various tissues. Extensive studies have elucidated the critical role of OPN in cell signaling such as regulation of cell proliferation, migration, inflammation, fibrosis and tumor progression. In the liver, OPN interacts with integrins, CD44, vimentin and MyD88 signaling, thereby induces infiltration, migration, invasion and metastasis of cells. OPN is highlighted as a chemoattractant for macrophages and neutrophils during injury in inflammatory liver diseases. OPN activates hepatic stellate cells (HSCs) to exert an enhancer in fibrogenesis. The role of OPN in hepatocellular carcinoma (HCC) has also generated significant interests, especially with regards to its role as a diagnostic and prognostic factor. Interestingly, OPN acts an opposing role in liver repair under different pathological conditions. This review summarizes the current understanding of OPN in liver diseases. Further understanding of the pathophysiological role of OPN in cellular interactions and molecular mechanisms associated with hepatic inflammation, fibrosis and cancer may contribute to the development of novel strategies for clinical diagnosis, monitoring and therapy of liver diseases. PMID:27570486

  3. [Early detection of chronic liver disease in primary care in the apparently health adult population].

    PubMed

    Caballería, Llorenç; Torán, Pere

    2012-12-01

    Liver diseases are highly prevalent and are a major health problem as they progress to more severe forms. In the west, cirrhosis and primitive liver cancer are among the first 10 causes of death in adults. Moreover, chronic liver inflammation, irrespective of cause, is usually asymptomatic. Consequently diagnosis tends to be established when the disease is in the advanced stages and is thus irreversible and with few treatment possibilities. Therefore, ideally, diagnosis would be established in the initial phases of chronic liver inflammation, which would allow the natural history of the disease to be altered by either halting or delaying progression. To date, physicians have been guided by alterations in liver function tests to identify the etiology of liver disease or-depending on the severity of involvement-the presence of liver disease. Abdominal ultrasound findings can also reveal alterations suggesting the presence of chronic liver disease. However, in the last few years, noninvasive methods have been designed. These include serological markers (direct and indirect) of fibrosis and radiological tests (especially elastography) based on measuring liver elasticity, which allow noninvasive quantification of the degree of fibrous tissue in the liver. The use of noninvasive methods may be highly useful in the early detection of liver diseases.

  4. Diagnosis of Alcoholic Liver Disease: Key Foundations and New Developments.

    PubMed

    Childers, Ryan E; Ahn, Joseph

    2016-08-01

    Alcoholic liver disease is a spectrum of conditions that include alcoholic fatty liver disease, alcoholic hepatitis, and chronic alcoholic liver disease. The diagnosis of alcoholic liver disease remains founded in an accurate patient history and detailed physical examination. Concurrent with the physical examination, objective data from laboratory, imaging, and histologic studies are helpful to confirm a diagnosis of alcoholic liver disease. Novel biomarkers, scoring systems, and imaging modalities are improving the ability to diagnose and manage alcoholic liver disease, but for most practicing clinicians, these have not been adopted widely because of their cost, but also because of limitations and uncertainty in their performance characteristics. PMID:27373609

  5. Management of thrombocytopenia in advanced liver disease

    PubMed Central

    Gangireddy, VGR; Kanneganti, PC; Sridhar, S; Talla, S; Coleman, T

    2014-01-01

    Thrombocytopenia (defined as a platelet count <150×109/L) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×109/L to 75×109/L) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease. PMID:25222481

  6. Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms

    PubMed Central

    Li, Fengyuan; Duan, Kangmin; Wang, Cuiling; McClain, Craig; Feng, Wenke

    2016-01-01

    Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD) encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration) approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed. PMID:26839540

  7. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    PubMed Central

    Gitto, Stefano; Villa, Erica

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis. PMID:27049380

  8. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    PubMed Central

    Bajpai, Meenu; Gupta, Shruti; Jain, Priyanka

    2016-01-01

    Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181) in females and 3.17% (21/661) in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%). The most common alloantibody identified was anti-E (11/44 cases, 25%), followed by anti-C (6/44 cases, 13.63%). Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization. PMID:27605851

  9. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    PubMed Central

    Bajpai, Meenu; Gupta, Shruti; Jain, Priyanka

    2016-01-01

    Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181) in females and 3.17% (21/661) in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%). The most common alloantibody identified was anti-E (11/44 cases, 25%), followed by anti-C (6/44 cases, 13.63%). Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization.

  10. Management of non-alcoholic fatty liver disease in 2015.

    PubMed

    Malhotra, Neel; Beaton, Melanie D

    2015-12-28

    There is no single pharmacologic therapy that has been approved to treat nonalcoholic fatty liver disease in the general population. The backbone of therapy currently includes intensive lifestyle modification with established targets for diet and weight loss. The use of unsweetened, unfiltered coffee along with limiting high fructose corn syrup have emerged as beneficial dietary recommendations. The use of empiric oral hypoglycemic agents and vitamin E, however, has not been widely accepted. Developing bariatric surgical techniques are promising, but additional studies with long-term follow up are needed before it can be widely recommended. Finally, liver transplantation is an increasingly frequent consideration once complications of end-stage disease have developed. The future treatment of those with nonalcoholic fatty liver disease will likely involve a personalized approach. The importance of the gut microbiome in mediating hepatocyte inflammation and intestinal permeability is emerging and may offer avenues for novel treatment. The study of anti-fibrotic agents such as pentoxifylline and FXR agonists hold promise and new pathways, such as hepatocyte cannabinoid receptor antagonists are being studied. With the incidence of obesity and the metabolic syndrome increasing throughout the developed world, the future will continue to focus on finding novel agents and new applications of existing therapies to help prevent and to mediate the progression of nonalcoholic fatty liver disease. PMID:26730275

  11. Nonalcoholic fatty liver disease: new treatments

    PubMed Central

    Hardy, Timothy; Anstee, Quentin M.; Day, Christopher P.

    2015-01-01

    Purpose of review Nonalcoholic fatty liver disease is the most common cause of liver dysfunction in the western world because of its close association with obesity, insulin resistance and dyslipidaemia. Nonalcoholic steatohepatitis (NASH) is a particular health concern due to the increased morbidity and mortality associated with progressive disease. At present, without specific targeted pharmacological therapies, the mainstay of therapy remains weight loss through dietary modification and lifestyle change; thus, the purpose of this review is to summarize the recent evidence for current and emerging therapies in NASH. Recent findings Some existing medications, including pioglitazones and angiotensin receptor antagonists, may be repurposed to help treat this condition. Vitamin E may improve histology in NASH, but safety issues limit its use. Recently, a number of novel agents specifically targeting nonalcoholic fatty liver disease pathogenesis have entered clinical trials, including the farnesoid X receptor agonist obeticholic acid, which has shown significant histological improvements in steatohepatitis and fibrosis. Summary Diet/lifestyle modification remains the mainstay of treatment. For patients with NASH and advanced fibrosis, current liver-directed pharmacotherapy with vitamin E and pioglitazone offer some benefits; obeticholic acid appears promising and is currently being tested. Comorbidities must be diagnosed and treated; cardiovascular disease remains a primary cause of death in these patients. PMID:25774446

  12. Coagulopathy in liver disease: a balancing act.

    PubMed

    Kujovich, Jody L

    2015-01-01

    Liver disease results in complex alterations of all 3 phases of hemostasis. It is now recognized that hemostasis is rebalanced in chronic liver disease. The fall in clotting factor levels is accompanied by a parallel fall in anticoagulant proteins. High von Willebrand factor levels counteract defects in primary hemostasis. Conventional coagulation tests do not fully reflect the derangement in hemostasis and do not accurately predict the risk of bleeding. Global coagulation assays (thrombin generation, thromboelastography) reflect the interaction between procoagulant factors, anticoagulant factors, platelets, and the fibrinolytic system and show promise for assessing bleeding risk and guiding therapy. These assays are not yet commercially approved or validated. Prevention of bleeding should not be aimed at correcting conventional coagulation tests. Thrombopoietin receptor agonists were shown to increase the platelet count in cirrhotic patients undergoing invasive procedures but may increase the risk of thrombosis. Rebalanced hemostasis in liver disease is precarious and may be tipped toward hemorrhage or thrombosis depending on coexisting circumstantial risk factors. Bacterial infection may impair hemostasis in cirrhosis by triggering the release of endogenous heparinoids. There are no evidence-based guidelines for hemostatic therapy of acute hemorrhage in liver disease. There is currently inadequate evidence to support the use of recombinant FVIIa, prothrombin complex concentrates, or tranexamic acid in acute variceal or other hemorrhage.

  13. Preventive Care in Chronic Liver Disease

    PubMed Central

    Riley, Thomas R; Smith, Jill P

    1999-01-01

    OBJECTIVE To identify preventive care measures that are appropriate for and specific to patients with chronic liver disease and to provide recommendations and information that can be shared with patients. MEASUREMENTS A review of the literature was undertaken using medlinefrom 1970 to present. Priority was given to randomized controlled studies, but case reports, case-control studies, and reviews were included. MAIN RESULTS Evidence for the avoidance of alcohol and other toxic substances, immunizations, and dietary modifications for chronic liver disease is summarized. In addition, measures that are effective in the mitigation of the complications of cirrhosis are reviewed. CONCLUSIONS Preventive care can play an important role in patients with chronic liver diseases. Based on the existing data, the preventive strategies of alcohol avoidance, hepatitis vaccination, avoidance of NSAIDs nonsteroidal anti-inflammatory drugs, iron supplementation when appropriate, and a low-fat diet are prudent in patients with chronic liver disease. Once cirrhosis develops, screening for hepatocellular cancer with α-fetoprotein testing and ultrasound, and screening for varices by endoscopy are justified. PMID:10571719

  14. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease.

  15. Wilson's disease; increased aluminum in liver.

    PubMed

    Yasui, M; Yoshimasu, F; Yase, Y; Uebayashi, Y

    1979-01-01

    Interaction of trace metal metabolism was studied in a patient with Wilson's dease. Atomic absorption analysis showed markedly increased urinary excretion of copper and aluminum and an increased aluminum content was found in the biopsied liver by neutron activation analysis. These findings suggest a complicated pathogenetic mechanism involving other metals besides copper in the Wilson's disease.

  16. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  17. Adipose tissue-liver axis in alcoholic liver disease.

    PubMed

    Wang, Zhi-Gang; Dou, Xiao-Bing; Zhou, Zhan-Xiang; Song, Zhen-Yuan

    2016-02-15

    Alcoholic liver disease (ALD) remains an important health problem worldwide. The disease spectrum is featured by early steatosis, steatohepatitis (steatosis with inflammatory cells infiltration and necrosis), with some individuals ultimately progressing to fibrosis/cirrhosis. Although the disease progression is well characterized, no effective therapies are currently available for the treatment in humans. The mechanisms underlying the initiation and progression of ALD are multifactorial and complex. Emerging evidence supports that adipose tissue dysfunction contributes to the pathogenesis of ALD. In the first part of this review, we discuss the mechanisms whereby chronic alcohol exposure contributed to adipose tissue dysfunction, including cell death, inflammation and insulin resistance. It has been long known that aberrant hepatic methionine metabolism is a major metabolic abnormality induced by chronic alcohol exposure and plays an etiological role in the pathogenesis of ALD. The recent studies in our group documented the similar metabolic effect of chronic alcohol drinking on methionine in adipose tissue. In the second part of this review, we also briefly discuss the recent research progress in the field with a focus on how abnormal methionine metabolism in adipose tissue contributes to adipose tissue dysfunction and liver damage. PMID:26909225

  18. Medical therapy for polycystic liver disease.

    PubMed

    Khan, S; Dennison, A; Garcea, G

    2016-01-01

    Introduction Somatostatin analogues and rapamycin inhibitors are two classes of drugs available for the management of polycystic liver disease but their overall impact is not clearly established. This article systematically reviews the literature on the medical management of polycystic liver disease. The outcomes assessed include reduction in liver volume and the impact on quality of life. Methods The English language literature published between 1966 and August 2014 was reviewed from a MEDLINE(®), PubMed, Embase™ and Cochrane Library search. Search terms included 'polycystic', 'liver', 'sirolimus', 'everolimus', 'PCLD', 'somatostatin', 'octreotide', 'lanreotide' and 'rapamycin'. Both randomised trials and controlled studies were included. References of the articles retrieved were also searched to identify any further eligible publications. The studies included were appraised using the Jadad score. Results Seven studies were included in the final review. Five studies, of which three were randomised trials, investigated the role of somatostatin analogues and the results showed a mean reduction in liver volume ranging from 2.9% at six months to 4.95 ±6.77% at one year. Only one randomised study examined the influence of rapamycin inhibitors. This trial compared dual therapy with everolimus and octreotide versus octreotide monotherapy. Liver volume reduced by 3.5% and 3.8% in the control and intervention groups respectively but no statistical difference was found between the two groups (p=0.73). Two randomised trials investigating somatostatin analogues assessed quality of life using SF-36(®). Only one subdomain score improved in one of the trials while two subdomain scores improved in the other with somatostatin analogue therapy. Conclusions Somatostatin analogues significantly reduce liver volumes after six months of therapy but have only a modest improvement on quality of life. Rapamycin inhibitors do not confer any additional advantage.

  19. Mechanisms linking nonalcoholic fatty liver disease with coronary artery disease.

    PubMed

    Nseir, W; Shalata, A; Marmor, A; Assy, N

    2011-12-01

    The most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is coronary artery disease (CAD), not chronic liver disease. Fatty liver increases cardiovascular risk by classical (dyslipidemia, hypertension, diabetes) and by less conventional mechanisms. Common pathways involved in the pathogenesis of fatty liver and CAD includes hepatic insulin resistance and sub clinical inflammation. The hepatic insulin resistance state of fatty liver infiltration is characterized by increased FFA, which causes lipotoxicity and impairs endothelium-dependent vasodilatation, increases oxidative stress, and has a cardio toxic effect. Additional metabolic risk factors include leptin, adiponectin, pro inflammatory cytokines [such as IL-6, C-reactive protein and plasminogen activator inhibitor-1 (PAI-1)], which together lead to increased oxidative stress and endothelial dysfunction, finally promoting coronary artery disease (CAD). When classical risk factors are superimposed on fatty liver accumulation, they may further increase the new metabolic risk factors, exacerbating CAD. The clinical implication is that patients with NAFLD are at higher risk (steatohepatitis, diabetes, obesity, atherogenic dyslipidemia) and should undergo periodic cardiovascular risk assessment including the Framingham score, cardiac effort test, and measurement of intimae-media thickening of the carotids arteries. This may improve risk stratification for CAD. PMID:21655948

  20. Imaging the earliest stages of Alzheimer's disease.

    PubMed

    Wu, William; Small, Scott A

    2006-12-01

    Historical progress in medicine can be charted along the lines of technical innovations that have visualized the invisible. One hundred years ago, Alois Alzheimer exploited newly developed histological stains to visualize his eponymonous disease in dead tissue under the microscope. Now, as we are entering the second century of Alzheimer's disease research, technical innovation has endowed us with a range of in vivo imaging techniques that promise to visualize Alzheimer' disease in living people. The earliest stage of Alzheimer's disease is characterized by cell-sickness, not cell-death, and can occur before the deposition of amyloid plaques or neurofibrillary tangles. In principle, 'functional' imaging techniques might be able to detect this early stage of the disease, a stage that was invisible to Alzheimer himself. Here, we will first define the neurobiological meaning of 'function' and then review the different approaches that measure brain dysfunction in Alzheimer' disease.

  1. Caroli's disease and orthotopic liver transplantation.

    PubMed

    Habib, Shahid; Shakil, Obaid; Couto, Osvaldo F; Demetris, Anthony J; Fung, John J; Marcos, Amadeo; Chopra, Kapil

    2006-03-01

    Caroli's disease is a rare congenital hepatic disease, characterized by segmental dilatation of the biliary tree. Patients who have recurrent bouts of biliary infection, particularly those with complications related to portal hypertension, may require orthotopic liver transplantation (OLT). Few case reports have described the outcome of OLT in patients with Caroli's disease and to date there is no large series reported in the literature. We retrospectively analyzed the outcome of OLT in patients with Caroli's disease who underwent OLT between 1982 and 2002 at Starzl Transplantation Institute, University of Pittsburgh. Patients were identified and data was collected by computerized search of the electronic database system. All patients had confirmation of diagnosis by histopathology of explanted liver. A total of 33 patients with Caroli's disease were listed for liver transplantation, 3 of whom were excluded, as they were not transplanted. A total of 90% had signs of hepatic decompensation at the time of OLT. Median posttransplantation follow-up was 7.7 yr. Short-term graft and patient survival at 1 month was 83% and 86%, whereas overall long-term graft survival rates at 1, 5, and 10 yr were 73%, 62%, and 53%, respectively, and patient survival rates were 76%, 65%, and 56%, respectively. Long-term outcome in patients who survived the first year after transplantation was significantly better. Their survival rate at 5 and 10 yr was 90% and 78%. On univariable analysis, recipient age, donor male gender, coexistent congenital hepatic fibrosis, and re-OLT were associated with poor patient survival. Eight patients were retransplanted, 3 of whom had primary nonfunction. A total of 13 patients died; the most common cause of death being sepsis and cardiovascular complications. Patients who died of sepsis had cholangitis pre-OLT. In conclusion, OLT is a form of curative and life-saving therapy in patients with Caroli's disease, especially in those with decompensated liver

  2. Bariatric surgery and nonalcoholic fatty liver disease.

    PubMed

    Bower, Guy; Athanasiou, Thanos; Isla, Alberto M; Harling, Leanne; Li, Jia V; Holmes, Elaine; Efthimiou, Evangelos; Darzi, Ara; Ashrafian, Hutan

    2015-07-01

    The rising prevalence of nonalcoholic fatty liver disease (NAFLD) is associated with the increasing global pandemic of obesity. These conditions cluster with type II diabetes mellitus and the metabolic syndrome to result in obesity-associated liver disease. The benefits of bariatric procedures on diabetes and the metabolic syndrome have been recognized for some time, and there is now mounting evidence to suggest that bariatric procedures improve liver histology and contribute to the beneficial resolution of NAFLD in obese patients. These beneficial effects derive from a number of weight-dependent and weight-independent mechanisms including surgical BRAVE actions (bile flow changes, restriction of stomach size, anatomical gastrointestinal rearrangement, vagal manipulation, enteric hormonal modulation) and subsequent effects such as reduced lipid intake, adipocytokine secretion, modulation of gut flora, improvements in insulin resistance and reduced inflammation. Here, we review the clinical investigations on bariatric procedures for NAFLD, in addition to the mounting mechanistic data supporting these findings. Elucidating the mechanisms by which bariatric procedures may resolve NAFLD can help enhance surgical approaches for metabolic hepatic dysfunction and also contribute toward developing the next generation of therapies aimed at reducing the burden of obesity-associated liver disease.

  3. [Parenteral nutrition-associated liver disease].

    PubMed

    Moreno Villares, J M

    2008-05-01

    Parenteral nutrition associated liver disease (PNALD) is an important problem in patients who require longterm parenteral nutrition as well as in preterm infants. Prevalence varies according to different series. Clinical presentation is different in adults and infants. Although since its first descriptions several hypothesis have been elucidated, the aetiology is not quite clear. It is possible that different factors could be involved. PNALD risk factors can be classified in three groups: 1) those derived from the lack of enteral nutrition stimulus; 2) parenteral nutrition components acting as toxic or the lack of specific nutrients and 3) those due to the underlying disease. If PNALD appears in short-term PN and it presents only as a mild elevation of liver enzymes, there is no need to treat. On the contrary, when direct bilirubin is > 2 mg/dL and lasts longer, there is a need to consider different causes and to minimize risk factors. We review the different approaches to manage PNALD, including optimizing enteral nutrition, modify parenteral solutions, use of specific nutrients -taurine, choline, etc.- or the use of drugs (mainly ursodeoxicolic acid). If liver disease progresses to cirrhosis a liver transplant must be considered.

  4. Endocrine causes of nonalcoholic fatty liver disease

    PubMed Central

    Marino, Laura; Jornayvaz, François R

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed. PMID:26494962

  5. Endocrine causes of nonalcoholic fatty liver disease.

    PubMed

    Marino, Laura; Jornayvaz, François R

    2015-10-21

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

  6. Interleukin-1 Family Cytokines in Liver Diseases

    PubMed Central

    Tsutsui, Hiroko; Cai, Xianbin; Hayashi, Shuhei

    2015-01-01

    The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra), and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation. Some require inflammasome-mediated processing for activation and release, whereas others serve as alarmins and are released following cell membrane rupture, for example, by pyroptosis or necroptosis. Thus, each ligand has the proper molecular process to exert its own biological functions. In this review, we will give a brief introduction to the IL-1 family cytokines and discuss their pivotal roles in the development of various liver diseases in association with immune responses. For example, an excess of IL-33 causes liver fibrosis in mice via activation and expansion of group 2 innate lymphoid cells to produce type 2 cytokines, resulting in cell conversion into pro-fibrotic M2 macrophages. Finally, we will discuss the importance of IL-1 family cytokine-mediated molecular and cellular networks in the development of acute and chronic liver diseases. PMID:26549942

  7. Alcoholic Liver Disease: Role of Cytokines.

    PubMed

    Neuman, Manuela G; Maor, Yaakov; Nanau, Radu M; Melzer, Ehud; Mell, Haim; Opris, Mihai; Cohen, Lawrence; Malnick, Stephen

    2015-01-01

    The present review spans a broad spectrum of topics dealing with alcoholic liver disease (ALD), including clinical and translational research. It focuses on the role of the immune system and the signaling pathways of cytokines in the pathogenesis of ALD. An additional factor that contributes to the pathogenesis of ALD is lipopolysaccharide (LPS), which plays a central role in the induction of steatosis, inflammation, and fibrosis in the liver. LPS derived from the intestinal microbiota enters the portal circulation, and is recognized by macrophages (Kupffer cells) and hepatocytes. In individuals with ALD, excessive levels of LPS in the liver affect immune, parenchymal, and non-immune cells, which in turn release various inflammatory cytokines and recruit neutrophils and other inflammatory cells. In this review, we elucidate the mechanisms by which alcohol contributes to the activation of Kupffer cells and the inflammatory cascade. The role of the stellate cells in fibrogenesis is also discussed. PMID:26343741

  8. New Tools in Experimental Cellular Therapy for the Treatment of Liver Diseases

    PubMed Central

    Ferrer, Jennifer R.; Chokechanachaisakul, Attasit; Wertheim, Jason A.

    2015-01-01

    The current standard of care for end stage liver disease is orthotopic liver transplantation (OLT). Through improvement in surgical techniques, immunosuppression, and general medical care, liver transplantation has become an effective treatment over the course of the last half-century. Unfortunately, due to the limited availability of donor organs, there is a finite limit to the number of patients who will benefit from this therapy. This review will discuss current research in experimental cellular therapies for acute, chronic, and metabolic liver failure that may be appropriate when liver transplantation is not an immediate option. PMID:26317066

  9. Complete Plasmodium falciparum liver-stage development in liver-chimeric mice.

    PubMed

    Vaughan, Ashley M; Mikolajczak, Sebastian A; Wilson, Elizabeth M; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H I

    2012-10-01

    Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase-deficient mouse (Fah-/-, Rag2-/-, Il2rg-/-, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS-to-blood-stage transition of a human malaria parasite.

  10. Obesity, fatty liver disease and intestinal microbiota

    PubMed Central

    Arslan, Nur

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations. PMID:25469013

  11. Obesity, fatty liver disease and intestinal microbiota.

    PubMed

    Arslan, Nur

    2014-11-28

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations.

  12. Lower Muscle Endurance in Patients with Alcoholic Liver Disease

    ERIC Educational Resources Information Center

    Andersen, Henning; Aagaard, Niels K.; Jakobsen, Johannes; Dorup, Inge; Vilstrup, Hendrik

    2012-01-01

    Patients with alcoholic liver disease often complain of restricted physical capacity, which could be due to decreased muscle endurance. The aim of this study was to assess the muscular endurance in patients with alcoholic liver disease. In a cross sectional study, 24 patients with alcoholic liver disease and 22 controls were evaluated using…

  13. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease

    PubMed Central

    Jamali, Raika; Razavizade, Mohsen; Arj, Abbas; Aarabi, Mohammad Hossein

    2016-01-01

    AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. RESULTS: Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0

  14. Nutritional lipid liver disease of grass carp Ctenopharyngodon idullus (C. et V.)

    NASA Astrophysics Data System (ADS)

    Lin, Ding; Mao, Yongqing; Cai, Fasheng

    1990-12-01

    The inadequate nutrient content of pellet feeds widely used in recent years in China for grass carp farming led to lipid liver degeneration in the fish. The present studies show that the pathological features of lipid liver disease are anaemia and hepatic ceroidosis. Other clinical features are; the ratio of liver to body weight exceeds 3% and lipid content exceeds 5%. Extreme infiltration of hepaiocytes by lipid results in the following deteriorative effects: swelling of the liver cells, increase of lipid droplets in the cytoplasm and dislocation of the nucleus, loss of cytoplasm staining affinity, and increased activities of GOT and GPT in serum. Lipid liver degeneration of grass carp can be divided into three stages: 1) deposition of liver lipid; 2) lipid infiltration of hepatic parenchyma; 3) atrophy of liver nucleus. The causes of lipid liver degeneration are complicated, but the main cause is assumed to be an imbalance of nutrients in daily feed and the lock of some lipotropic substances.

  15. 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

  16. Level of urinary liver-type fatty acid-binding protein is associated with cardiac markers and electrocardiographic abnormalities in type-2 diabetes with chronic kidney disease stage G1 and G2.

    PubMed

    Maeda, Yoshiteru; Suzuki, Atsushi; Ishii, Junnichi; Sekiguchi-Ueda, Sahoko; Shibata, Megumi; Yoshino, Yasumasa; Asano, Shogo; Hayakawa, Nobuki; Nakamura, Kazuhiro; Akiyama, Yasukazu; Kitagawa, Fumihiko; Sakuishi, Toshiaki; Fujita, Takashi; Hashimoto, Shuji; Ozaki, Yukio; Itoh, Mitsuyasu

    2015-05-01

    Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 μg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p < 0.0001). Median (25th-75th percentile) eGFR was 82 (72-95) mL/min/1.73 m2. We divided patients into four subgroups (group 1, L-FABP ≤8.4 μg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 μg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 μg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 μg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2.

  17. IMPAIRED HOMOCYSTEINE TRANSSULFURATION IS AN INDICATOR OF ALCOHOLIC LIVER DISEASE

    PubMed Central

    Medici, Valentina; M.Peerson, Janet; Stabler, Sally P.; French, Samuel W.; Gregory, Jesse F.; Virata, Maria Catrina; Albanese, Antony; Bowlus, Christopher L.; Devaraj, Sridevi; Panacek, Edward A.; Rahim, Nazir; Richards, John R.; Rossaro, Lorenzo; Halsted, Charles H.

    2010-01-01

    Background & Aims Although abnormal hepatic methionine metabolism plays a central role in the pathogenesis of experimental alcoholic liver disease (ALD), its relationship to the risk and severity of clinical ALD is not known. The aim of this clinical study was to determine the relationship between serum levels of methionine metabolites in chronic alcoholics and the risk and pathological severity of ALD. Methods Serum levels of liver function biochemical markers, vitamin B6, vitamin B12, folate, homocysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, cystathionine, cysteine, α-aminobutyrate, glycine, serine, and dimethylglycine were measured in 40 ALD patients, of whom 24 had liver biopsies, 26 were active drinkers without liver disease, and 28 were healthy subjects. Results Serum homocysteine was elevated in all alcoholics, whereas ALD patients had low vitamin B6 with elevated cystathionine and decreased α-aminobutyrate/cystathionine ratios, consistent with decreased activity of vitamin B6 dependent cystathionase. The α-aminobutyrate/cystathionine ratio predicted the presence of ALD, while cystathionine correlated with the stage of fibrosis in all ALD patients. Conclusions The predictive role of the α- aminobutyrate/cystathionine ratio for the presence of ALD and the correlation between cystathionine serum levels with the severity of fibrosis point to the importance of the homocysteine transsulfuration pathway in ALD and may have important diagnostic and therapeutic implications. PMID:20561703

  18. Secondary causes of nonalcoholic fatty liver disease

    PubMed Central

    Kneeman, Jacob M.; Misdraji, Joseph

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the developing world, found in 17-30% of the population in Western countries and 2-4% worldwide. Defined as the accumulation of fatty acid content greater than 5% of liver weight, NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis. The pathophysiology of NAFLD involves increased de novo synthesis of fatty acids in hepatocytes, the retention of lipids due to impaired hepatocyte apolipoprotein secretion or beta-oxidation. The well-known primary causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance. However, other less common conditions can cause a similar clinical and histologic picture, and should be considered in patients who present with NAFLD but do not have traditional risk factors. In this review, we discuss uncommon but important causes of NAFLD, including inborn errors of metabolism, iatrogenic causes, viral hepatitis, and nutritional disorders to provide practicing clinicians with an understanding of the less well recognized causes of NAFLD. PMID:22570680

  19. Nuclear receptors and nonalcoholic fatty liver disease.

    PubMed

    Cave, Matthew C; Clair, Heather B; Hardesty, Josiah E; Falkner, K Cameron; Feng, Wenke; Clark, Barbara J; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A; McClain, Craig J; Prough, Russell A

    2016-09-01

    Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

  20. Nuclear receptors and nonalcoholic fatty liver disease.

    PubMed

    Cave, Matthew C; Clair, Heather B; Hardesty, Josiah E; Falkner, K Cameron; Feng, Wenke; Clark, Barbara J; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A; McClain, Craig J; Prough, Russell A

    2016-09-01

    Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

  1. Non-invasive diagnosis of alcoholic liver disease

    PubMed Central

    Mueller, Sebastian; Seitz, Helmut Karl; Rausch, Vanessa

    2014-01-01

    Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH. PMID:25356026

  2. Lipophilic bisphosphonates are potent inhibitors of Plasmodium liver-stage growth.

    PubMed

    Singh, Agam Prasad; Zhang, Yonghui; No, Joo-Hwan; Docampo, Roberto; Nussenzweig, Victor; Oldfield, Eric

    2010-07-01

    Nitrogen-containing bisphosphonates, drugs used to treat bone resorption diseases, also have activity against a broad range of protists, including blood-stage Plasmodium spp. Here, we show that new-generation "lipophilic" bisphosphonates designed as anticancer agents that block protein prenylation also have potent activity against Plasmodium liver stages, with a high (>100) therapeutic index. Treatment of mice with the bisphosphonate BPH-715 and challenge with Plasmodium berghei sporozoites revealed complete protection (no blood-stage parasites after 28 days). There was also activity against blood-stage forms in vitro and a 4-day delay in the prepatent period in vivo. The lipophilic bisphosphonates have activity against a Plasmodium geranylgeranyl diphosphate synthase (GGPPS), as well as low nM activity against human farnesyl and geranylgeranyl diphosphate synthases. The most active inhibitor in vitro and in vivo had enzyme inhibitory activity similar to that of the other, less active compounds but was more lipophilic. Lipophilic bisphosphonates are thus promising leads for novel antimalarials that target liver-stage infection.

  3. Mesenchymal stromal cell therapy in liver disease: opportunities and lessons to be learnt?

    PubMed Central

    Owen, Andrew

    2015-01-01

    End-stage liver disease is responsible for 30,000 deaths per year in the United States alone, and it is continuing to increase every year. With liver transplantation the only curative treatment currently available, new therapies are in great demand. Mesenchymal stem cells (MSC) offer an opportunity to both treat liver inflammatory damage, as well as reverse some of the changes that occur following chronic liver injury. With the ability to regulate both the innate and adaptive immune system, as well as both inhibit and promote apoptosis of effector inflammatory cells, there are numerous therapeutic opportunities for MSC in acute and chronic liver disease. This article critically appraises the potential therapeutic roles of MSC in liver disease, as well as the barriers to their adoption into clinical practice. PMID:26316587

  4. Mesenchymal stromal cell therapy in liver disease: opportunities and lessons to be learnt?

    PubMed

    Owen, Andrew; Newsome, Philip N

    2015-11-15

    End-stage liver disease is responsible for 30,000 deaths per year in the United States alone, and it is continuing to increase every year. With liver transplantation the only curative treatment currently available, new therapies are in great demand. Mesenchymal stem cells (MSC) offer an opportunity to both treat liver inflammatory damage, as well as reverse some of the changes that occur following chronic liver injury. With the ability to regulate both the innate and adaptive immune system, as well as both inhibit and promote apoptosis of effector inflammatory cells, there are numerous therapeutic opportunities for MSC in acute and chronic liver disease. This article critically appraises the potential therapeutic roles of MSC in liver disease, as well as the barriers to their adoption into clinical practice. PMID:26316587

  5. Stem cell differentiation and human liver disease

    PubMed Central

    Zhou, Wen-Li; Medine, Claire N; Zhu, Liang; Hay, David C

    2012-01-01

    Human stem cells are scalable cell populations capable of cellular differentiation. This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells. Such an approach has the potential to improve our understanding of human biology and treating disease. In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases. In recent years, efficient hepatic differentiation from human stem cells has been achieved by several research groups including our own. In this review we provide an overview of the field and discuss the future potential and limitations of stem cell technology. PMID:22563188

  6. A Sporozoite- and Liver Stage-expressed Tryptophan-rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine Candidate*

    PubMed Central

    Jaijyan, Dabbu Kumar; Singh, Himanshu; Singh, Agam Prasad

    2015-01-01

    The liver stages of the malaria parasite are clinically silent and constitute ideal targets for causal prophylactic drugs and vaccines. Cellular and molecular events responsible for liver stage development are poorly characterized. Here, we show that sporozoite, liver stage tryptophan-rich protein (SLTRiP) forms large multimers. Mice immunized with a purified recombinant SLTRiP protein gave high antibody titers in both inbred and outbred mice. Immunized mice showed highly significant levels of protection upon challenge with sporozoites and exhibited 10,000-fold fewer parasite 18S-rRNA copy numbers in their livers. The protection offered by immunization with SLTRiP came mainly from T-cells, and antibodies had little role to play despite their high titers. Immunofluorescence assays showed that SLTRiP is expressed in the sporozoite and early to late liver stages of malaria parasites. SLTRiP protein is exported to the cytosol of infected host cells during the early hours of parasite infection. Parasites deficient in SLTRiP were moderately defective in liver stage parasite development. A transcriptome profile of SLTRiP-deficient parasite-infected hepatocytes highlighted that SLTRiP interferes with multiple pathways in the host cell. We have demonstrated a role for SLTRiP in sporozoites and the liver stage of malaria parasites. PMID:25960542

  7. Treatment selection for stage IIIA Hodgkin's disease patients

    SciTech Connect

    Prosnitz, L.R.; Cooper, D.; Cox, E.B.; Kapp, D.S.; Farber, L.R.

    1985-08-01

    Two treatment policies for the therapy of patients with Stage IIIA Hodgkin's disease are compared. From 1969-1976, 49 newly diagnosed and pathologically staged IIIA patients received total nodal irradiation (TNI) alone (no liver irradiation). Although actuarial survival was 80% at 5 years and 68% at 10 years, actuarial freedom from relapse was only 38% at 5 years. Accordingly, a new treatment policy was instituted in 1976. Patients with either CS IIIA disease, multiple splenic nodules, IIIA with a large mediastinal mass or III/sub 2/, received combined modality therapy (combination chemotherapy and irradiation). All others received TNI. Thirty-six patients have been treated under the new program. The actuarial survival is 90% at 5 years and the relapse-free survival is 87%, suggesting the superiority of this approach. Complications from the treatments are discussed.

  8. Hepatocyte transplantation for inherited metabolic diseases of the liver.

    PubMed

    Jorns, C; Ellis, E C; Nowak, G; Fischler, B; Nemeth, A; Strom, S C; Ericzon, B G

    2012-09-01

    Inherited metabolic diseases of the liver are characterized by deficiency of a hepatic enzyme or protein often resulting in life-threatening disease. The remaining liver function is usually normal. For most patients, treatment consists of supportive therapy, and the only curative option is liver transplantation. Hepatocyte transplantation is a promising therapy for patients with inherited metabolic liver diseases, which offers a less invasive and fully reversible approach. Procedure-related complications are rare. Here, we review the experience of hepatocyte transplantation for metabolic liver diseases and discuss the major obstacles that need to be overcome to establish hepatocyte transplantation as a reliable treatment option in the clinic.

  9. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    PubMed

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD.

  10. Herbal medicines and nonalcoholic fatty liver disease.

    PubMed

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-08-14

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future. PMID:27570425

  11. Herbal medicines and nonalcoholic fatty liver disease

    PubMed Central

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future. PMID:27570425

  12. Herbal medicines and nonalcoholic fatty liver disease.

    PubMed

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-08-14

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future.

  13. Regression of nodular liver lesions in Wilson's disease.

    PubMed

    Kozic, D; Svetel, M; Petrovic, I; Sener, R N; Kostic, V S

    2006-09-01

    Long-term follow-up abdominal imaging studies have not been reported previously in patients with the hepatic form of Wilson's disease (WD). This paper reports the case of a 35-year-old woman with symptoms dating back several months and with multiple, nodular liver lesions. The lesions were hyperdense on non-enhanced computed tomography and hypointense on T2-weighted magnetic resonance (MR) images. A diagnosis of WD was established several weeks after her admission to hospital, and chelating treatment was commenced promptly. No abnormalities were found on follow-up MR examinations of the abdomen and brain 4.5 years later. These imaging features suggest that so long as WD is diagnosed in the initial stages, liver nodules can regress with time and complete healing can be achieved with continuous decoppering treatment. PMID:16950693

  14. Computed tomography of the liver in von Gierke's disease.

    PubMed

    Biondetti, P R; Fiore, D; Muzzio, P C

    1980-10-01

    The computed tomography findings in the liver of a patient with von Gierke's disease are presented. Precontrast scans demonstrated diffuse decreased density throughout the liver. In the postcontrast scans, a focal right sided hyperdense area was visualized. PMID:6931833

  15. Aetiology and pathogenesis of alcoholic liver disease.

    PubMed

    Lieber, C S

    1993-09-01

    Until the 1960s, liver disease of the alcoholic patient was attributed exclusively to dietary deficiencies. Since then, however, our understanding of the impact of alcoholism on nutritional status has undergone a progressive evolution. Alcohol, because of its high energy content, was at first perceived to act exclusively as 'empty calories' displacing other nutrients in the diet, and causing primary malnutrition through decreased intake of essential nutrients. With improvement in the overall nutrition of the population, the role of primary malnutrition waned and secondary malnutrition was emphasized as a result of a better understanding of maldigestion and malabsorption caused by chronic alcohol consumption and various diseases associated with chronic alcoholism. At the same time, the concept of the direct toxicity of alcohol came to the forefront as an explanation for the widespread cellular injury. Some of the hepatotoxicity was found to result from the metabolic disturbances associated with the oxidation of ethanol via the liver alcohol dehydrogenase (ADH) pathway and the redox changes produced by the generated NADH, which in turn affects the metabolism of lipids, carbohydrates, proteins and purines. Exaggeration of the redox change by the relative hypoxia which prevails physiologically in the perivenular zone contributes to the exacerbation of the ethanol-induced lesions in zone 3. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last twenty years have culminated in the molecular elucidation of the ethanol-inducible cytochrome P450IIE1 (CYP2E1) which contributes not only to ethanol metabolism and tolerance, but also to the selective hepatic perivenular toxicity of various xenobiotics. Their activation by CYP2E1 now provides an understanding for the increased susceptibility of the heavy drinker to the toxicity of industrial solvents, anaesthetic agents, commonly prescribed drugs, 'over the counter' analgesics, chemical

  16. MRI of diffuse liver disease: characteristics of acute and chronic diseases.

    PubMed

    Chundru, Surya; Kalb, Bobby; Arif-Tiwari, Hina; Sharma, Puneet; Costello, James; Martin, Diego R

    2014-01-01

    Diffuse liver disease, including chronic liver disease, affects tens of millions of people worldwide, and there is a growing need for diagnostic evaluation as treatments become more readily available, particularly for viral liver diseases. Magnetic resonance imaging (MRI) provides unique capabilities for noninvasive characterization of the liver tissue that rival or surpass the diagnostic utility of liver biopsies. There has been incremental improvement in the use of standardized MRI sequences, acquired before and after administration of a contrast agent, for the evaluation of diffuse liver disease and the study of the liver parenchyma and blood supply. More recent developments have led to methods for quantifying important liver metabolites, including lipids and iron, and liver fibrosis, the hallmark of chronic liver disease. Here, we review the MRI techniques and diagnostic features associated with acute and chronic liver disease. PMID:24808418

  17. Therapeutic RNA Manipulation in Liver Disease

    PubMed Central

    Kerr, Thomas A.; Davidson, Nicholas O.

    2010-01-01

    Summary Posttranscriptional regulation of gene expression is increasingly recognized as a model for inherited and acquired disease. Recent work has expanded understanding of the range of mechanisms that regulate several of these distinct steps including mRNA splicing, trafficking, and/or stability. Each of these pathways is implicated in disease pathogenesis and each represent important avenues for therapeutic intervention. This review will summarize important mechanisms controlling mRNA processing and the regulation of mRNA degradation, including the role of miRNAs and RNA binding proteins. These pathways provide important opportunities for therapeutic targeting directed at splicing and degradation in order to attenuate genetic defects in RNA metabolism. We will highlight developments in vector development and validation for therapeutic manipulation of mRNA expression with a focus on potential applications in metabolic and immune-mediated liver disease. PMID:19918970

  18. Spleen Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a New Method for Staging Liver Fibrosis in a Piglet Model

    PubMed Central

    2013-01-01

    Objective To explore spleen hemodynamic alteration in liver fibrosis with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and to determine how to stage liver fibrosis with spleen DCE-MRI parameters. Materials and Methods Sixteen piglets were prospectively used to model liver fibrosis staged by liver biopsy, and underwent spleen DCE-MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease. DCE-MRI parameters including time to peak (TTP), positive enhancement integral (PEI), maximum slope of increase (MSI) and maximum slope of decrease (MSD) of spleen were measured, and statistically analyzed to stage this disease. Results Spearman's rank correlation tests showed that TTP tended to increase with increasing stages of liver fibrosis (r = 0.647, P<0.001), and that PEI tended to decrease from stage 0 to 4 (r = −0.709, P<0.001). MSD increased slightly from stage 0 to 2 (P>0.05), and decreased from stage 2 to 4 (P<0.05). MSI increased from stage 0 to 1, and decreased from stage 1 to 4 (all P>0.05). Mann-Whitney tests demonstrated that TTP and PEI could classify fibrosis between stage 0 and 1–4, between 0–1 and 2–4, between 0–2 and 3–4, or between 0–3 and 4 (all P<0.01). MSD could discriminate between 0–2 and 3–4 (P = 0.006), or between 0–3 and 4 (P = 0.012). MSI could not differentiate between any two stages. Receiver operating characteristic analysis illustrated that area under receiver operating characteristic curve (AUC) of TTP was larger than of PEI for classifying stage ≥1 and ≥2 (AUC = 0.851 and 0.783, respectively). PEI could best classify stage ≥3 and 4 (AUC = 0.903 and 0.96, respectively). Conclusion Spleen DCE-MRI has potential to monitor spleen hemodynamic alteration and classify liver fibrosis stages. PMID:24376732

  19. Probiotics in the treatment of the liver diseases.

    PubMed

    Kirpich, Irina A; McClain, Craig J

    2012-02-01

    The concept that interactions between the gut, the liver, and the immune system play an important role in liver diseases is an old concept that has recently seen a resurgence in interest. Altered intestinal bacterial flora and gut-associated endotoxemia are increasingly recognized as critical components in both nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Probiotics have been proposed in the treatment and prevention of many conditions, including the liver diseases. Probiotics are live microorganisms that, when consumed in adequate amounts, confer a health benefit to the host. There are many mechanisms by which probiotics enhance intestinal health and influence the gut-liver axis, including modulation of the intestinal microflora, modification of intestinal barrier function, and immunomodulation. The present review summarizes the recent studies highlighting the role of the intestinal microflora in the development of NAFLD and ALD and the potential efficacy of probiotics as a therapeutic strategy for liver diseases.

  20. Ohio solid organ transplantation consortium criteria for liver transplantation in patients with alcoholic liver disease

    PubMed Central

    Hajifathalian, Kaveh; Humberson, Annette; Hanouneh, Mohamad A; Barnes, David S; Arora, Zubin; Zein, Nizar N; Eghtesad, Bijan; Kelly, Dympna; Hanouneh, Ibrahim A

    2016-01-01

    AIM To evaluate risk of recidivism on a case-by-case basis. METHODS From our center’s liver transplant program, we selected patients with alcoholic liver disease who were listed for transplant based on Ohio Solid Organ Transplantation Consortium (OSOTC) exception criteria. They were considered to have either a low or medium risk of recidivism, and had at least one or three or more months of abstinence, respectively. They were matched based on gender, age, and Model for End-Stage Liver Disease (MELD) score to controls with alcohol-induced cirrhosis from Organ Procurement and Transplant Network data. RESULTS Thirty six patients with alcoholic liver disease were approved for listing based on OSOTC exception criteria and were matched to 72 controls. Nineteen patients (53%) with a median [Inter-quartile range (IQR)] MELD score of 24 (13) received transplant and were followed for a median of 3.4 years. They were matched to 38 controls with a median (IQR) MELD score of 25 (9). At one and five years, cumulative survival rates (± standard error) were 90% ± 7% and 92% ± 5% and 73% ± 12% and 77% ± 8% in patients and controls, respectively (Log-rank test, P = 0.837). Four (21%) patients resumed drinking by last follow-up visit. CONCLUSION Compared to traditional criteria for assessment of risk of recidivism, a careful selection process with more flexibility to evaluate eligibility on a case-by-case basis can lead to similar survival rates after transplantation. PMID:27721920

  1. Endoplasmic reticulum stress in liver disease.

    PubMed

    Malhi, Harmeet; Kaufman, Randal J

    2011-04-01

    The unfolded protein response (UPR) is activated upon the accumulation of misfolded proteins in the endoplasmic reticulum (ER) that are sensed by the binding immunoglobulin protein (BiP)/glucose-regulated protein 78 (GRP78). The accumulation of unfolded proteins sequesters BiP so it dissociates from three ER-transmembrane transducers leading to their activation. These transducers are inositol requiring (IRE) 1α, PKR-like ER kinase (PERK), and activating transcription factor (ATF) 6α. PERK phosphorylates eukaryotic initiation factor 2 alpha (eIF2α) resulting in global mRNA translation attenuation, and concurrently selectively increases the translation of several mRNAs, including the transcription factor ATF4, and its downstream target CHOP. IRE1α has kinase and endoribonuclease (RNase) activities. IRE1α autophosphorylation activates the RNase activity to splice XBP1 mRNA, to produce the active transcription factor sXBP1. IRE1α activation also recruits and activates the stress kinase JNK. ATF6α transits to the Golgi compartment where it is cleaved by intramembrane proteolysis to generate a soluble active transcription factor. These UPR pathways act in concert to increase ER content, expand the ER protein folding capacity, degrade misfolded proteins, and reduce the load of new proteins entering the ER. All of these are geared toward adaptation to resolve the protein folding defect. Faced with persistent ER stress, adaptation starts to fail and apoptosis occurs, possibly mediated through calcium perturbations, reactive oxygen species, and the proapoptotic transcription factor CHOP. The UPR is activated in several liver diseases; including obesity associated fatty liver disease, viral hepatitis, and alcohol-induced liver injury, all of which are associated with steatosis, raising the possibility that ER stress-dependent alteration in lipid homeostasis is the mechanism that underlies the steatosis. Hepatocyte apoptosis is a pathogenic event in several liver

  2. Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease? - A mechanistic hypothesis.

    PubMed

    de Medeiros, Ivanildo Coutinho; de Lima, Josivan Gomes

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are so similar that only a detailed history of alcohol intake can distinguish one from the other. Because subjects with NAFLD produce significantly more endogenous ethanol (EE) than controls, some researchers suspected that these similarities are not merely coincidental. For this reason, it was attempted to show that NAFLD is actually an endogenous alcoholic fatty liver disease (EAFLD). However, negligible blood-alcohol concentration (BAC) and the inability of gut microbiota to produce hepatotoxic concentrations of EE rejected this hypothesis. To clarify these conflicting results, we provide a mechanistic framework explaining how NAFLD may be an EAFLD. First of all, the key finding is that ethanol is a prodrug, enabling the idea that AFLD may develop with negligible/absent BAC. Second, extrahepatic acetaldehyde (ACD) alone recapitulates AFLD and is about 330-fold more hepatotoxic than that generated inside the liver. Third, gut microbiota can even produce much larger amounts of EE than those currently considered cirrhotogenic for man. Fourth, an extensive gut-liver axis first-pass metabolism of ethanol prevents the development of significant BAC in NAFLD. Fifth, all genes involved in EE metabolism are upregulated in the livers of patients with nonalcoholic steatohepatitis (NASH). Last, overexpression of the gene encoding alcohol dehydrogenase (ADH) 4 implicates liver exposure to high concentrations of EE. In conclusion, this work provides mechanistic explanation supporting the assumption that NAFLD may indeed be an EAFLD. If validated by further testing, the hypothesis may help develop novel therapeutic and preventive strategies against this ubiquitous condition.

  3. Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease? - A mechanistic hypothesis.

    PubMed

    de Medeiros, Ivanildo Coutinho; de Lima, Josivan Gomes

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are so similar that only a detailed history of alcohol intake can distinguish one from the other. Because subjects with NAFLD produce significantly more endogenous ethanol (EE) than controls, some researchers suspected that these similarities are not merely coincidental. For this reason, it was attempted to show that NAFLD is actually an endogenous alcoholic fatty liver disease (EAFLD). However, negligible blood-alcohol concentration (BAC) and the inability of gut microbiota to produce hepatotoxic concentrations of EE rejected this hypothesis. To clarify these conflicting results, we provide a mechanistic framework explaining how NAFLD may be an EAFLD. First of all, the key finding is that ethanol is a prodrug, enabling the idea that AFLD may develop with negligible/absent BAC. Second, extrahepatic acetaldehyde (ACD) alone recapitulates AFLD and is about 330-fold more hepatotoxic than that generated inside the liver. Third, gut microbiota can even produce much larger amounts of EE than those currently considered cirrhotogenic for man. Fourth, an extensive gut-liver axis first-pass metabolism of ethanol prevents the development of significant BAC in NAFLD. Fifth, all genes involved in EE metabolism are upregulated in the livers of patients with nonalcoholic steatohepatitis (NASH). Last, overexpression of the gene encoding alcohol dehydrogenase (ADH) 4 implicates liver exposure to high concentrations of EE. In conclusion, this work provides mechanistic explanation supporting the assumption that NAFLD may indeed be an EAFLD. If validated by further testing, the hypothesis may help develop novel therapeutic and preventive strategies against this ubiquitous condition. PMID:25956735

  4. Mechanisms of disease progression in nonalcoholic fatty liver disease.

    PubMed

    Jou, Janice; Choi, Steve S; Diehl, Anna Mae

    2008-11-01

    Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of hepatic pathology, ranging from simple steatosis (also called nonalcoholic fatty liver or NAFL) in its most benign form, to cirrhosis in its most advanced form. Nonalcoholic steatohepatitis (NASH) is an intermediate level of hepatic pathology. Hepatocyte accumulation of triglyceride is a hallmark of NAFL and NASH, but this sometimes subsides once cirrhosis has developed. Triglyceride storage per se is not hepatotoxic. Rather, it is a marker of increased exposure of hepatocytes to potentially toxic fatty acids. NAFL progresses to NASH when adaptive mechanisms that protect hepatocytes from fatty acid-mediated lipotoxicity become overwhelmed and rates of hepatocyte death begin to outstrip mechanisms that normally regenerate dead hepatocytes. This triggers repair responses that involve activation of hepatic stellate cells to myofibroblasts. The myofibroblasts generate excessive matrix and produce factors that stimulate expansion of liver progenitor populations. The progenitor cells produce chemokines to attract various kinds of inflammatory cells to the liver. They also differentiate to replace the dead hepatocytes. The intensity of these repair responses generally parallel the degree of hepatocyte death, resulting in variable distortion of the hepatic architecture with fibrosis, infiltrating immune cells, and regenerating epithelial nodules. As in other types of chronic liver injury, cirrhosis ensues in patients with NAFLD when repair is extreme and sustained, but ultimately unsuccessful, at reconstituting healthy hepatic epithelia. PMID:18956293

  5. Prevention and treatment of drug-induced liver disease.

    PubMed

    Speeg, K V; Bay, M K

    1995-12-01

    Many drugs may cause liver damage; some damage is predictable, but most is not. The most important preventive measure is judicious drug use by the prescribing physician. Early recognition of hepatotoxicity and cessation of the offending agent is essential for treatment. The best example of a specific treatment for drug-induced liver disease is N-acetylcysteine treatment for acetaminophen hepatotoxicity. Many examples are cited of other attempts at treatment in animal models of drug-induced liver disease. If drug-induced liver disease leads to fulminant hepatic failure, intensive management of the resulting complications is required. Liver transplantation may be the only treatment option.

  6. Transient elastography compared to liver biopsy and morphometry for predicting fibrosis in pediatric chronic liver disease: Does etiology matter?

    PubMed Central

    Behairy, Behairy El-Sayed; Sira, Mostafa Mohamed; Zalata, Khaled Refat; Salama, El-Sayed Ebrahem; Abd-Allah, Mohamed Ahmed

    2016-01-01

    AIM: To evaluate transient elastography (TE) as a noninvasive tool in staging liver fibrosis compared with liver biopsy and morphometry in children with different chronic liver diseases. METHODS: A total of 90 children [50 with chronic hepatitis C virus (HCV), 20 with autoimmune hepatitis (AIH) and 20 with Wilson disease] were included in the study and underwent liver stiffness measurement (LSM) using TE. Liver biopsies were evaluated for fibrosis, qualitatively, by Ishak score and quantitatively by fibrosis area fraction (FAF) using digital image analysis (morphometry). LSM was correlated with fibrosis and other studied variables using spearman correlation. A stepwise multiple regression analysis was also performed to examine independent factors associated with LSM. Different cut-off values of LSM were calculated for predicting individual fibrosis stages using receiver-operating characteristic curve. Cut-off values with optimal clinical performance (optimal sensitivity and specificity simultaneously) were selected. RESULTS: The majority of HCV group had minimal activity (80%) and no/mild fibrosis (72%). On the other hand, the majority of AIH group had mild to moderate activity (70%) and moderate to severe fibrosis (95%) and all Wilson disease group had mild to moderate activity (100%) and moderate to severe fibrosis (100%). LSM correlated significantly with both FAF and Ishak scores and the correlation appeared better with the latter (r = 0.839 vs 0.879, P < 0.0001 for both). LSM discriminated individual stages of fibrosis with high performance. Sensitivity ranged from 81.4% to 100% and specificity ranged from 75.0% to 97.2%. When we compared LSM values for the same stage of fibrosis, they varied according to the different etiologies. Higher values were in AIH (16.15 ± 7.23 kPa) compared to Wilson disease (8.30 ± 0.84 kPa) and HCV groups (7.43 ± 1.73 kPa). Multiple regression analysis revealed that Ishak fibrosis stage was the only independent variable

  7. Association between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in middle age patient with non-alcoholic fatty liver disease

    PubMed Central

    Kalantari, Hamid; Moradi, Farhad; Hassanzade, Akbar

    2016-01-01

    Background: Liver biopsy is required to diagnose non-alcoholic steatohepatitis in patients with suspected non-alcoholic fatty liver disease (NAFLD). This study aimed to examine the relationship between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in patient with NAFLD. Materials and Methods: In this cross-sectional study, a total of 180 patients, with an age range of 18-60 year old, with NAFLD based on ultrasonograghic findings were evaluated. Age, sex, body mass index, diabetes mellitus, hypertension, family history of liver disease and laboratory parameters recorded for all patients. Hence, grade of steatosis and stage of fibrosis were evaluated by liver biopsy. Results: A total of 220 patients were enrolled. Liver biopsy was performed in 180 patients. Mean age was 43 ± 10.6 years old and 66% were male. Ultrasonograghic findings showed mild, moderate and severe NAFLD was define in 100 (55.5%), 72 (40%) and 8 (4.5%) of patients, respectively. Liver biopsies showed that steatosis scores of <5%, 5-33% and 33-66% was define in 56 (31%), 116 (64%) and 9 (5%) of patients, respectively. Furthermore, fibrosis was defined as follow; none 92 (51%), mild 68 (38%), moderate 11 (6%), bridging 5 (3%) and cirrhosis 3 (2%) patients. There was no statistically significant relationship between ultrasonograghic findings and steatosis scores (P = 0.44), but statistically significant relationship was found between ultrasonograghic findings and fibrosis stage (P = 0.017). Conclusion: Findings revealed that, in patients with NAFLD, ultrasonographic finding were not in associate to steatosis, but were in relation with fibrosis stage. PMID:27563632

  8. Non-alcoholic fatty liver disease: non-invasive investigation and risk stratification.

    PubMed

    Dyson, J K; McPherson, S; Anstee, Q M

    2013-12-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum of liver disease, from simple steatosis through to cirrhosis. As the worldwide rates of obesity have increased, NAFLD has become the commonest cause of liver disease in many developed countries, affecting up to a third of the population. The majority of patients have simple steatosis that carries a relatively benign prognosis. However, a significant minority have non-alcoholic steatohepatitis, and have increased liver related and cardiovascular mortality. Identifying those at risk of progressive disease is crucial. Liver biopsy remains the gold standard investigation for assessing stage of disease but its invasive nature makes it impractical for widespread use as a prognostic tool. Non-invasive tools for diagnosis and disease staging are required, reserving liver biopsy for those patients where it offers clinically relevant additional information. This review discusses the non-invasive modalities available for assessing steatosis, steatohepatitis and fibrosis. We propose a pragmatic approach for the assessment of patients with NAFLD to identify those at high risk of progressive disease who require referral to specialist services. PMID:23940130

  9. Fatigue in liver disease: Pathophysiology and clinical management

    PubMed Central

    Swain, Mark G

    2006-01-01

    Fatigue is the most commonly encountered symptom in patients with liver disease, and it has a significant impact on their quality of life. However, although some progress has been made with regard to the understanding of the processes which may generate fatigue in general, the underlying cause(s) of liver disease-associated fatigue remain incompletely understood. The present review describes recent advances which have been made in our ability to measure fatigue in patients with liver disease in the clinical setting, as well as in our understanding of potential pathways which are likely important in the pathogenesis of fatigue associated with liver disease. Specifically, experimental findings suggest that fatigue associated with liver disease likely occurs as a result of changes in neurotransmission within the brain. In conclusion, a reasonable approach to help guide in the management of the fatigued patient with liver disease is presented. PMID:16550262

  10. Osteopontin: Versatile modulator of liver diseases.

    PubMed

    Nagoshi, Sumiko

    2014-01-01

    Osteopontin (OPN) is a multifunctional protein, involved in pathological conditions including inflammation, immunity, angiogenesis, fibrosis and cancer progression in various tissues. Hepatic inflammation and fibrosis induced by feeding with a diet deficient in methionine and choline (MCD diet) were markedly attenuated in OPN knockout mice when compared with wild-type mice in the model of non-alcoholic steatohepatitis (NASH). Hepatic cholangiocytes, myofibroblastic stellate cells and natural killer T cells were suggested to secret OPN in mice fed an MCD diet. Plasma and hepatic OPN levels were significantly higher in patients with NASH with advanced fibrosis than in those with early fibrosis. Hepatic OPN mRNA level was correlated with hepatic neutrophil infiltration and fibrosis in patients with alcoholic liver diseases. In those with hepatocellular carcinoma (HCC), OPN levels in plasma and HCC were prognostic factors after liver resection or transplantation. Downregulation of OPN inhibited tumor growth and lung metastasis in nude mice implanted with HCC cells. The single nucleotide polymorphism in the promoter region of the OPN gene was shown to be associated with activity of hepatitis in chronic hepatitis C patients, prognosis in patients with HCC, and growth and lung metastasis of HCC xenografts in nude mice. OPN was reported to be a downstream effecter of Hedgehog pathway, which modulates hepatic fibrosis and carcinogenesis. This review focuses on the roles of OPN in hepatic inflammation, fibrosis and cancer progression. Further elucidation of cellular interactions and molecular mechanisms associated with OPN actions may contribute to development of novel strategies for treatment of the liver diseases. PMID:23701387

  11. Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Ur Rahman, Zia; Hurairah, Abu

    2016-01-01

    Our objective was to study nonalcoholic fatty liver disease (NAFLD) as a relevant risk factor associated with hepatocellular carcinoma (HCC) in patients with and without cirrhosis. HCC is a common cancer worldwide that predominantly involves patients with hepatic cirrhosis. HCC has recently been linked to NAFLD, the hepatic manifestation of obesity and related metabolic disorders. This association is alarming due to the high prevalence of NAFLD globally, which may contribute to the rising incidence of HCC. A 31-year-old female with a history of dyslipidemia, hypertension, and diabetes mellitus presented with abdominal pain that persisted for six months. The pain was associated with gastrointestinal symptoms and weight loss. She was drug-free and a nonalcoholic and a nonsmoker. The physical examination was unremarkable. The abdominal exam showed a soft and non-tender abdomen, with no organomegaly or ascites. The laboratory evaluation was unremarkable. The imaging studies showed a hypodense lesion in the right hepatic lobe with strong arterial enhancement. Subsequently, the patient underwent a liver biopsy. The histopathology results were consistent with HCC. The patient underwent an uneventful segment VI liver resection and tumor-free margins were achieved. In our patient, NAFLD was designated as an independent etiology for HCC, without cirrhosis. Our patient recovered well and has been disease free for over a year. HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk of HCC. These results provide new targets for surveillance, prevention, early recognition, and effective treatment of HCC associated with NAFLD. PMID:27733959

  12. Dietary fructose in nonalcoholic fatty liver disease.

    PubMed

    Vos, Miriam B; Lavine, Joel E

    2013-06-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in adults and children. A number of genetic and environmental factors are known to predispose individuals to NAFLD. Certain dietary sugars, particularly fructose, are suspected to contribute to the development of NAFLD and its progression. The increasing quantity of fructose in the diet comes from sugar additives (most commonly sucrose and high fructose corn syrup) in beverages and processed foods. Substantial links have been demonstrated between increased fructose consumption and obesity, dyslipidemia, and insulin resistance. Growing evidence suggests that fructose contributes to the development and severity of NAFLD. In human studies, fructose is associated with increasing hepatic fat, inflammation, and possibly fibrosis. Whether fructose alone can cause NAFLD or if it serves only as a contributor when consumed excessively in the setting of insulin resistance, positive energy balance, and sedentary lifestyle is unknown. Sufficient evidence exists to support clinical recommendations that fructose intake be limited through decreasing foods and drinks high in added (fructose-containing) sugars. PMID:23390127

  13. Ideal Experimental Rat Models for Liver Diseases

    PubMed Central

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  14. Management of Stage IIIA Hodgkin's disease

    SciTech Connect

    Timothy, A.R.; Sutcliffe, S.B.J.; Lister, A.; Wrigley, P.F.M.; Jones, A.E.

    1980-02-01

    Forty patients with pathological Stage IIIA Hodgkin's disease were allocated to receive either total modal irradiation (TNI) or 6 cycles of chemotherapy with Nitrogen Mustard (Mustine), Vinblastine, Procarbazine and Prednisolone (MVPP) as initial treatment. The complete remission rate for both groups was 100%, with 5-year actuarial disease-free survival figures of 74 and 87% for TNI and MVPP respectively (median duration of follow-up= 48 months). Eighty-eight percent of TNI treated patients were alive at 5 years compared with 100% in the MVPP group. Three patients died, two who were treated with TNI and one who received MVPP. Treatment related morbidity included one patient with osteonecrosis and one with a second malignancy. Given the length of follow-up available, these results demonstrate no significant difference between TNI and MVPP for patients with Stage IIIA disease; it is unlikely that further patient entry into this particular study will allow any conclusion to be reached regarding the optimal form of management. We would recommend that individual disease characteristics within Stage IIIA be used as a basis for future treatment decisions with the understanding that further information regarding morbidity may become available with prolonged follow-up.

  15. Chronic Liver Disease and American Indians/Alaska Natives

    MedlinePlus

    ... Disease Chronic Liver Disease and American Indians/Alaska Natives Among American Indians and Alaska Natives, chronic liver disease is ... 54. 1 At a glance – Cancer Rates for American Indian/Alaska Natives (2008-2012) Cancer Incidence Rates per 100,000 – ...

  16. Liver diseases in pregnancy: Diseases not unique to pregnancy

    PubMed Central

    Almashhrawi, Ashraf A; Ahmed, Khulood T; Rahman, Rubayat N; Hammoud, Ghassan M; Ibdah, Jamal A

    2013-01-01

    Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. Few challenges arise in reaching an accurate diagnosis in light of such physiological changes. Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment. Other challenges entail the methods of treatment and their safety for both the mother and the baby. This review summarizes liver diseases that are not unique to pregnancy. We focus on viral hepatitis and its mode of transmission, diagnosis, effect on the pregnancy, the mother, the infant, treatment, and breast-feeding. Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson’s disease, Budd Chiari and portal vein thrombosis in pregnancy are also discussed. Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis. Variceal bleeding can happen in up to 38% of cirrhotic pregnant women. Management of portal hypertension during pregnancy is discussed. Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones. We discuss some of the interventions for gallstones in pregnancy if symptoms arise. Finally, we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy. PMID:24282352

  17. Liver diseases in pregnancy: diseases not unique to pregnancy.

    PubMed

    Almashhrawi, Ashraf A; Ahmed, Khulood T; Rahman, Rubayat N; Hammoud, Ghassan M; Ibdah, Jamal A

    2013-11-21

    Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. Few challenges arise in reaching an accurate diagnosis in light of such physiological changes. Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment. Other challenges entail the methods of treatment and their safety for both the mother and the baby. This review summarizes liver diseases that are not unique to pregnancy. We focus on viral hepatitis and its mode of transmission, diagnosis, effect on the pregnancy, the mother, the infant, treatment, and breast-feeding. Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, Budd Chiari and portal vein thrombosis in pregnancy are also discussed. Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis. Variceal bleeding can happen in up to 38% of cirrhotic pregnant women. Management of portal hypertension during pregnancy is discussed. Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones. We discuss some of the interventions for gallstones in pregnancy if symptoms arise. Finally, we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy.

  18. Systemic symptoms in non-alcoholic fatty liver disease.

    PubMed

    Newton, Julia L

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in the Western world and the incidence of the disease is constantly increasing. Most patients with NAFLD do not present with symptoms directly attributable to their underlying liver disease. It is increasingly recognized, however, that those with NAFLD describe a range of non-specific symptoms, which include fatigue and daytime sleepiness, may be the presenting problem and can impact dramatically upon quality of life in this patient group. The recognition of systemic symptoms in NAFLD has important implications for patients as many are potentially modifiable with targeted interventions. Fatigue appears to be a significant problem in NAFLD and the severity of fatigue is not associated with severity of NAFLD or any parameters of liver damage. Instead, fatigue in these patients shows a strong relationship with the symptom of daytime sleepiness and autonomic dysfunction. Daytime sleepiness can frequently be associated with obstructive sleep apnoea in those with NAFLD and is therefore treatable with evidence-based interventions. Recent studies have confirmed the presence of autonomic nervous system dysfunction in those with early stages of NAFLD. The presence of autonomic nervous system dysfunction leads to symptoms such as postural dizziness and syncope and is also associated with a number of clinical consequences in hepatic and non-hepatic diseases such as cognitive dysfunction, falls and fall-related injuries. On direct questioning, problems with memory and concentration are frequently described by those with NAFLD, with our studies confirming that 50% of NAFLD patients experience mild cognitive symptoms and up to 46% moderate or severe cognitive impairment. There were no positive correlations between cognitive symptoms and biochemical or histological markers of liver damage severity, confirming that cognitive impairment in early-stage NAFLD is not related to hepatic encephalopathy. Falls are

  19. The Role of Oxidative Stress and Antioxidants in Liver Diseases.

    PubMed

    Li, Sha; Tan, Hor-Yue; Wang, Ning; Zhang, Zhang-Jin; Lao, Lixing; Wong, Chi-Woon; Feng, Yibin

    2015-11-02

    A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

  20. The Role of Oxidative Stress and Antioxidants in Liver Diseases

    PubMed Central

    Li, Sha; Tan, Hor-Yue; Wang, Ning; Zhang, Zhang-Jin; Lao, Lixing; Wong, Chi-Woon; Feng, Yibin

    2015-01-01

    A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed. PMID:26540040

  1. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development.

    PubMed

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C; Hedgepeth, John W; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E; Amacher, Sharon L; Goessling, Wolfram

    2016-10-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic vs. pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease.

  2. Epigenetic Modifications in the Biology of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Pirola, Carlos J.; Scian, Romina; Gianotti, Tomas Fernández; Dopazo, Hernán; Rohr, Cristian; Martino, Julio San; Castaño, Gustavo O.; Sookoian, Silvia

    2015-01-01

    Abstract The 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification whose role in the pathogenesis of metabolic-related complex diseases remains unexplored; 5-hmC appears to be prevalent in the mitochondrial genome. The Ten-Eleven-Translocation (TET) family of proteins is responsible for catalyzing the conversion of 5-methylcytosine to 5-hmC. We hypothesized that epigenetic editing by 5-hmC might be a novel mechanism through which nonalcoholic fatty liver disease (NAFLD)-associated molecular traits could be explained. Hence, we performed an observational study to explore global levels of 5-hmC in fresh liver samples of patients with NAFLD and controls (n = 90) using an enzyme-linked-immunosorbent serologic assay and immunohistochemistry. We also screened for genetic variation in TET 1–3 loci by next generation sequencing to explore its contribution to the disease biology. The study was conducted in 2 stages (discovery and replication) and included 476 participants. We observed that the amount of 5-hmC in the liver of both NAFLD patients and controls was relatively low (up to 0.1%); a significant association was found with liver mitochondrial DNA copy number (R = 0.50, P = 0.000382) and PPARGC1A-mRNA levels (R = −0.57, P = 0.04). We did not observe any significant difference in the 5-hmC nuclear immunostaining score between NAFLD patients and controls; nevertheless, we found that patients with NAFLD (0.4 ± 0.5) had significantly lower nonnuclear-5-hmC staining compared with controls (1.8 ± 0.8), means ± standard deviation, P = 0.028. The missense p.Ile1123Met variant (TET1-rs3998860) was significantly associated with serum levels of caspase-generated CK-18 fragment-cell death biomarker in the discovery and replication stage, and the disease severity (odds ratio: 1.47, 95% confidence interval: 1.10–1.97; P = 0.005). The p.Ile1762Val substitution (TET2-rs2454206) was associated with liver PPARGC1A-methylation and

  3. MicroRNAs in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Baffy, György

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disorder. Strongly linked to obesity and diabetes, NAFLD has the characteristics of complex diseases with substantial heterogeneity. Accordingly, our ability to predict the risk of advanced NAFLD and provide efficient treatment may improve by a better understanding of the relationship between genotype and phenotype. MicroRNAs (miRNAs) play a major role in the fine-tuning of gene expression and they have recently emerged as novel biomarkers and therapeutic tools in the management of NAFLD. These short non-coding RNA sequences act by partial repression or degradation of targeted mRNAs. Deregulation of miRNAs has been associated with different stages of NAFLD, while their biological role in the pathogenesis remains to be fully understood. Systems biology analyses based on predicted target genes have associated hepatic miRNAs with molecular pathways involved in NAFLD progression such as cholesterol and lipid metabolism, insulin signaling, oxidative stress, inflammation, and pathways of cell survival and proliferation. Moreover, circulating miRNAs have been identified as promising noninvasive biomarkers of NAFLD and linked to disease severity. This rapidly growing field is likely to result in major advances in the pathomechanism, prognostication, and treatment of NAFLD. PMID:26690233

  4. [The diagnostic value of the aminophenazone breath test in chronic liver diseases].

    PubMed

    Sensing, H; Treutler, J; Haustein, K O; Hüller, G

    1991-09-01

    In 230 patients (90 females, 140 males aged between 20 and 73 years, average age 47.8 years) with and without exception histologically and/or laparoscopically ascertained chronic liver diseases (degenerative damages of liver parenchyma in 45, fatty liver stage I in 28, fatty liver stage II in 36, cholangiohepatitis in 4, chronic persisting hepatitis in 31, chronic active hepatitis in 57 and liver cirrhosis in 59 cases) the incorporation of the aminophenazon breathing test in the so-called laboratory chemical liver spectrum was controlled. The restriction of the microsomal biotransformation established by means of the aminophenazon breathing test behaved parallel to the degree of severity of the disease. The aminophenazon breathing test was performed in the modification after Haustein and Schenker (1985). The largest delays in the decomposition were found in the complete cirrhotic transformation of the liver. The unequivocally pathologic result of the aminophenazon breathing test in severe irreversible damages of the liver parenchyma was confirmed by the formation of correlations with parameters of the conventional laboratory spectrum of the liver. Thus the restriction of the performance of the synthesis of the liver for coagulation factors and albumins was parallel to the loss of function of the mixed functional oxidases. In all patients with chronic liver diseases a connection between the value of the thromboplastin time (Quick's test) and result of the breathing test was found. Positive linear correlation between serum albumin and results of the breathing test could also be proved particularly in the group of the severe chronic inflammatory liver diseases. In chronic fibrosing liver diseases there were positive inverse correlations between gamma-globulin concentration in the serum and thymol turbidity test on the one hand as well as the aminophenazon breathing test on the other. There were no correlations between liver enzyme and aminophenazon breathing test. The

  5. Nutrition and Alcoholic Liver Disease: Effects of Alcoholism on Nutrition, Effects of Nutrition on Alcoholic Liver Disease, and Nutritional Therapies for Alcoholic Liver Disease.

    PubMed

    Dasarathy, Srinivasan

    2016-08-01

    Malnutrition is the most frequent and nearly universal consequence in alcoholic liver disease (ALD) that adversely affects clinical outcomes. Sarcopenia or skeletal muscle loss is the major component of malnutrition in liver disease. There are no effective therapies to prevent or reverse sarcopenia in ALD because the mechanisms are not well understood. Consequences of liver disease including hyperammonemia, hormonal perturbations, endotoxemia and cytokine abnormalities as well as the direct effects of alcohol and its metabolites contribute to sarcopenia in ALD. This article focuses on the prevalence, methods to quantify malnutrition, specifically sarcopenia and potential therapies including novel molecular targeted treatments. PMID:27373615

  6. Immune mechanisms in alcoholic liver disease

    PubMed Central

    Vidali, Matteo

    2009-01-01

    Growing evidence indicates that inflammatory reactions play an important role in the pathogenesis of alcoholic liver disease (ALD). The implication of immunity in fueling chronic inflammation in ALD has emerged from clinical and experimental evidence showing the recruitment and the activation of lymphocytes in the inflammatory infiltrates of ALD and has received further support by the recent demonstration of a role of Th17 lymphocytes in alcoholic hepatitis. Nonetheless, the mechanisms by which alcohol triggers adaptive immune responses are still incompletely characterized. Patients with advanced ALD show a high prevalence of circulating IgG and T-lymphocytes towards epitopes derived from protein modification by hydroxyethyl free radicals (HER) and end-products of lipid peroxidation. In both chronic alcohol-fed rats and heavy drinkers the elevation of IgG against lipid peroxidation-derived antigens is associated with an increased production of pro-inflammatory cytokines/chemokines and with the severity of histological signs of liver inflammation. Moreover, CYP2E1-alkylation by HER favors the development of anti-CYP2E1 auto-antibodies in a sub-set of ALD patients. Altogether, these results suggest that allo- and auto-immune reactions triggered by oxidative stress might contribute to fuel chronic hepatic inflammation during the progression of ALD. PMID:19809845

  7. Hypertension in end-stage renal disease.

    PubMed

    Appleby, C; Foley, R N

    2002-03-01

    Chronic renal failure is common. Recent estimates from the United States suggest that one in 10 adults has an elevated serum creatinine. Hypertension and renal disease are intimately connected at many levels, and clearly accelerate each other s course. Hypertension is an almost universal feature of end-stage renal disease, a state of frightening cardiovascular risk. Surprisingly, most recent observational studies have shown an association between low blood pressure and increased mortality, a result that may engender therapeutic nihilism in the absence of large randomised trials. This observation may be due to reverse causality, as the age and cardiovascular comorbidity of patients reaching end-stage renal disease is considerable. When outcomes other than death are considered, especially progressive left ventricular hypertrophy, but also ischaemic heart disease and congestive heart failure, more predictable and expected associations are seen, with rising blood pressure appearing to be a deleterious parameter. Uraemia appears to be a state of premature senescence, and arterial rigidity, whose clinical corollary is wide pulse pressure, is a characteristic feature. Recent observational studies have focused on pulse pressure, rather than the traditional approach of analysing its components, systolic and diastolic blood pressure, in isolation. High pulse pressure appears to be a marker of short survival in dialysis patients, but disentangling this association from old age and pre-existing cardiovascular conditions is challenging. Remarkably, and regrettably, no large scale randomised controlled studies examining strategies that tackle the issue of hypertension in dialysis patients have yet to be initiated.

  8. Metabolic syndrome and non-alcoholic fatty liver disease in liver surgery: The new scourges?

    PubMed Central

    Cauchy, François; Fuks, David; Zarzavadjian Le Bian, Alban; Belghiti, Jacques; Costi, Renato

    2014-01-01

    The aim of this topic highlight is to review relevant evidence regarding the influence of the metabolic syndrome (MS) and its associated liver manifestation, non-alcoholic fatty liver disease (NAFLD), on the development of liver cancer as well as their impact on the results of major liver surgery. MS and NAFLD, whose incidences are significantly increasing in Western countries, are leading to a changing profile of the patients undergoing liver surgery. A MEDLINE search was performed for relevant articles using the key words “metabolic syndrome”, “liver resection”, “liver transplantation”, “non alcoholic fatty liver disease”, “non-alcoholic steatohepatitis” and “liver cancer”. On one hand, the MS favors the development of primary liver malignancies (hepatocellular carcinoma and cholangiocarcinoma) either through NAFLD liver parenchymal alterations (steatosis, steatohepatitis, fibrosis) or in the absence of significant underlying liver parenchyma changes. Also, the existence of NAFLD may have a specific impact on colorectal liver metastases recurrence. On the other hand, the postoperative period following partial liver resection and liver transplantation is at increased risk of both postoperative complications and mortality. These deleterious effects seem to be related to the existence of liver specific complications but also higher cardio-vascular sensitivity in a setting of MS/NAFLD. Finally, the long-term prognosis after curative surgery joins that of patients operated on with other types of underlying liver diseases. An increased rate of patients with MS/NAFLD referred to hepatobiliary units has to be expected. The higher operative risk observed in this subset of patients will require specific improvements in their perioperative management. PMID:24868324

  9. Use of statins in patients with liver disease.

    PubMed

    Tandra, Sweta; Vuppalanchi, Raj

    2009-08-01

    Cardiovascular disease is as common in individuals with chronic liver disease as in the general population. Moreover, recent data suggest that patients with nonalcoholic fatty liver disease (NAFLD) may have a cardiovascular risk greater than that conferred by the conventional risk factors. There is unequivocal evidence that cardiovascular disease is an important cause of morbidity and mortality in this patient population and thus requires consideration of aggressive therapy with lipid-lowering agents such as statins. Because all statins are hepatically cleared and can cause elevations in liver biochemistries, there is a concern that patients with underlying liver disease may be at increased risk for hepatotoxicity. However, recent data, along with an assessment of statin safety by the Liver Expert Panel, suggest that statins are generally well tolerated in patients with chronic liver disease such as NAFLD, primary biliary cirrhosis, and hepatitis C virus. These drugs also appear to be safe in patients with stable/compensated cirrhosis. However, decompensated cirrhosis and acute liver failure should be considered contraindications for lipid-lowering therapy as these patients are unlikely to benefit because of their generally grave prognosis. Although routine hepatic biochemical test monitoring is recommended, the cost-effectiveness of this approach has been questioned. The benefit of statins in patients with underlying liver disease who are otherwise important candidates for statin therapy far outweighs the risk of a very rare event of serious liver injury. PMID:19627660

  10. Zebrafish Models of Human Liver Development and Disease

    PubMed Central

    Wilkins, Benjamin J.; Pack, Michael

    2016-01-01

    The liver performs a large number of essential synthetic and regulatory functions that are acquired during fetal development and persist throughout life. Their disruption underlies a diverse group of heritable and acquired diseases that affect both pediatric and adult patients. Although experimental analyses used to study liver development and disease are typically performed in cell culture models or rodents, the zebrafish is increasingly used to complement discoveries made in these systems. Forward and reverse genetic analyses over the past two decades have shown that the molecular program for liver development is largely conserved between zebrafish and mammals, and that the zebrafish can be used to model heritable human liver disorders. Recent work has demonstrated that zebrafish can also be used to study the mechanistic basis of acquired liver diseases. Here, we provide a comprehensive summary of how the zebrafish has contributed to our understanding of human liver development and disease. PMID:23897685

  11. Nutritional Considerations for Dogs and Cats with Liver Disease.

    PubMed

    Norton, Rebecca D; Lenox, Catherine E; Manino, Paul; Vulgamott, James C

    2016-01-01

    The goals of nutritional management of liver disease in the dog and cat are directed at treating the clinical manifestations as opposed to treating the underlying cause. Specifically, the clinician strives to avoid overwhelming the remaining metabolic capacities of the damaged liver while providing sufficient nutrients for regeneration. A brief overview of liver diseases and associated clinical signs encountered in the dog and cat and a review of specific nutrients are discussed as well as amounts and sources of nutrients recommended to meet nutritional goals in the diseased liver.

  12. Nutritional Considerations for Dogs and Cats with Liver Disease.

    PubMed

    Norton, Rebecca D; Lenox, Catherine E; Manino, Paul; Vulgamott, James C

    2016-01-01

    The goals of nutritional management of liver disease in the dog and cat are directed at treating the clinical manifestations as opposed to treating the underlying cause. Specifically, the clinician strives to avoid overwhelming the remaining metabolic capacities of the damaged liver while providing sufficient nutrients for regeneration. A brief overview of liver diseases and associated clinical signs encountered in the dog and cat and a review of specific nutrients are discussed as well as amounts and sources of nutrients recommended to meet nutritional goals in the diseased liver. PMID:26606205

  13. In silico identification of genetically attenuated vaccine candidate genes for Plasmodium liver stage.

    PubMed

    Kumar, Hirdesh; Frischknecht, Friedrich; Mair, Gunnar R; Gomes, James

    2015-12-01

    Genetically attenuated parasites (GAPs) that lack genes essential for the liver stage of the malaria parasite, and therefore cause developmental arrest, have been developed as live vaccines in rodent malaria models and recently been tested in humans. The genes targeted for deletion were often identified by trial and error. Here we present a systematic gene - protein and transcript - expression analyses of several Plasmodium species with the aim to identify candidate genes for the generation of novel GAPs. With a lack of liver stage expression data for human malaria parasites, we used data available for liver stage development of Plasmodium yoelii, a rodent malaria model, to identify proteins expressed in the liver stage but absent from blood stage parasites. An orthology-based search was then employed to identify orthologous proteins in the human malaria parasite Plasmodium falciparum resulting in a total of 310 genes expressed in the liver stage but lacking evidence of protein expression in blood stage parasites. Among these 310 possible GAP candidates, we further studied Plasmodium liver stage proteins by phyletic distribution and functional domain analyses and shortlisted twenty GAP-candidates; these are: fabB/F, fabI, arp, 3 genes encoding subunits of the PDH complex, dnaJ, urm1, rS5, ancp, mcp, arh, gk, lisp2, valS, palm, and four conserved Plasmodium proteins of unknown function. Parasites lacking one or several of these genes might yield new attenuated malaria parasites for experimental vaccination studies.

  14. Acoustic radiation force impulse imaging for assessing liver fibrosis in alcoholic liver disease

    PubMed Central

    Kiani, Anita; Brun, Vanessa; Lainé, Fabrice; Turlin, Bruno; Morcet, Jeff; Michalak, Sophie; Le Gruyer, Antonia; Legros, Ludivine; Bardou-Jacquet, Edouard; Gandon, Yves; Moirand, Romain

    2016-01-01

    AIM: To evaluate the performance of elastography by ultrasound with acoustic radiation force impulse (ARFI) in determining fibrosis stage in patients with alcoholic liver disease (ALD) undergoing alcoholic detoxification in relation to biopsy. METHODS: Eighty-three patients with ALD undergoing detoxification were prospectively enrolled. Each patient underwent ARFI imaging and a liver biopsy on the same day. Fibrosis was staged according to the METAVIR scoring system. The median of 10 valid ARFI measurements was calculated for each patient. RESULTS: Sixty-nine males and thirteen females (one patient excluded due to insufficient biopsy size) were assessed with a mean alcohol consumption of 132.4 ± 128.8 standard drinks per week and mean cumulative year duration of 17.6 ± 9.5 years. Sensitivity and specificity were respectively 82.4% (0.70-0.95) and 83.3% (0.73-0.94) (AUROC = 0.87) for F ≥ 2 with a cut-off value of 1.63m/s; 82.4% (0.64-1.00) and 78.5% (0.69-0.89) (AUROC = 0.86) for F ≥ 3 with a cut-off value of 1.84m/s; and 92.3% (0.78-1.00] and 81.6% (0.72-0.90) (AUROC = 0.89) for F = 4 with a cut-off value of 1.94 m/s. CONCLUSION: ARFI is an accurate, non-invasive and easy method for assessing liver fibrosis in patients with ALD undergoing alcoholic detoxification. PMID:27239119

  15. Monogenic diseases that can be cured by liver transplantation.

    PubMed

    Fagiuoli, Stefano; Daina, Erica; D'Antiga, Lorenzo; Colledan, Michele; Remuzzi, Giuseppe

    2013-09-01

    While the prevalence of most diseases caused by single-gene mutations is low and defines them as rare conditions, all together, monogenic diseases account for approximately 10 in every 1000 births according to the World Health Organisation. Orthotopic liver transplantation (LT) could offer a therapeutic option in monogenic diseases in two ways: by substituting for an injured liver or by supplying a tissue that can replace a mutant protein. In this respect, LT may be regarded as the correction of a disease at the level of the dysfunctional protein. Monogenic diseases that involve the liver represent a heterogeneous group of disorders. In conditions associated with predominant liver parenchymal damage (i.e., genetic cholestatic disorders, Wilson's disease, hereditary hemochromatosis, tyrosinemia, α1 antitrypsin deficiency), hepatic complications are the major source of morbidity and LT not only replaces a dysfunctional liver but also corrects the genetic defect and effectively cures the disease. A second group includes liver-based genetic disorders characterised by an architecturally near-normal liver (urea cycle disorders, Crigler-Najjar syndrome, familial amyloid polyneuropathy, primary hyperoxaluria type 1, atypical haemolytic uremic syndrome-1). In these defects, extrahepatic complications are the main source of morbidity and mortality while liver function is relatively preserved. Combined transplantation of other organs may be required, and other surgical techniques, such as domino and auxiliary liver transplantation, have been attempted. In a third group of monogenic diseases, the underlying genetic defect is expressed at a systemic level and liver involvement is just one of the clinical manifestations. In these conditions, LT might only be partially curative since the abnormal phenotype is maintained by extrahepatic synthesis of the toxic metabolites (i.e., methylmalonic acidemia, propionic acidemia). This review focuses on principles of diagnosis, management

  16. A Stage Model of Stress and Disease.

    PubMed

    Cohen, Sheldon; Gianaros, Peter J; Manuck, Stephen B

    2016-07-01

    In this article, we argued that the term stress has served as a valuable heuristic, helping researchers to integrate traditions that illuminate different stages of the process linking stressful life events to disease. We provided a short history of three traditions in the study of stress: the epidemiological, psychological, and biological. The epidemiological tradition focuses on defining which circumstances and experiences are deemed stressful on the basis of consensual agreement that they constitute threats to social or physical well-being. The psychological tradition focuses on individuals' perceptions of the stress presented by life events on the basis of their appraisals of the threats posed and the availability of effective coping resources. The biological tradition focuses on brain-based perturbations of physiological systems that are otherwise essential for normal homeostatic regulation and metabolic control. The foci of these three traditions have informed elements of a stage model of disease, wherein events appraised as stressful are viewed as triggering affective states that in turn engender behavioral and biological responses having possible downstream implications for disease. PMID:27474134

  17. Gut microbiota and probiotics in chronic liver diseases.

    PubMed

    Cesaro, Claudia; Tiso, Angelo; Del Prete, Anna; Cariello, Rita; Tuccillo, Concetta; Cotticelli, Gaetano; Del Vecchio Blanco, Camillo; Loguercio, Carmelina

    2011-06-01

    There is a strong relationship between liver and gut: the portal system receives blood from the gut, and intestinal blood content activates liver functions. The liver, in turn, affects intestinal functions through bile secretion into the intestinal lumen. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of complications of liver cirrhosis, such as infections, hepatic encephalopathy, spontaneous bacterial peritonitis, and renal failure. Probiotics have been suggested as a useful integrative treatment of different types of chronic liver damage, for their ability to augment intestinal barrier function and prevent bacterial translocation. This review summarizes the main literature findings about the relationships between gut microbiota and chronic liver disease, both in the pathogenesis and in the treatment by probiotics of the liver damage. PMID:21163715

  18. Insulin receptor gene expression in normal and diseased bovine liver.

    PubMed

    Liu, G W; Zhang, Z G; Wang, J G; Wang, Z; Xu, C; Zhu, X L

    2010-11-01

    The aim of the present study was to compare insulin receptor (IR) gene expression in normal bovine liver (n=7) with samples of liver from cows in the perinatal period with ketosis (n=7) and cows with fatty liver (n=7). Gene expression was determined by internally controlled reverse transcriptase polymerase chain reaction (RT-PCR). The expression of IR mRNA in the liver of ketotic dairy cows was higher than in cows with fatty liver, but in both disease groups the expression was substantially lower than that in normal liver. Reduced expression of IR mRNA in fatty liver indicates that responses to insulin are markedly decreased, which might be due to insulin resistance. The relatively lower IR mRNA expression in the liver tissue of dairy cows with ketosis might enhance gluconeogenesis and lipid mobilization to relieve energy negative balance.

  19. Phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease

    PubMed Central

    Sanchez-Pareja, Andrea; Clément, Sophie; Peyrou, Marion; Spahr, Laurent; Negro, Francesco; Rubbia-Brandt, Laura; Foti, Michelangelo

    2016-01-01

    AIM: To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease. METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffin-embedded liver sections of patients with non-alcoholic fatty liver disease (NAFLD) (n = 44) or alcoholic liver disease (ALD) (n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients’ clinical history. RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis (r = 0.3061, P = 0.0459) and the BMI (r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor (P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients (P < 0.0001). CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN

  20. Adjuvant sorafenib after heptectomy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma patients

    PubMed Central

    Xia, Feng; Wu, Li-Li; Lau, Wan-Yee; Huan, Hong-Bo; Wen, Xu-Dong; Ma, Kuan-Sheng; Li, Xiao-Wu; Bie, Ping

    2016-01-01

    AIM: To investigate the efficacy and safety of adjuvant sorafenib after curative resection for patients with Barcelona Clinic Liver Cancer (BCLC)-stage C hepatocellular carcinoma (HCC). METHODS: Thirty-four HCC patients, classified as BCLC-stage C, received adjuvant sorafenib for high-risk of tumor recurrence after curative hepatectomy at a tertiary care university hospital. The study group was compared with a case-matched control group of 68 patients who received curative hepatectomy for HCC during the study period in a 1:2 ratio. RESULTS: The tumor recurrence rate was markedly lower in the sorafenib group (15/34, 44.1%) than in the control group (51/68, 75%, P = 0.002). The median disease-free survival was 12 mo in the study group and 10 mo in the control group. Tumor number more than 3, macrovascular invasion, hilar lymph nodes metastasis, and treatment with sorafenib were significant factors of disease-free survival by univariate analysis. Tumor number more than 3 and treatment with sorafenib were significant risk factors of disease-free survival by multivariate analysis in the Cox proportional hazards model. The disease-free survival and cumulative overall survival in the study group were significantly better than in the control group (P = 0.034 and 0.016, respectively). CONCLUSION: Our study verifies the potential benefit and safety of adjuvant sorafenib for both decreasing HCC recurrence and extending disease-free and overall survival rates for patients with BCLC-stage C HCC after curative resection. PMID:27340354

  1. The clinical utility of FibroScan(®) as a noninvasive diagnostic test for liver disease.

    PubMed

    Wilder, Julius; Patel, Keyur

    2014-01-01

    An important aspect of managing chronic liver disease is assessing for evidence of fibrosis. Historically, this has been accomplished using liver biopsy, which is an invasive procedure associated with risk for complications and significant sampling and observer error, limiting the accuracy for determination of fibrosis stage. Hence, several serum biomarkers and imaging methods for noninvasive assessment of liver fibrosis have been developed. In this article, we review the current literature on an important noninvasive imaging modality to measure tissue elastography (FibroScan(®)). This ultrasound-based technique is now increasingly available in many countries and has been shown to be a reliable and safe noninvasive means of assessing disease severity in chronic liver disease of varying etiology.

  2. Assessment of fibrotic liver disease with multimodal nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Lu, Fake; Zheng, Wei; Tai, Dean C. S.; Lin, Jian; Yu, Hanry; Huang, Zhiwei

    2010-02-01

    Liver fibrosis is the excessive accumulation of extracellular matrix proteins such as collagens, which may result in cirrhosis, liver failure, and portal hypertension. In this study, we apply a multimodal nonlinear optical microscopy platform developed to investigate the fibrotic liver diseases in rat models established by performing bile duct ligation (BDL) surgery. The three nonlinear microscopy imaging modalities are implemented on the same sectioned tissues of diseased model sequentially: i.e., second harmonic generation (SHG) imaging quantifies the contents of the collagens, the two-photon excitation fluorescence (TPEF) imaging reveals the morphology of hepatic cells, while coherent anti-Stokes Raman scattering (CARS) imaging maps the distributions of fats or lipids quantitatively across the tissue. Our imaging results show that during the development of liver fibrosis (collagens) in BDL model, fatty liver disease also occurs. The aggregated concentrations of collagen and fat constituents in liver fibrosis model show a certain correlationship between each other.

  3. Circulating Markers of Liver Function and Cardiovascular Disease Risk.

    PubMed

    Targher, Giovanni; Byrne, Christopher D

    2015-11-01

    Measurement of serum concentrations of various liver enzymes and other nonenzymatic proteins and metabolites of heme metabolism (eg, bilirubin) is often undertaken in clinical practice. Measurement of these liver function tests is simple, quick, and relatively inexpensive. However, interpreting the liver function test results in patients without evidence of liver disease is often challenging. Concentrations of some of liver enzymes, such as γ-glutamyltransferase or alkaline phosphatase, and concentrations of liver-derived metabolites, such as bilirubin, may be influenced by metabolic processes beyond the liver, sometimes making interpretation of the test results difficult. This scenario frequently occurs both in individuals at risk of cardiovascular disease and in patients with known cardiovascular disease, often resulting in the clinicians ignoring the test results. In this brief review, we discuss the evidence for associations between key serum liver function tests and cardiovascular disease risk and where associations are robust; we provide an interpretation for possible mechanistic links between the liver function test and cardiovascular disease.

  4. Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite.

    PubMed

    Singh, Agam Prasad; Buscaglia, Carlos A; Wang, Qian; Levay, Agata; Nussenzweig, Daniel R; Walker, John R; Winzeler, Elizabeth A; Fujii, Hodaka; Fontoura, Beatriz M A; Nussenzweig, Victor

    2007-11-01

    The liver stages of malaria are clinically silent but have a central role in the Plasmodium life cycle. Liver stages of the parasite containing thousands of merozoites grow inside hepatocytes for several days without triggering an inflammatory response. We show here that Plasmodium uses a PEXEL/VTS motif to introduce the circumsporozoite (CS) protein into the hepatocyte cytoplasm and a nuclear localization signal (NLS) to enter its nucleus. CS outcompetes NFkappaB nuclear import, thus downregulating the expression of many genes controlled by NFkappaB, including those involved in inflammation. CS also influences the expression of over one thousand host genes involved in diverse metabolic processes to create a favorable niche for the parasite growth. The presence of CS in the hepatocyte enhances parasite growth of the liver stages in vitro and in vivo. These findings have far reaching implications for drug and vaccine development against the liver stages of the malaria parasite.

  5. Thrombosis in end-stage renal disease.

    PubMed

    Casserly, Liam F; Dember, Laura M

    2003-01-01

    Although renal failure has classically been associated with a bleeding tendency, thrombotic events are common among patients with end-stage renal disease (ESRD). A variety of thrombosis-favoring hematologic alterations have been demonstrated in these patients. In addition, "nontraditional" risk factors for thrombosis, such as hyperhomocysteinemia, endothelial dysfunction, inflammation, and malnutrition, are present in a significant proportion of chronic dialysis patients. Hemodialysis (HD) vascular access thrombosis, ischemic heart disease, and renal allograft thrombosis are well-recognized complications in these patients. Deep venous thrombosis and pulmonary embolism are viewed as rare in chronic dialysis patients, but recent studies suggest that this perception should be reconsidered. Several ESRD treatment factors such as recombinant erythropoietin (EPO) administration, dialyzer bioincompatibility, and calcineurin inhibitor administration may have prothrombotic effects. In this article we review the pathogenesis and clinical manifestations of thrombosis in ESRD and evaluate the evidence that chronic renal failure or its management predisposes to thrombotic events.

  6. 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.

  7. Vitamin A deficiency in patients with hepatitis C virus-related chronic liver disease.

    PubMed

    Peres, W A F; Chaves, G V; Gonçalves, J C S; Ramalho, A; Coelho, H S M

    2011-12-01

    Hepatitis C virus (HCV) infection is associated with oxidative stress and vitamin A possesses antioxidant activity. The objective of the present study was to investigate vitamin A nutritional status in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC), according to biochemical, functional and dietetic indicators correlating these findings with liver function, liver damage and death. Vitamin A nutritional status was analysed by serum retinol levels, dietetic indicators and functional indicators. A total of 140 patients with HCV-related liver disease were enrolled. Vitamin A deficiency was detected in 54·3 % of all patients, and there was a progressive drop in serum retinol levels from chronic hepatitis C patients towards cirrhosis and HCC patients. Increased total bilirubin, liver transaminases and prothrombin time, presence of hepatic encephalopathy and ascites were related to reduced serum retinol levels, and values ≤ 0·78 μmol/l of serum retinol were associated with liver-related death. A high prevalence of inadequate intake of vitamin A was observed in all stages of chronic liver disease. The functional indicator was not an adequate parameter for evaluating the vitamin A nutritional status. Therefore, serum retinol concentration is related to severity of the disease, liver complications and mortality. The effectiveness of nutritional counselling and measures of intervention in this group in improving vitamin A nutritional status should be examined further in a controlled study. PMID:21736776

  8. Urinary Biomarkers at Early ADPKD Disease Stage

    PubMed Central

    Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

    2015-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our

  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. Cell therapy for liver diseases: current medicine and future promises.

    PubMed

    Alejandra, Meza-Ríos; Juan, Armendáriz-Borunda; Ana, Sandoval-Rodríguez

    2015-06-01

    Liver diseases are a major health problem worldwide since they usually represent the main causes of death in most countries, causing excessive costs to public health systems. Nowadays, there are no efficient current therapies for most hepatic diseases and liver transplant is infrequent due to the availability of organs, cost and risk of transplant rejection. Therefore, alternative therapies for liver diseases have been developed, including cell-based therapies. Stem cells (SCs) are characterized by their self-renewing capacity, unlimited proliferation and differentiation under certain conditions into tissue- or organ-specific cells with special functions. Cell-based therapies for liver diseases have been successful in experimental models, showing anti-inflammatory, antifibrogenic and regenerative effects. Nowadays, clinical trials using SCs for liver pathologies are increasing in number, and those that have reached publication have achieved favorable effects, encouraging us to think that SCs will have a potential clinical use in a short time.

  11. Non-invasive Diagnosis of Fibrosis in Non-alcoholic Fatty Liver Disease

    PubMed Central

    Arora, Anil; Sharma, Praveen

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed as well as in developing countries. Its prevalence continues to rise currently affecting approximately 20-30% of adults and 10% of children in the United States. Non-alcoholic fatty liver disease represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign non-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several non-invasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. There has been a substantial development of non-invasive risk scores, biomarker panels, and radiological modalities to identify at risk patients with NAFLD without recourse to liver biopsy on a routine basis. Examples include combination of serum markers like NAFLD fibrosis score (NFS), BARD score, fibrometer, FIB4, and non-invasive tools like fibroscan which assess fibrosis in patients with NAFLD. Other markers of fibrosis that have been evaluated include high-sensitivity C-reactive protein, plasma pentraxin 3, interleukin-6, and cytokeratin-18. This review focuses on the methods currently available in daily clinical practice in hepatology and touches briefly on the potential future markers under investigation. PMID:25755423

  12. Study on Assessment of Renal Function in Chronic Liver Disease

    PubMed Central

    Das, Nupur; Paria, Baishakhi; Sarkar, Sujoy

    2015-01-01

    Introduction: Renal dysfunction is common in chronic liver disease. The cause of this renal dysfunction is either multi-organ involvement in acute conditions or secondary to advanced liver disease. Objectives: The study was undertaken to assess the renal function in chronic liver diseases and find out the association of alteration of renal function with gradation of liver disease. (assessed by child-pugh criteria) and to find out the association of alteration of renal function among the cases of chronic liver disease of different aetiology. Materials and Methods: This cross-sectional, observational study was undertaken in Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver disease after considering the exclusion criteria. The patients were interviewed with a pre-designed and pre-tested schedule, examined clinically, followed by some laboratory investigations relevant to diagnose the aetiology of chronic liver disease, and to assess the severity of liver and renal dysfunction. Data was analysed by standard statistical method. Results: Eighty six percent of the patients were male and the mean age of study population was 43.58 y, 68% patients suffered from alcoholic liver disease, followed by 14% patients had chronic Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal syndrome and 14% had IgA deposition. The distribution of serum urea and creatinine across the categories of Child Pugh classification tested by Mann-Whitney test and the distribution was statistically significant. Conclusion: The present study has found significant association between severity of liver dysfunction and certain parameters of renal dysfunction. PMID:25954647

  13. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

    PubMed

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully. PMID:27649152

  14. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

    PubMed

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

  15. Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus

    PubMed Central

    Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

    2016-01-01

    The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully. PMID:27649152

  16. Large-scale analysis of factors influencing nonalcoholic fatty liver disease and its relationship with liver enzymes.

    PubMed

    Bi, W R; Yang, C Q; Shi, Q; Xu, Y; Cao, C P; Ling, J; Wang, X Y

    2014-01-01

    Serum liver enzyme levels are often used effectively for the evaluation of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the associations between serum liver enzyme levels and risks for NAFLD in over 8000 cases in a large-scale analysis. A cross-sectional survey with multiple stages and random samplings was performed from May 2007 to May 2009 on 8102 workers at Tongji University. A questionnaire was given, assessments of physical measurements, plasma glucose, lipid profiles, and liver enzymes were made, and real-time liver ultrasounds conducted. The prevalence of NAFLD in Tongji University was 22.2%. It was higher in males than in females (P = 0.0023). The body mass index, waist-to-hip ratio, serum total triglycerides, serum total cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) values were all higher in the NAFLD group than in the control group. For moderate and severe NAFLD patients, the ALT, AST and GGT values were significantly increased, high density lipoprotein cholesterol was decreased, and drinking much, heavy entertainment and less exercise were more prevalent (P < 0.001). There were strong correlations between serum liver enzyme levels and NAFLD (P < 0.001), with GGT being a more sensitive marker for NAFLD than ALT or AST. ALT and GGT were independent predictors for NAFLD, and GGT was a better predictor than ALT for NAFLD. PMID:25117346

  17. Genetics of liver disease: From pathophysiology to clinical practice.

    PubMed

    Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

    2015-04-01

    Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients.

  18. Interactions Between the Intestinal Microbiome and Liver Diseases

    PubMed Central

    Schnabl, Bernd; Brenner, David A.

    2014-01-01

    The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease. PMID:24440671

  19. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis

    PubMed Central

    2013-01-01

    Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD. PMID:24133660

  20. Single-Pass Percutaneous Liver Biopsy for Diffuse Liver Disease Using an Automated Device: Experience in 154 Procedures

    SciTech Connect

    Rivera-Sanfeliz, Gerant Kinney, Thomas B.; Rose, Steven C.; Agha, Ayad K.M.; Valji, Karim; Miller, Franklin J.; Roberts, Anne C.

    2005-06-15

    Purpose: To describe our experience with ultrasound (US)-guided percutaneous liver biopsies using the INRAD 18G Express core needle biopsy system.Methods: One hundred and fifty-four consecutive percutaneous core liver biopsy procedures were performed in 153 men in a single institution over 37 months. The medical charts, pathology reports, and radiology files were retrospectively reviewed. The number of needle passes, type of guidance, change in hematocrit level, and adequacy of specimens for histologic analysis were evaluated.Results: All biopsies were performed for histologic staging of chronic liver diseases. The majority of patients had hepatitis C (134/153, 90.2%). All patients were discharged to home after 4 hr of postprocedural observation. In 145 of 154 (94%) biopsies, a single needle pass was sufficient for diagnosis. US guidance was utilized in all but one of the procedures (153/154, 99.4%). The mean hematocrit decrease was 1.2% (44.1-42.9%). Pain requiring narcotic analgesia, the most frequent complication, occurred in 28 of 154 procedures (18.2%). No major complications occurred. The specimens were diagnostic in 152 of 154 procedures (98.7%).Conclusions: Single-pass percutaneous US-guided liver biopsy with the INRAD 18G Express core needle biopsy system is safe and provides definitive pathologic diagnosis of chronic liver disease. It can be performed on an outpatient basis. Routine post-biopsy monitoring of hematocrit level in stable, asymptomatic patients is probably not warranted.

  1. Antioxidant Mechanisms in Nonalcoholic Fatty Liver Disease.

    PubMed

    Liu, Wensheng; Baker, Susan S; Baker, Robert D; Zhu, Lixin

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents a broad spectrum of histological abnormalities with clinical presentations ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH). Some NAFLD patients may progress to cirrhosis and ultimately hepatocellular carcinoma (HCC). Hepatic steatosis, the hallmark of NAFLD, is defined by the accumulation of triglycerides (TGs) in more than 5% of the hepatocytes. NASH is characterized by inflammation along with variable degrees of fibrosis in addition to steatosis. NAFLD has been considered to be the hepatic manifestation of metabolic syndrome (MS), as it is frequently associated with MS conditions such as insulin resistance (IR) and obesity. Hepatic steatosis mainly results from disrupted homeostasis of lipid metabolism in the setting of IR. Although the mechanism underlying the progression from steatosis to NASH is still not fully elucidated, mounting evidence has suggested oxidative stress (OS) to be a key driving force. Elevated OS has been well documented in NAFLD patients. OS can cause direct damages to lipid, protein, and DNA molecules and trigger the inflammatory and fibrogenesis signaling pathways, which promotes the progression from steatosis to NASH. OS may also have various effects on antioxidant defense mechanisms. Overproduced reactive oxygen species (ROS) may directly deplete antioxidant molecules such as glutathione (GSH) and inhibit the activities of antioxidant enzymes such as superoxide dismutase (SOD). ROS may also induce the expression of antioxidant genes to counteract the OS effects. The aim of this review is to discuss oxidative stress and antioxidant mechanisms in NAFLD.

  2. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  3. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  4. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  5. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  6. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  7. Addiction specialist's role in liver transplantation procedures for alcoholic liver disease

    PubMed Central

    Dom, Geert; Peuskens, Hendrik

    2015-01-01

    Although liver transplantation (LT) is performed increasingly for patients with end-stage alcoholic liver disease (ALD), the topic remains controversial. Traditionally, the role of an addiction specialist focused on the screening and identification of patients with a high risk on relapse in heavy alcohol use. These patients were in many cases subsequently excluded from a further LT procedure. Recently, awareness is growing that not only screening of patients but also offering treatment, helping patients regain and maintain abstinence is essential, opening up a broader role for the addiction specialist (team) within the whole of the transplant procedure. Within this context, high-risk assessment is proposed to be an indication of increasing addiction treatment intensity, instead of being an exclusion criterion. In this review we present an overview regarding the state of the art on alcohol relapse assessment and treatment in patients with alcohol use disorders, both with and without ALD. Screening, treatment and monitoring is suggested as central roles for the addiction specialist (team) integrated within transplant centers. PMID:26301051

  8. Associating liver partition with portal vein ligation and staged hepatectomy (ALPPS) for the treatment of liver tumors in children.

    PubMed

    Wiederkehr, Julio Cesar; Avilla, Sylvio Gilberto; Mattos, Elisângela; Coelho, Izabel Meister; Ledesma, Jorge Alberto; Conceição, Alexandra Fernandes; Wiederkehr, Henrique Aguiar; Wiederkehr, Barbara Aguiar

    2015-07-01

    Resection is the only curative treatment option for primary and secondary malignant tumors of the liver. Although curative resection is associated with long-term survival rates, it can only be performed in 10% of patients with primary tumors and 25% of patients with liver metastases. Liver insufficiency is one of the most serious postoperative complications of patients undergoing extensive liver resections. When total liver resection is necessary liver transplant is mandatory, with the burden of long-term immunosuppression and its complications. Among several different strategies to increase the resectability of liver tumors, portal vein occlusion (embolization or ligature), bilateral tumor resection in two stages, and resection combined with loco regional therapy are the most popular. A new strategy for patients with marginally resectable liver tumors previously considered to be unresectable was formally reported by Baumgart et al. in 2011, originally developed by Hans Schlitt in 2007. This technique consists of a two-staged hepatectomy with initial portal vein ligation and in situ splitting of the liver parenchyma, and it is known as ALPPS (associating liver partition with portal vein ligation for staged hepatectomy). The aim of this study is to present the first series of pediatric patients with marginally resectable liver tumors previously considered to be unresectable treated with two-stage hepatectomy with initial portal vein ligation and in situ splitting of the liver parenchyma. Two patients were diagnosed with hepatoblastoma, and one each with rhabdomyosarcoma, hepatocellular carcinoma, and nodular focal hyperplasia. ALPPS technique was considered whenever the future liver remnant (FLR) was 40% or less of the total liver volume (TLV) determined by CT or MRI scans. The ratio of FLR to TLV before the first procedure ranged from 0.15 to 0.38, with a mean±sd of 0.253±0.07. In all patients, a rapid growth of the FLR was observed. Estimates of the FRL volume

  9. Biomarkers in nonalcoholic fatty liver disease-the emperor has no clothes?

    PubMed

    Sanal, Madhusudana Girija

    2015-03-21

    Fatty liver is present in over ten percentage of the world population and it is a growing public health problem. Nonalcoholic fatty liver disease (NAFLD) is not a single disease, but encompasses a spectrum of diseases of different etiologies. It is difficult to find highly specific and sensitive diagnostic biomarkers when a disease is very complex. Therefore, we should aim to find relevant prognostic markers rather than accurate diagnostic markers which will help to minimize the frequency of liver biopsies to evaluate disease progression. There are several biomarker panels commercially available, however, there is no clear evidence that more sophisticated panels are better compared to simple criteria such as, presence of diabetes over five years, metabolic syndrome, obesity, obstructive sleep apnea, aspartate transaminase/alanine transaminase (ALT) ratio > 0.8 or ferritin levels > 1.5 times normal in patients with over six month history of raised ALT and/or ultrasonological evidence of fat in the liver. Currently the biomarker panels are not a replacement for a liver biopsy. However the need and benefit of liver biopsy in NAFLD is questionable because there is no convincing evidence that biopsy and detailed staging of NAFLD improves the management of NAFLD and benefits the patient. After all there is no evidence based treatment for NAFLD other than management of lifestyle and components of "metabolic syndrome". PMID:25805928

  10. [Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016].

    PubMed

    Pár, Alajos; Pár, Gabriella

    2016-06-19

    In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease. PMID:27287838

  11. [Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016].

    PubMed

    Pár, Alajos; Pár, Gabriella

    2016-06-19

    In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease.

  12. Nephrolithiasis-induced end stage renal disease

    PubMed Central

    Ounissi, M; Gargueh, T; Mahfoudhi, M; Boubaker, K; Hedri, H; Goucha, R; Abderrahim, E; Ben Hamida, F; Ben Abdallah, T; El Younsi, F; Ben Maiz, H; Kheder, A

    2010-01-01

    Introduction: Nephrolithiasis still remains a too frequent and underappreciated cause of end stage renal disease (ESRD). Methods and patients: Of the entire cohort of 7128 consecutive patients who started maintenance dialysis in our nephrology department between January 1992 and December 2006, a total of 45 patients (26 women, 19 men) had renal stone disease as the cause of ESRD. The type of nephrolithiasis was determined in 45 cases and etiology in 42. The treatment and evolution of stone disease and patient’s survival were studied. Results: The overall proportion of nephrolithiasis related ESRD was 0.63%. The mean age was 48.4 years. Infection stones (struvite) accounted for 40%, calcium stones, 26.67% (primary hyperparathyroidism:15.56%; familial hypercalciuria: 4.44%, unknown etiology: 6.66%), primary hyperoxaluria type 1, 17.78% and uric acid lithiasis in 15.56% of cases. The mean delay of the evolution of the stone renal disease to chronic renal failure was 85.8 months. The feminine gender, obesity and elevated alkaline phosphatases >128 IU/L were significantly correlated with fast evolution of ESRD. The median evolution to ESRD was 12 months. The normal body mass index (BMI), medical treatment of stone and primary hyperoxaluria type 1 were correlated with fast evolution to ESRD. All patients were treated by hemodialysis during a mean evolution of 60 months. Sixteen patients died. The patient's survival rate at 1, 3 and 5 years was 97.6, 92.8 and 69% respectively. Hypocalcemia, cardiopathy and normal calcium-phosphate product were significantly correlated with lower survival rate. Conclusion: Severe forms of nephrolithiasis remain an underestimated cause of ESRD. These findings highlight the crucial importance of accurate stone analysis and metabolic evaluation to provide early diagnosis and efficient treatment for conditions leading to ESRD. PMID:21694924

  13. Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease

    PubMed Central

    Dauvergne, Maxime; Moktefi, Anissa; Rabant, Marion; Vigneau, Cécile; Kofman, Tomek; Burtey, Stephane; Corpechot, Christophe; Stehlé, Thomas; Desvaux, Dominique; Rioux-Leclercq, Nathalie; Rouvier, Philippe; Knebelmann, Bertrand; Boffa, Jean-Jacques; Frouget, Thierry; Daugas, Eric; Jablonski, Mathieu; Dahan, Karine; Brocheriou, Isabelle; Remy, Philippe; Grimbert, Philippe; Lang, Philippe; Chazouilleres, Oliver; Sahali, Dil; Audard, Vincent

    2015-01-01

    Abstract The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined. We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens. The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was <1.5 years in 5 patients. MN was associated with a broad spectrum of liver diseases including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease. Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test was performed under specific immunosuppressive treatment in 3 out of 9 patients. Seven of the 9 patients with available renal tissue specimens displayed enhanced expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver parenchyma from these patients or in normal liver tissue. The study of immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4 predominating. Detection of PLA2R antibodies in glomeruli but not in liver parenchyma is a common finding in patients with MN associated with autoimmune liver disease, suggesting that these autoantibodies are not exclusively detected in idiopathic MN. PMID:26222864

  14. Nuclear Accident Crisis and Liver Disease: A Summary on Evidences

    PubMed Central

    Wiwanitkit, Viroj

    2013-01-01

    The present global concern is on the adverse effect due to exposure to nuclides expelled from the disrupted nuclear power plant accident in Japan. The exposure can induce several adverse effects. In this specific brief review, the author summarizes the evidences on the effect on liver. Discussion is focused on several liver diseases. PMID:25125994

  15. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development

    PubMed Central

    Vaughan, Ashley M; O'Neill, Matthew T; Tarun, Alice S; Camargo, Nelly; Phuong, Thuan M; Aly, Ahmed S I; Cowman, Alan F; Kappe, Stefan H I

    2009-01-01

    Intracellular malaria parasites require lipids for growth and replication. They possess a prokaryotic type II fatty acid synthesis (FAS II) pathway that localizes to the apicoplast plastid organelle and is assumed to be necessary for pathogenic blood stage replication. However, the importance of FAS II throughout the complex parasite life cycle remains unknown. We show in a rodent malaria model that FAS II enzymes localize to the sporozoite and liver stage apicoplast. Targeted deletion of FabB/F, a critical enzyme in fatty acid synthesis, did not affect parasite blood stage replication, mosquito stage development and initial infection in the liver. This was confirmed by knockout of FabZ, another critical FAS II enzyme. However, FAS II-deficient Plasmodium yoelii liver stages failed to form exo-erythrocytic merozoites, the invasive stage that first initiates blood stage infection. Furthermore, deletion of FabI in the human malaria parasite Plasmodium falciparum did not show a reduction in asexual blood stage replication in vitro. Malaria parasites therefore depend on the intrinsic FAS II pathway only at one specific life cycle transition point, from liver to blood. PMID:19068099

  16. Liver-Stage Specific Response among Endemic Populations: Diet and Immunity

    PubMed Central

    Dalai, Sarat Kumar; Yadav, Naveen; Patidar, Manoj; Patel, Hardik; Singh, Agam Prasad

    2015-01-01

    Developing effective anti-malarial vaccine has been a challenge for long. Various factors including complex life cycle of parasite and lack of knowledge of stage specific critical antigens are some of the reasons. Moreover, inadequate understanding of the immune responses vis-à-vis sterile protection induced naturally by Plasmodia infection has further compounded the problem. It has been shown that people living in endemic areas take years to develop protective immunity to blood stage infection. But hardly anyone believes that immunity to liver-stage infection could be developed. Various experimental model studies using attenuated parasite suggest that liver-stage immunity might exist among endemic populations. This could be induced because of the attenuation of parasite in liver by various compounds present in the diet of endemic populations. PMID:25852693

  17. Encephalopathy in Wilson disease: copper toxicity or liver failure?

    PubMed

    Ferenci, Peter; Litwin, Tomasz; Seniow, Joanna; Czlonkowska, Anna

    2015-03-01

    Hepatic encephalopathy (HE) is a complex syndrome of neurological and psychiatric signs and symptoms that is caused by portosystemic venous shunting with or without liver disease irrespective of its etiology. The most common presentation of Wilson disease (WD) is liver disease and is frequently associated with a wide spectrum of neurological and psychiatric symptoms. The genetic defect in WD leads to copper accumulation in the liver and later in other organs including the brain. In a patient presenting with Wilsonian cirrhosis neuropsychiatric symptoms may be caused either by the metabolic consequences of liver failure or by copper toxicity. Thus, in clinical practice a precise diagnosis is a great challenge. Contrary to HE in neurological WD consciousness, is very rarely disturbed and pyramidal signs, myoclonus dominate. Asterixis and many other clinical symptoms may be present in both disease conditions and are quite similar. However details of neurological assessment as well as additional examinations could help in differential diagnosis.

  18. Liver transplantation for Wilson's disease in pediatric patients: decision making and timing.

    PubMed

    Narumi, S; Umehara, M; Toyoki, Y; Ishido, K; Kudo, D; Kimura, N; Kobayashi, T; Sugai, M; Hakamada, K

    2012-03-01

    Transplantation for Wilson's disease occupies 1/3 of the cases for metabolic diseases in Japan. At the end of 2009, 109 transplantations had been performed including three deceased donor cases in the Japanese registry. We herein discuss problems of transplantation for Wilson's disease as well as its indication, timing, and social care. We retrospectively reviewed four fulminant cases and two chronic cases who underwent living donor liver transplantation. There were two boys and two girls. Four adolescents of average age 11.3 years underwent living donor liver transplantation. Duration from onset to transplantation ranged from 10 to 23 days. Average Model for End-stage Liver Disease (MELD) score was 27.8 (range=24-31). All patients were administrated chelates prior to transplantation. MELD, New Wilson's index, Japanese scoring for liver transplantation, and liver atrophy were useful tools for transplantation decision making; however, none of them was an independent decisive tool. Clinical courses after transplantation were almost uneventful. One girl, however, developed an acute rejection episode due to noncompliance at 3 years after transplantation. All patients currently survive without a graft loss. No disease recurrence had been noted even using living related donors. Two adults evaluated for liver transplantation were listed for deceased donor liver transplantation. Both candidates developed cirrhosis despite long-term medical treatment. There were no appropriate living donors for them. There are many problems in transplantation for Wilson's disease. The indications for liver transplantation should be considered individually using some decision-making tools. The safety of the living donor should be paid the most attention.

  19. [THE MODERN CONCEPTS OF HEMOSTASIS SYSTEM UNDER CHRONIC DISEASES OF LIVER: THE PUBLICATIONS REVIEW].

    PubMed

    Batirova, A S; Bakanov, M I; Surkov, A N

    2015-08-01

    The disorder of system of hemostasis under chronic diseases of liver results in coagulation imbalance affecting both primary and secondary hemostasis. The shifting of hemostasis balance beyond the limits of physiological standards in such patients can result either in bleeding or thrombosis. For a long time already it is considered that in patients with chronic diseases of liver alterations in hemostasis system and occurrence of bleeding are very often interrelated. However results of such screening coagulation tests as prothrombin time and activated partial thromboplastin time poorly correlate with onset and duration of bleeding, for example after liver biopsy and also with occurrence of gastro-intestinal bleeding in patients with terminal stage of diseases of liver The foreign publications of last decade contest concept of cause and effect relationship between changes of indicators of screening coagulation tests and risk of development of bleeding in patients with chronic diseases of liver The publications also dispute both usefulness of the given tests in evaluation of hemorrhages and expediency of therapeutic strategies in the case of correction of anomalous results of mentioned tests. This issue in patients with rare diseases is factually unexplored. For example, there are single publications concerning patients with glycogenous disease type. The bleeding in such patients begin in early childhood They are related to dysfunction of thrombocytes and decreasing of particular oligomers of von Willebrand factor Hence, disorders in various chains of hemostasis system in patients with chronic diseases of liver are characterized by many unresolved issues that hinder furthering of development of diagnostic biomarkers. At that, diagnostic of coagulopathies and correction of pathological conditions in such patients the new tests are to be developed to monitor states of hemostasis system in patients with chronic diseases of liver, rare nosologic forms included. PMID

  20. Chronic liver disease: evaluation by magnetic resonance

    SciTech Connect

    Stark, D.D.; Goldberg, H.I.; Moss, A.A.; Bass, N.M.

    1984-01-01

    Magnetic resonance (MR) imaging distinguished hepatitis from fatty liver and cirrhosis in a woman with a history of alcohol abuse. Anatomic and physiologic manifestations of portal hypertension were also demonstrated by MR.

  1. Lipids in Liver Disease: Looking Beyond Steatosis

    PubMed Central

    SCHWABE, ROBERT F.; MAHER, JACQUELYN J.

    2014-01-01

    See “Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury,” by Moustafa T, Fickert P, Magnes C, et al, on page 140; and “A high-cholesterol diet exacerbates liver fibrosis in mice via accumulation of free cholesterol in hepatic stellate cells,” by Teratani T, Tomita K, Suzuki T, et al, on page 152. PMID:22107717

  2. Veno-occlusive disease of the liver in captive cheetah.

    PubMed

    Gosselin, S J; Loudy, D L; Tarr, M J; Balistreri, W F; Setchell, K D; Johnston, J O; Kramer, L W; Dresser, B L

    1988-01-01

    Liver tissues from 126 captive cheetah were evaluated by light microscopy and histochemistry; eight animals were evaluated by electron microscopy. The main hepatic lesion, a vascular lesion resembling veno-occlusive disease (VOD) of the liver and characterized by subendothelial fibrosis and proliferation of smooth muscle-like cells in the central veins, was seen in 60% of the sexually mature cheetah. Although this hepatic vascular lesion was seen in cheetah as young as 1 year of age, the most severe lesions, usually associated with liver failure, were found in cheetah between the ages of 6 and 11. There was no sex predisposition, and in approximately 40% of the VOD cases, liver disease was not suspected clinically or at necropsy. VOD was found in other felidae, especially in the snow leopard. High levels of vitamin A in livers, as well as in diets of the cheetah, could be a contributing factor in the development of VOD in some groups of cheetah.

  3. Connexin and pannexin signaling in gastrointestinal and liver disease

    PubMed Central

    Maes, Michaël; Yanguas, Sara Crespo; Willebrords, Joost; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Gap junctions, which mediate intercellular communication, are key players in digestive homeostasis. They are also frequently involved in gastrointestinal and liver pathology. This equally holds true for connexin hemichannels, the structural precursors of gap junctions, and pannexin channels, connexin-like proteins assembled in a hemichannel configuration. Both connexin hemichannels and pannexin channels facilitate extracellular communication and drive a number of deteriorative processes, such as cell death and inflammation. Connexins, pannexins and their channels underlie a wide spectrum of gastrointestinal and liver diseases, including gastritis and peptic ulcer disease, inflammatory intestinal conditions, acute liver failure, cholestasis, hepatitis and steatosis, liver fibrosis and cirrhosis, infectious gastrointestinal pathologies, and gastrointestinal and liver cancer. This could open promising perspectives for the characterization of new targets and biomarkers for therapeutic and diagnostic clinical purposes in the area of gastroenterology and hepatology. PMID:26051630

  4. Utility of Noninvasive Markers of Fibrosis in Cholestatic Liver Diseases.

    PubMed

    Corpechot, Christophe

    2016-02-01

    Methods of liver fibrosis assessment have changed considerably in the last 20 years, and noninvasive markers now have been recognized as major first-line tools in the management of patients with chronic viral hepatitis infection. But what about the efficiency and utility of these surrogate indices for the more uncommon chronic cholestatic liver diseases, namely primary biliary cirrhosis and primary sclerosing cholangitis? This article provides clinicians with a global overview of what is currently known in the field. Both diagnostic and prognostic aspects of noninvasive markers of fibrosis in cholestatic liver diseases are presented and discussed.

  5. An inhibitor of interleukin-6 trans-signalling, sgp130, contributes to impaired acute phase response in human chronic liver disease

    PubMed Central

    Lemmers, A; Gustot, T; Durnez, A; Evrard, S; Moreno, C; Quertinmont, E; Vercruysse, V; Demetter, P; Franchimont, D; Le Moine, O; Geerts, A; Devière, J

    2009-01-01

    In chronic liver disease, high circulating interleukin (IL)-6 contrasts with a poor acute phase response. We evaluated the impact of liver and circulating IL-6-receptor (IL-6R) forms on IL-6 bioactivity in chronic liver disease. IL-6, soluble IL-6-receptor and sgp130 levels were assayed in plasma from 45 patients with alcoholic liver disease, 84 with hepatitis C virus (HCV) infection undergoing transjugular liver biopsies and 15 healthy subjects. IL-6R mRNA was quantified on liver extracts from 54 patients with alcoholic liver disease with or without cirrhosis and 18 HCV-infected patients. The effect of gp130–Fc on fibrinogen secretion induced by IL-6 trans-signalling was evaluated on hepatocyte cultures. Levels of plasma IL-6 and sgp130, but not soluble IL-6R, increased with the stage of chronic liver disease, and correlated significantly with disease severity. Alcoholic liver disease patients had higher plasma IL-6 levels than hepatitis C, but lower liver IL-6R expression. In alcoholic and HCV-related liver diseases, liver IL-6R expression decreased with advanced fibrosis stage. In vitro, on hepatocytes, gp130–Fc blunted the acute phase response while soluble IL-6R enhanced IL-6 stimulation. In advanced chronic liver disease, high plasma IL-6 is associated with low liver IL-6R expression. This situation enables high plasma sgp130 to act as a major negative regulator of liver IL-6 trans-signalling, as demonstrated functionally here on hepatocytes. This might explain the poor acute phase response induced by IL-6 in chronic liver disease. PMID:19438606

  6. Innate immune signaling and gut-liver interactions in non-alcoholic fatty liver disease

    PubMed Central

    Trautwein, Christian

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and covers a disease spectrum ranging from steatosis to inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The innate immune response in the liver plays an important role during NAFLD progression. In addition, changes in the intestinal microbial balance and bacterial translocation can further affect disease progression. Immune cells in the liver recognize cell damage or pathogen invasion with intracellular or surface-expressed pattern recognition receptors (PRRs), subsequently initiating signaling cascades that trigger the release of factors promoting the inflammatory response during NAFLD progression. Therefore, mechanisms by which cells of the immune system are activated and recruited into the liver and how these cells cause injury and stress are important for understanding the inflammatory response during NAFLD. PMID:25568861

  7. Therapeutic Effects of Mesenchymal Stem Cells for Patients with Chronic Liver Diseases: Systematic Review and Meta-analysis.

    PubMed

    Kim, Gaeun; Eom, Young Woo; Baik, Soon Koo; Shin, Yeonghee; Lim, Yoo Li; Kim, Moon Young; Kwon, Sang Ok; Chang, Sei Jin

    2015-10-01

    Based on their ability to differentiate into multiple cell types including hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been suggested as an effective therapy for chronic liver diseases. The aim of this study was to evaluate the safety, efficacy and therapeutic effects of MSCs in patients with chronic liver disease through a literature-based examination. We performed a systematic review (SR) and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to identify clinical studies in which patients with liver diseases were treated with MSC therapy. Of the 568 studies identified by the initial literature search, we analyzed 14 studies and 448 patients based on our selection criteria. None of the studies reported the occurrence of statistically significant adverse events, side effects or complications. The majority of the analyzed studies showed improvements in liver function, ascites and encephalopathy. In particular, an MA showed that MSC therapy improved the total bilirubin level, the serum albumin level and the Model for End-stage Liver Disease (MELD) score after MSC treatment. Based on these results, MSC transplantation is considered to be safe for the treatment of chronic liver disease. However, although MSCs are potential therapeutic agents that may improve liver function, in order to obtain meaningful insights into their clinical efficacy, further robust clinical studies must be conducted to evaluate the clinical outcomes, such as histological improvement, increased survival and reduced liver-related complications, in patients with chronic liver disease.

  8. Opioid Drugs in Patients With Liver Disease: A Systematic Review

    PubMed Central

    Soleimanpour, Hassan; Safari, Saeid; Shahsavari Nia, Kavous; Sanaie, Sarvin; Alavian, Seyed Moayed

    2016-01-01

    Context The liver, one of the most important organs of the body, is known to be responsible for several functions. The functional contribution of the liver to the metabolism of carbohydrates, protein, drugs and toxins, fats and cholesterol and many other biological processes are still unknown. Liver disorders are classified into two types: acute and chronic. Different drugs are used in liver diseases to treat and control pain. Most pain relief medications such as opioids are metabolized via the liver; therefore, the adverse reactions of drugs are probably higher for patients with liver disease. The current study aimed to evaluate the effects of opioid drugs on patients with liver disease; therefore, it is necessary to select suitable opioids for such patients. Evidence Acquisition This review was written by referring to research literature including 70 articles and four textbooks published from 1958 to 2015 on various reputable sites. Searches were carried out on the key phrases of narcotic pain relievers (opioids), acute and chronic hepatic failure, opioid adverse drug reactions, drug-induced liver injury (DILI) and other similar keywords. References included a variety of research papers (descriptive and analytical), intervention and review articles. Results In patients with liver disease, administration of opioid analgesics should be observed, accurately. As a general rule, lower doses of drugs should be administered at regular intervals based on the signs of drug accumulation. Secondly, the interactions of opioid drugs with different levels of substrates of the P450 cytochrome enzyme should be considered. Conclusions Pain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids. Opioids should be used cautiously since they can cause sedation, constipation and sudden encephalopathy effects. Since the clearance of these drugs in patients with hepatic insufficiency is decreased

  9. Diagnosis, disease stage, and distress of Chinese cancer patients

    PubMed Central

    Huang, Boyan; Chen, Huiping; Deng, Yaotiao; Yi, Tingwu; Wang, Yuqing

    2016-01-01

    Background The objective is to assess how cancer patients know about their diagnosis what they know about their real stage, and the relationship between cancer stage and psychological distress. Methods A questionnaire including the Distress Thermometer was delivered to 422 cancer inpatients. Multivariate logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results Most of patients (68.7%) knew the bad news immediately after diagnosis. Half of patients knew their diagnosis directly from medical reports. Nearly one third of patients were informed by doctors. Cancer stages, which patients believed, differed significantly from their real disease stages (P<0.001). Over half of patients did not know their real disease stages. Patients with stage I–III cancer were more likely to know their real disease stage than patients with stage IV cancer (P<0.001). Distress scores of cancer patients were determined by the real cancer stage (P=0.012), not the stage which patients believed. Conclusions Although most of participants knew the bad news immediately after diagnosis, less than half of them knew their real disease stage. Patient with stage I–III cancer was more likely to know the real disease stage and had a DT score <4 than patient with stage IV disease. PMID:27004220

  10. Management of Alcohol Dependence in Patients with Liver Disease

    PubMed Central

    Addolorato, Giovanni; Mirijello, Antonio; Leggio, Lorenzo; Ferrulli, Anna; Landolfi, Raffaele

    2016-01-01

    Alcohol dependence represents a chronic and relapsing disease affecting nearly 10% of the general population both in the United States and in Europe, with a widespread burden of morbidity and mortality. Alcohol dependence represents the most common cause of liver damage in the Western Countries. Although alcoholic liver disease is associated primarily with heavy drinking, continued alcohol consumption, even in low doses after the onset of liver disease, increases the risk of severe consequences, including mortality. Consequently the ideal treatment of patients affected by alcohol dependence and alcoholic liver disease should aim at achieving long-term total alcohol abstinence and preventing relapse. The aim of the present review is to provide an update on the management of alcohol dependence in patients with alcoholic liver disease. Increasing evidences suggests the usefulness of psychosocial interventions and medications combined in order to reduce alcohol intake, promote abstinence and prevent relapse in alcohol dependent patients. Disulfiram, naltrexone and acamprosate have been approved for this indication; gamma-hydroxybutyric acid (GHB) is approved in Italy and Austria. However, these drugs have not been tested in patients with advanced liver disease. Amongst other emerging pharmacotherapies for alcoholism, topiramate, ondansetron, and baclofen seem the most promising ones. Both topiramate and ondansetron hold a safe profile in alcoholic patients; however, none of them has been tested in alcoholic patients with advanced liver disease. To date, baclofen represents the only anti-craving medication formally tested in a randomized clinical trial in alcoholic patients affected by liver cirrhosis, although additional confirmatory studies are warranted. PMID:23456576

  11. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development.

    PubMed

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C; Hedgepeth, John W; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E; Amacher, Sharon L; Goessling, Wolfram

    2016-10-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic vs. pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. PMID:27474396

  12. Fontan-associated liver disease: Implications for heart transplantation.

    PubMed

    Greenway, Steven C; Crossland, David S; Hudson, Mark; Martin, Steven R; Myers, Robert P; Prieur, Tim; Hasan, Asif; Kirk, Richard

    2016-01-01

    Chronic liver diseases are associated with multiple complications, including cirrhosis, portal hypertension, ascites, synthetic dysfunction and hepatocellular carcinoma, and these processes are increasingly recognized in post-Fontan patients. Fontan-associated liver disease (FALD) can be defined as abnormalities in liver structure and function that result from the Fontan circulation and are not related to another disease process. FALD arises due to chronic congestion of the liver created by the elevated venous pressure and low cardiac output of the Fontan circulation, which may be superimposed on previous liver injury. Pathology studies have generally shown that FALD worsens as time post-Fontan increases, but the prevalence of FALD is not well defined because the majority of Fontan patients, even those with significant hepatic fibrosis, appear to be asymptomatic and biochemical or functional hepatic abnormalities are usually subtle or absent. Alternate non-invasive investigations, derived from the study of other chronic liver diseases, have been tested in small series of pediatric and adult Fontan patients, but they have been confounded by congestion and do not correlate well with liver biopsy findings. Liver disease can complicate Fontan circulatory failure and may even be significant enough to be considered a contraindication to heart transplantation or require combined heart-liver transplantation. The search for the optimal management strategy continues in the setting of increasing numbers of Fontan patients surviving to adulthood and being referred for heart transplantation. Thus, in this review we attempt to define the scope and significance of FALD and address transplant-related assessment and management of this challenging disorder. PMID:26586487

  13. Circulating microRNAs as Potential Biomarkers in Non-Alcoholic Fatty Liver Disease and Hepatocellular Carcinoma

    PubMed Central

    Afonso, Marta B.; Rodrigues, Pedro M.; Simão, André L.; Castro, Rui E.

    2016-01-01

    Obesity and metabolic syndrome are growing epidemics worldwide and greatly responsible for many liver diseases, including nonalcoholic fatty liver disease (NAFLD). NAFLD often progresses to cirrhosis, end-stage liver failure and hepatocellular carcinoma (HCC), the most common primary liver cancer and one of the leading causes for cancer-related deaths globally. Currently available tools for the diagnosis of NAFLD staging and progression towards HCC are largely invasive and of limited accuracy. In light of the need for more specific and sensitive noninvasive molecular markers, several studies have assessed the potential of circulating microRNAs (miRNAs) as biomarkers of liver injury and hepatocarcinogenesis. Indeed, extracellular miRNAs are very stable in the blood, can be easily quantitated and are differentially expressed in response to different pathophysiological conditions. Although standardization procedures and larger, independent studies are still necessary, miRNAs constitute promising, clinically-useful biomarkers for the NAFLD-HCC spectrum. PMID:26950158

  14. Pediatric liver transplantation in metabolic disease: clinical decision making.

    PubMed

    Shneider, Benjamin L

    2002-02-01

    Proper utilization of liver transplantation in the management of pediatric metabolic diseases requires a comprehensive understanding of both metabolic disease and the risk and benefits of transplantation. This brief review focuses on issues that pertain to the treatment of tyrosinemia type I, bile acid biosynthesis disorders, primary hyperoxaluria, Crigler-Najjar Type I, and mitochondrial diseases. These entities are used as prototypes to illustrate many of the principles that are applied in a more general sense to the management of metabolic diseases. The natural history of these disorders are considered in the context of the risks of liver transplantation. Indications, contraindications, and both current and future alternatives to transplantation, are considered.

  15. [Peritoneoscopy and liver biopsy in the diagnosis of liver disease (author's transl)].

    PubMed

    Leuschner, U; Leuschner, M; Strohm, W D; Hübner, K; Kurtz, W; Hagenmüller, F

    1981-12-01

    In two prospective studies including 962 patients and one retrospective study including 165 patients the problem was investigated, to what extend ultrasonography might change the diagnostic value of clinical examination, peritoneoscopy, guided liver biopsy and blind liver biopsy. It turned out, that liver biopsy is the method of choice in diffuse-parenchymatous disease (e.g. chronic active hepatitis, chronic persistent hepatitis, fatty liver), whereas laparoscopy is to be preferred if focal lesions (e.g. liver carcinoma) are present. Diffuse liver disease was present in 80% of the cases investigated; in this group of patients the diagnostic value of blind biopsy is equivalent to the diagnostic value of guided biopsy. Thus, blind biopsy does yield satisfactory results in most patients if it is possible to differentiate between diffuse and focal disease by ultrasonography. Such differentiation could be achieved in 77-98% of our cases, thus ultrasonography could intake a decrease in numbers of peritoneoscopies and an increase of blind liver biopsy.

  16. Modeling of liver metastatic disease with applied drug therapy.

    PubMed

    Filipovic, Nenad; Djukic, Tijana; Saveljic, Igor; Milenkovic, Petar; Jovicic, Gordana; Djuric, Marija

    2014-07-01

    Colorectal carcinoma is acknowledged as the second leading cause of total cancer-related death in the European Region. The majority of deaths related to colorectal carcinoma are connected with liver metastatic disease. Approximately, in 25% of all patients, liver metastatic disease is diagnosed at the same time as the primary diagnosis, while up to a quarter of others would develop liver metastases in the course of the illness. In this study, we developed reaction-diffusion model and analyzed the effect of drug therapy on liver metastatic disease for a specific patient. Tumor volumes in specific time points were obtained using CT scan images. The nonlinear function for cell proliferation rate as well as data about clinically applied drug therapy was included in the model. Fitting procedure was used for parameter estimation. Good agreement of numerical and experimental results shows the feasibility and efficacy of the proposed system. PMID:24831076

  17. Hyperphosphatemia in end-stage renal disease.

    PubMed

    Indridason, Olafur S; Quarles, L Darryl

    2002-07-01

    Hyperphosphatemia occurs universally in end-stage renal disease (ESRD) unless efforts are made to prevent positive phosphate balance. Positive phosphate balance results from the loss of renal elimination of phosphate and continued obligatory intestinal absorption of dietary phosphate. Increased efflux of phosphate from bone because of excess parathyroid hormone-mediated bone resorption can also contribute to increased serum phosphate concentrations in the setting of severe hyperparathyroidism. It is important to treat hyperphosphatemia because it contributes to the pathogenesis of hyperparathyroidism, vascular calcifications, and increased cardiovascular mortality in ESRD patients. Attaining a neutral phosphate balance, which is the key to the management of hyperphosphatemia in ESRD, is a challenge. Control of phosphorus depends on its removal during dialysis and the limitation of gastrointestinal absorption by dietary phosphate restriction and chelation of phosphate. Knowledge of the quantitative aspects of phosphate balance is useful in optimizing our use of phosphate binders, dialysis frequency, and vitamin D sterols. The development of new phosphate binders and efforts to find new ways to inhibit gastrointestinal absorption of phosphate will lead to improvements in the control of serum phosphate levels in ESRD. PMID:12203200

  18. Proteomic analysis of liver tissue from HBx-transgenic mice at early stages of hepatocarcinogenesis.

    PubMed

    Kim, Sun-Young; Lee, Phil Young; Shin, Hye-Jun; Kim, Do Hyung; Kang, Sunghyun; Moon, Hyung-Bae; Kang, Sang Won; Kim, Jin-Man; Park, Sung Goo; Park, Byoung Chul; Yu, Dae-Yeul; Bae, Kwang-Hee; Lee, Sang Chul

    2009-11-01

    The hepatitis B virus X-protein (HBx), a multifunctional viral regulator, participates in the viral life cycle and in the development of hepatocellular carcinoma (HCC). We previously reported a high incidence of HCC in transgenic mice expressing HBx. In this study, proteomic analysis was performed to identify proteins that may be involved in hepatocarcinogenesis and/or that could be utilized as early detection biomarkers for HCC. Proteins from the liver tissue of HBx-transgenic mice at early stages of carcinogenesis (dysplasia and hepatocellular adenoma) were separated by 2-DE, and quantitative changes were analyzed. A total of 22 spots displaying significant quantitative changes were identified using LC-MS/MS. In particular, several proteins involved in glucose and fatty acid metabolism, such as mitochondrial 3-ketoacyl-CoA thiolase, intestinal fatty acid-binding protein 2 and cytoplasmic malate dehydrogenase, were differentially expressed, implying that significant metabolic alterations occurred during the early stages of hepatocarcinogenesis. The results of this proteomic analysis provide insights into the mechanism of HBx-mediated hepatocarcinogenesis. Additionally, this study identifies possible therapeutic targets for HCC diagnosis and novel drug development for treatment of the disease.

  19. Expression patterns and action analysis of genes associated with drug-induced liver diseases during rat liver regeneration

    PubMed Central

    Ning, Qian-Ji; Qin, Shao-Wei; Xu, Cun-Shuan

    2006-01-01

    AIM: To study the action of the genes associated with drug-induced liver diseases at the gene transcriptional level during liver regeneration (LR) in rats. METHODS: The genes associated with drug-induced liver diseases were obtained by collecting the data from databases and literature, and the gene expression changes in the regenerating liver were checked by the Rat Genome 230 2.0 array. RESULTS: The initial and total expression numbers of genes occurring in phases of 0.5-4 h after partial hepatectomy (PH), 4-6 h after PH (G0/G1 transition), 6-66 h after PH (cell proliferation), 66-168 h after PH (cell differentiation and structure-function reconstruction) were 21, 3, 9, 2 and 21, 9, 19, 18, respectively. It is illustrated that the associated genes were mainly triggered at the initial stage of LR and worked at different phases. According to their expression similarity, these genes were classified into 5 types: only up-regulated (12 genes), predominantly up-regulated (4 genes), only down-regulated (11 genes), predominantly down-regulated (3 genes), and approximately up-/down-regulated (2 genes). The total times of their up- and down-expression were 130 and 79, respectively, demonstrating that expression of most of the genes was increased during LR, while a few decreased. The cell physiological and biochemical activities during LR were staggered according to the time relevance and were diverse and complicated in gene expression patterns. CONCLUSION: Drug metabolic capacity in regenerating liver was enhanced. Thirty-two genes play important roles during liver regeneration in rats. PMID:17109518

  20. MR imaging features of focal liver lesions in Wilson disease.

    PubMed

    Dohan, Anthony; Vargas, Ottavia; Dautry, Raphael; Guerrache, Youcef; Woimant, France; Hamzi, Lounis; Boudiaf, Mourad; Poujois, Aurelia; Faraoun, Sid Ahmed; Soyer, Philippe

    2016-09-01

    Hepatic involvement in Wilson disease (WD) manifests as a diffuse chronic disease in the majority of patients. However, in a subset of patients focal liver lesions may develop, presenting with a wide range of imaging features. The majority of focal liver lesions in patients with WD are benign nodules, but there are reports that have described malignant liver tumors or dysplastic nodules in these patients. Because of the possibility of malignant transformation of liver nodules, major concerns have been raised with respect to the management and follow-up of patients with WD in whom focal liver lesions have been identified. The assessment of liver involvement in patients with WD is generally performed with ultrasonography. However, ultrasonography conveys limited specificity so that magnetic resonance (MR) imaging is often performed to improve lesion characterization. This review was performed to illustrate the spectrum of MR imaging features of focal liver lesions that develop in patients with WD. It is assumed that familiarity with the MR imaging presentation of focal liver lesions in WD may help clarify the actual nature of hepatic nodules in patients with this condition. PMID:27116011

  1. MR imaging features of focal liver lesions in Wilson disease.

    PubMed

    Dohan, Anthony; Vargas, Ottavia; Dautry, Raphael; Guerrache, Youcef; Woimant, France; Hamzi, Lounis; Boudiaf, Mourad; Poujois, Aurelia; Faraoun, Sid Ahmed; Soyer, Philippe

    2016-09-01

    Hepatic involvement in Wilson disease (WD) manifests as a diffuse chronic disease in the majority of patients. However, in a subset of patients focal liver lesions may develop, presenting with a wide range of imaging features. The majority of focal liver lesions in patients with WD are benign nodules, but there are reports that have described malignant liver tumors or dysplastic nodules in these patients. Because of the possibility of malignant transformation of liver nodules, major concerns have been raised with respect to the management and follow-up of patients with WD in whom focal liver lesions have been identified. The assessment of liver involvement in patients with WD is generally performed with ultrasonography. However, ultrasonography conveys limited specificity so that magnetic resonance (MR) imaging is often performed to improve lesion characterization. This review was performed to illustrate the spectrum of MR imaging features of focal liver lesions that develop in patients with WD. It is assumed that familiarity with the MR imaging presentation of focal liver lesions in WD may help clarify the actual nature of hepatic nodules in patients with this condition.

  2. Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

    PubMed

    Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

    2015-10-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem. PMID:26620035

  3. The Circulatory System in Liver Disease.

    PubMed

    Hollenberg, Steven M; Waldman, Brett

    2016-07-01

    In the cirrhotic liver, distortion of the normal liver architecture is caused by structural and vascular changes. Portal hypertension is often associated with a hyperdynamic circulatory syndrome in which cardiac output and heart rate are increased and systemic vascular resistance is decreased. The release of several vasoactive substances is the primary factor involved in the reduction of mesenteric arterial resistance, resulting in sodium and water retention with eventual formation of ascites. Management of these patients with acute cardiac dysfunction often requires invasive hemodynamic monitoring in an intensive care unit setting to tailor decisions regarding use of fluids and vasopressors.

  4. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    SciTech Connect

    Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  5. Molecular mechanisms of alcoholic liver disease: innate immunity and cytokines.

    PubMed

    Miller, Andrew M; Horiguchi, Norio; Jeong, Won-Il; Radaeva, Svetlana; Gao, Bin

    2011-05-01

    Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases worldwide, causing fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma. In the past few decades, significant progress has been made in our understanding of the molecular mechanisms underlying alcoholic liver injury. Activation of innate immunity components such as Kupffer cells, LPS/TLR4, and complements in response to alcohol exposure plays a key role in the development and progression of alcoholic liver disease (ALD). LPS activation of Kupffer cells also produces IL-6 and IL-10 that may play a protective role in ameliorating ALD. IL-6 activates signal transducer and activator of transcription 3 (STAT3) in hepatocytes and sinusoidal endothelial cells, while IL-10 activates STAT3 in Kupffer cells/macrophages, subsequently protecting against ALD. In addition, alcohol consumption also inhibits some components of innate immunity such as natural killer (NK) cells, a type of cells that play key roles in anti-viral, anti-tumor, and anti-fibrotic defenses in the liver. Ethanol inhibition of NK cells likely contributes significantly to the pathogenesis of ALD. Understanding the roles of innate immunity and cytokines in alcoholic liver injury may provide insight into novel therapeutic targets in the treatment of alcoholic liver disease. PMID:21284667

  6. Immunology in the liver--from homeostasis to disease.

    PubMed

    Heymann, Felix; Tacke, Frank

    2016-02-01

    The liver is a central immunological organ with a high exposure to circulating antigens and endotoxins from the gut microbiota, particularly enriched for innate immune cells (macrophages, innate lymphoid cells, mucosal-associated invariant T (MAIT) cells). In homeostasis, many mechanisms ensure suppression of immune responses, resulting in tolerance. Tolerance is also relevant for chronic persistence of hepatotropic viruses or allograft acceptance after liver transplantation. The liver can rapidly activate immunity in response to infections or tissue damage. Depending on the underlying liver disease, such as viral hepatitis, cholestasis or NASH, different triggers mediate immune-cell activation. Conserved mechanisms such as molecular danger patterns (alarmins), Toll-like receptor signalling or inflammasome activation initiate inflammatory responses in the liver. The inflammatory activation of hepatic stellate and Kupffer cells results in the chemokine-mediated infiltration of neutrophils, monocytes, natural killer (NK) and natural killer T (NKT) cells. The ultimate outcome of the intrahepatic immune response (for example, fibrosis or resolution) depends on the functional diversity of macrophages and dendritic cells, but also on the balance between pro-inflammatory and anti-inflammatory T-cell populations. As reviewed here, tremendous progress has helped to understand the fine-tuning of immune responses in the liver from homeostasis to disease, indicating promising targets for future therapies in acute and chronic liver diseases. PMID:26758786

  7. Liver transplantation in glycogen storage disease type I

    PubMed Central

    2014-01-01

    Glycogen storage disease type I (GSDI), an inborn error of carbohydrate metabolism, is caused by defects in the glucose-6-transporter/glucose-6-phosphatase complex, which is essential in glucose homeostasis. Two types exist, GSDIa and GSDIb, each caused by different defects in the complex. GSDIa is characterized by fasting intolerance and subsequent metabolic derangements. In addition to these clinical manifestations, patients with GSDIb suffer from neutropenia with neutrophil dysfunction and inflammatory bowel disease. With the feasibility of novel cell-based therapies, including hepatocyte transplantations and liver stem cell transplantations, it is essential to consider long term outcomes of liver replacement therapy. We reviewed all GSDI patients with liver transplantation identified in literature and through personal communication with treating physicians. Our review shows that all 80 GSDI patients showed improved metabolic control and normal fasting tolerance after liver transplantation. Although some complications might be caused by disease progression, most complications seemed related to the liver transplantation procedure and subsequent immune suppression. These results highlight the potential of other therapeutic strategies, like cell-based therapies for liver replacement, which are expected to normalize liver function with a lower risk of complications of the procedure and immune suppression. PMID:24716823

  8. Liver-derived human mesenchymal stem cells: a novel therapeutic source for liver diseases.

    PubMed

    Wang, Yini; Yu, Xiaopeng; Chen, Ermei; Li, Lanuan

    2016-01-01

    Mesenchymal stem cells (MSCs) represent an attractive cell type for research and therapy due to their ability to proliferate, differentiate, modulate immune reactions, and secrete trophic factors. MSCs exist in a multitude of tissues, including bone marrow, umbilical cord, and adipose tissues. Moreover, MSCs have recently been isolated from the liver. Compared with other MSC types, liver-derived human MSCs (LHMSCs) possess general morphologies, immune functions, and differentiation capacities. Interestingly, LHMCSs produce higher levels of pro-angiogenic, anti-inflammatory, and anti-apoptotic cytokines than those of bone marrow-derived MSCs. Thus, these cells may be a promising therapeutic source for liver diseases. This paper summarizes the biological characteristics of LHMSCs and their potential benefits and risks for the treatment of liver diseases. PMID:27176654

  9. Herbal medicine in the treatment of liver diseases.

    PubMed

    Stickel, F; Schuppan, D

    2007-04-01

    Herbal drugs have become increasingly popular and their use is widespread. Licensing regulations and pharmacovigilance regarding herbal products are still incomplete and clearcut proof of their efficacy in liver diseases is sparse. Nevertheless, a number of herbals show promising activity including silymarin for antifibrotic treatment, phyllantus amarus in chronic hepatitis B, glycyrrhizin to treat chronic viral hepatitis, and a number of herbal combinations from China and Japan that deserve testing in appropriate studies. Apart from therapeutic properties, reports are accumulating about liver injury after the intake of herbals, including those advertised for liver diseases. Acute and/or chronic liver damage occurred after ingestion of some Chinese herbs, herbals that contain pyrrolizidine alkaloids, germander, greater celandine, kava, atractylis gummifera, callilepsis laureola, senna alkaloids, chaparral and many others. Since the evidence supporting the use of botanicals to treat chronic liver diseases is insufficient and only few of them are well standardised and free of potential serious side effects, most of these medications are not recommended outside clinical trials. Particularly with regard to the latter, adequately powered randomised-controlled clinical trials with well-selected end points are needed to assess the role of herbal therapy for liver diseases. PMID:17331820

  10. Bleeding and clotting disorders in pediatric liver disease.

    PubMed

    Wicklund, Brian M

    2011-01-01

    The coagulopathy of liver disease in pediatric patients presents an unusual set of challenges. Little pediatric data have been published, so this review is based largely on adult studies. There is a precarious balance between deficiencies of clotting factors and anticoagulation factors in liver disease that result in abnormal prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests that would suggest a bleeding tendency, yet the patients can form a clot and are at risk of thromboembolic disease. Attention has centered on thromboelastography and thrombin-generation assays to clarify the patient's ability to control bleeding, but these tests are not routinely available to many treating physicians.

  11. Treatment of autoimmune liver disease: current and future therapeutic options

    PubMed Central

    Trivedi, Palak J.

    2013-01-01

    Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice. PMID:23634279

  12. Chronic liver disease in Kuala Lumpur, Malaysia: a clinical study.

    PubMed

    Kudva, M V; Zawawi, M M

    1990-08-01

    This study was undertaken to analyse the clinical spectrum of chronic liver disease (cirrhosis, and others with portal hypertension) in Kuala Lumpur. Eighty patients were diagnosed over a 6-year period. Twenty-two had biopsy proven cirrhosis while 58 others had portal hypertension with clinical and biochemical evidence of chronic liver disease. The commonest aetiology was alcohol (36%), followed by the idiopathic variety and hepatitis B. The male to female ratio was 4.4:1. Indians had a high prevalence of alcohol-associated chronic liver disease. Overall, ascites was the commonest presentation. Eight patients presented with hepatocellular carcinoma. Spontaneous bacterial peritonitis was diagnosed in 13% of patients undergoing abdominal paracentesis. Gallstones were detected in 37% of patients who underwent ultrasonography. Diabetes mellitus and peptic ulcer disease were noted in 22% and 31% of patients respectively.

  13. Polycystic liver diseases: advanced insights into the molecular mechanisms.

    PubMed

    Perugorria, Maria J; Masyuk, Tatyana V; Marin, Jose J; Marzioni, Marco; Bujanda, Luis; LaRusso, Nicholas F; Banales, Jesus M

    2014-12-01

    Polycystic liver diseases are genetic disorders characterized by progressive bile duct dilatation and/or cyst development. The large volume of hepatic cysts causes different symptoms and complications such as abdominal distension, local pressure with back pain, hypertension, gastro-oesophageal reflux and dyspnea as well as bleeding, infection and rupture of the cysts. Current therapeutic strategies are based on surgical procedures and pharmacological management, which partially prevent or ameliorate the disease. However, as these treatments only show short-term and/or modest beneficial effects, liver transplantation is the only definitive therapy. Therefore, interest in understanding the molecular mechanisms involved in disease pathogenesis is increasing so that new targets for therapy can be identified. In this Review, the genetic mechanisms underlying polycystic liver diseases and the most relevant molecular pathways of hepatic cystogenesis are discussed. Moreover, the main clinical and preclinical studies are highlighted and future directions in basic as well as clinical research are indicated.

  14. Focus on emerging drugs for the treatment of patients with non-alcoholic fatty liver disease

    PubMed Central

    Federico, Alessandro; Zulli, Claudio; de Sio, Ilario; Del Prete, Anna; Dallio, Marcello; Masarone, Mario; Loguercio, Carmela

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations. Fatty liver disease encompasses a spectrum of hepatic pathology, ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Moreover, NAFLD is often associated with other metabolic conditions, such as diabetes mellitus type 2, dyslipidemia and visceral obesity. The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities. Diet and physical exercise are considered the first line of treatment for patients with NAFLD, but their results on therapeutic efficacy are often contrasting. Behavior therapy is necessary most of the time to achieve a sufficient result. Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and, often, little evidence supporting the real efficacy. Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Urgently, new pharmacological approaches are needed. Here, we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules. PMID:25492998

  15. The coagulopathy of liver disease: does vitamin K help?

    PubMed

    Saja, Maha F; Abdo, Ayman A; Sanai, Faisal M; Shaikh, Shaffi A; Gader, Abdel Galil M Abdel

    2013-01-01

    Vitamin K is frequently administered in cirrhotic patients to correct their coagulopathy, but evidence for such practice is lacking. We aimed to assess whether vitamin K administration increases the levels of the vitamin K-dependent factor VII (FVII), protein C, and protein S in patients with different stages of liver dysfunction. Eighty-nine patients were recruited into four groups: group 1 [hepatitis B virus (HBV) inactive carriers, n = 23]; group 2 [chronic HBV and hepatitis C virus (HCV) hepatitis, n = 21]; group 3 (cirrhosis, n = 24); group 4 (hepatocellular carcinoma, n = 21); and a healthy control group (n = 39). A single dose of 10 mg of vitamin K1 was administered subcutaneously to all patients. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, FVII, protein C, total and free protein S, and proteins induced by vitamin K absence (PIVKA)-II (des-gamma-carboxy prothrombin) were measured at baseline and 72 h after vitamin K administration. There was progressive increment in baseline PIVKA-II, and decrements in fibrinogen, FVII, protein C, and protein S across study groups (P < 0.0001). Compared to baseline, vitamin K administration did not affect the measured parameters, whereas TT showed no reduction in any of the groups. Protein C levels declined in group 2, whereas FVII, total and free protein S did not increase in any group, for all parameters. Vitamin K therapy does not cause significant improvements in the majority of coagulation parameters and hence does not seem to be routinely indicated in patients with liver disease.

  16. The effect of inflammatory cytokines in alcoholic liver disease.

    PubMed

    Kawaratani, Hideto; Tsujimoto, Tatsuhiro; Douhara, Akitoshi; Takaya, Hiroaki; Moriya, Kei; Namisaki, Tadashi; Noguchi, Ryuichi; Yoshiji, Hitoshi; Fujimoto, Masao; Fukui, Hiroshi

    2013-01-01

    Alcohol is the most common cause of liver disease in the world. Chronic alcohol consumption leads to hepatocellular injury and liver inflammation. Inflammatory cytokines, such as TNF-α and IFN-γ, induce liver injury in the rat model of alcoholic liver disease (ALD). Hepatoprotective cytokines, such as IL-6, and anti-inflammatory cytokines, such as IL-10, are also associated with ALD. IL-6 improves ALD via activation of the signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL-10 inhibits alcoholic liver inflammation via activation of STAT3 in Kupffer cells and the subsequent inhibition of liver inflammation. Alcohol consumption promotes liver inflammation by increasing translocation of gut-derived endotoxins to the portal circulation and activating Kupffer cells through the LPS/Toll-like receptor (TLR) 4 pathways. Oxidative stress and microflora products are also associated with ALD. Interactions between pro- and anti-inflammatory cytokines and other cytokines and chemokines are likely to play important roles in the development of ALD. The present study aims to conduct a systemic review of ALD from the aspect of inflammation. PMID:24385684

  17. Autoantibodies in the diagnosis and management of liver disease.

    PubMed

    Czaja, Albert J; Norman, Gary L

    2003-10-01

    Autoantibodies are nonpathogenic manifestations of immune reactivity, and they may occur in acute and chronic liver diseases. Autoantibodies may be consequences rather than causes of the liver injury, and they should be regarded as diagnostic clues rather than etiologic markers. Conventional autoantibodies used in the categorization of autoimmune liver disease are antinuclear antibodies, smooth muscle antibodies, antibodies to liver/kidney microsome type 1, antimitochondrial antibodies, and atypical perinuclear anti-neutrophil cytoplasmic antibodies. Ancillary autoantibodies that enhance diagnostic specificity, have prognostic connotation, or direct treatment are antibodies to endomysium, tissue transglutaminase, histones, doubled-stranded DNA, and actin. Autoantibodies that have an emerging diagnostic and prognostic significance are antibodies to soluble liver antigen/liver pancreas, asialoglycoprotein receptor, liver cytosol type 1, and nuclear pore complex antigens. Autoantibodies of uncertain clinical value that remain under investigation are antibodies to chromatin, lactoferrin, and Saccharomyces cervisiae. Continued recognition and characterization of autoantibodies should improve diagnostic precision, provide prognostic indices, and elucidate target autoantigens. These advances may in turn clarify pathogenic mechanisms, facilitate the development of animal models, and generate novel site-specific therapies. PMID:14506390

  18. Obesity and non-alcoholic fatty liver disease: Disparate associations among Asian populations

    PubMed Central

    Wong, Robert J; Ahmed, Aijaz

    2014-01-01

    Obesity is a global epidemic contributing to an increasing prevalence of obesity-related systemic disorders, including nonalcoholic fatty liver disease. The rising prevalence of nonalcoholic steatohepatitis (NASH) will in the near future lead to end-stage liver disease in a large cohort of patients with NASH-related cirrhosis and NASH is predicted to be a leading indication for liver transplantation in the coming decade. However, the prevalence of obesity and the progression of hepatic histological damage associated with NASH exhibit significant ethnic disparities. Despite a significantly lower body mass index and lower rates of obesity compared to other ethnic groups, Asians continue to demonstrate a significant prevalence of hypertension, diabetes, metabolic syndrome and NASH. Ethnic disparities in central adiposity and visceral fat distribution have been hypothesized to contribute to these ethnic disparities. The current review focuses on the epidemiology of obesity and NASH among Asian populations. PMID:24868320

  19. Nonalcoholic fatty liver disease and the heart in children and adolescents.

    PubMed

    Pacifico, Lucia; Chiesa, Claudio; Anania, Caterina; De Merulis, Antonio; Osborn, John Frederick; Romaggioli, Sara; Gaudio, Eugenio

    2014-07-21

    Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease (NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome (MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease. PMID:25083079

  20. Predictive value of excretory urography, ultrasonography, computerized tomography, and liver and bone scan in the staging of bilharzial bladder cancer in Saudi Arabia

    SciTech Connect

    Hanash, K.A.; Bissada, N.K.; Abla, A.; Esmail, D.; Dowling, A.

    1984-07-01

    The role of ultrasonography, computed tomography (CT), and radioisotopic scanning in the staging of bilharzial bladder cancer has not been reported previously. Forty patients with invasive bladder cancer seen at the King Faisal Specialist Hospital and Research Centre between January 1978 and June 1981 underwent complete preoperative workup for staging of their tumors prior to radical cystectomy. The preoperative radiologic investigations included excretory urography (IVP), ultrasonography (US), CT of the pelvis, and liver and bone scans. The results of these investigations were compared with the operative and pathologic staging. Ninety-three percent of the patients with bilharzial cancer had evidence of ureteric obstruction on IVP compared with 22% of the nonbilharzial cancer patients. The presence of ureteric obstruction in these patients did not correlate with the stage of the disease with 83% of the patients with superficial tumors (T1 and T2) having hydroureteronephrosis. Ultrasonography and CT had an 83% accuracy in the staging of superficial tumors. Stage T3 tumors were understaged in 14% of the cases. Ultrasonography did not differentiate Stages T3 and T4 tumors while CT scan differentiated these two stages in 57% of the cases. Bone scan failed to reveal evidence of metastatic disease in any of the bilharzial cancer patients. Liver scan was suspicious for liver metastases in two patients with bilharzial cancers in whom open liver biopsy revealed only hepatic bilharziasis. Of all the radiographic studies, US or preferably CT scan seem to be of some value in the staging of bilharzial tumors localized to the bladder. Bone and liver scans are probably of no cost effective benefit.

  1. Orthotropic liver transplantation for intractable neurological manifestations of Wilson's disease.

    PubMed

    Sutariya, Vaibhav K; Tank, Anad H; Modi, Pranjal R

    2015-01-01

    Wilson's disease (WD) is an inherited autosomal recessive disorder characterized by copper accumulation and toxicity, affecting mainly the liver and brain. Orthotopic liver transplantation (OLT) is the definitive therapy for patients with WD. Acute fulminant hepatic failure and decompensated cirrhosis are well-established indications for OLT. Patients with severe neurologic impairment can also be benefited by OLT. Here, we present a patient who underwent OLT for isolated neurological WD.

  2. Clinical approaches to non-alcoholic fatty liver disease

    PubMed Central

    Schwenger, Katherine JP; Allard, Johane P

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leading to fibrosis and potentially cirrhosis, and it is one of the most common causes of liver disease worldwide. NAFLD is associated with other medical conditions such as metabolic syndrome, obesity, cardiovascular disease and diabetes. NASH can only be diagnosed through liver biopsy, but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis, reducing the need for liver biopsy and risk to patients. Disease progression varies between individuals and is linked to a number of risk factors. Mechanisms involved in the pathogenesis are associated with diet and lifestyle, influx of free fatty acids to the liver from adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines production, reduced very low-density lipoprotein secretion and intestinal microbiome. Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD. Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial. Omega 3 polyunsaturated fatty acids and statins may offer additional benefits. Bariatric surgery should be considered in morbidly obese patients. More research is needed to assess the impact of these treatments on a long-term basis. The objective of this article is to briefly review the diagnosis, management and treatment of this disease in order to aid clinicians in managing these patients. PMID:24587650

  3. Nonalcoholic Fatty Liver Disease Management: Dietary and Lifestyle Modifications.

    PubMed

    Nguyen, Vi; George, Jacob

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of abnormalities that can range from bland liver fat (steatosis), to hepatic inflammation and liver injury (steatohepatitis). It is estimated that NAFLD will become the principal cause of liver disease in Western nations and the leading indication for liver transplantation. Advancements in disease recognition and management are therefore paramount. Although the development of new, reliable drug therapies is vital, lifestyle interventions remain the most effective treatment modality. In addition to weight loss as a primary measure of treatment success, there is growing recognition that other endpoints, including the prevention or delay of diabetes onset, reduced cardiovascular events, prevention of cancer, and improved overall mortality, are equally important outcomes that can be independently modified by lifestyle change. Moreover, NAFLD is inextricably part of a complex, systemic disease process that is linked with deeply entrenched maladaptive lifestyle behaviors. Thus, a holistic, multidisciplinary, and individualized approach to disease management will be the key to achieving any realistic population-level change.

  4. FDA Facilitates Research on Earlier Stages of Alzheimer's Disease

    MedlinePlus

    ... Updates FDA Facilitates Research on Earlier Stages of Alzheimer's Disease Share Tweet Linkedin Pin it More sharing ... disease.” back to top New Paths for New Alzheimer’s Drugs FDA’s draft guidance aims to encourage research ...

  5. Trends in the management and burden of alcoholic liver disease

    PubMed Central

    Mathurin, Philippe; Bataller, Ramon

    2016-01-01

    Summary Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe and is the leading cause of death among adults with excessive alcohol consumption. There is a dose-response relationship between the amount of alcohol consumed and the risk of ALD. The relative risk of cirrhosis increases in subjects who consume more than 25 g/day. The burden of alcohol-attributable liver cirrhosis and liver cancer is high and is entirely preventable. Health agencies should develop population-based policies to reduce the prevalence of harmful and/or hazardous alcohol consumption and foster research in this field to provide new diagnostic and therapeutic tools. Disease progression of patients with ALD is heavily influenced by both genetic and environmental factors. Non-invasive methods for the diagnosis of fibrosis have opened new perspectives in the early detection of advanced ALD in asymptomatic patients. Alcoholic hepatitis, the most severe form of ALD, carries a high short-term mortality (around 30–50% at 3 months). Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis but duration of therapy should be adapted to early response. Liver transplantation is the best option for patients with severe liver dysfunction. However, alcohol relapse after transplantation remains a critical issue and drinking habits of transplanted patients need to be routinely screened. PMID:25920088

  6. OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver disease.

    PubMed

    Paschetta, Elena; Belci, Paola; Alisi, Anna; Liccardo, Daniela; Cutrera, Renato; Musso, Giovanni; Nobili, Valerio

    2015-01-01

    Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors. OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population. Several studies suggest that the chronic intermittent hypoxia (CIH) of OSAS patients may per se trigger liver injury, inflammation, and fibrogenesis, promoting NAFLD development and the progression from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells. In this review, we focus on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor (HIF), nuclear factor kappa B (NF-κB), YKL-40, unfolded protein response, and hypoxic adipose tissue inflammation, which all could provide novel potential therapeutic approaches for the management of NAFLD patients with OSAS. PMID:25873773

  7. Review article: hepatitis vaccination in patients with chronic liver disease.

    PubMed

    Reiss, G; Keeffe, E B

    2004-04-01

    Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.

  8. Orthotopic liver transplantation in an adult with cholesterol ester storage disease.

    PubMed

    Ambler, Graeme K; Hoare, Matthew; Brais, Rebecca; Shaw, Ashley; Butler, Andrew; Flynn, Paul; Deegan, Patrick; Griffiths, William J H

    2013-01-01

    Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit. PMID:23430518

  9. Methanobactin reverses acute liver failure in a rat model of Wilson disease

    PubMed Central

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K.; Schirmacher, Peter; DiSpirito, Alan A.; Bandow, Nathan; Baral, Bipin S.; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P.; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A.; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H.J.; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz

    2016-01-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration– and European Medicines Agency–approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  10. Methanobactin reverses acute liver failure in a rat model of Wilson disease.

    PubMed

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Kabiri, Yaschar; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K; Schirmacher, Peter; DiSpirito, Alan A; Bandow, Nathan; Baral, Bipin S; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A; Adamski, Jerzy; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H J; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz; Zischka, Hans

    2016-07-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration- and European Medicines Agency-approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  11. Oily fish, coffee and walnuts: Dietary treatment for nonalcoholic fatty liver disease.

    PubMed

    Gupta, Vikas; Mah, Xian-Jun; Garcia, Maria Carmela; Antonypillai, Christina; van der Poorten, David

    2015-10-01

    Rates of non-alcoholic fatty liver disease (NAFLD) are increasing worldwide in tandem with the metabolic syndrome, with the progressive form of disease, non-alcoholic steatohepatitis (NASH) likely to become the most common cause of end stage liver disease in the not too distant future. Lifestyle modification and weight loss remain the main focus of management in NAFLD and NASH, however, there has been growing interest in the benefit of specific foods and dietary components on disease progression, with some foods showing protective properties. This article provides an overview of the foods that show the most promise and their potential benefits in NAFLD/NASH, specifically; oily fish/ fish oil, coffee, nuts, tea, red wine, avocado and olive oil. Furthermore, it summarises results from animal and human trials and highlights potential areas for future research. PMID:26457022

  12. Oily fish, coffee and walnuts: Dietary treatment for nonalcoholic fatty liver disease

    PubMed Central

    Gupta, Vikas; Mah, Xian-Jun; Garcia, Maria Carmela; Antonypillai, Christina; van der Poorten, David

    2015-01-01

    Rates of non-alcoholic fatty liver disease (NAFLD) are increasing worldwide in tandem with the metabolic syndrome, with the progressive form of disease, non-alcoholic steatohepatitis (NASH) likely to become the most common cause of end stage liver disease in the not too distant future. Lifestyle modification and weight loss remain the main focus of management in NAFLD and NASH, however, there has been growing interest in the benefit of specific foods and dietary components on disease progression, with some foods showing protective properties. This article provides an overview of the foods that show the most promise and their potential benefits in NAFLD/NASH, specifically; oily fish/ fish oil, coffee, nuts, tea, red wine, avocado and olive oil. Furthermore, it summarises results from animal and human trials and highlights potential areas for future research. PMID:26457022

  13. Lipid peroxidation may not be important in an early stage of alcohol-induced liver injury

    SciTech Connect

    Inomata, T.; Rao, G.A.; Tsukamoto, H.

    1986-03-01

    Role of lipid peroxidation (LP) in alcoholic liver injury (ALI) is still controversial. The authors have previously described a rat model which produced the sequential injury from alcoholic fatty liver to liver necrosis and fibrosis. In the present study, the authors have examined the degree of LP and GSH/GSSG ratio in the liver to investigate whether the LP can be identified in an early stage of progressive ALI. Six pairs of male Wistar rats were continuously infused intragastrically for 30 days with a high fat diet (25% total calories) plus either ethanol or isocaloric amount of dextrose. Following intoxication, the content of diene conjugates in mitochondrial and microsomal lipids as well as the liver GSH/GSSG ratio were determined by the diene difference spectrum and fluorometry, respectively. The UV absorption at 234nm by mitochondrial lipid from alcoholic rats (0.668 +/- 0.023 OD/mg) was significantly (p<0.05) lower than that of controls (0.977 +/- 0.102 OD/mg). The microsomal lipid, however, exhibited a similar absorbance in the two groups (0.986 +/- 0.086 vs 1.149 +/- 0.091 OD/mg0. Similarly, no difference in the ratio of GSH/GSSG was found (6.05 +/- 0.27 vs 5.35 +/- 0.44). These results do not support a concept that LP is an important pathogenetic factor for the progression of alcoholic fatty liver to liver necrosis.

  14. Two-stage liver transplantation: an effective procedure in urgent conditions.

    PubMed

    Montalti, Roberto; Busani, Stefano; Masetti, Michele; Girardis, Massimo; Di Benedetto, Fabrizio; Begliomini, Bruno; Rompianesi, Gianluca; Rinaldi, Laura; Ballarin, Roberto; Pasetto, Alberto; Gerunda, Giorgio E

    2010-01-01

    Temporary portocaval shunt and total hepatectomy is a technique used in the presence of toxic liver syndrome because of fulminant hepatic failure, hepatic trauma, primary non-function (PNF), and eclampsia. We performed this technique on four patients. An indication for anhepatic state was severe hemodynamic instability in three of them. Etiologies of these three patients were as follows: PNF after liver transplantation, ischemic hepatitis after right hepatic artery embolization, and massive reperfusion syndrome during a liver transplantation. In the fourth patient, during the liver transplantation when hepatic artery was ligated, a kidney carcinoma in the donor graft was discovered. We decided to complete the hepatectomy and to construct a temporary portocaval shunt. Mean anhepatic phases were 19 h and 15 min. All patients survived the two-stage liver transplantation procedure without major complications. Our cases demonstrated that temporary portocaval shunt while awaiting urgent liver transplantation could be an effective "bridge" in selected patients who develop toxic liver syndrome; however, a short time between portocaval shunt and transplantation and careful intensive care managements are mandatory.

  15. Silymarin inhibits the progression of fibrosis in the early stages of liver injury in CCl₄-treated rats.

    PubMed

    Clichici, Simona; Olteanu, Diana; Nagy, Andras-Laszlo; Oros, Adrian; Filip, Adriana; Mircea, Petru A

    2015-03-01

    Liver fibrosis, a common condition occurring during the evolution of almost all chronic liver diseases, is the consequence of hepatocyte injury that leads to the activation of Kupffer cells and hepatic stellate cells (HSC). Silymarin (Si) is a herbal product widely used for its hepatoprotective potential. Our study aims to investigate the effects of two different doses of Silymarin on a CCl4-induced model of liver fibrosis with a focus on the early stages of liver injury. Fifty Wistar rats were randomly divided into five groups (n=10): control group (sunflower oil twice a week); CMC group (carboxymethyl cellulose five times a week, sunflower oil twice a week); CCl4 group (CCl4 in sunflower oil, by gavage, twice a week); CCl4+Si 50 group (CCl4 twice a week, Silymarin 50 mg/b.w. in CMC five times a week); and CCl4+Si 200 group (similar to the previous group, with Si 200 mg/b.w.). One month after the experiment began we explored hepato-cytolysis (aminotransferases and lactate dehydrogenase), oxidative stress, fibrosis (histological score, hyaluronic acid), markers of HSC activation (transforming growth factor β1 [TGF-β1], and α-smooth muscle actin [α-SMA] expression by western blot) and activation of Kupffer cells by immunohistochemistry. Our data showed that Si 50 mg/b.w. had the capacity of reducing oxidative stress, hepato-cytolysis, fibrosis, activation of Kupffer cells, and the expression of α-SMA and TGF-β1 with better results than Si 200 mg/b.w. Thus, the usual therapeutic dose of Silymarin, administered in the early stages of fibrotic changes is capable of inhibiting the fibrogenetic mechanism and the progression of initial liver fibrosis. PMID:25133972

  16. Liver stiffness: a novel parameter for the diagnosis of liver disease

    PubMed Central

    Mueller, Sebastian; Sandrin, Laurent

    2010-01-01

    The noninvasive quantitation of liver stiffness (LS) by ultrasound based transient elastography using FibroScan® has revolutionized the diagnosis of liver diseases, namely liver cirrhosis. Alternative techniques such as acoustic radiation impulse frequency imaging or magnetic resonance elastography are currently under investigation. LS is an excellent surrogate marker of advanced fibrosis (F3) and cirrhosis (F4) outscoring all previous noninvasive approaches to detect cirrhosis. LS values below 6 kPa are considered as normal and exclude ongoing liver disease. LS of 8 and 12.5 kPa represent generally accepted cut-off values for F3 and F4 fibrosis. LS highly correlates with portal pressure, and esophageal varices are likely at values >20 kPa. Many other factors may also increase LS such as hepatic infiltration with tumor cells, mast cells (mastocytosis), inflammatory cells (all forms of hepatitis) or amyloidosis. In addition, LS is directly correlated with the venous pressure (eg, during liver congestion) and is increased during mechanic cholestasis. Thus, LS should always be interpreted in the context of clinical, imaging and laboratory findings. Finally, LS has helped to better understand the molecular mechanisms underlying liver fibrosis. The novel pressure-stiffness-fibrosis sequence hypothesis is introduced. PMID:24367208

  17. Hypoxia and Hypoxia Inducible Factors: Diverse Roles in Liver Diseases

    PubMed Central

    Nath, Bharath; Szabo, Gyongyi

    2011-01-01

    Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The Hypoxia Inducible Factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review, we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the hypoxia inducible factors and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as other liver diseases in both human disease as well as murine models. PMID:22120903

  18. Telomere and telomerase in chronic liver disease and hepatocarcinoma.

    PubMed

    Carulli, Lucia; Anzivino, Claudia

    2014-05-28

    The pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (HCC) whereas others have a benign course. Therefore, a genetic predisposition may contribute to the development of cirrhosis and HCC. Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years. In addition to the results from epidemiological studies, polymorphisms studies and data on twins, the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed. Here we review the literature on telomerase mutations, telomere shortening and liver disease including hepatocellular carcinoma. PMID:24876749

  19. Results of radiotherapy for stage I and II Hodgkin's disease

    SciTech Connect

    Lowery, G.S.; Ferree, C.R.; Raben, M.

    1982-06-01

    Fifty-six patients with pathologically staged I and II (A and B) Hodgkin's disease were treated with radiation therapy. Three-year relapse-free survival, total survival, and complications were analyzed. Chemotherapy was valuable as rescue treatment and as part of the initial treatment in patients with stage IIB disease. Complications were minimal.

  20. A Plasmodium yoelii Mei2-Like RNA Binding Protein Is Essential for Completion of Liver Stage Schizogony

    PubMed Central

    Dankwa, Dorender A.; Davis, Marshall J.

    2016-01-01

    Plasmodium parasites employ posttranscriptional regulatory mechanisms as their life cycle transitions between host cell invasion and replication within both the mosquito vector and mammalian host. RNA binding proteins (RBPs) provide one mechanism for modulation of RNA function. To explore the role of Plasmodium RBPs during parasite replication, we searched for RBPs that might play a role during liver stage development, the parasite stage that exhibits the most extensive growth and replication. We identified a parasite ortholog of the Mei2 (Meiosis inhibited 2) RBP that is conserved among Plasmodium species (PlasMei2) and exclusively transcribed in liver stage parasites. Epitope-tagged Plasmodium yoelii PlasMei2 was expressed only during liver stage schizogony and showed an apparent granular cytoplasmic location. Knockout of PlasMei2 (plasmei2−) in P. yoelii only affected late liver stage development. The P. yoelii plasmei2− liver stage size increased progressively until late in development, similar to wild-type parasite development. However, P. yoelii plasmei2− liver stage schizonts exhibited an abnormal DNA segregation phenotype and failed to form exoerythrocytic merozoites. Consequently the cellular integrity of P. yoelii plasmei2− liver stages became increasingly compromised late in development and the majority of P. yoelii plasmei2− underwent cell death by the time wild-type liver stages mature and release merozoites. This resulted in a complete block of P. yoelii plasmei2− transition from liver stage to blood stage infection in mice. Our results show for the first time the importance of a Plasmodium RBP in the coordinated progression of late liver stage schizogony and maturation of new invasive forms. PMID:26883588

  1. A Plant-Derived Morphinan as a Novel Lead Compound Active against Malaria Liver Stages

    PubMed Central

    Carraz, Maëlle; Jossang, Akino; Franetich, Jean-François; Siau, Anthony; Ciceron, Liliane; Hannoun, Laurent; Sauerwein, Robert; Frappier, François; Rasoanaivo, Philippe; Snounou, Georges; Mazier, Dominique

    2006-01-01

    Background The global spread of multidrug–resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s. Methods and Findings Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P. yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory concentration [IC50] 3.1 μM, therapeutic index [TI] 14) and P. falciparum (IC50 4.2 μM, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition being most pronounced during the early developmental stages. One derivative, N-cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was selected for its lower toxicity (IC50 3.3 μM, TI 46, and IC50 42.4 μM, TI 60, on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral administration of NCP-tazopsine completely protected mice from a sporozoite challenge. Unlike the parent molecule, the derivative was uniquely active against Plasmodium hepatic stages. Conclusions A readily obtained semisynthetic derivative of a plant-derived compound, tazopsine, has been shown to be specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug severely restricts the pressure for the selection of drug resistance to a parasite stage limited both in numbers and duration, thus allowing researchers to envisage the incorporation of a true causal

  2. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications

    PubMed Central

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-01-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  3. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications.

    PubMed

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-08-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  4. The generation of carcinogenic etheno-DNA adducts in the liver of patients with nonalcoholic fatty liver disease

    PubMed Central

    Linhart, Kirsten-Berit; Glassen, Katharina; Peccerella, Teresa; Waldherr, Rüdiger; Linhart, Heinz; Bartsch, Helmut

    2015-01-01

    Background Nonalcoholic fatty liver disease (NAFLD), in particular its more aggressive form nonalcoholic steatohepatitis (NASH) is increasingly observed as a cause of end stage liver disease and hepatocellular carcinoma (HCC). Reactive oxygen species (ROS) are an important factor in the pathogenesis of HCC. ROS can react with polyunsaturated fatty acids derived from membrane phospholipids resulting in the production of reactive aldehydes as lipid oxidation (LPO) byproducts, such as 4-hydroxynonenal (4 HNE). 4 HNE can react with DNA to form mutagenic exocyclic etheno-DNA adducts. ROS is induced by inflammatory processes, but also by induction of cytochrome P450 2E1 (CYP2E1), as seen with chronic alcohol consumption. Methods Immunohistochemical detection of CYP2E1, 4 HNE and hepatic exocyclic etheno-DNA adducts was performed on liver sections from 39 patients with NFLD. Spearman rank correlation was calculated to examine possible correlations. Results Exocyclic etheno-DNA adducts were detected and correlated significantly with 4 HNE, but not with CYP2E1. Conclusions This is the first description of highly carcinogenic exocyclic etheno-DNA adducts in NAFLD patients. We could show that exocyclic etheno-DNA adducts significantly correlated with lipid peroxidation product 4 HNE, but not with CYP2E1, implying that in NAFLD ROS generation with consecutive DNA damage is rather inflammation driven through various cytokines than by induction of CYP2E1. PMID:26005678

  5. Lipid emulsions in the treatment and prevention of parenteral nutrition-associated liver disease in infants and children.

    PubMed

    Nandivada, Prathima; Fell, Gillian L; Gura, Kathleen M; Puder, Mark

    2016-02-01

    Long-term parenteral nutrition (PN) carries the risk of progressive liver disease in infants with intestinal failure. Although PN-associated liver disease (PNALD) is multifactorial in etiology, components of soybean oil lipid emulsions have been implicated in the disease's pathogenesis. Historically, infants with PNALD who were unable to wean from PN to full enteral feeding developed cirrhosis and end-stage liver disease, which require liver transplantation to survive. Over the past 2 decades, novel strategies for the management of parenteral lipids have improved morbidity and mortality from PNALD in infants with intestinal failure. Current strategies for the treatment of PNALD include restricting the dose of parenteral soybean oil lipid emulsion and/or replacing the soybean oil with a parenteral fish-oil lipid emulsion or emulsions of mixed-lipid sources. The purpose of this report is to review published data that evaluate these strategies in parenteral lipid management for the treatment and prevention of PNALD. PMID:26791189

  6. Pathogenesis of veno-occlusive liver disease after radiation

    SciTech Connect

    Fajardo, L.F.; Colby, T.V.

    1980-11-01

    Radiation-induced liver disease is characterized structurally by progressive fibrous obliteration of central veins (veno-occlusive disease (VOD)). The pathogenesis is unknown. Samples of liver from 11 patients with radiation-induced VOD were studied by light and electron microscopy for evidence of central vein thrombosis. The patients had received fractionated radiation with total doses of 1850 to 4050 rads, or single doses of 1000 rads. In addition, six patients had received chemotherapy. We postulate that ionizing radiation injures preferentially the endothelial cells of central veins, which leads to focal deposition of fibrin. The resulting fibrin network is eventually replaced by collagen, causing fibrous occlusion.

  7. Nonalcoholic Fatty Liver Disease and the Gut Microbiome.

    PubMed

    Boursier, Jerome; Diehl, Anna Mae

    2016-05-01

    Recent progress has allowed a more comprehensive study of the gut microbiota. Gut microbiota helps in health maintenance and gut dysbiosis associates with chronic metabolic diseases. Modulation of short-chain fatty acids and choline bioavailability, lipoprotein lipase induction, alteration of bile acid profile, endogenous alcohol production, or liver inflammation secondary to endotoxemia result from gut dysbiosis. Modulation of the gut microbiota by pre/probiotics gives promising results in animal, but needs to be evaluated in human before use in clinical practice. Gut microbiota adds complexity to the pathophysiology of nonalcoholic fatty liver disease but represents an opportunity to discover new therapeutic targets.

  8. ADV36 adipogenic adenovirus in human liver disease

    PubMed Central

    Trovato, Francesca M; Catalano, Daniela; Garozzo, Adriana; Martines, G Fabio; Pirri, Clara; Trovato, Guglielmo M

    2014-01-01

    Obesity and liver steatosis are usually described as related diseases. Obesity is regarded as exclusive consequence of an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Non-alcoholic fatty liver disease (NAFLD), is a condition whose natural history is related to, but not completely explained by over-nutrition, obesity and insulin resistance. There is evidence that environmental infections, and notably adipogenic adenoviruses (ADV) infections in humans, are associated not only with obesity, which is sufficiently established, but also with allied conditions, such as fatty liver. In order to elucidate the role, if any, of previous ADV36 infection in humans, we investigated association of ADV36-ADV37 seropositivity with obesity and fatty liver in humans. Moreover, the possibility that lifestyle-nutritional intervention in patients with NAFLD and different ADV36 seropositive status, achieves different clinical outcomes on ultrasound bright liver imaging, insulin resistance and obesity was challenged. ADV36 seropositive patients have a more consistent decrease in insulin resistance, fatty liver severity and body weight in comparison with ADV36 seronegative patients, indicating a greater responsiveness to nutritional intervention. These effects were not dependent on a greater pre-interventional body weight and older age. These results imply that no obvious disadvantage - and, seemingly, that some benefit - is linked to ADV36 seropositivity, at least in NAFLD. ADV36 previous infection can boost weight loss and recovery of insulin sensitivity under interventional treatment. PMID:25356033

  9. Liver Fibrosis Staging with MR Elastography: Comparison of Diagnostic Performance between Patients with Chronic Hepatitis B and Those with Other Etiologic Causes.

    PubMed

    Chang, Won; Lee, Jeong Min; Yoon, Jeong Hee; Han, Joon Koo; Choi, Byung Ihn; Yoon, Jung Hwan; Lee, Kyoung Bun; Lee, Kwang-Woong; Yi, Nam-Joon; Suh, Kyung-Suk

    2016-07-01

    Purpose To evaluate the diagnostic performance of magnetic resonance (MR) elastography in staging liver fibrosis in patients with chronic hepatitis B (CHB) and other etiologic causes. Materials and Methods This retrospective study was institutional review board-approved and the requirement for informed consent was waived. Before surgery, MR elastographic imaging was performed in 352 patients with chronic liver diseases (281 patients with CHB, 71 patients without CHB) and hepatocellular carcinomas and 64 living liver donor candidates. Liver stiffness (LS) values were measured on quantitative shear-stiffness maps of MR elastography, and the diagnostic performance of MR elastography in staging liver fibrosis was evaluated by using receiver operating characteristic curve analysis and the Obuchowski measure with the histopathologic analysis of liver fibrosis in the CHB group and in the group composed of other etiologic causes. In 120 patients (97 with CHB, 23 without CHB) and 51 donors, diagnostic performance of MR elastography was validated. Results Areas under the curve of LS values for the diagnosis of significant fibrosis (≥stage F2), severe fibrosis (≥stage F3), and cirrhosis (stage F4) in the CHB group were 0.972 (95% confidence interval: 0.948, 0.987), 0.946 (95% confidence interval: 0.916, 0.968), and 0.920 (95% confidence interval: 0.885, 0.947), respectively. Obuchowski measures were similarly high in the CHB group and in the group composed of other etiologic causes (0.970 vs 0.977). However, the estimated cutoff value for stage F4 in the group with CHB was substantially lower than in the participants with other etiologic causes: 3.67 kPa versus 4.65 kPa. In the validation study for stage F1 or greater, stage F2 or greater, stage F3 or greater, and stage F4, the Youden indexes were 0.807, 0.842, 0.806, and 0.639, respectively, in the group with CHB, and 0.783, 0.900, 1.000, and 0.917, respectively, in the group without CHB. Conclusion The diagnostic

  10. Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease

    PubMed Central

    Eslam, Mohammed; Hashem, Ahmed M.; Leung, Reynold; Romero-Gomez, Manuel; Berg, Thomas; Dore, Gregory J.; Chan, Henry L.K.; Irving, William L.; Sheridan, David; Abate, Maria L.; Adams, Leon A.; Mangia, Alessandra; Weltman, Martin; Bugianesi, Elisabetta; Spengler, Ulrich; Shaker, Olfat; Fischer, Janett; Mollison, Lindsay; Cheng, Wendy; Powell, Elizabeth; Nattermann, Jacob; Riordan, Stephen; McLeod, Duncan; Armstrong, Nicola J.; Douglas, Mark W.; Liddle, Christopher; Booth, David R.; George, Jacob; Ahlenstiel, Golo; Ampuero, Javier; Bassendine, Margaret; Wong, Vincent W. S.; Rosso, Chiara; White, Rose; Mezzabotta, Lavinia; Suppiah, Vijayaprakash; Michalk, Monika; Malik, Barbara; Matthews, Gail; Applegate, Tanya; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R.; Santaro, Rosanna

    2015-01-01

    Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis. PMID:25740255

  11. Gut Microbiota and Host Reaction in Liver Diseases

    PubMed Central

    Fukui, Hiroshi

    2015-01-01

    Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD), especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases. PMID:27682116

  12. Treatment of non-alcoholic fatty liver disease

    PubMed Central

    Tolman, Keith G; Dalpiaz, Anthony S

    2007-01-01

    Non-alcoholic fatty liver disease, defined as the presence of macrovascular steatosis in the presence of less than 20 gm of alcohol ingestion per day, is the most common liver disease in the USA. It is most commonly associated with insulin resistance/type 2 diabetes mellitus and obesity. It is manifested by steatosis, steatohepatitis, cirrhosis, and, rarely, hepatocellular carcinoma. Hepatic steatosis results from an imbalance between the uptake of fat and its oxidation and export. Insulin resistance, predisposing to lipolysis of peripheral fat with mobilization to and uptake of fatty acids by the liver, is the most consistent underlying pathogenic factor. It is not known why some patients progress to cirrhosis; however, the induction of CYP 2E1 with generation of reactive oxygen species appears to be important. Treatment is directed at weight loss plus pharmacologic therapy targeted toward insulin resistance or dyslipidemia. Bariatric surgery has proved effective. While no pharmacologic therapy has been approved, emerging data on thiazolidinediones have demonstrated improvement in both liver enzymes and histology. There are fewer, but promising data, with statins which have been shown to be hepatoprotective in other liver diseases. The initial enthusiasm for ursodeoxycholic acid has not been supported by histologic studies. PMID:18516264

  13. Gut Microbiota and Host Reaction in Liver Diseases

    PubMed Central

    Fukui, Hiroshi

    2015-01-01

    Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD), especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases.

  14. Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma.

    PubMed

    Ozçay, Figen; Canan, Oğuz; Bilezikçi, Banu; Torgay, Adnan; Karakayali, Hamdi; Haberal, Mehmet

    2006-01-01

    We described six children with heritable liver disease and hepatocellular carcinoma treated with living-related liver transplantation. Underlying liver diseases were type-1 tyrosinemia (three patients), progressive familial intrahepatic cholestasis type II (two patients), and Wilson's disease (one patient). Two of the tumors were found incidentally during liver transplantation. Number of nodules was 12, 15, 3, 2, and 1 (in two patients). Three patients were treated with chemotherapy before the procedure. Chemotherapy was not given to any patient after liver transplantation. The mean follow-up was 17.7 +/- 6 months (range: 7-24). All patients are tumor recurrence free. Both graft and patient survival rates are 100% at a median of 18.5 months follow-up. Physicians in charge of treating children with heritable liver disease should screen them periodically for the development of hepatocellular carcinoma. Liver transplantation may offer these children better survival rates.

  15. [Legionnaire's disease with predominant liver involvement].

    PubMed

    Magro Molina, A; Plaza Poquet, V; Giner Galvañ, V

    2002-04-01

    Like other pneumonias due to atypical agents, pneumonia due to Legionela Pneumophila has no characteristic clinical facts, although fever and non-productive cough are almost constant and diarrhea with changes in mental status are common. Hyponatremia and moderate transient hypertransaminasemia are common too. Severe systemic affectation after hematogenous dissemination similar to those described with typical bacterial pneumonias is a prominent difference with other atypical agents, with high mortality rates in the absence of appropriate treatment. Etiological diagnosis is very difficult and it is normally achieved late in the course of the infection. Because of diagnostic difficulties and potential mortality in predisposed patients, empirical antibiotherapy has been extensively recommended. We present a patient affected by critical community-acquired pneumonia due to Legionela Pneumophila serogroup 1 with liver alteration as the main manifestation and good response to empirical antibiotherapy with claritromycine and rifampin. We recommended the empirical use of such therapy in those pneumonias without microbiological diagnosis and torpid evolution.

  16. The role of the liver in immunity to blood-stage murine malaria.

    PubMed Central

    Dockrell, H M; de Souza, J B; Playfair, J H

    1980-01-01

    Mice vaccinated with fixed parasitized red blood cells and Bordetella pertussis can clear an otherwise lethal Plasmodium yoelii infection in 7 days; this protection is abolished by splenectomy before vaccination. Most mice splenectomized following vaccination were able to clear their infections, although their recovery was delayed. When labelled parasitized red cells were injected into mice during an infection, splenic uptake fell from day 3 onwards while uptake by the liver increased. Lymphocytes (mainly T cells) formed the majority of the live cells extracted from livers 7 days after infection, although blasts and myeloid cells were also present. Infected livers from vaccinated mice contained most cells. Less marked increases were observed 7 days after P. berghei infection of vaccinated mice. Examination of liver tissue showed that the sinusoids contained increased numbers of cells and suggested that activation of Kupffer cells was occurring, particularly in vaccinated mice infected with P. yoelii. Homing experiments confirmed the increased trapping of various cells in livers of vaccinated mice infected with P. yoelii. These results suggest an important role for the liver in recovery from blood-stage malaria infection. Images Figure 7 PMID:7439934

  17. Non-alcoholic Fatty Liver Disease: East Versus West

    PubMed Central

    Agrawal, Swastik; Duseja, Ajay K

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West. PMID:25755421

  18. Non-alcoholic Fatty Liver Disease: East Versus West.

    PubMed

    Agrawal, Swastik; Duseja, Ajay K

    2012-06-01

    Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West. PMID:25755421

  19. Insulin resistance in clinical and experimental alcoholic liver disease

    PubMed Central

    Carr, Rotonya M.; Correnti, Jason

    2015-01-01

    Alcoholic liver disease (ALD) is the number one cause of liver failure worldwide; its management costs billions of health care dollars annually. Since the advent of the obesity epidemic, insulin resistance and diabetes have become common clinical findings in patients with ALD; and the development of insulin resistance predicts the progression from simple steatosis to cirrhosis in ALD patients. Both clinical and experimental data implicate the impairment of several mediators of insulin signaling in ALD, and experimental data suggest that insulin-sensitizing therapies improve liver histology. This review explores the contribution of impaired insulin signaling in ALD and summarizes the current understanding of the synergistic relationship between alcohol and nutrient excess in promoting hepatic inflammation and disease. PMID:25998863

  20. Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

    PubMed

    Keeffe, Emmet B

    2006-01-01

    A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

  1. Sexual dysfunction in chronic liver disease: is liver transplantation an effective cure?

    PubMed

    Burra, Patrizia; Germani, Giacomo; Masier, Annalisa; De Martin, Eleonora; Gambato, Martina; Salonia, Andrea; Bo, Patrizio; Vitale, Alessandro; Cillo, Umberto; Russo, Francesco Paolo; Senzolo, Marco

    2010-06-27

    The goal of liver transplantation is not only to ensure patient long-term survival but also to offer the opportunity to achieve psychologic and physical integrity. Quality of life after liver transplantation may be affected by unsatisfactory sexual function. Before liver transplantation, sexual dysfunction and sex hormone disturbances are reported in men and women mainly due to abnormality of physiology of the hypothalamic-pituitary-gonadal axis and, in some cases, origin of liver disease. Successful liver transplantation should theoretically restore hormonal balance and improve sexual function both in men and women, thus improving the reproductive performance. However, after transplantation, up to 25% of patients report persistent sexual dysfunction, and approximately one third of patients describe the appearance of de novo sexual dysfunction. Despite the described high prevalence of this condition, epidemiologic data are relatively scant. Further studies on pathophysiology and risk factors in the field of sexual function after liver transplantation along with new strategies to support and inform patients on the waiting list and after surgery are needed.

  2. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions.

    PubMed

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-09-28

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle

  3. Status quo of chronic liver diseases, including hepatocellular carcinoma, in Mongolia.

    PubMed

    Jazag, Amarsanaa; Puntsagdulam, Natsagnyam; Chinburen, Jigjidsuren

    2012-06-01

    Because Mongolia has much higher liver disease burden than any other regions of the world, it is necessary to provide information on real-time situation of chronic liver disease in Mongolia. In this article, we reviewed studies performed in Mongolia from 2000 to 2011 on seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among healthy individuals and patients with chronic liver diseases, and on the practice patterns for the management of liver cirrhosis and hepatocellular carcinoma (HCC). According to previous reports, the seroprevalence of HBV and HCV in general population in Mongolia is very high (11.8% and 15% for HBV and HCV, respectively). Liver cirrhosis is also highly prevalent, and mortality from liver cirrhosis remained high for the past decade (about 30 deaths per 100,000 populations per year). Among patients with cirrhosis, 40% and 39% are positive for HBsAg and anti-HCV, respectively, and 20% are positive for both. The seroprevalence is similar for HCC and more than 90% of HCC patients are positive for either HBV or HCV. The incidence of HCC in Mongolia is currently among the highest in the world. The mortality from HCC is also very high (52.2 deaths per 100,000 persons per year in 2010). Partly due to the lack of established surveillance systems, most cases of HCC are diagnosed at an advanced stage. The mortality from liver cirrhosis and HCC in Mongolia may be reduced by implementation of antiviral therapy program and control of alcohol consumption.

  4. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

    PubMed Central

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended

  5. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions.

    PubMed

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-09-28

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle

  6. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

    PubMed Central

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended

  7. A Post-Developmental Genetic Screen for Zebrafish Models of Inherited Liver Disease

    PubMed Central

    Kim, Seok-Hyung; Wu, Shu-Yu; Baek, Jeong-In; Choi, Soo Young; Su, Yanhui; Flynn, Charles R.; Gamse, Joshua T.; Ess, Kevin C.; Hardiman, Gary; Lipschutz, Joshua H.; Abumrad, Naji N.; Rockey, Don C.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease. PMID:25950913

  8. A post-developmental genetic screen for zebrafish models of inherited liver disease.

    PubMed

    Kim, Seok-Hyung; Wu, Shu-Yu; Baek, Jeong-In; Choi, Soo Young; Su, Yanhui; Flynn, Charles R; Gamse, Joshua T; Ess, Kevin C; Hardiman, Gary; Lipschutz, Joshua H; Abumrad, Naji N; Rockey, Don C

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease.

  9. Nonalcoholic fatty liver disease: An overview of current insights in pathogenesis, diagnosis and treatment

    PubMed Central

    Schreuder, Tim CMA; Verwer, Bart J; van Nieuwkerk, Carin MJ; Mulder, Chris JJ

    2008-01-01

    Estimates of people suffering from overweight (one billion) and obesity (300 million) are increasing. The accumulation of triglycerides in the liver, in the absence of excess alcohol intake, has been described in the early sixties. It was not until 1980, however, that Ludwig et al named this condition nonalcoholic steatohepatitis (NASH). Subsequently, nonalcoholic fatty liver disease (NAFLD) has been used as a general name for conditions ranging from simple steatosis through steatohepatitis to end-stage liver disease (cirrhosis). Many studies have demonstrated the significant correlation with obesity and insulin resistance. Other studies have revealed a significant correlation between hepatic steatosis, cardiovascular disease and increased intima-media thickness. WHO estimated that at least two million patients will develop cirrhosis due to hepatic steatosis in the years to come. Longitudinal cohort studies have demonstrated that those patients with cirrhosis have a similar risk to develop hepatocellular carcinoma as those with other causes of cirrhosis. Taken all together, NAFLD has become the third most important indication for liver transplantation. Therefore, training programmes in internal medicine, gastroenterology and hepatology should stress the importance of diagnosing this entity and treat properly those at risk for developing complications of portal hypertension and concomittant cardiovascular disease. This review will focus on the clinical characteristics, pathophysiology, imaging techniques and the readily available therapeutic options. PMID:18442193

  10. Experimental models of non-alcoholic fatty liver disease in rats

    PubMed Central

    Kucera, Otto; Cervinkova, Zuzana

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease. PMID:25024595

  11. Experimental models of non-alcoholic fatty liver disease in rats.

    PubMed

    Kucera, Otto; Cervinkova, Zuzana

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease.

  12. Novel Action of Carotenoids on Non-Alcoholic Fatty Liver Disease: Macrophage Polarization and Liver Homeostasis

    PubMed Central

    Ni, Yinhua; Zhuge, Fen; Nagashimada, Mayumi; Ota, Tsuguhito

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis. PMID:27347998

  13. [Research advances in pediatric nonalcoholic fatty liver disease].

    PubMed

    Dai, Dong-Ling

    2015-01-01

    In recent years, nonalcoholic fatty liver disease (NAFLD) has increased because of the growing prevalence of obesity and overweight in the pediatric population. It has become the most common form of chronic liver diseases in children and the related research on NAFLD is expanded. The "two-hit" and "multiple hit" hypothesis have been widely accepted, and some research has shown that genetic, diet structure and environmental factors appear to play a crucial role in the development of pediatric NAFLD. Though it is expected by researchers, there is not an available satisfactory noninvasive marker for the diagnosis of this disease. Fortunately, some new non-invasive prediction scores for pediatric NAFLD have been developed. There is currently no established special therapy, and lifestyle intervention should be adequate for most cases of NAFLD in children. This article reviews the advances in the current knowledge and ideas concerning pediatric NAFLD, and discusses the diagnosis, perspective therapies and scoring methods for this disease.

  14. Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease.

    PubMed

    Aqel, Bashar; DiBaise, John K

    2015-12-01

    The incidence of nonalcoholic fatty liver disease (NAFLD) continues to increase with prevalence estimates ranging from 17%-33%, making it is the most common cause of chronic liver disease in North America. Its importance is due to not only its prevalence but also its association with increased cardiovascular morbidity and progression to cirrhosis in a subset of patients. NAFLD encompasses a pathologic spectrum of disease, from relatively benign accumulation of lipid (steatosis) to progressive nonalcoholic steatohepatitis associated with inflammation, fibrosis, and necrosis. Nonalcoholic steatohepatitis remains an important phenotypic state because this subgroup of patients is deemed at high risk for developing cirrhosis and progressing to liver failure requiring transplantation or to death. Gut microbiota has recently been identified as regulators of energy homeostasis and fat deposition, thereby implicating them in the development of obesity and associated metabolic diseases. The growing evidence that alteration in gut microbiota (dysbiosis) may affect liver pathology may allow for a better understanding of its role in the pathogenesis of NAFLD, help to identify patients at risk of progression, and expose a microbial target for prevention and therapeutic intervention. In this review, we discuss the growing evidence that highlights the relationship between gut microbiota and its association with NAFLD. PMID:26449892

  15. Isolated polycystic liver disease and aneurism: a case report

    PubMed Central

    Fassiadis, Nikolaos; Lampaki, Sofia; Tsavlis, Drosos; Tsiouda, Theodora; Kougioumtzi, Ioanna; Machairiotis, Nikolaos; Pavlidis, Pavlos; Charalampidis, Charalampos; Tsakiridis, Kosmas

    2016-01-01

    Isolated polycystic liver disease (PCLD) has not been associated with aneurysms and concomitant PLD has not been reported previously in association with bilateral popliteal aneurysms. A case of a middle-aged man with PLD, marfanoid habitus and bilateral popliteal aneurysms is presented. PMID:27275480

  16. Structural and functional hepatocyte polarity and liver disease.

    PubMed

    Gissen, Paul; Arias, Irwin M

    2015-10-01

    Hepatocytes form a crucially important cell layer that separates sinusoidal blood from the canalicular bile. They have a uniquely organized polarity with a basal membrane facing liver sinusoidal endothelial cells, while one or more apical poles can contribute to several bile canaliculi jointly with the directly opposing hepatocytes. Establishment and maintenance of hepatocyte polarity is essential for many functions of hepatocytes and requires carefully orchestrated cooperation between cell adhesion molecules, cell junctions, cytoskeleton, extracellular matrix and intracellular trafficking machinery. The process of hepatocyte polarization requires energy and, if abnormal, may result in severe liver disease. A number of inherited disorders affecting tight junction and intracellular trafficking proteins have been described and demonstrate clinical and pathophysiological features overlapping those of the genetic cholestatic liver diseases caused by defects in canalicular ABC transporters. Thus both structural and functional components contribute to the final hepatocyte polarity phenotype. Many acquired liver diseases target factors that determine hepatocyte polarity, such as junctional proteins. Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus. However, the molecular mechanisms underlying these defects are not well understood. Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases.

  17. Alcoholism and liver disease in Mexico: genetic and environmental factors.

    PubMed

    Roman, Sonia; Zepeda-Carrillo, Eloy Alfonso; Moreno-Luna, Laura Eugenia; Panduro, Arturo

    2013-11-28

    Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide.

  18. Alcoholism and liver disease in Mexico: Genetic and environmental factors

    PubMed Central

    Roman, Sonia; Zepeda-Carrillo, Eloy Alfonso; Moreno-Luna, Laura Eugenia; Panduro, Arturo

    2013-01-01

    Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide. PMID:24307790

  19. Structural and functional hepatocyte polarity and liver disease

    PubMed Central

    Gissen, Paul; Arias, Irwin M.

    2015-01-01

    Summary Hepatocytes form a crucially important cell layer that separates sinusoidal blood from the canalicular bile. They have a uniquely organized polarity with a basal membrane facing liver sinusoidal endothelial cells, while one or more apical poles can contribute to several bile canaliculi jointly with the directly opposing hepatocytes. Establishment and maintenance of hepatocyte polarity is essential for many functions of hepatocytes and requires carefully orchestrated cooperation between cell adhesion molecules, cell junctions, cytoskeleton, extracellular matrix and intracellular trafficking machinery. The process of hepatocyte polarization requires energy and, if abnormal, may result in severe liver disease. A number of inherited disorders affecting tight junction and intracellular trafficking proteins have been described and demonstrate clinical and pathophysiological features overlapping those of the genetic cholestatic liver diseases caused by defects in canalicular ABC transporters. Thus both structural and functional components contribute to the final hepatocyte polarity phenotype. Many acquired liver diseases target factors that determine hepatocyte polarity, such as junctional proteins. Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus. However, the molecular mechanisms underlying these defects are not well understood. Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases. PMID:26116792

  20. Late nonalcoholic fatty liver disease with cirrhosis: a pathologic case of lost or mistaken identity.

    PubMed

    Lefkowitch, Jay H; Morawski, John L

    2012-02-01

    Late-stage nonalcoholic fatty liver disease (NAFLD) may present clinically and/or pathologically as cryptogenic cirrhosis. The subject of this report, a middle-aged obese man with diabetes, underwent liver biopsy at the time of laparoscopic cholecystectomy because the liver surface appeared nodular and thickened. The biopsy showed relatively nondescript cirrhosis at initial low-power microscopic inspection, but glycogenated hepatocyte nuclei (consistent with diabetes), sparse macrovesicular fat, and very rare foci of residual mild steatohepatitis were later found. Slender fibrous septa (without significant inflammation and often enclosing microvessels) were present and interconnected to portal tracts. Immunostains for cytokeratin 7, ubiquitin, and glutamine synthetase provided additional histologic data supporting NAFLD as the cause of the cirrhosis in this case. A strategic pathologic approach is discussed, which can be utilized for the pathologic assessment of cirrhosis of unknown cause, particularly when late NAFLD is suspected.

  1. An Evaluation of the Usefulness of Extracorporeal Liver Support Techniques in Patients Hospitalized in the ICU for Severe Liver Dysfunction Secondary to Alcoholic Liver Disease

    PubMed Central

    Piechota, Mariusz; Piechota, Anna

    2016-01-01

    Background The mortality rate in patients with severe liver dysfunction secondary to alcoholic liver disease (ALD) who do not respond to the standard treatment is exceptionally high. Objectives The main aim of this study was to evaluate the usefulness of applying extracorporeal liver support techniques to treat this group of patients. Patients and Methods The data from 23 hospital admissions of 21 patients with ALD who were admitted to the department of anesthesiology and intensive therapy (A&IT) at the Dr Wł. Biegański Regional Specialist Hospital in Łódź between March 2013 and July 2015 were retrospectively analyzed. Results A total of 111 liver dialysis procedures were performed during the 23 hospitalizations, including 13 dialyses using fractionated plasma separation and adsorption (FPSA) with the Prometheus® system, and 98 procedures using the single pass albumin dialysis (SPAD) system. Upon admission to the intensive care unit (ICU), the median (interquartile range [IQR]) Glasgow coma scale (GCS), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE) II, and simplified acute physiology score (SAPS) II scores were 15 (14 - 15), 9 (7 - 13), 17 (14 - 24), and 32 (22 - 50), respectively. The ICU, 30-day, and three-month mortality rates were 43.48%, 39.13%, and 73.91%, respectively. As determined by the receiver operative characteristic (ROC) analysis for single-factor models, the significant predictors of death in the ICU included the patients’ SOFA, APACHE II, SAPS II, and model of end-stage liver disease modified by the united network for organ sharing (MELD UNOS Modification) scores; the duration of stay (in days) in the A&IT Department; and bile acid, creatinine and albumin levels upon ICU admission. The ROC analysis indicated the significant discriminating power of the SOFA, APACHE II, SAPS II, and MELD UNOS modification scores on the three-month mortality rate. Conclusions The application of

  2. Mitophagy: therapeutic potentials for liver disease and beyond.

    PubMed

    Lee, Sooyeon; Kim, Jae-Sung

    2014-12-01

    Mitochondrial integrity is critical for maintaining proper cellular functions. A key aspect of regulating mitochondrial homeostasis is removing damaged mitochondria through autophagy, a process called mitophagy. Autophagy dysfunction in various disease states can inactivate mitophagy and cause cell death, and defects in mitophagy are becoming increasingly recognized in a wide range of diseases from liver injuries to neurodegenerative diseases. Here we highlight our current knowledge on the mechanisms of mitophagy, and discuss how alterations in mitophagy contribute to disease pathogenesis. We also discuss mitochondrial dynamics and potential interactions between mitochondrial fusion, fission and mitophagy. PMID:25584143

  3. Circulating RNA Molecules as Biomarkers in Liver Disease

    PubMed Central

    Enache, Liviu S.; Enache, Elena L.; Ramière, Christophe; Diaz, Olivier; Bancu, Ligia; Sin, Anca; André, Patrice

    2014-01-01

    Liver disease is a major cause of morbidity and mortality worldwide. As in other fields of medicine, there is a stringent need for non-invasive markers to improve patient diagnostics, monitoring and prognostic ability in liver pathology. Cell-free circulating RNA molecules have been recently acknowledged as an important source of potential medical biomarkers. However, many aspects related to the biology of these molecules remain to be elucidated. In this review, we summarize current concepts related to the origin, transportation and possible functions of cell-free RNA. We outline current development of extracellular RNA-based biomarkers in the main forms of non-inherited liver disease: chronic viral hepatitis, hepatocellular carcinoma, non-alcoholic fatty liver, hepato-toxicity, and liver transplantation. Despite recent technological advances, the lack of standardization in the assessment of these markers makes their adoption into clinical practice difficult. We thus finally review the main factors influencing quantification of circulating RNA. These factors should be considered in the reporting and interpretation of current findings, as well as in the proper planning of future studies, to improve reliability and reproducibility of results. PMID:25272224

  4. Management of Non-alcoholic Fatty Liver Disease and Steatohepatitis

    PubMed Central

    Le, Thuy-Anh; Loomba, Rohit

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes and chronic liver disease in the US with expected rise in incidence paralleling the epidemic of obesity. A subset of patients with NAFLD have the progressive form of NAFLD that is termed non-alcoholic steatohepatitis (NASH), which is characterized by specific features on liver histology including hepatocellular ballooning degeneration, lobular inflammation, and zone-3 steatosis with or without peri-sinusoidal fibrosis. Non-alcoholic steatohepatitis can progress to cirrhosis and result in liver-related death. Insulin resistance is commonly seen in patients with NASH and often co-exists with other features of the metabolic syndrome including hypertension, hyperlipidemia, and obesity. Although weight loss through lifestyle modifications including dietary changes and increased physical exercise remains the backbone of management of NASH, it has proved challenging for patients to achieve and maintain weight loss goals. Thus, it is often necessary to couple lifestyle changes with another pharmacologic treatment for NASH. Insulin sensitizers including the biguanides (metformin), thiazolidinediones (pioglitazone and rosiglitazone), and glucagon-like peptide-1 receptor agonists (exenatide) are large groups of medications that have been studied for the treatment of NASH. Other agents with anti-inflammatory, anti-apoptotic, or anti-fibrotic properties which have been studied in NASH include vitamin E, pentoxifylline, betaine, and ursodeoxycholic acid. This review will provide a detailed summary on the clinical data behind the full spectrum of treatments that exist for NASH and suggest management recommendations. PMID:25755424

  5. Gut-Liver Axis, Nutrition, and Non Alcoholic Fatty Liver Disease

    PubMed Central

    Kirpich, Irina A.; Marsano, Luis S.; McClain, Craig J.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called ”gut-liver axis”, play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host’s metabolism contributing to NAFLD development. PMID:26151226

  6. Nonalcoholic fatty liver disease: a challenge for pediatricians.

    PubMed

    Nobili, Valerio; Alkhouri, Naim; Alisi, Anna; Della Corte, Claudia; Fitzpatrick, Emer; Raponi, Massimiliano; Dhawan, Anil

    2015-02-01

    Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is considered the most common form of chronic liver disease in children. Several factors contribute to NAFLD development, including race/ethnicity, genetic factors, environmental exposures, and alterations in the gut microbiome. The histologic spectrum of NAFLD ranges from simple steatosis to the more aggressive nonalcoholic steatohepatitis (NASH). Fibrosis and eventually cirrhosis can develop from NAFLD during childhood. Diagnosing advanced disease is challenging and may require a liver biopsy, highlighting the urgent need for reliable, noninvasive markers of disease severity. The mainstay of treatment for NAFLD remains lifestyle modifications and weight loss. Probiotics and ω-3 fatty acids may ameliorate disease progression. Recent data have suggested that vitamin E may be considered as a NASH-specific therapy in children, and there are several ongoing human studies evaluating different therapeutic targets for NAFLD. We provide an up-to-date review of the risk factors, diagnosis, and treatment to manage this common disease in children.

  7. Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

    PubMed Central

    He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

    2016-01-01

    Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

  8. Updated TDP-43 in Alzheimer's disease staging scheme.

    PubMed

    Josephs, Keith A; Murray, Melissa E; Whitwell, Jennifer L; Tosakulwong, Nirubol; Weigand, Stephen D; Petrucelli, Leonard; Liesinger, Amanda M; Petersen, Ronald C; Parisi, Joseph E; Dickson, Dennis W

    2016-04-01

    In this study, we update the TDP-43 in Alzheimer's disease staging scheme by assessing the topography of TDP-43 in 193 cases of Alzheimer's disease, in 14 different brain regions (eight previously described plus six newly reported) and use conditional probability to model the spread of TDP-43 across the 14 brain regions. We show that in addition to the eight original regions we previously reported [amygdala, entorhinal cortex, subiculum, dentate gyrus of the hippocampus, occipitotemporal cortex, inferior temporal cortex, middle frontal cortex and basal ganglia (putamen/globus pallidum)] that TDP-43 is also deposited in the insular cortex, ventral striatum, basal forebrain, substantia nigra, midbrain tectum, and the inferior olive of the medulla oblongata, in Alzheimer's disease. The conditional probability analysis produced six significantly different stages (P < 0.01), and suggests that TDP-43 deposition begins in the amygdala (stage 1), then moves to entorhinal cortex and subiculum (stage 2); to the dentate gyrus of the hippocampus and occipitotemporal cortex (stage 3); insular cortex, ventral striatum, basal forebrain and inferior temporal cortex (stage 4); substantia nigra, inferior olive and midbrain tectum (stage 5); and finally to basal ganglia and middle frontal cortex (stage 6). This updated staging scheme is superior to our previous staging scheme, classifying 100% of the cases (versus 94% in the old scheme), based on criteria provided, and shows clinical significance with some regions and with increasing stage. We discuss the relevance of the updated staging scheme, as well as its impact on the prion-like hypothesis of protein spread in neurodegenerative disease. We also address the issue of whether frontotemporal lobar degeneration with TDP-43 could be the primary pathology in stage 6.

  9. Systemic Complications of Nonalcoholic Fatty Liver Disease: When the Liver Is Not an Innocent Bystander.

    PubMed

    Vanni, Ester; Marengo, Andrea; Mezzabotta, Lavinia; Bugianesi, Elisabetta

    2015-08-01

    The top three leading causes of death in patients with nonalcoholic fatty liver disease (NAFLD) in descending order are cardiovascular disease, cancer, and liver disease. It is clear now that the increased risk of metabolic and macro- and microvascular complications in NAFLD stems from the associated features of metabolic syndrome. However, NAFLD itself may contribute to the spectrum of risk factors associated with insulin resistance. The primary focus of this review is to summarize the main systemic associations of NAFLD, as well as to discuss the mechanisms that link them to NAFLD. Hepatic lipid accumulation in NAFLD impairs hepatic glucose and lipid metabolism further increasing the risk of type 2 diabetes mellitus and of cardiovascular disease, independently of established risk factors. The incidence, prevalence, and severity of these complications are proportional to the histological severity of liver damage suggesting that NAFLD, but particularly nonalcoholic steatohepatitis, can also contribute to the low-grade inflammatory state through the systemic release of several markers of inflammation, oxidative stress, and of procoagulant factors. The clinical implication of these findings is that patients with NAFLD require a multidisciplinary evaluation, with a major focus on type 2 diabetes mellitus and cardiovascular disease complications and may benefit from more intensive surveillance and early treatment interventions to decrease the risk for cardiovascular and kidney complications. PMID:26378641

  10. May Patients with Alcohol Liver Disease Benefit from Herbal Medicines?

    PubMed

    Milosevic, Natasa; Milanovic, Maja; Turkulov, Vesna; Medić-Stojanoska, Milica; Abenavoli, Ludovico; Milic, Natasa

    2016-01-01

    Alcoholism is currently listed as the third leading cause of death. Chronic alcohol consumption brings serious medical complications like gastrointestinal, cardiovascular, musculoskeletal, respiratory system disorders. Liver can be seriously damage by alcohol misuse. Alcoholic Liver Disease (ALD) is the first important warning sign of alcohol abuse. Since effective therapies for ALD are still limited, natural products in the treatment of ALD become very important. In this regard, there have been done very few clinical trials with poor results. Silymarin, glycyrrhizin, garlic show some promising results in ALD patients while the in vivo and in vitro studies with green tee, quercetin and curcumin indicate positive effect on patients with ALD. PMID:27457345

  11. [Studies on the mode of progression of alcoholic liver disease].

    PubMed

    Yoshida, N; Hatori, T; Ueno, Y; Shibata, M; Sadamoto, T; Yamamuro, W; Sumino, Y; Nonaka, H; Sugimoto, M; Abei, T

    1991-12-01

    In order to elucidate the mode of progression of alcoholic liver disease, relationships among the drinking style, laboratory data, anti-HCV antibody and histological changes were investigated on 36 patients in whom the liver biopsy was repeatedly done. Following results were obtained (1) In the group of continuous drinking over 100g ethanol per day, histological progression was found in 11 of 13 patients (85%) regardless of positive anti-HCV. On the other hand, in the group of abstinence or temperance less than 60g daily alcohol intake, histological improvement was found in 6 of 11 patients (55%). (2) Histological improvement was predominantly seen by abstinence or temperance in the cases with lower levels of serum IgA and adenosine deaminase (ADA) on hospitalization and those with rapid decrease in serum gamma-GTP after hospitalization. In conclusion, the amount of ethanol was considered to be the most important factor to affect on a progression of alcoholic liver diseases. Assessment of laboratory data such as IgA and ADA on hospitalization and change in gamma-GTP after hospitalization were also thought to be useful in foreseeing the prognosis of alcoholic liver disease.

  12. NK Cell Subtypes as Regulators of Autoimmune Liver Disease

    PubMed Central

    2016-01-01

    As major components of innate immunity, NK cells not only exert cell-mediated cytotoxicity to destroy tumors or infected cells, but also act to regulate the functions of other cells in the immune system by secreting cytokines and chemokines. Thus, NK cells provide surveillance in the early defense against viruses, intracellular bacteria, and cancer cells. However, the effecter function of NK cells must be exquisitely controlled to prevent inadvertent attack against normal “self” cells. In an organ such as the liver, where the distinction between immunotolerance and immune defense against routinely processed pathogens is critical, the plethora of NK cells has a unique role in the maintenance of homeostasis. Once self-tolerance is broken, autoimmune liver disease resulted. NK cells act as a “two-edged weapon” and even play opposite roles with both regulatory and inducer activities in the hepatic environment. That is, NK cells act not only to produce inflammatory cytokines and chemokines, but also to alter the proliferation and activation of associated lymphocytes. However, the precise regulatory mechanisms at work in autoimmune liver diseases remain to be identified. In this review, we focus on recent research with NK cells and their potential role in the development of autoimmune liver disease. PMID:27462349

  13. NK Cell Subtypes as Regulators of Autoimmune Liver Disease.

    PubMed

    Jiao, Guohui; Wang, Bangmao

    2016-01-01

    As major components of innate immunity, NK cells not only exert cell-mediated cytotoxicity to destroy tumors or infected cells, but also act to regulate the functions of other cells in the immune system by secreting cytokines and chemokines. Thus, NK cells provide surveillance in the early defense against viruses, intracellular bacteria, and cancer cells. However, the effecter function of NK cells must be exquisitely controlled to prevent inadvertent attack against normal "self" cells. In an organ such as the liver, where the distinction between immunotolerance and immune defense against routinely processed pathogens is critical, the plethora of NK cells has a unique role in the maintenance of homeostasis. Once self-tolerance is broken, autoimmune liver disease resulted. NK cells act as a "two-edged weapon" and even play opposite roles with both regulatory and inducer activities in the hepatic environment. That is, NK cells act not only to produce inflammatory cytokines and chemokines, but also to alter the proliferation and activation of associated lymphocytes. However, the precise regulatory mechanisms at work in autoimmune liver diseases remain to be identified. In this review, we focus on recent research with NK cells and their potential role in the development of autoimmune liver disease. PMID:27462349

  14. [Monoethylglycinexylidide--a metabolite of lidocaine--as an index of liver function in chronic hepatic parenchymal diseases].

    PubMed

    Kupcová, V; Turecký, L; Szántová, M; Schmidtová, K

    1999-01-01

    The changes of biotransformation enzyme system (b.e.s.) activity and capacity in liver diseases significantly influence the metabolism of various xenobiotics. Lidocaine is metabolised through oxidative N-deethylation by b.e.s. resulting in the production of monoethylglycinexylide (MEGX). The aim of this study was the determination of serum MEGX concentration as a model substance for indirect evaluation of liver b.e.s. function in patients with liver steatofibrosis and cirrhosis and the assessment of the possibilities to use it as a quantitave test of liver functional state. The study group consisted of 53 patients, 36 of them with liver disease of different etiology (postviral, ethyltoxic, cryptogenic, liver cirrhosis on the basis of autoimmune hepatitis, liver cirrhosis induced by primary sclerosing cholangitis, primary biliary cirrhosis in the stage of cirrhosis, Wilson's disease in the stage of cirrhosis), 7 patients with liver steatofibrosis and 10 control persons. After intravenous administration of lidocaine (1 mg/kg of body weight), concentration of MEGX was assessed by fluorescence polarization immunoassay (FPIA) using Tdx system in venous blood. The concentration was assesed prior to administration of lidocaine and 15 and 30 minutes after. In the group of liver steatofibrosis the concentrations in the 15th minute after administration were lower comparing to controls, in the 30th minute the difference was less significant. The values of MEGX in cirrhosis group were significantly decreased 15 and 30 minutes after lidocaine administration in comparison with control group. The cirrhosis group was divided into two subgroups: compensated (Ci c) and decompensated (Ci d) and independently of this division into three parts according to score system of Child-Pugh classification (Ci A, Ci B, Ci C). The concentrations 15 and 30 minutes after lidocaine administration in patients with Ci c and Ci d were significantly different, similarly there were statistically

  15. Cell-based therapies of liver diseases: age-related challenges

    PubMed Central

    Yarygin, Konstantin N; Lupatov, Alexei Y; Kholodenko, Irina V

    2015-01-01

    The scope of this review is to revise recent advances of the cell-based therapies of liver diseases with an emphasis on cell donor’s and patient’s age. Regenerative medicine with cell-based technologies as its integral part is focused on the structural and function