Journal of Hepatology

BACKGROUND & AIMS: Advanced liver fibrosis is an important diagnostic target in non-alcoholic fatty liver disease (NAFLD) as it defines the subgroup of patients with impaired prognosis. The non-invasive diagnosis of advanced fibrosis is currently limited by the suboptimal positive predictive value and the grey zone (representing indeterminate diagnosis) of fibrosis tests. The combination of fibrosis tests significantly improves the diagnosis of liver fibrosis in chronic hepatitis C...

Porphyrias are rare inherited disorders caused by specific enzyme dysfunctions in the heme synthesis pathway resulting in abnormal accumulation of specific pathway intermediates. The symptoms depend upon the chemical characteristics of these substances. Porphyrins are photoreactive and cause photocutaneous lesions on sunlight-exposed areas, whereas accumulation of porphyrin precursors is related to acute neurovisceral attacks. Current therapies are suboptimally effective, and mostly address symptoms rather than underlying disease mechanisms...

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BACKGROUND & AIMS: A comprehensive analysis of changes in symptoms and functioning during and after direct acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) has not been conducted for patients treated in real-world clinical settings. We evaluated patient-reported outcomes (PROs) in a diverse cohort of HCV patients treated with commonly-prescribed DAAs. METHODS: PROP UP is a U.S. multicenter observational study of 1,601 HCV patients treated with DAAs in 2016-2017...

BACKGROUND & AIMS: Questions remain about the effect of hepatocellular carcinoma (HCC) on response to interferon-free direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC) patients compared to those without HCC. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response among CHC patients with active, inactive and no HCC. METHODS: PubMed, Embase, Web of Science, and the Cochrane Controlled Trials Register were searched from 1/1/2013 to 9/24/2018...

BACKGROUND: Population-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001-2014) and DAA therapy (2015-2017) eras in New South Wales (NSW), Australia. METHODS: HCV notifications (1993-2016) were linked to hospital admissions (2001-2017) and mortality (1995-2017)...

BACKGROUND & AIMS: Hepatitis B virus (HBV) spreads through the infected liver paralleled by secretion into the blood. HBV-susceptible in vitro infection models do not efficiently amplify viral progeny or support cell-to-cell spread. We sought to establish a cell culture system for the amplification of infectious HBV from clinical specimens. METHODS: Selection of an HBV-susceptible sodium-taurocholate cotransporting polypeptide-overexpressing HepG2 cell clone (HepG2-NTCPsec+) producing high titers of infectious progeny virus...

BACKGROUND AND AIMS: Cells of hematopoietic origin, including macrophages, are generally radiation sensitive but a subset of Kupffer cells (KCs) is relatively radioresistant. Here we focused on the identity of the radioresistant KCs in unmanipulated mice and the mechanism of radioresistance. METHODS: We employed Emr1- and inducible CX3Cr1-based fate-mapping strategies combined with the RiboTag reporter to identify the total KCs and the embryo-derived KCs respectively...

BACKGROUND AND AIM: It is unclear if reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it holds prognostic information beyond visceral adipose tissue (VAT) loss. In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independent of VAT changes. METHODS: In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC+28g walnuts/day) diets with/without moderate physical activity (PA)...

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BACKGROUND & AIMS: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Although HDV-associated liver disease is considered immune-mediated, adaptive immune responses against HDV are weak. Thus, the role of several other cell-mediated mechanisms such as those driven by mucosa-associated invariant T (MAIT) cells, a group of innate-like T cells being highly enriched in the human liver, have not been extensively studied in clinical HDV infection. METHODS: MAIT cells from a sizeable cohort of chronic HDV patients were analyzed ex vivo and in vitro after stimulation...

BACKGROUND AND AIMS: Chronic liver injury often results in activation of hepatic myofibroblasts and development of liver fibrosis. Hepatic myofibroblasts may originate from three major sources; Hepatic Stellate Cells (HSCs), Portal Fibroblasts (PFs), or fibrocytes. Their contribution to liver fibrosis varies dependent on the etiology of liver injury. Here we assessed the composition of hepatic myofibroblasts in multidrug resistance gene 2 knockout (Mdr2-/- ) mice, a genetic model that resembles primary sclerosing cholangitis in patients...

BACKGROUND & AIMS: Little is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors. METHODS: We analyzed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database. We compared data between patients with NASH versus other etiologies...

BACKGROUND: & Aims: PD-L1 expression on antigen-presenting cells (APCs) is essential for T cell impairment, and PD-L1-expressing macrophages may mechanistically shape and therapeutically predict the clinical efficacy of PD-L1/PD-1 blockade. Despite the clinical success fostered by immune checkpoint inhibitors, the mechanisms underlying PD-L1 upregulation in human tumor microenvironments remain an enigma. METHODS: Monocytes/macrophages were purified from peripheral blood, non-tumor, or paired tumor tissues of patients with hepatocellular carcinoma (HCC), and their possible glycolytic switch was evaluated...

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