Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA-C).

Introduction: Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct-acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2-year survival for patients receiving HCV DAA therapy.

Methods: Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016-2021 were followed up for 2 years.

High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy.

Background And Aims: Accurate biomarkers to predict outcomes following discontinuation of nucleos(t)ide analogue (NA) therapy are needed. We evaluated serum hepatitis B core-related antigen (HBcrAg) level as a biomarker for predicting outcomes after NA discontinuation.

Methods: Patients with HBeAg-negative chronic hepatitis B (CHB) without cirrhosis were enrolled in a prospective trial evaluating clinical outcomes until 96 weeks after NA discontinuation.

Human Amniotic Epithelial Cell Transplantation is Safe and Well Tolerated in Patients with Compensated Cirrhosis: A First-in-Human Trial.

Placenta-derived human amniotic epithelial cells (hAEC) exhibit anti-inflammatory and anti-fibrotic effects in cirrhosis models. We conducted a first-in-human phase I clinical trial to assess the safety and tolerability of hAEC in adults with compensated cirrhosis. We examined increasing and repeated doses of hAEC in 9 patients in 3 cohorts.

Broadening and strengthening the health providers caring for patients with chronic hepatitis C may improve continuity of care.

Background: Direct-acting antiviral (DAA) therapies for hepatitis C virus infection (HCV) lead to excellent rates of sustained virological response (SVR). However, loss to follow-up (LTFU) for SVR testing remains a challenge. We examine factors associated with LTFU in a real-world setting.

Time-Restricted Fasting Improves Liver Steatosis in Non-Alcoholic Fatty Liver Disease-A Single Blinded Crossover Trial.

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with visceral adiposity. We assessed the effectiveness of time-restricted fasting (TRF) for 16 h daily without calorie restrictions compared to standard care (SC; diet and lifestyle advice) in improving visceral adiposity and steatosis via controlled attenuation parameter (CAP).

Methods: In a prospective single-blind randomized controlled trial, 32 participants with NAFLD were randomly assigned to TRF or SC for 12 weeks.

Local fistula injection of allogeneic human amnion epithelial cells is safe and well tolerated in patients with refractory complex perianal Crohn's disease: a phase I open label study with long-term follow up.

Background: Local fistula injection of mesenchymal stromal/stem cells (MSC) is effective for complex perianal Crohn's fistulas but is also expensive and requires specialised facilities for cell revival before administration. Human amnion epithelial cells (hAEC) are non-MSC cells with therapeutic properties. The primary aim of this study was safety of hAEC therapy.

Cannabidiol-induced crosstalk of apoptosis and macroautophagy in colorectal cancer cells involves p53 and Hsp70.

Although it has been established that cannabidiol (CBD), the major non-psychoactive constituent of cannabis, exerts antitumoral activities, the exact mechanism(s) via which tumor cells are killed by CBD are not well understood. This study provides new insights into the potential mechanisms of CBD-induced mutual antagonism of apoptosis and macroautophagy using wild type (HCT116 p53wt, LS174T p53wt), knockout (HCT116 p53) and mutant (SW480 p53mut) human colorectal cancer cells (CRC). CBD causes a more pronounced loss in the viability of p53wt cells than p53 and p53mut cells, and a 5-week treatment with CBD reduced the volume of HCT116 p53wt xenografts in mice, but had no effect on the volume of HCT116 p53 tumors.

First-in-human randomized study of RNAi therapeutic RG6346 for chronic hepatitis B virus infection.

Background & Aims: RG6346 is an N-acetyl-D-galactosamine (GalNAc)-conjugated, double-stranded RNA interference agent targeting the HBV genome S-region. We investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RG6346 in healthy volunteers and patients with chronic HBV infection (CHB).

Methods: This first-in-human, adaptive, randomized, double-blinded, phase I study recruited three groups of participants: Group A, 30 healthy volunteers received single-dose RG6346 at 0.

Baseline serum HBV RNA is associated with the risk of hepatitis flare after stopping nucleoside analog therapy in HBeAg-negative participants.

Background And Aims: HBV RNA in peripheral blood reflects HBV cccDNA transcriptional activity and may predict clinical outcomes. The prospective Melbourne HBV-STOP trial studied nucleot(s)ide analog discontinuation in HBeAg-negative non-cirrhotic participants with long-term virological suppression. Ninety-six weeks after stopping treatment, the proportion of participants with virological relapse (HBV DNA > 2000 IU/mL), biochemical relapse (ALT > 2 × ULN and HBV DNA > 2000 IU/mL), or hepatitis flare (ALT > 5 × ULN and HBV DNA > 2000 IU/mL) was 89%, 58%, and 38%, respectively.

Healthcare utilisation and costing for decompensated chronic liver disease hospitalisations at a Victorian network.

Background: The economic burden of decompensated chronic liver disease (CLD) on Australian healthcare services is poorly characterised.

Aims: To evaluate the in-patient healthcare utilisation costs associated with decompensated CLD at Monash Health, an Australian tertiary healthcare service.

Methods: The current retrospective cost analysis examined patients with decompensated CLD admitted between 1 January 2012 and 31 December 2018.

A home-based, multidisciplinary liver optimisation programme for the first 28 days after an admission for acute-on-chronic liver failure (LivR well): a study protocol for a randomised controlled trial.

Background: Acute-on-chronic liver failure (ACLF) represents a rising global healthcare burden, characterised by increasing prevalence among patients with decompensated cirrhosis who have a 28-day transplantation-free mortality of 33.9%. Due to disease complexity and a high prevalence of socio-economic disadvantage, there are deficits in quality of care and adherence to guideline-based treatment in this cohort.

Liver stiffness (Fibroscan®) is a predictor of all-cause mortality in people with non-alcoholic fatty liver disease.

Background And Aims: Progressive liver fibrosis related to non-alcoholic fatty liver disease (NAFLD) is associated with all-cause and liver-related mortality. We assessed vibration-controlled transient elastography (VCTE) as a predictor of mortality.

Method: Data from patients who underwent VCTE for NAFLD at four large health services in Victoria, Australia between the years 2008 and 2019 were linked to state-wide data registries.

Combination treatments including the small-interfering RNA JNJ-3989 induce rapid and sometimes prolonged viral responses in patients with CHB.

Background & Aims: RNA interference therapy has been shown to reduce hepatitis B surface antigen (HBsAg) levels in preclinical models, which could confer functional cure in patients with chronic hepatitis B. This phase IIa trial (ClinicalTrials.gov Identifier: NCT03365947) assessed the safety and efficacy of the small-interfering RNA JNJ-73763989 (JNJ-3989) plus a nucleos(t)ide analogue (NA), with/without the capsid assembly modulator JNJ-56136379 (JNJ-6379) in patients with chronic hepatitis B.

Performance of carbendazim removal using constructed wetlands for the Ethiopian floriculture industry.

Carbendazim is a pesticide commonly used in Ethiopian flower farms and has harmful effects on aquatic, invertebrate, and mammalian life. Previous studies have explored ways to remedy carbendazim toxicity; however, the use of constructed wetland (CW) systems for carbendazim removal from farm water runoff has not been explored in depth. The primary aim of this study was to investigate the efficacy of a CW system for carbendazim removal from wastewater runoff.

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

Background: First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection.

Methods: Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016-2019 were included in the study.

Liver Disease and Poor Adherence Limit Hepatitis C Cure: A Real-World Australian Treatment Cohort.

Background And Aims: In 2016, direct-acting antiviral (DAA) treatment for hepatitis C (HCV) became available through Australia's universal health care system, with the aim of HCV elimination. We report real-world effectiveness of DAA HCV treatment in Australia from a clinically well-informed cohort, enriched for cirrhosis and prior HCV treatment.

Methods: 3413 patients were recruited from 26 hospital liver clinics across Australia from February 2016 to June 2020.

Stopping nucleot(s)ide analogues in non-cirrhotic HBeAg-negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels.

Background And Aims: Current guidelines recommend long-term nucleot(s)ide analogue (NA) therapy for patients with HBeAg-negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss.

Methods: We performed a prospective multi-centre cohort study of stopping NA therapy.

Fourier-Transform Infra-Red Microspectroscopy Can Accurately Diagnose Colitis and Assess Severity of Inflammation.

The diagnosis and management of inflammatory bowel disease relies on histological assessment, which is costly, subjective, and lacks utility for point-of-care diagnosis. Fourier-transform infra-red spectroscopy provides rapid, non-destructive, reproducible, and automatable label-free biochemical imaging of tissue for diagnostic purposes. This study characterises colitis using spectroscopy, discriminates colitis from healthy tissue, and classifies inflammation severity.

Integrating Hepatitis C Virus Treatment Programs Within Community Mental Health.

Conventional models of health care for the hepatitis C virus (HCV) underserve people with serious mental illness. In a 6-month proof-of-concept study, colocated HCV care coordination was assessed within community mental health settings. The program, which relied on referrals to a visiting hepatologist and was augmented by a part-time nurse practitioner, received 18 referrals for HCV management.

Activation of PPARα by Fenofibrate Attenuates the Effect of Local Heart High Dose Irradiation on the Mouse Cardiac Proteome.

Radiation-induced cardiovascular disease is associated with metabolic remodeling in the heart, mainly due to the inactivation of the transcription factor peroxisome proliferator-activated receptor alpha (PPARα), thereby inhibiting lipid metabolic enzymes. The objective of the present study was to investigate the potential protective effect of fenofibrate, a known agonist of PPARα on radiation-induced cardiac toxicity. To this end, we compared, for the first time, the cardiac proteome of fenofibrate- and placebo-treated mice 20 weeks after local heart irradiation (16 Gy) using label-free proteomics.

Determinants of Hepatitis C Virus Prevalence in People With Serious Mental Illness: A Systematic Review and Meta-Analysis.

To perform a meta-analysis of hepatitis C virus (HCV) prevalence in people with serious mental illness (SMI) and to systematically review barriers to care with the contention that both individual complications and HCV community transmission can be reduced with enhanced health care strategies. PubMed, Scopus, Embase, CINAHL, and Web of Science were searched for articles published in English between April 21, 1989, and July 1, 2020. The terms and were cross-referenced with and .

Hepatitis C virus in people with serious mental illness: an analysis of the care cascade at a tertiary health service with a pilot 'identify and treat' strategy.

Background: People with serious mental illness (SMI) are underserved from a hepatitis C virus (HCV) screening and treatment perspective.

Aims: To examine the HCV care cascade in people with SMI and to pilot a supported HCV treatment integration programme.

Methods: HCV prevalence was retrospectively analysed from 4492 consecutive individuals admitted to a tertiary hospital mental health service between January 2017 and December 2018.

Partial-Brain Radiation-Induced Microvascular Cognitive Impairment in Juvenile Murine Unilateral Hippocampal Synaptic Plasticity.

Purpose: Radiation-induced cognitive deficits have a severe negative impact on pediatric brain tumor patients. The severity of cognitive symptoms is related to the age of the child when radiation was applied, with the most severe effects seen in the youngest. Previous studies using whole-brain irradiation in mice confirmed these findings.

Addressing the liver progenitor cell response and hepatic oxidative stress in experimental non-alcoholic fatty liver disease/non-alcoholic steatohepatitis using amniotic epithelial cells.

Background: Non-alcoholic fatty liver disease is the most common liver disease globally and in its inflammatory form, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis and hepatocellular carcinoma (HCC). Currently, patient education and lifestyle changes are the major tools to prevent the continued progression of NASH. Emerging therapies in NASH target known pathological processes involved in the progression of the disease including inflammation, fibrosis, oxidative stress and hepatocyte apoptosis.