The gut microbiota is reported to modulate the immune response in hepatocellular carcinoma (HCC). Here, we employ metagenomic and metabolomic studies to characterise gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) related cirrhosis, with or without HCC, and evaluate its effect on the peripheral immune response in an ex vivo model. We find that dysbiosis characterises the microbiota of patients with NAFLD-cirrhosis, with compositional and functional shifts occurring with HCC development. Gene function of the microbiota in NAFLD-HCC supports short chain fatty acid production, and this is confirmed by metabolomic studies. Ex vivo studies show that bacterial extracts from the NAFLD-HCC microbiota, but not from the control groups, elicit a T cell immunosuppressive phenotype, characterised by expansion of regulatory T cells and attenuation of CD8 + T cells. Our study suggest that the gut microbiota in NAFLD-HCC is characterised by a distinctive microbiome/metabolomic profile, and can modulate the peripheral immune response.

Due to the rising prevalence of obesity and type II diabetes mellitus, non‐alcoholic fatty liver disease is becoming the leading cause of chronic liver disease in the Western world. In some patients, simple steatosis can result in non‐alcoholic steatohepatitis which over time can lead to liver cirrhosis and its associated sequelae, including hepatocellular carcinoma. Early identification and management of patients at risk with intensive dietary and lifestyle modification are essential to prevent the development of advanced liver disease and its complications. In this review, we will discuss the epidemiology of non‐alcoholic fatty liver disease, pathogenesis, diagnosis, management and surveillance strategies to offset the morbidity and mortality of this disease, as well as liver and non‐liver‐related complications.

Substantial hurdles identified by participants include cultural differences, language difficulties, cultural beliefs, stigma and misinformation. These data demonstrate the need for the greater dissemination of information in culturally and linguistically appropriate mediums to raise awareness about viral hepatitis, pathogenesis and available treatments.

There were gaps in the knowledge of GPs particularly concerning natural history, diagnosis, treatment availability and management of pregnant or lactating women with viral hepatitis. Specific educational initiatives targeting these deficits are required as well as increased availability of language resources for managing patients from a non-English-speaking background.

Summary Background Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). Aim To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. Methods We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. Results A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre‐treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Conclusion Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre‐treatment IgG levels.

Background Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 −/− mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development. Results Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred. Conclusion In Mdr2 −/− mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development.

Background Homelessness is an increasing societal and health issue associated with high rates of substance abuse and mental health disorders. Homeless people die more often and at a younger age than others. Aim To identify health needs and improve healthcare for homeless men. Methods A physician‐led clinic was established on‐site at the Mission Australia Centre in Sydney, incorporating: (i) liver screening, including portable fibroscan testing, and on‐site treatment of hepatitis C; (ii) a mental health clinic, staffed by a psychiatrist; and (iii) a nurse‐led clinic to follow up medical issues and deliver vaccinations. Patient data were recorded prospectively to determine what medical problems were encountered so as to drive future healthcare planning. Results A total of 257 men was assessed between November 2011 and December 2017. In that time, 561 men resided at the Centre. Of these 257 men who attended the clinic, 61% were <45 years old; 69% were current and 8% former smokers; 62% had a history of chronic alcoholic abuse and 66% other substance abuse; 64% had one or more of depression, anxiety, psychosis or another mental health disorder and 44% had metabolic syndrome features, 38% cardiovascular disease, 29% hepatitis C and 21% a respiratory disorder. Conclusion The main health needs of homeless men fall into the categories of mental health; cardiovascular, respiratory and metabolic disorders and addictions and hepatitis C. Establishing on‐site clinics at homeless shelters with expertise to address these issues will likely improve the well‐being of these men, reduce hospital admissions and prolong their lives.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1‐year‐olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year‐to‐year decrease in new HCV‐ and HBV‐related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.