Inflammasome-Driven Fatal Acute-on-Chronic Liver Failure Triggered by Mild COVID-19.

Inflammasome is linked to many inflammatory diseases, including COVID-19 and autoimmune liver diseases. While severe COVID-19 was reported to exacerbate liver failure, we report a fatal acute-on-chronic liver failure (ACLF) in a stable primary biliary cholangitis-autoimmune hepatitis overlap syndrome patient triggered by a mild COVID-19 infection. Postmortem liver biopsy showed sparse SARS-CoV-2-infected macrophages with extensive ASC (apoptosis-associated speck-like protein containing a CARD) speck-positive hepatocytes, correlating with elevated circulating ASC specks and inflammatory cytokines, and depleted blood monocyte subsets, indicating widespread liver inflammasome activation.

A rapid method to assess the multi-functionality of adoptively transferred engineered TCR T cells.

Introduction: The clinical efficacy of chimeric antigen and T cell receptor (TCR) T cell immunotherapies is attributed to their ability to proliferate and persist . Since the interaction of the engineered T cells with the targeted tumour or its environment might suppress their function, their functionality should be characterized not only before but also after adoptive transfer.

Materials And Methods: We sought to achieve this by adapting a recently developed Severe acute respiratory syndrome (SARS-CoV-2) rapid whole blood T cell assay to stimulate engineered TCR T cells in small volumes of whole blood (<1 ml) without cellular purification.

The utility of non-invasive tests to assess advanced fibrosis in Asian subjects with chronic hepatitis B and concomitant hepatic steatosis.

Background: Chronic hepatitis B (CHB) is endemic to Asia and is a leading cause of liver-related morbidity. The prevalence of concomitant CHB and hepatic steatosis (HS) is increasing in Asia. Non-invasive tests (NITs) including FIB-4, NFS and APRI assess fibrosis in populations with a single aetiology, but not in subjects with concomitant CHB and HS.

Hepatic steatosis and metabolic risk factors among patients with chronic hepatitis B: The multicentre, prospective CAP-Asia study.

We aimed to compare the severity of liver disease, metabolic profile and cardiovascular disease (CVD) risk of chronic hepatitis B (CHB) patients with and without hepatic steatosis and patients with non-alcoholic fatty liver disease (NAFLD). Patients with NAFLD and CHB were prospectively enrolled from 10 Asian centres. Fibroscan was performed for all patients and hepatic steatosis was defined based on controlled attenuation parameter >248 dB/m.

Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP).

Objective: To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC.

Methods: A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5.

Clinical and economic evaluation of a surveillance protocol to manage hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

Study Objective: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

Design: Prospective, single-arm study.

Setting: National Cancer Centre, Singapore.

Empower to connect and connect to empower: experience in using a humanistic approach to improve patients' access to, and experience of, care in isolation wards during the COVID-19 outbreak in Singapore.

Patients admitted to the isolation ward during the COVID-19 outbreak face multiple psychosocial stressors including the disruptive experience of being in quarantine, anxiety over contracting a newly emerging infectious disease and limited access to their healthcare team. This quality improvement project aims to leverage on technology to improve patients' access to, and experience of, care while in isolation.Patients admitted to two isolation wards in Singapore General Hospital (SGH) between 28 February and 19 March 2020 were each provided an iPad loaded with the MyCare application (app), curated materials and mobile games.

Immunosuppressive Drug-Resistant Armored T-Cell Receptor T Cells for Immune Therapy of HCC in Liver Transplant Patients.

Background And Aims: HBV-specific T-cell receptor (HBV-TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by the concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is to molecularly engineer TCR-T cells that could retain their polyfunctionality in such patients while minimizing the associated risk of organ rejection.

Approach And Results: We first analyzed how immunosuppressive drugs can interfere with the in vivo function of TCR-T cells in liver transplanted patients with HBV-HCC recurrence receiving HBV-TCR T cells and in vitro in the presence of clinically relevant concentrations of immunosuppressive tacrolimus (TAC) and mycophenolate mofetil (MMF).

Unhealthy lifestyle habits and physical inactivity among Asian patients with non-alcoholic fatty liver disease.

Background & Aims: Lifestyle modification is the cornerstone for the management of non-alcoholic fatty liver disease (NAFLD). We aim to understand lifestyle habits of NAFLD patients, compare across Asian regions and identify area of deficiency.

Methods: In the multi-centre controlled attenuation parameter (CAP)-Asia study, we collected clinical data and lifestyle habit data of NAFLD patients from Singapore, mainland China, Hong Kong, Taiwan and Malaysia.

Hepatitis C virus antigen detection is an appropriate test for screening and early diagnosis of hepatitis C virus infection in at-risk populations and immunocompromised hosts.

Early diagnosis remains key for effective prevention and treatment. Unfortunately, current screening with anti-hepatitis C virus antibody (anti-HCV Ab) test may have limited utility in the diagnosis of HCV infection and reinfection. This is of special concern to at-risk population, such as immunocompromised hosts and end-stage renal failure patients on hemodialysis.

Prescription patterns of outpatients and the potential of multiplexed pharmacogenomic testing.

Background: Pre-emptive pharmacogenomic (PGx) testing is potentially an efficient approach to improve drug safety and efficacy but the target population to test is unclear.

Objectives: We aim to describe the prescription pattern of PGx drugs among adult medical outpatients.

Methods: We estimated the 5-year cumulative incidence (CI) for receiving three groups of PGx drugs using competing risks analysis: (i) all PGx drugs, (ii) PGx drugs with guidelines and (iii) PGx drugs with serious clinical effects.

Clinical profile of non-alcoholic fatty liver disease in nonobese patients.

Background And Aim: Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome. Worryingly, it has been increasingly reported among nonobese patients. This study aims to analyse patient characteristics of biopsy-proven NAFLD in an Asian cohort and explore differences stratified by body mass index (BMI).

Validation of the Expanded Baveno-VI Criteria for Screening Gastroscopy in Asian Patients with Compensated Advanced Chronic Liver Disease.

Background: The expanded Baveno-VI criteria may further reduce the need for screening gastroscopy compared to Baveno-VI criteria.

Aim: We sought to validate the performance of these criteria in a cohort of compensated advanced chronic liver disease (cACLD) patients with predominantly hepatitis B infection.

Methods: Consecutive cACLD patients from 2006 to 2012 with paired liver stiffness measurements and screening gastroscopy within 1 year were included.

Presence of Hepatic Steatosis Does Not Increase the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Over Long Follow-Up.

Background: Chronic hepatitis B (CHB) infection and nonalcoholic fatty liver disease (NAFLD) are liver diseases which may lead to hepatocellular carcinoma (HCC) formation. Both disease entities have been attributed independently to increase risk of HCC development. While concomitant hepatic steatosis in patients with CHB are becoming more frequent in view of increasing NAFLD prevalence, there is no conclusive evidence linking presence of hepatic steatosis and increased HCC risk in patients with CHB infection.

Suboptimal treatment of dyslipidemia in patients with nonalcoholic fatty liver disease.

Background And Aim: Nonalcoholic fatty liver disease (NAFLD) patients often have dyslipidemia, and optimal treatment of dyslipidemia lowers the risk of cardiovascular disease and mortality. Our aim was to study the prescription of statin and low-density lipoprotein cholesterol treatment targets in NAFLD patients.

Methods: Consecutive NAFLD patients attending five clinics in Asia were included in this study.

Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy.

Background & Aims: Hepatocellular carcinoma (HCC) is often associated with hepatitis B virus (HBV) infection. Cells of most HBV-related HCCs contain HBV-DNA fragments that do not encode entire HBV antigens. We investigated whether these integrated HBV-DNA fragments encode epitopes that are recognized by T cells and whether their presence in HCCs can be used to select HBV-specific T-cell receptors (TCRs) for immunotherapy.

Optimal liver stiffness measurement values for the diagnosis of significant fibrosis and cirrhosis in chronic liver disease in Singapore.

Introduction: Despite the widespread use of transient elastography for non-invasive assessment of liver fibrosis, the optimal cut-off liver stiffness measurement (LSM) values remain unclear. This study aimed to validate the optimal cut-off LSM values for significant fibrosis and cirrhosis in patients with chronic liver disease (CLD).

Methods: Prospective multicentre data of CLD patients who underwent paired liver biopsy and LSM was analysed to determine the optimal cut-off LSM values for predicting significant fibrosis (METAVIR F ≥ 2) and cirrhosis (METAVIR F4).

Prevalence of hepatitis C virus infection and the IL28B genotype polymorphism among blood donors and high-risk populations.

Introduction: To study the prevalence of hepatitis C virus (HCV) infection in blood donor (BD), haemodialysis (HD) and intravenous drug user (IVDU) populations in Singapore and assess the IL28B polymorphism if HCV positive.

Methods: The BD population were healthy volunteers, the HD population were patients who were on haemodialysis for at least six months of follow-up between January 2009 and December 2014. IVDU population was from inmates at halfway houses who consented.

Real world experience with pegylated interferon and ribavirin in hepatitis C genotype 1 population with favourable polymorphism.

Conventional hepatitis C treatment using pegylated interferon (PEG-IFN) and ribavirin is associated with significant side effects. polymorphism can predict response to treatment, with CC genotype having a better response. gene deficiency protects against clinically significant anaemia induced by treatment.

Development of hepatocellular carcinoma in chronic hepatitis B patients with advanced fibrosis is independent of viral genotype.

Hepatitis B is leading cause of liver related morbidity in Asia with predominant genotypes B and C in East-Asia. Data on Serum, intrahepatic viral-markers, and long-term follow-up of prevalent genotypes (GT) B and C in patients with biopsy proven advanced fibrosis are sparse. To compare serum, intrahepatic viral-markers and development of hepatocellular carcinoma (HCC) in GT-B and C in patients with advanced fibrosis (Ishak ≥ 4).

Perceptions of non-alcoholic fatty liver disease - an Asian community-based study.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is closely related to metabolic syndrome and its risk factors. Worldwide, epidemiological studies have reported NAFLD prevalence rates of 5% to 30% depending on geographical variations. While epidemiological data suggest a progressively increasing prevalence of metabolic risk factors in Singapore, there are limited data about NAFLD per se in the community.

Epidemiology and Clinical Evolution of Liver Cirrhosis in Singapore.

Introduction: Liver cirrhosis is a common cause of morbidity and mortality and an important burden on the healthcare system. There is limited literature on liver cirrhosis in Singapore. We aimed to describe the epidemiology and clinical characteristics of cirrhotic patients seen in an ambulatory setting in a tertiary referral centre.