Journal of Hepatology

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BACKGROUND & AIMS: MSDC-0602K is a novel insulin sensitizer designed to preferentially target the mitochondrial pyruvate carrier while minimizing direct binding to the transcriptional factor PPARγ. Herein, we aimed to assess the efficacy and safety of MSDC-0602K in patients with non-alcoholic steatohepatitis. METHODS: Patients with biopsy-confirmed NASH and fibrosis (F1-F3) were randomized to daily oral placebo, or 1 of 3 MSDC-0602K doses in a 52-week double-blind study...

BACKGROUND & AIMS: 8-week glecaprevir/pibrentasvir demonstrates high rates of sustained virological response at post-treatment week 12 (SVR12) across hepatitis C virus (HCV) genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. METHODS: EXPEDITION-8 was a single-arm, multicenter, phase 3b trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% confidence interval (CI) of the SVR12 rate in (1) patients with GT1,2,4-6 in the per-protocol (PP) population, (2) patients with GT1,2,4-6 in the intention-to-treat (ITT) population, (3) patients with GT1-6 in the PP population, and (4) patients with GT1-6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations...

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No abstract text is available yet for this article.

BACKGROUND AND AIMS: We evaluated whether the clinical course of acute on chronic liver failure (ACLF) between time of listing and liver transplantation (LT) affects one-year post-transplant survival. METHODS: We identified patients from the UNOS database who were transplanted within 28 days of listing, and categorized them by ACLF grade at waitlist registration and LT, per the EASL-CLIF definition. RESULTS: 3,636 patients listed with ACLF-3 underwent LT within 28-days...

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No abstract text is available yet for this article.

BACKGROUND AND AIMS: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) has high efficacy and limited toxicity. We hypothesised that efficacy of glecaprevir-pibrentasvir for chronic HCV with a simplified treatment monitoring schedule would be non-inferior to a standard treatment monitoring schedule. METHODS: In this open-label multicentre phase 3b trial, treatment-naïve adults with chronic HCV without cirrhosis were randomly assigned (2:1) to receive glecaprevir-pibrentasvir 300mg-120mg daily for eight weeks administered with a simplified or standard monitoring strategy...

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in adults and children. Along with obesity, diabetes and insulin resistance, genetic factors strongly impact on NAFLD development and progression. Dysregulated bile acid metabolism and the fibroblast growth factor 19 (FGF19) pathway play a pivotal role in NAFLD pathogenesis. However, it remains to be defined the mechanism through which the FGF19 receptor system is associated with liver damage in NAFLD...

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No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND AND AIMS: Tumor heterogeneity has been frequently reported in patients with hepatocellular carcinoma (HCC). The reliability of single-region tumor samples for evaluating immune tumor microenvironment is also debatable. We conducted a prospective study to analyze the similarity in immune tumor microenvironments among different regions of a single tumor. METHODS: Multiregion sampling was performed from newly resected tumors. The immune tumor microenvironment was evaluated by immunohistochemical (IHC) staining of programmed cell death receptor ligand 1 (PD-L1), CD4, CD8, CD20, forkhead box P3, dendritic cell-lysosomal associated membrane protein, CD68, myeloperoxidase, and tertiary lymphoid structures (TLSs)...

BACKGROUND: Farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), increases total and low-density lipoprotein cholesterol (LDL-C) in patients with nonalcoholic steatohepatitis (NASH). The present study evaluated the impact of OCA therapy on lipoprotein sub-particles. METHOD: The study included 196 patients (99 OCA group and 97 placebo) who were enrolled in the FLINT trial and had samples available for lipid analysis and liver biopsies at enrollment and end-of-treatment (EOT) at 72 weeks...

BACKGROUND &AIMS: We aimed to describe the incidence of liver related events (LRE) in a population of hepatitis C compensated advanced chronic liver disease (cACLD) patients who achieved sustained virological response (SVR) after direct-acting antiviral (DAA) therapy and identify non-invasive parameters to predict the occurrence of LRE. METHODS: This two-center prospective study included 572 cACLD patients who had been treated with DAA and had achieved SVR. Patients had liver stiffness measurement (LSM) ≥10 kPa at baseline and had never decompensated (Child Pugh class A)...

OBJECTIVE: To investigate the perioperative use of Omega-3 polyunsaturated fatty acids (Ω3-FA) to reduce post-operative complications after liver surgery. SUMMARY BACKGROUND DATA: In a variety of animal models, Ω3-FA disclosed strong protective effects in alleviating hepatic ischemia/reperfusion injury and steatosis with enhancement of regeneration after major tissue loss. Given these benefits along with its safety profile, we hypothesized that perioperative administration of Ω3-FA in patients undergoing liver surgery may ameliorate the post-operative course...

BACKGROUND & AIMS: Whether non-selective beta blockers (NSBBs) are deleterious in patients with end stage cirrhosis and refractory ascites or not is debated with contrasting results. We hypothesized that only a subset of patients with impaired cardiac performance could be at increased risk of mortality on the waiting list for liver transplantation if receiving NSBBs. METHODS: The study included 584 consecutive patients with cirrhosis evaluated for transplantation between 1999 and 2014...

The gut-liver axis refers to the bidirectional relationship between the gut and its microbiota, and the liver, resulting from the integration of signals generated by dietary, genetic and environmental factors. This reciprocal interaction is established through the vascular route of the portal vein that carries gut-derived products directly to the liver, and the liver feed-back route of bile and antibody secretion to the intestine. The intestinal mucosal and vascular barrier is the functional and anatomical structure that serves as a playground for the interactions between the gut and the liver, limiting the systemic dissemination of microbes and toxins while allowing nutrients to access the circulation and to reach the liver...

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