Extrachromosomal DNA (ecDNA) drives hepatocellular carcinoma malignancy through high-copy amplification of chromosome 1q21-derived PIP5K1A oncogene.

Extrachromosomal circular DNA (eccDNA) drives oncogene amplification in multiple malignancies, yet its landscape and clinical relevance in hepatocellular carcinoma (HCC) remain poorly characterized. Here, we performed Circle-seq and RNA-seq on six pairs of HCC tumors and adjacent non-tumor tissues, identifying a 3 Mb extrachromosomal DNA (ecDNA) from chromosome 1q21 in 50 % tumor samples. This ecDNA contained multiple genes, but functional analysis prioritized PIP5K1A due to its central role in PI3K/AKT signaling and association with poor prognosis.

Effect of Hypertension on Long-term Adverse Clinical Outcomes and Liver Fibrosis Progression in MASLD.

Background & Aims: Hypertension is common in metabolic dysfunction-associated steatotic liver disease (MASLD), but its impact on long-term clinical outcomes and disease progression remains unclear. This study investigated the association of hypertension and risk of adverse clinical outcomes and progression of liver stiffness/fibrosis in MASLD.

Methods: Three multicenter prospective cohorts were analyzed: the UK BioBank (UKBB) cohort to assess the risk of adverse clinical outcomes, the VCTE-Prognosis cohort to assess liver stiffness/fibrosis progression, and the Paired Liver Biopsy cohort to assess histologic liver fibrosis progression.

Longitudinal Changes in Fibrosis Markers: Monitoring Stiffness/Fibrosis Progression and Prognostic Outcomes in MASLD.

Background & Aims: Fibrosis-4 Index (FIB-4) is a noninvasive tool for assessing liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). However, its role of dynamic FIB-4 for assessing fibrosis progression and predicting clinical outcomes remains unclear. The aim of this study was to examine the association between changes in FIB-4 and changes in liver stiffness, fibrosis progression, and outcomes in MASLD.

A Novel Risk Prediction Model for Hepatocellular Carcinoma in MASLD: A Multinational, Multicenter Cohort Study.

Background And Aims: It is unclear that which cardiometabolic risk factors (CMRFs) are significantly associated with hepatocellular carcinoma (HCC) development in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to develop and validate a novel CMRF-based HCC risk prediction model in MASLD.

Methods: This multicenter cohort study recruited 77,677 MASLD patients from 20 medical centers in Korea and other Asian and Western countries (2004-2023).

Impact of first and further decompensation in patients with compensated ACLD due to MASLD.

Background & Aims: First and further decompensation events mark key transitions in the natural history of cirrhosis and significantly influence mortality risk. We assessed the cumulative incidence of first and further (acute and non-acute) decompensation and evaluated their impact on liver-related death (LR-D) in patients with compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: We conducted an international, multicenter (17 centers), retrospective study involving 6,061 consecutive patients with cACLD due to MASLD, diagnosed either clinically (liver stiffness measurement >10 kPa) or histologically (F3-F4 fibrosis).

Non-invasive risk-based surveillance of hepatocellular carcinoma in patients with metabolic dysfunction-associated steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of the general population and is the fastest growing cause of hepatocellular carcinoma (HCC). Current guidelines recommend HCC surveillance in patients with cirrhosis when annual HCC incidence exceeds 1% without specifying the role of non-invasive tests in patient selection.

Objective: To define non-invasive test thresholds to select patients with MASLD for HCC surveillance.

Effect of Antidiabetic Drug Classes on the Risk of Liver-Related Events in Individuals With T2D and MASLD.

Background: We investigated the use of type 2 diabetes (T2D) medications, including pioglitazone, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, in individuals with T2D and metabolic dysfunction-associated steatotic liver disease (MASLD), and explored the effect of these medications on long-term risk of liver-related events (LREs) and progression of liver stiffness in a retrospective cohort study.

Methods: We enrolled 7867 individuals with T2D and MASLD from 16 tertiary referral centers between February 2004 and January 2023. We recorded the use of pioglitazone, GLP-1RAs, and SGLT-2 inhibitors and analyzed the effects of these antihyperglycemic medications on the risk of developing incident LREs and the progression of liver stiffness over a median of 5.

Lifestyle modification programme for people living with HIV with metabolic dysfunction-associated steatotic liver disease: a randomised controlled trial.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease among people living with HIV, and preliminary evidence shows that lifestyle modification can reduce liver fat in people living with HIV with MASLD. We aimed to assess a dietitian-led lifestyle modification programme in inducing resolution of MASLD in this population.

Methods: In this single-blind, randomised controlled trial at the Prince of Wales Hospital, Hong Kong, people living with HIV with fatty liver defined by intrahepatic triglyceride content ≥5% on proton magnetic resonance spectroscopy (H-MRS) were enrolled if they were aged 18 years or older, were on antiretroviral therapy, and had HIV RNA of ≤50 copies per mL for 6 months or longer.

From "Burnt-Out" to "Burning-Out": Capturing Liver Fat Loss in Patients With Advanced Metabolic Dysfunction-Associated Steatotic Liver Disease From a Dynamic Perspective.

Background & Aims: The absence of hepatic fat in advanced fibrosis has been documented in metabolic dysfunction-associated steatotic liver disease ("burnt-out" MASLD). However, whether hepatic fat loss occurs continuously with fibrosis progression is controversial. We proposed a "burning-out" concept to describe this process and analyze the long-term outcomes of "burnt-out" and "burning-out" MASLD.

Prognostic performance of the two-step clinical care pathway in metabolic dysfunction-associated steatotic liver disease.

Background & Aims: Current guidelines recommend a two-step approach for risk stratification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) involving Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or similar second-line tests. This study aimed to examine the prognostic performance of this approach.

Methods: The VCTE-Prognosis study was a longitudinal study of patients with MASLD who had undergone VCTE examinations at 16 centres from the US, Europe and Asia with subsequent follow-up for clinical events.

Exploring the mediating role of blood metabolites in the relationship between gut microbiota and gastric cancer risk: a Mendelian randomization study.

Background: Prior studies have established correlations between gut microbiota (GM) dysbiosis, circulating metabolite alterations, and gastric cancer (GC) risk. However, the causal nature of these associations remains uncertain.

Methods: We utilized summary data from genome-wide association studies (GWAS) on GM (European, n=8,956), blood metabolites (European, n=120,241; East Asian, n=4,435), and GC (European, n=476,116; East Asian, n=167,122) to perform a bidirectional Mendelian randomization (MR) analysis, investigating the causal effects of GM and metabolites on GC risk.

Inhibition of DNMT1 attenuates experimental food allergy.

Background: The treatment of food allergy (FA) needs improvement. The treatment of immune disorders can be improved by regulating epigenetic marks, which is a promising method. The objective of this research is to alleviate experimental FA by employing an inhibitor of DNA methyltransferase-1 (DNMT1).

Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease.

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis.

Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD.

A Liver Stiffness-Based Etiology-Independent Machine Learning Algorithm to Predict Hepatocellular Carcinoma.

Background & Aims: The existing hepatocellular carcinoma (HCC) risk scores have modest accuracy, and most are specific to chronic hepatitis B infection. In this study, we developed and validated a liver stiffness-based machine learning algorithm (ML) for prediction and risk stratification of HCC in various chronic liver diseases (CLDs).

Methods: MLs were trained for prediction of HCC in 5155 adult patients with various CLDs in Korea and further tested in 2 prospective cohorts from Hong Kong (HK) (N = 2732) and Europe (N = 2384).

MAFLD fibrosis score: Using routine measures to identify advanced fibrosis in metabolic-associated fatty liver disease.

Background: Early screening may prevent fibrosis progression in metabolic-associated fatty liver disease (MAFLD).

Aims: We developed and validated MAFLD fibrosis score (MFS) for identifying advanced fibrosis (≥F3) among MAFLD patients.

Methods: This cross-sectional, multicentre study consecutively recruited MAFLD patients receiving tertiary care (Malaysia as training cohort [n = 276] and Hong Kong and Wenzhou as validation cohort [n = 431]).

Diagnostic and prognostic performance of the SAFE score in non-alcoholic fatty liver disease.

Background & Aims: The steatosis-associated fibrosis estimator (SAFE) score was developed to detect clinically significant liver fibrosis in patients with NAFLD in the United States. We compare the performance of the SAFE score and other non-invasive tests to diagnose liver fibrosis and to correlate the scores with liver-related outcomes in patients with NAFLD in Hong Kong.

Methods: This was a retrospective cohort study involving two data sets.

Risk and predictors of hepatic decompensation in grey zone patients by the Baveno VII criteria: A competing risk analysis.

Background: Baveno VII was proposed for non-invasive identification of clinically significant portal hypertension. However, a substantial proportion of patients is classified in the grey zone (i.e.

Clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomised controlled trial.

Objective: We aimed to test the hypothesis that automated fibrosis score calculation and electronic reminder messages could increase the detection of advanced liver disease in patients with type 2 diabetes.

Design: In this pragmatic randomised controlled trial at five general medical or diabetes clinics in Hong Kong and Malaysia, we randomly assigned patients in a 1:1 ratio to the intervention group with Fibrosis-4 index and aspartate aminotransferase-to-platelet ratio index automatically calculated based on routine blood tests, followed by electronic reminder messages to alert clinicians of abnormal results, or the control group with usual care. The primary outcome was the proportion of patients with increased fibrosis scores who received appropriate care (referred for hepatology care or specific fibrosis assessment) within 1 year.