Comparative Risk of Hepatitis B Virus Reactivation in Patients Receiving Immune Checkpoint Inhibitors or Tyrosine Kinase Inhibitors for Liver Cancer.

Background: Current and past hepatitis B virus (HBV) infection remains the leading cause of liver cancer in endemic areas.

Aim: To examine the risk of HBV reactivation (HBVr) in patients receiving immune checkpoint inhibitors (ICI) for liver cancer.

Methods: Patients with current or past HBV infection receiving systemic treatments for liver cancer from March 2015 to March 2023 were identified using a territory-wide electronic database in Hong Kong.

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.

Efficacy and Safety of Tenofovir Alafenamide (TAF) and Tenofovir Disoproxil Fumarate (TDF) Followed by TAF in Chronic Hepatitis B Patients of East Asian Ethnicity Following 5 Years of Treatment.

Background: Tenofovir alafenamide (TAF) has shown non-inferior efficacy to tenofovir disoproxil fumarate (TDF), with superior bone and renal safety.

Aim: To characterise 5-year TAF efficacy and safety in patients of East Asian ethnicity from pivotal Phase 3 studies.

Methods: Patients were randomised (2:1) to receive TAF or TDF for up to 3 years of double-blind treatment, followed by open-label TAF.

Microbiological Profile of Bacterial Infections in Patients With Cirrhosis Over Time: A 20-year Territory-wide Study.

Background & Aims: Antimicrobial resistance (AMR) complicates the management of bacterial infections in cirrhosis, whereas detailed microbiology data remain scarce. This study aimed to characterize the bacteriological landscape in patients with cirrhosis and assess their impact on mortality.

Methods: All admissions of adult patients with cirrhosis between 2001 and 2021 were identified using a territory-wide database in Hong Kong.

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).

Recognisable Alcohol Use Significantly Increases the Risk of Adverse Outcomes in Patients With Hepatitis B Virus-Related Cirrhosis.

Chronic hepatitis B virus (HBV) infection is a major contributor to cirrhosis, hepatic events and mortality, even when antiviral treatments are used. However, alcohol consumption may compromise these benefits. This study evaluated the impact of alcohol use on outcomes in patients with HBV-related cirrhosis.

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.

Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: A population-based multi-cohort study.

Background & Aims: Evaluating five cardiometabolic risk factors (CMRFs) is crucial for diagnosing metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigated the impact of CMRFs on hepatic fibrosis and long-term clinical outcomes in patients with MASLD.

Methods: Two cross-sectional cohorts (Korean magnetic resonance elastography [n = 6,684] and US vibration-controlled transient elastography [n = 6,230]) were included to assess the impact of five CMRFs and their combinations on hepatic fibrosis.

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.

Long-Term Dynamic Changes of Alanine Aminotransferase Levels Are Associated With Liver-Related Events in Nucleos(t)ide Analogue-Treated Chronic Hepatitis B Patients in China.

Background: The role of alanine aminotransferase (ALT) dynamics during nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB) is unclear. We aimed to evaluate the correlation between ALT dynamics and liver-related events (LRE), and explore the optimal threshold of ALT during NA treatment.

Methods: We enrolled 18,129 NA-treated patients, comprising 3104 patients from the Search-B study (NCT02167503) and 15,025 patients from a real-world cohort in Hong Kong.

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.

Increased risk of HCC in HBeAg-negative indeterminate phase compared with HBeAg-negative chronic infection.

Background And Aims: The outcomes and benefits of antiviral therapy in patients with indeterminate phase HBeAg-negative chronic hepatitis B are not well described in treatment guidelines. We examined HCC risk among these patients.

Approach And Results: We identified all non-cirrhotic treatment-naïve patients with HBeAg-negative chronic hepatitis B who received ≥1 test for HBV DNA and HBeAg.

The new definition of metabolic dysfunction-associated steatotic liver disease: the role of ultrasound and elastography.

In 2023, nonalcoholic fatty liver disease was renamed metabolic dysfunction-associated steatotic liver disease by the American and European liver associations. This new nomenclature recognizes metabolic dysfunction as the central driver of the disease, and the diagnostic criteria now require the presence of hepatic steatosis plus at least one of five cardiometabolic risk factors. B-mode ultrasonography remains the most common and practical method for detecting hepatic steatosis, although newer ultrasound techniques based on attenuation, backscatter, and speed of sound have gained traction as tools to diagnose and quantify hepatic steatosis.

Cost-Effectiveness of Universal Screen-and-Treat Strategies for Reducing Morbidity and Mortality of Chronic Hepatitis B in a High-Endemicity City.

In the setting of high hepatitis B virus (HBV) endemicity, we studied the cost-effectiveness of universal HBV screen-and-treat strategies for averting HBV-related morbidity and mortality in Hong Kong, where diagnosis and treatment coverages are low. An age-sex-specific compartmental model for 2000-2040 was developed, with the incorporation of population-based screening strategies targeting different age groups. With a one-time HBV screening programme in 2025-2029, 3.

ALADDIN: A Machine Learning Approach to Enhance the Prediction of Significant Fibrosis or Higher in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Introduction: The recent US Food and Drug Administration approval of resmetirom for treating metabolic dysfunction-associated steatohepatitis in patients necessitates patient selection for significant fibrosis or higher (≥F2). No existing vibration-controlled transient elastography (VCTE) algorithm targets ≥F2.

Methods: The mAchine Learning ADvanceD fibrosis and rIsk metabolic dysfunction-associated steatohepatitis Novel predictor (ALADDIN) study addressed this gap by introducing a machine-learning-based web calculator that estimates the likelihood of significant fibrosis using routine laboratory parameters with and without VCTE.

Pharmacological Treatment of Ascites: Challenges and Controversies.

Ascites is the most common complication from cirrhosis related to portal hypertension and depicts the onset of hepatic decompensation. Ranging from uncomplicated to refractory ascites, the progression carries prognostic value by reflecting the deterioration of underlying cirrhosis and portal hypertension. Diuretics have been the mainstay of treatment to control ascites, but the side effects heighten when the dosage is escalated.

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.

The Impact of Hepatitis B Surface Antigen Reduction via Small Interfering RNA Treatment on Natural and Vaccine (BRII-179)-Induced Hepatitis B Virus-Specific Humoral and Cellular Immune Responses.

Background & Aims: The impact of hepatitis B surface antigen (HBsAg) reduction from small interfering RNA (siRNA) treatments on hepatitis B virus (HBV)-specific immunity of individuals with chronic hepatitis B (CHB) has not been adequately analyzed in humans. We conducted a phase 2a study treating CHB participants with nine 4-weekly doses of HBV-targeted siRNA elebsiran (BRII-835), either alone (n = 10) or in combination with a virus-like particle-based therapeutic vaccine (BRII-179) containing Pre-S1, Pre-S2, and S antigens, coadministered with (n = 39) or without (n = 41) interferon alfa.

Methods: We analyzed longitudinally for 72 weeks virologic, clinical, and immunologic parameters, including HBsAg, alanine aminotransferase, hepatitis B surface antibody (anti-HBs), the neutralizing activity of representative sera, and frequency and cytokine secretion ability of T cells specific for Pre-S1, Pre-S2, and S both directly ex vivo and after in vitro expansion.

Role of noninvasive tests on the prediction of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without cirrhosis: a systematic review and meta-analysis of aggregate and individual patient data.

Background: Nonalcoholic fatty liver disease (NAFLD) has been identified as an emerging risk factor for hepatocellular carcinoma (HCC). Identifying non-cirrhotic NAFLD patients at risk for HCC is crucial. We aimed to investigate the utility of noninvasive tests (NITs) as predictors for HCC and to determine optimal and cost-effective NIT cutoffs for HCC surveillance in non-cirrhotic NAFLD patients.

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.

Concomitant Usage of H1-Antihistamines and Immune Checkpoint Inhibitors on Cancer Patient Survival.

Purpose: Recent research (Li et al. 2021) suggests an upregulated expression and activation of H1 receptors on macrophages in the tumor microenvironment, and concomitant H1-antihistamine use is associated with improved overall survival in patients with lung and skin cancers receiving immunotherapy. Therefore, we retrospectively evaluated the impacts of H1-antihistamine use in cancer patients during immunotherapy.

Extreme Hot Weather Events and Risk of Hospitalization for Cardiovascular and Respiratory Diseases in Older People in Hong Kong in 2012-2018.

Background: The older population is more vulnerable to the impact of extreme hot weather events (EHWEs), although the impact on the frailer institutionalized older population was seldom assessed. Our objective was to assess the relationship between EHWEs and hospitalization risks among institutionalized and community-dwelling older people.

Methods: We used territory-wide hospitalization records of Hong Kong from the year 2012 to 2018 to assess the associations between EHWEs and cardiovascular and respiratory disease hospitalizations in the population aged 65 or above.