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Concept: Cirrhosis

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In recent years primary biliary cirrhosis is mostly diagnosed in patients who are asymptomatic, however a proportion of cases still present with typical complaints such as fatigue and/or pruritus.

Concepts: Medical terms, Cirrhosis, Gastroenterology, Hepatology, Bilirubin, Primary biliary cirrhosis, Primary sclerosing cholangitis, Autoimmune hepatitis

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Alcohol abuse with/without cirrhosis is associated with an impaired gut barrier and inflammation. Gut microbiota can transform primary bile acids(BA) to secondary BAs which can adversely impact the gut barrier. Aim: Define the effect of active alcohol intake on fecal BA levels, ileal & colonic inflammation in cirrhosis. Methods: Five age-matched groups; two non-cirrhotic (control and drinkers) & three cirrhotic [(NAlc:non-alcoholic (non-drinkers),AbsAlc: abstinent alcoholic for >3mths & CurrAlc:(currently drinking)] were included. Fecal and serum BA analysis, serum endotoxin and stool microbiota using pyro-sequencing were performed. A subgroup of controls, NAlc and CurrAlc underwent ileal and sigmoid colonic biopsies on which mRNA expression of TNF-α, IL1β,IL6 and Cox-2 were performed. Results: 103 patients (19 healthy, 6 non-cirrhotic drinkers, 10 CurrAlc, 38 AbsAlc and 30 NAlc, age 56 yrs, median MELD:10.5) were included. Five each of healthy, CurrrAlc and NAlc underwent ileal/colonic biopsies. Endotoxin, serum conjugated DCA and stool total BAs and secondary/primary BA ratios were highest in current drinkers. On biopsies, a significantly higher mRNA expression of TNF-α, IL1β,IL6 and Cox-2 in colon but not ileum was seen in CurrAlc compared to NAlc & controls. Conclusion: Active alcohol use in cirrhosis is associated with a significant increase in the secondary BA formation compared to abstinent alcoholic cirrhotics and non-alcoholic cirrhotics. This increase in secondary BAs is associated with a significant increase in expression of inflammatory cytokines in colonic mucosa but not ileal mucosa, which may contribute to alcohol-induced gut barrier injury.

Concepts: Alcohol, Gut flora, Digestive system, Cirrhosis, Alcoholism, Bile, Alcohol abuse, Feces

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Over the last four decades, chronic ethanol feeding studies in rodents using either ad libitum feeding or intragastric infusion models have significantly enhanced our understanding of the pathogenesis of alcoholic liver disease (ALD). Recently, we developed a chronic plus binge alcohol feeding model in mice that is similar to the drinking patterns of many alcoholic hepatitis patients: a history of chronic drinking and recent excessive alcohol consumption. Chronic+binge ethanol feeding synergistically induced steatosis, liver injury, and neutrophil infiltration in mice, which may be useful for the study of early alcoholic liver injury and inflammation. Using this chronic+binge model, researchers have begun to identify novel mechanisms that participate in the pathogenesis of alcoholic liver injury, thereby revealing novel therapeutic targets. In this review article, we briefly discuss several mouse models of ALD with a focus on the chronic+binge ethanol feeding model.

Concepts: Alcohol, Cirrhosis, Alcoholism, Alcohol abuse, Alcoholic beverage, Beer, Drinking culture, Alcoholic liver disease

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The association between liver cirrhosis (LC) and herpes zoster has rarely been studied. We investigated the hypothesis that LC, known as an immunodeficiency disease, may increase the risk of herpes zoster using a national health insurance database in Taiwan.

Concepts: Cirrhosis, Liver

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Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV) infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5-6, as the outcome variable. A new index, referred to as Nordic Liver Index (NoLI) in the paper, was based on the model: Log-odds (predicting cirrhosis) = -12.17+ (age×0.11) + (BMI (kg/m2)×0.23) + (D7-lathosterol (μg/100 mg cholesterol)×(-0.013)) + (Platelet count (x109/L)×(-0.018)) + (Prothrombin-INR×3.69). The area under the ROC curve (AUROC) for prediction of cirrhosis was 0.91 (95% CI 0.86-0.96). The index was validated in a separate cohort of 83 patients and the AUROC for this cohort was similar (0.90; 95% CI: 0.82-0.98). In conclusion, the new index may complement other methods in diagnosing cirrhosis in patients with chronic HCV infection.

Concepts: Cirrhosis, Hepatitis, Liver, Hepatocellular carcinoma, Bilirubin, Hepatitis C, Hepatitis B, Wilson's disease

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Conventional proteomic approaches have thus far been unable to identify novel serum biomarkers for ovarian cancer that are more sensitive and specific than the current clinically used marker, CA-125. Because endogenous peptides are smaller and may enter the circulation more easily than proteins, a focus on the low-molecular-weight region may reveal novel biomarkers with enhanced sensitivity and specificity. In this study, we deciphered the peptidome of ascites fluid from 3 ovarian cancer patients and 3 benign individuals (ascites fluid from patients with liver cirrhosis).

Concepts: Sensitivity and specificity, Cirrhosis, Ascites, Ovarian cancer

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Understanding the impact of hepatitis B virus (HBV) coinfection on HIV outcomes in the HAART era continues to be a critical priority given the high prevalence of coinfection and the potential for impaired immunologic, virologic and clinical recovery.

Concepts: Antiretroviral drug, HIV, AIDS, Cirrhosis, Hepatitis, Hepatitis B, Virology, Hepatitis B virus

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Hepatocellular carcinoma (HCC) is a major health problem worldwide. Moreover, the liver cancer field is evolving rapidly, with early diagnosis, new therapies, and a better understanding of HCC’s biology and development. Accurate staging is important for determining prognosis and selecting the most appropriate treatment for each patient. Surgical intervention remains the most effective treatment for HCC and is the only potentially curative modality. However, in HCC patients, overall survival is also independently affected by underlying liver disease and cirrhosis, which in turn affect the applicability and efficacy of treatment. Although several staging classification and prognostic scoring systems have been proposed for determining the stage and prognosis of HCC, no consensus exists on the best classification method. The most common staging classification systems include tumor-node-metastasis stage, Okuda staging, Cancer of the Liver Italian Program score, Barcelona Clinic Liver Cancer staging classification, the French, the Chinese University Prognostic Index, Japanese Integrated Scoring, and the Tokyo score. Radiologists should be aware of the different staging classification systems for HCC and familiar with the system relevant to their respective referring clinicians, as it will provide pertinent radiological evaluation for multidisciplinary management.

Concepts: Cancer, Carcinoma in situ, Lung cancer, Cancer staging, Cirrhosis, Liver, Hepatocellular carcinoma, Radiology

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Our objective was to explore the short-term effects of preoperative serum hepatitis B virus DNA level (HBV DNA) on postoperative hepatic function in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma (HCC).

Concepts: Cancer, Cirrhosis, Hepatitis, Liver, Hepatitis C, Hepatitis B, Hepatitis A, Hepatitis B virus

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IMPORTANCE In patients with low viral loads, high levels of hepatitis B surface antigen (HBsAg) have been shown to predict development of hepatocellular carcinoma (HCC). Whether high levels of HBsAg increase the risk for HCC recurrence after hepatic resection remains unknown. OBJECTIVE To investigate the association between levels of HBsAg and the risk for tumor recurrence after curative resection in HCC patients with low levels of hepatitis B virus (HBV) DNA. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective analysis of the clinical data of 1062 patients with low HBV DNA levels (<200 IU/mL) who underwent partial hepatectomy for HCC. In particular, we investigated the association between levels of HBsAg and recurrence of HCC. EXPOSURE Partial hepatectomy for HCC. MAIN OUTCOMES AND MEASURES The risk for first tumor recurrence between patients with high and low HBsAg levels. We calculated cumulative incidences and hazard ratios after adjusting for competing mortality. RESULTS The risk for tumor recurrence increased with HBsAg levels of 1000 IU/mL or greater. When we compared the groups with low (<1000 IU/mL) and high (≥1000 IU/mL) HBsAg levels, the 5-year disease-free survival rate (46.1% vs 34.1% [P = .002]) and the overall survival rate (57.5% vs 48.8% [P = .004]) were better in the group with low HBsAg levels. On multivariate analysis, hepatitis B e antigen seropositivity, HBsAg level of 1000 IU/mL or greater, tumor size of greater than 5 cm, blood transfusion, surgical margin of less than 1.0 cm, the presence of satellite nodules, and the presence of portal vein tumor thrombus were independent risk factors for HCC recurrence. When compared with hepatitis B e antigen status, HBsAg level better predicted recurrence of HCC. CONCLUSIONS AND RELEVANCE A preoperative HBsAg level of 1000 IU/mL or greater is an independent risk factor for HCC recurrence in patients with low HBV DNA levels.

Concepts: Cancer, Chemotherapy, Cirrhosis, Hepatitis, Hepatitis C, Hepatitis B, Hepatitis B virus, Blood transfusion