Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model.

Primary liver cancer is an increasing problem worldwide and is associated with significant mortality. A popular method of modeling liver cancer in mice is plasmid hydrodynamic tail vein injection (HTVI). However, plasmid-HTVI models rarely recapitulate the chronic liver injury which precedes the development of most human liver cancer.

Branched-chain amino acid supplementation does not improve measures of sarcopenia in cirrhosis: results of a randomised controlled trial.

Background: Sarcopenia is associated with adverse outcomes in cirrhosis. Branched-chain amino acids (BCAA) target several pathways that lead to muscle loss in this population.

Aims: We aimed to evaluate the impact of BCAA supplementation on sarcopenia measures in patients with cirrhosis.

Alcohol intake is associated with a decreased risk of developing primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) is a chronic progressive liver disease of unknown aetiology characterised by immune-mediated destruction of small and medium-sized intrahepatic bile ducts. There are few well-established risk factors and epidemiological studies are needed to further evaluate the pathogenesis of the disease.

Aim: To evaluate the relationship between alcohol intake, smoking and marijuana use with PBC development.

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.

Mas-related G protein-coupled receptor type D antagonism improves portal hypertension in cirrhotic rats.

Splanchnic vasodilatation contributes to the development and aggravation of portal hypertension (PHT). We previously demonstrated that in cirrhosis, angiotensin- mediates splanchnic vasodilatation through the Mas receptor (MasR). In this study, we investigated whether the recently characterized second receptor for angiotensin-(1-7), Mas-related G protein-coupled receptor type D (MrgD), contributes to splanchnic vasodilatation in cirrhotic and noncirrhotic PHT.

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.

Malnutrition and low muscle strength are independent predictors of clinical outcomes and healthcare costs after liver transplant.

Background & Aims: Malnutrition and sarcopenia are associated with increased morbidity and mortality in cirrhosis but conflicting data are reported after liver transplantation (LT), with little known about the economic burden of malnutrition at LT. This study aims to investigate the impact of pre-transplant malnutrition and muscle strength on post-transplant clinical outcomes and healthcare costs.

Methods: Pre-transplant nutritional status (via subjective global assessment, SGA) and handgrip strength (HGS) were assessed in patients transplanted from 2009-2017.

Angiotensin Converting Enzyme-2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is frequently associated with type 2 diabetes. However, there is no specific medical therapy to treat this condition. Angiotensin-converting enzyme 2 (ACE2) of the protective renin angiotensin system generates the antifibrotic peptide angiotensin-(1-7) from profibrotic angiotensin II peptide.

Epidemiology and Prognostic Significance of Rapid Response System Activation in Patients Undergoing Liver Transplantation.

Patients undergoing liver transplantation have a high risk of perioperative clinical deterioration. The Rapid Response System is an intensive care unit-based approach for the early recognition and management of hospitalized patients identified as high-risk for clinical deterioration by a medical emergency team (MET). The etiology and prognostic significance of clinical deterioration events is poorly understood in liver transplant patients.

Clinical outcomes of patients with two small hepatocellular carcinomas.

Background: Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear.

Identification of a Latitude Gradient in the Prevalence of Primary Biliary Cholangitis.

Introduction: The prevalence of primary biliary cholangitis (PBC) reported in different countries varies significantly and seems to have a latitudinal gradient with the highest prevalence reported in higher latitudes, as has been observed with other autoimmune diseases. This study aimed to determine whether there is a latitudinal gradient of PBC prevalence in Australia using 2 methods of case ascertainment.

Methods: We investigated the latitudinal variation of PBC prevalence across the states and territories of Australia (latitudinal range 18.

Update on New Aspects of the Renin-Angiotensin System in Hepatic Fibrosis and Portal Hypertension: Implications for Novel Therapeutic Options.

There is considerable experimental evidence that the renin angiotensin system (RAS) plays a central role in both hepatic fibrogenesis and portal hypertension. Angiotensin converting enzyme (ACE), a key enzyme of the classical RAS, converts angiotensin I (Ang I) to angiotensin II (Ang II), which acts via the Ang II type 1 receptor (AT1R) to stimulate hepatic fibrosis and increase intrahepatic vascular tone and portal pressure. Inhibitors of the classical RAS, drugs which are widely used in clinical practice in patients with hypertension, have been shown to inhibit liver fibrosis in animal models but their efficacy in human liver disease is yet to be tested in adequately powered clinical trials.

Cardiac Risk Stratification in Liver Transplantation: Results of a Tiered Assessment Protocol Based on Traditional Cardiovascular Risk Factors.

Coronary artery disease (CAD) confers increased perioperative risk in patients undergoing liver transplantation (LT). Although routine screening for CAD is recommended, there are limited data on the effectiveness of screening strategies. We evaluated the safety and efficacy of a 3-tiered cardiac risk-assessment protocol that stratifies patients based on age and traditional cardiac risk factors.

Cirrhotic portal hypertension: From pathophysiology to novel therapeutics.

Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow.

Safety and efficacy of outpatient continuous terlipressin infusion for the treatment of portal hypertensive complications in cirrhosis.

Background/aim: Therapeutic options are limited for patients with hepatorenal syndrome (HRS), diuretic refractory ascites and hepatic hydrothorax who are awaiting liver transplant. We assessed the safety and efficacy of continuous terlipressin infusion (CTI) for treating these conditions in an outpatient setting.

Method: All patients treated with CTI from May 2013 through March 2018 at our institution were initiated in-hospital on bolus dose terlipressin therapy for 24-72 h prior to commencing CTI for home therapy.

Comparison of Thromboelastography and Conventional Coagulation Tests in Patients With Severe Liver Disease.

Objective: Thromboelastography (TEG) may provide rapid and clinically important coagulation information in acutely ill patients with chronic liver disease (CLD). Our objective was to describe the relationship between TEG and conventional coagulation tests (CCTs), which has not been previously explored in this population.

Methods: In acutely ill patients with severe CLD (Child-Pugh score > 9, category C), we conducted a prospective observational study investigating coagulation assessment as measured by both CCTs and TEG.

Continuous terlipressin infusion is associated with improved diet intake and muscle strength in patients awaiting liver transplant.

Background & Aims: Portal hypertension contributes to the pathogenesis of malnutrition and sarcopenia in cirrhosis via multiple mechanisms. Terlipressin is a vasopressin analogue that we administer via continuous outpatient infusion, as a bridge to transplantation in patients with hepatorenal syndrome or refractory ascites. We describe, for the first time, the impact of outpatient terlipressin on nutritional and muscle parameters.

Risk stratification in acute variceal bleeding: Comparison of the AIMS65 score to established upper gastrointestinal bleeding and liver disease severity risk stratification scoring systems in predicting mortality and rebleeding.

Background And Aim: Risk stratification is recommended in all patients with acute variceal bleeding (AVB). It remains unclear whether liver disease severity or upper gastrointestinal bleeding (UGIB) scoring algorithms offer superior predictive ability. We aimed to validate the AIMS65 score as a predictor of mortality in AVB, and to compare AIMS65 with established UGIB and liver disease severity risk stratification scores.

Liver-Targeted Angiotensin Converting Enzyme 2 Therapy Inhibits Chronic Biliary Fibrosis in Multiple Drug-Resistant Gene 2-Knockout Mice.

There is a large unmet need for effective therapies for cholestatic disorders, including primary sclerosing cholangitis (PSC), a disease that commonly results in liver failure. Angiotensin (Ang) II of the renin Ang system (RAS) is a potent profibrotic peptide, and Ang converting enzyme 2 (ACE2) of the alternate RAS breaks down Ang II to antifibrotic peptide Ang-(1-7). In the present study, we investigated long-term effects of ACE2 delivered by an adeno-associated viral vector and short-term effects of Ang-(1-7) peptide in multiple drug-resistant gene 2-knockout (Mdr2-KO) mice.