The PNPLA3 I148M variant is associated with immune cell infiltration and advanced fibrosis in MASLD: a prospective genotype-phenotype study.

Background: Increasing evidence reveals that immune cells significantly contribute to metabolic dysfunction-associated steatotic liver disease (MASLD) progression. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant has been linked to hepatic inflammation and fibrosis; however, its role in immune cell infiltration and activation within the liver remains unclear.

Methods: Seventy patients with MASLD were prospectively enrolled.

Development and validation of a risk prediction model for patients with hepatocellular carcinoma receiving atezolizumab-bevacizumab.

Background And Aims: Atezolizumab plus bevacizumab (AB) has become the standard first-line treatment for advanced HCC. However, identifying reliable prognostic biomarkers remains a critical challenge. We aimed to develop a comprehensive scoring system to predict overall survival (OS) in advanced HCC patients receiving first-line AB.

Prediction of long-term HBsAg seroclearance in patients with HBeAg-negative chronic hepatitis B.

Background & Aims: Predicting the long-term HBsAg seroclearance, an ideal endpoint, is relevant for decision-making regarding antiviral therapy for patients with chronic hepatitis B (CHB). This study aimed to identify predictors and develop a prediction model for HBsAg seroclearance in patients with HBeAg-negative CHB.

Methods: A total of 2,032 untreated HBeAg-negative patients who underwent a 2-year baseline observation period were enrolled.

Subset of Child-Pugh Score 7 Shows Comparable Survival Outcomes to Child-Pugh Score 6 in Hepatocellular Carcinoma Patients Treated with Atezolizumab and Bevacizumab.

Purpose: Given the limited data on the effectiveness of Atezolizumab plus Bevacizumab (Ate/Bev) in HCC patients with a Child-Pugh score (CPS) of 7, this study aims to evaluate the treatment's efficacy in this population and identify specific CPS 7 subgroups that may benefit from it.

Experimental Design: This study included patients with advanced HCC who received Ate/Bev as first-line therapy between September 2020 and December 2023 at seven university hospitals. The primary outcome was OS, while secondary outcomes included PFS and treatment response.

Incorporating ALBI Grade with Geriatric Nutritional Risk Index Enhances Hepatocellular Carcinoma Risk Stratification.

Introduction: Despite its prognostic impact, nutritional status has not yet been integrated into the assessment of hepatocellular carcinoma (HCC). This study investigated the association between geriatric nutritional risk index (GNRI) and overall survival (OS) in patients with HCC using a nationwide registry.

Methods: Data from the Korea Central Cancer Registry between 2008 and 2019 were analyzed.

Predicting Mortality and Cirrhosis-Related Complications with MELD3.0: A Multicenter Cohort Analysis.

Background: /Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score.

Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019.

Dynamic Peripheral T-Cell Analysis Identifies On-Treatment Prognostic Biomarkers of Atezolizumab plus Bevacizumab in Hepatocellular Carcinoma.

Introduction: Variability in response to atezolizumab plus bevacizumab (AB) treatment of hepatocellular carcinoma (HCC) underscores the critical need for the development of effective biomarkers. We sought to identify peripheral blood biomarkers reflecting response to AB treatment.

Methods: We analyzed dynamic changes in peripheral blood mononuclear cells from a prospective, multicenter cohort of 65 patients with HCC, using flow cytometry to evaluate the T-cell population before and 3 weeks after the first AB treatment.

Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis.

Background/aims: Epithelial-to-mesenchymal transition (EMT) plays a crucial role in hepatic fibrogenesis and liver repair in chronic liver disease. Our research highlights the antifibrotic potential of placenta-derived mesenchymal stem cells (PD-MSCs) and the role of phosphatase of regenerating liver-1 (PRL-1) in promoting liver regeneration.

Methods: We evaluated the efficacy of PD-MSCs overexpressing PRL-1 (PD-MSCsPRL-1) in a bile duct ligationinduced rat injury model, focusing on their ability to regulate EMT.

Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity.

Background/aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.

Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.

Performance of Noninvasive Indices for Discrimination of Metabolic Dysfunction-Associated Steatotic Liver Disease in Young Adults.

Background/aims: Although numerous noninvasive steatosis indices have been developed to assess hepatic steatosis, whether they can be applied to young adults in the evaluation of metabolic dysfunction-associated steatotic liver disease (MASLD) remains uncertain.

Methods: Data from patients under 35 years of age who visited the Liver Health Clinic at the Armed Forces Goyang Hospital between July 2022 and January 2024 were retrospectively collected. Steatosis was diagnosed on the basis of a controlled attenuation parameter score ≥250 dB/m.

Chitinase 1: a novel therapeutic target in metabolic dysfunction-associated steatohepatitis.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by persistent inflammatory cascades, with macrophage activation playing a pivotal role. Chitinase 1 (CHIT1), produced by activated macrophages, is a key player in this cascade. In this study, we aimed to explore the role of CHIT1 in MASH with progressive liver fibrosis.

The Critical Role of Regulatory T Cells in Immune Tolerance and Rejection Following Liver Transplantation: Interactions With the Gut Microbiome.

Liver transplantation (LT) is the ultimate treatment for patients with end-stage liver disease or early hepatocellular carcinoma. In the context of LT, because of the unique immunological characteristics of human liver allograft, 5%-20% of selected LT recipients can achieve operational tolerance. Nonetheless, there remains a risk of rejection in LT patients.

The Impact of Histologic Portal T-Cell Density on the Clinical Outcomes in Hepatic Graft-versus-Host Disease and Autoimmune Liver Diseases.

Hepatic graft-versus-host disease (GVHD) significantly impacts morbidity and mortality among allogeneic hematopoietic stem cell transplant recipients. However, the relationship between clinical and immunopathological phenotypes and their influence on clinical outcomes in hepatic GVHD is not well understood. In this study, we aimed to study the implications of portal T-cell infiltration on the clinical outcomes in hepatic GHVD and its similarities to autoimmune liver disease.

The prognostic impact of psychiatric intervention on alcohol-associated liver disease: The UK Biobank cohort study.

Background/aims: Alcohol-associated liver disease (ALD) is a public health concern. ALD patients often have psychiatric comorbidities, but the effects of psychiatric interventions on ALD are not well-established. This study explores the prognostic impact of psychiatric intervention on ALD within UK Biobank cohort.

Analysis of Immune-Related Adverse Events of Atezolizumab and Bevacizumab in Patients with Hepatocellular Carcinoma: A Multicentre Cohort Study.

Introduction: Despite the emergence of atezolizumab and bevacizumab (A + B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A + B treatment.

Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A + B regimen from September 2020 to December 2022.

Differential HBV replicative markers and covalently closed circular DNA transcription in immune-active chronic hepatitis B with and without HBeAg.

Background And Aims: Molecular processes driving immune-active chronic hepatitis B (CHB) with and without hepatitis B e antigen (HBeAg) remain incompletely understood. This study aimed to investigate expression profiles of serum and intrahepatic HBV markers and replicative activity of HBV in CHB patients with or without HBeAg.

Methods: This study recruited 111 untreated immune-active CHB (60 HBeAg-positive and 51 HBeAg-negative) patients and quantified intrahepatic covalently closed circular DNA (cccDNA), pre-genomic RNA (pgRNA), total HBV DNA (tDNA), and replicative intermediates as well as serum HBV markers (HBV DNA, hepatitis B surface antigen, hepatitis B core-related antigen).

Effect of Biliary Drainage on the Prognosis of Patients with Hepatocellular Carcinoma and Bile Duct Invasion.

Background/aims: Bile duct invasion (BDI) is rarely observed in patients with advanced hepatocellular carcinoma (HCC), leading to hyperbilirubinemia. However, the efficacy of pretreatment biliary drainage for HCC patients with BDI and obstructive jaundice is currently unclear. Thus, the aim of this study was to assess the effect of biliary drainage on the prognosis of these patients.

Impact of Korean Military Service on the Prevalence of Steatotic Liver Disease: A Longitudinal Study of Pre-enlistment and In-Service Health Check-Ups.

Background/aims: Young Korean men are obligated to serve in the military for 18 to 21 months. We investigated the effects of military service on steatotic liver disease (SLD) and other metabolic parameters.

Methods: Pre-enlistment health check-up performed from 2019 to 2022 and in-service health check-up performed from 2020 to 2022 were merged as paired data.

Efficacy comparison of high-genetic barrier nucleos(t)ide analogues in treatment-naïve chronic hepatitis B patients: a network meta-analysis.

Background/aims: Four high-genetic barrier nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB), namely entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and besifovir dipivoxil maleate (BSV), have been established. The aim of this study is to investigate the efficacy of four high-genetic barrier NAs using a network meta-analysis of randomized trials and propensity score-matched cohorts.

Methods: Systematic search was performed using PubMed, Cochrane library, and EMBASE and included randomized controlled trials and cohort studies that used propensity score matching.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

Background And Aim: Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD).

Methods: This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA < 20 IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021.

Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study.

Background: Atezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial.

Materials And Methods: This real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177).

Results: First, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups.

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation.

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation.

The Portal Venous Pulsatility Index and Main Portal Vein Diameter as Surrogate Markers for Liver Fibrosis in Nonalcoholic Fatty Liver Disease and Metabolic-Dysfunction-Associated Steatotic Liver Disease.

(1) Background: Despite numerous noninvasive methods for assessing liver fibrosis, effective ultrasound parameters remain limited. We aimed to identify easily measurable ultrasound parameters capable of predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and metabolic-dysfunction-associated steatotic liver disease (MASLD); (2) Methods: The data of 994 patients diagnosed with NAFLD via ultrasound at the Armed Forces Goyang Hospital were retrospectively collected from June 2022 to July 2023. A liver stiffness measurement (LSM) ≥ 8.

Extracellular Superoxide Dismutase Attenuates Hepatic Oxidative Stress in Nonalcoholic Fatty Liver Disease through the Adenosine Monophosphate-Activated Protein Kinase Activation.

Oxidative stress is key in type 2 diabetes-associated nonalcoholic fatty liver disease (NAFLD). We explored whether extracellular superoxide dismutase (EC-SOD) activates adenosine monophosphate-activated protein kinase (AMPK) to enhance antioxidant synthesis and lipid metabolism in NAFLD. Human recombinant EC-SOD (hEC-SOD) was administered to 8-week-old male C57BLKS/J / mice through intraperitoneal injection once a week for 8 weeks.