Journal of Hepatology

BACKGROUND & AIMS: The pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD) and steatohepatitis (NASH) is likely due to the interaction between a deranged metabolic milieu and local mediators of hepatic inflammation and fibrosis. We undertook this study to elucidate the interplay between macrophage activation, insulin resistance (IR) in target organs/tissues and hepatic damage. METHODS: In 40 non-diabetic patients with biopsy-proven NAFLD we assessed 1) Endogenous Glucose Production (EGP), Glucose Clearance and indexes of IR in the adipose tissue (Adipo-IR and Lipo-IR) and in the liver (Hep-IR) by tracers infusion ([6,6-2H2]glucose and [2H5]glycerol); 2) macrophage activity (by soluble sCD163) and 3) hepatic expression of CD163 (hCD163)...

BACKGROUND & AIMS: The development of hepatic models capable of long-term expansion with competent liver functionality in a personalized setting is technically challenging. Stem cell-based organoid technologies can provide an alternative source of patient-derived primary hepatocytes. However, self-renewing and functionally competent human pluripotent stem cell (PSC)-derived hepatic organoids are still lacking. METHODS: We developed a novel method to efficiently and reproducibly generate functionally mature human hepatic organoids derived from PSCs, including human embryonic stem cells and induced PSCs...

BACKGROUND & AIMS: As an NAD+ -dependent deacetylase and a key epigenetic regulator, sirtuin 6 (SIRT6) has been implicated in the regulation of metabolism, DNA repair, and inflammation. However, the role of SIRT6 in alcoholic liver disease (ALD) remains unclear. The aim of this study was to investigate the function and mechanism of SIRT6 in ALD pathogenesis. METHODS: We developed and characterized Sirt6 knockout (KO) and transgenic (Tg) mouse models that were treated with either control or ethanol diet...

BACKGROUND AND AIMS: Hepatitis C virus (HCV)-specific CD8+ T cells are functionally impaired in chronic hepatitis C. Even though HCV can now rapidly and sustainably be cleared from chronically infected patients, reverberation of HCV clearance on virus-specific CD8+ T cells still remains elusive. Here, we aimed to investigate if HCV clearance by direct acting antivirals (DAA) could restore the functionality of exhausted HCV-specific CD8+ T cell responses. METHODS: HCV-specific CD8+ T cells in PBMC obtained during and 6 months following IFN-free DAA therapy of 40 chronically HCV infected patients were analyzed for comprehensive phenotypes, proliferation, cytokine production, mitochondrial fitness and response to immune-check-point blockades...

BACKGROUND AND AIMS: Pathological bacterial translocation (PBT) in liver cirrhosis (LC) is the hallmark for spontaneous bacterial infections increasing mortality several-fold. Factors known to contribute to PBT in LC are among others an increased intestinal permeability of which however, the mucus layer has not been addressed so far in detail. A clear route of translocation for luminal intestinal bacteria is yet to be defined but we hypothesize that the recently described gut vascular barrier (GVB) is impaired in experimental portal hypertension leading to increased accessibility of the vascular compartment for translocating bacteria...

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection contributes to the development of autoimmune disorders such as cryoglobulinemia vasculitis (CV). However, it remains unclear why only some HCV-infected individuals develop CV. HCV-CV is characterized by expansions of anergic CD19+ CD27+ CD21low/- atypical memory B cells (AtM). Here, we report the mechanisms by which AtM participate to HCV-associated autoimmunity. METHODS: Phenotype and function of peripheral AtM were studied by multi-color flow cytometry and co-culture assays with effector T cells and regulatory T cells in twenty chronicallyHCV-CV patients, 10 chronicallyHCV-infected patients without CV and 8 healthy donors...

BACKGROUND & AIMS: We undertook a cross-sectional study of children/adolescents with and without non-alcoholic fatty liver disease (NAFLD) to compare the prevalence of prediabetes and diabetes, and to examine the role of abnormal glucose tolerance as a predictor of liver disease severity. METHODS: We recruited a cohort of 599 Caucasian children/adolescents with biopsy-proven NAFLD, and 118 children/adolescents without NAFLD, who were selected to be similar for age, sex, body mass index and waist circumference to those with NAFLD...

BACKGROUND & AIMS: Excessive alcohol drinking is one of the major causes of hepatocellular carcinoma (HCC). Approximately 30-40% Asian population are deficient for aldehyde dehydrogenase 2 (ALDH2), a key enzyme to detoxify the ethanol metabolite acetaldehyde. However, how ALDH2 deficiency affects alcohol-related HCC remains obscure. METHODS: ALDH2 polymorphism in 646 patients with viral hepatitis B (HBV) infection with or without alcohol drinking was studied...

BACKGROUND AND AIMS: Although Non-alcoholic fatty liver disease (NAFLD), Non-alcoholic steatohepatitis (NASH) and NASH with advanced fibrosis are closely associated with type 2 diabetes mellitus (T2DM), their global prevalence rates have not been not well described. Our aim was to estimate the prevalence of NAFLD, NASH, and advanced fibrosis among T2DM patients by regions of the world. METHODS: PubMed, Ovid-Medline, EMBASE and Web of Science were searched from January 1989 to September 2018 for terms involving NAFLD, NASH, and T2DM...

BACKGROUND: Most hepatitis C virus (HCV) infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where Vosevi® may not be available...

BACKGROUND & AIMS: Cerebral oxidative stress plays an important role in the pathogenesis of hepatic encephalopathy (HE) but the underlying mechanisms are incompletely understood. Here we analyzed a role of heme oxygenase (HO) 1, iron and NADPH oxidase 4 (Nox4) for the induction of oxidative stress and senescence in HE. METHODS: Gene and protein expression in human post mortem brain samples was analyzed by gene array and Western blot analysis. Mechanisms and functional consequences of HO1 upregulation were studied in NH4 Cl-exposed astrocytes in vitro by Western blot, qPCR and super-resolution microscopy...

BACKGROUND: Death rates on liver transplant waiting lists range from 5%-25%. Herein, we report a unique experience with 50 anonymous persons who volunteered to address this gap by offering to donate part of their liver to a recipient with whom they had no biological connection or prior relationship (A-LLD). METHODS: Candidates were screened to confirm excellent physical, mental, social, and financial health. Demographics and surgical outcomes were analyzed. Qualitative interviews after donation examined motivation and experiences...

BACKGROUND & AIMS: Recently the Amsterdam-Oxford model (AOM) was introduced; a prognostic model to assess the risk of death and/or liver transplantation (LT) in primary sclerosing cholangitis (PSC). We aimed to validate and assess the utility of the AOM. METHODS: Clinical and laboratory data were collected from PSC diagnosis until the last visit or time of LT or death. The AOM was calculated at yearly intervals following PSC diagnosis. Discriminatory performance was assessed by calculation of the C-statistic and prediction accuracy by comparing the predicted survival with the observed survival in Kaplan-Meier estimates...

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BACKGROUND AND AIMS: The nuclear farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has been developed for the treatment of liver diseases. We aimed to determine whether OCA treatment increases the risk of gallstone formation. METHODS: Twenty patients awaiting laparoscopic cholecystectomy were randomized to treatment with OCA (25 mg/day) or placebo for three weeks before surgery. Serum bile acids (BAs), the BA synthesis marker C4 (7α-hydroxy-cholest-4-ene-3-one), and fibroblast growth factor 19 (FGF19) were measured before and after treatment...

Non-alcoholic fatty liver disease (NAFLD) is a global public health concern. Its natural history, the development of non-alcoholic steatohepatitis (NASH) and fibrosis, is highly variable, prone to endogenous (e.g., genetics, microbiota) and exogenous (e.g., nutrition, alcohol, physical activity) disease modifiers, and can fluctuate over time. The complexity of its pathophysiology is reflected by the multitude of pharmacological targets in development. NASH clinical trials have provided valuable insight that is applicable to future trial design...

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No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.