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.

Non-invasive tests of fibrosis in the management of MASLD: revolutionising diagnosis, progression and regression monitoring.

With the recent conditional approval of resmetirom by the US Food and Drug Administration, the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) has potentially entered a new era, requiring a comprehensive understanding of the strengths and weaknesses of non-invasive tests (NITs) for diagnosing and monitoring MASLD-related fibrosis. This article focuses on F2/F3 liver fibrosis and summarises the current application status of NITs, including serum biomarkers, imaging methods and their combined use in the management of MASLD. The article highlights the application of NITs in several areas, including diagnosis and baseline stratification, monitoring progression of fibrosis, prediction of liver-related clinical events, as well as assessment of disease regression, remission and long-term liver-related outcomes.

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.

Attenuation of the second peak of bimodal recurrence of HBV-related HCC after curative treatment in the antiviral era.

Background & Aims: Recurrence in patients with hepatocellular carcinoma (HCC) treated with curative surgery or ablation follows a bimodal pattern, with early recurrence peaking at 6 months to 1 year, and late recurrence peaking at 3 to 4 years. We postulate that the use of antiviral therapy may reduce late recurrence by improving control of chronic inflammation.

Methods: Patients with positive HBsAg and HCC (HBV-related HCC) who received curative surgery or ablation from October 2000 to July 2017 were recruited from Prince of Wales Hospital in Hong Kong.

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.

Modeling Reductions in Liver Fat: Comparing Noninvasive Tests to Magnetic Resonance Imaging-Proton Density Fat Fraction.

Background And Aims: Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an accurate, noninvasive tool for diagnosing metabolic dysfunction-associated steatotic liver disease, but its feasibility is limited in routine clinical practice. We aimed to assess the clinical utility of alternative, cost-efficient approaches for assessing liver fat changes and their relationship with MRI-PDFF changes.

Methods: This is a secondary analysis of a phase 2a study that included adults with metabolic dysfunction-associated steatotic liver disease who received clesacostat, a selective, reversible inhibitor of acetyl-CoA carboxylase.

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.

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.

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.

The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment.