The Proteomic Profiling of Circulating Extracellular Vesicles of Western Diet and Chemical-Induced Murine MASH Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent chronic liver condition that can progress to severe complications such as metabolic dysfunction-associated steatohepatitis (MASH). Despite its growing burden, there are no reliable non-invasive biomarkers for tracking disease progression. In this study, we established a murine MASLD/MASH model using a high-fat diet and chemical (CCl) induction.

Expert consensus on clinical usefulness of M2BPGi for managing chronic liver diseases.

Chronic liver disease is a major global health concern, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Accurate fibrosis staging is essential for clinical management, yet liver biopsy remains invasive. Non-invasive tools such as transient elastography and serum biomarkers provide alternatives, but conventional markers like APRI and FIB-4 have limitations.

Impact of metabolic dysfunction on treatment responses to nucleos(t)ide analogues in chronic hepatitis B: a retrospective multi-center REAL-B cohort study.

Background: Metabolic dysfunction is associated with liver disease but it is unclear if it would impact responses to antiviral treatment in chronic hepatitis B (CHB) patients.

Methods: Using data from an international consortium of 4507 treatment-naïve CHB patients who initiated nucleos(t)ide analogues (NAs) between January 2004 and August 2024 from 32 centers and propensity-score matching (PSM) to balance the background of patients with and without metabolic disease (diabetes, obesity, dyslipidemia, or hypertension), we compared their biochemical (BR), virologic (VR), and complete (CR) response.

Findings: More than half (54.

Steatotic Liver Disease-Related Polygenetic Risk Score Prediction of Hepatocellular Carcinoma in Nucleotide/Nucleoside Analog-Treated Chronic Hepatitis B.

Background And Aims: We aimed to investigate the association between steatotic liver disease-related genetic risk and hepatocellular carcinoma (HCC) in Taiwanese patients with chronic hepatitis B (CHB) treated with nucleotide/nucleoside analogs (NAs).

Methods: We enrolled 745 Taiwanese patients with CHB treated with NAs and analyzed the incidence and risk factors for HCC. Steatotic liver disease (SLD)-related single nucleotide polymorphisms (SNPs) were tested, and a polygenetic risk score (PRS) for hepatocellular carcinoma was created.

Dynamics of Cardiometabolic Risk Factors Are Linked to the Risk of Hypertension and Diabetes in MASLD.

This study investigates the impact of cardiometabolic risk factors (CMRF) on the prevalence and incidence of hypertension (HTN) and diabetes mellitus (DM) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and nonsteatotic liver disease (non-SLD), using both cross-sectional and longitudinal data. A total of 32,569 Taiwanese adults without viral hepatitis or significant alcohol consumption who underwent health checkups from 1999 to 2013 were analyzed cross-sectionally. Among them, 27,109 individuals free of HTN and DM at baseline and within 1 year of enrollment were followed longitudinally.

Association of CD33 genetic variants with neurocognitive profiles in chronic viral hepatitis.

Background: CD33 has been implicated in the pathogenesis of Alzheimer's disease primarily through its role in inhibiting the clearance of beta-amyloid (Aβ). However, genetic studies yield mixed results and it is unclear whether the impact of CD33 is specific to Alzheimer's disease or related to broader neurodegenerative processes. Interestingly, CD33 has also been shown to interact with the hepatitis B (HBV) and C viruses (HCV).

Type 2 diabetes mellitus as an independent predictor of significant fibrosis in treatment-naïve chronic hepatitis B patients with concurrent hepatic steatosis.

Background And Aims: Type 2 diabetes mellitus (T2DM), hepatic steatosis (HS), and chronic hepatitis B (CHB) frequently co-exist, but the association of T2DM with liver histology has not been well characterized. The study investigated the impact of T2DM on the presence and severity of liver fibrosis and inflammation in CHB patients with biopsy-proven HS (CHB-HS).

Approach And Results: We enrolled CHB-HS patients who underwent liver biopsy from 19 medical centers (5 countries/regions) from 1990 to 2024.

Effects of Sofosbuvir/Velpatasvir Therapy on Extrahepatic Manifestations in Patients With Type 2 Diabetes and Chronic Hepatitis C: Insights From a Nationwide Hepatitis C Virus Registry in Taiwan.

This study examines the impact of hepatitis C virus (HCV) eradication through sofosbuvir/velpatasvir (SOF/VEL) treatment on glycated hemoglobin (HbA1c) levels in patients with chronic hepatitis C and type 2 diabetes mellitus (T2DM). Utilizing data from the Taiwan HCV Registry, a retrospective analysis was conducted on 2180 patients who met the inclusion criteria, 695 of whom had T2DM. HbA1c levels significantly decreased in the diabetes group from 7.

Long-term risk of depression and the impact of risk factors among chronic hepatitis C patients after successful antiviral therapy: A nationwide real-world Taiwanese cohort (T-COACH).

Background: Chronic hepatitis C virus (HCV) infection is associated with an increased risk of neuropsychiatric disorders, including depression. However, the impact of interferon (IFN)-based therapy, after achieving a sustained virologic response (SVR), on the long-term risk of depressive disorders remains unclear. Thus, we evaluated the incidence of new-onset depression and the impact of risk factors on patients with chronic hepatitis C following antiviral therapy.

Retrospective analysis of steatosis effect on antiviral response and hepatocellular carcinoma risk in chronic hepatitis C.

Hepatic steatosis is increasingly the leading cause of liver disease and suboptimal virologic response in chronic hepatitis C virus (CHC) infections worldwide. In Taiwan, the prevalence of cirrhosis and liver disease among CHC patients with steatosis has surged, influenced mainly by Westernized dietary habits. This retrospective study aimed to assess how varying degrees of hepatic steatosis impact the severity of liver fibrosis and hepatocellular carcinoma (HCC) risk in CHC patients undergoing pegylated interferon (Peg-IFN) and ribavirin (RBV) treatment.

A Point-of-Care Model for Hepatitis C Elimination in Remote Islands of Taiwan.

Timely and efficient diagnosis of hepatitis C virus (HCV) infection remains the effective approach for the subsequent care cascade of HCV treatment. It is of importance in under-resourced areas. The study aimed to assess the feasibility of a point-of-care (POC) model by a rapid diagnostic test and subsequent confirmational HCV RNA test in remote islands where traffic is an additional hurdle for health care.

Impact of Hepatitis C Virus Clearance on Cardiovascular Risk: A Real-World Experience From the Nationwide Taiwan Hepatitis C Virus Registry.

Hepatitis C virus (HCV) infection is associated with an increased risk of cardiovascular disease (CVD); however, the impact of interferon (IFN)-based therapy on cardiovascular outcomes remains unclear. This nationwide cohort study included 7411 patients with HCV from The Taiwanese Chronic Hepatitis C Cohort registry who received IFN-based therapy between 2003 and 2014. Patients were categorized into sustained virological response (SVR) (n = 5785) and non-SVR (n = 1676) groups.

Toripalimab plus bevacizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma (HEPATORCH): a randomised, open-label, phase 3 trial.

Background: Although several PD-1 or PD-L1 inhibitors combined with antiangiogenic agents have been approved as first-line treatment of advanced hepatocellular carcinoma, treatment needs remain unmet given the high incidence and mortality of hepatocellular carcinoma and due to factors such as regional approval status, medical insurance restrictions, and cost considerations. In this phase 3 HEPATORCH study, we aimed to compare the efficacy and safety of toripalimab plus bevacizumab versus sorafenib in patients with previously untreated advanced hepatocellular carcinoma.

Methods: We did a randomised, open-label, phase 3 study in 57 hospitals across mainland China, Taiwan, and Singapore.

Distribution, Characteristics, and Natural History of Diverse Types of Indeterminate Chronic Hepatitis B: A REAL-B Study.

Background And Aims: Chronic hepatitis B (CHB) with indeterminate phase comprises a heterogeneous group of patients. We determined the prevalence of indeterminate CHB overall and characterised novel types and phase transition probabilities of novel types of indeterminate CHB.

Methods: CHB patients were enrolled retrospectively from 24 centres (9 countries/regions).

The Role of Mitochondrial AKT1 Signaling in Renal Tubular Injury of Metabolic Syndrome.

Introduction: Metabolic syndrome (MetS) is increasingly recognized as a contributor to kidney disease, yet the underlying mechanisms remain poorly defined. Recent studies suggest a pivotal role for mitochondrial dysfunction in renal injury. We hypothesized that mitochondrial AKT1 signaling in renal tubules plays a critical role in MetS-related kidney injuries.

Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study).

Background/aims: Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C virus (HCV) infection. The long-term hepatic and extrahepatic outcomes of DAAs in chronic hepatitis C (CHC) patients receiving curative antivirals are elusive.

Methods: CHC patients were retrieved from two phase III sofosbuvir-based clinical trials conducted from 2013-2014.

Circulating let-7 Predicts Hepatic Fibrogenesis of 12-Month Post-Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus.

Chronic hepatitis B virus (HBV) infection is associated with potential complications of liver cirrhosis and hepatocellular carcinoma. To date, there are no effective and noninvasive clinical markers that can predict the risk of liver fibrosis early and accurately in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogs (NAs). This study aimed to investigate the association of circulating let-7b/c/g levels with the severity of hepatic fibrosis with a FIB-4 index of 1.

Mitochondrial mt12361A>G increased risk of metabolic dysfunction-associated steatotic liver disease among non-diabetes.

Background: Insulin resistance, lipotoxicity, and mitochondrial dysfunction contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). Mitochondrial dysfunction impairs oxidative phosphorylation and increases reactive oxygen species production, leading to steatohepatitis and hepatic fibrosis. Artificial intelligence (AI) is a potent tool for disease diagnosis and risk stratification.

Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues.

Background/aims: Given the increase in prevalence of metabolic diseases, we investigated their long-term impacts on the outcomes of chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogue (NA) treatment.

Methods: We analyzed data from CHB patients for whom initiated NA treatment from 30 centers. We balanced patient characteristics with and without metabolic disease (diabetes, obesity, dyslipidemia, and hypertension) via propensity-score matching (PSM) to evaluate adverse outcomes.

Posttreatment FIB-4 score change predicts hepatocellular carcinoma in chronic hepatitis C patients: Findings from the Taiwan hepatitis C registry program.

Purpose: This study investigated whether Fibrosis-4 (FIB-4) score and its change can serve as predictors of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C (CHC) infection receiving direct-acting antivirals (DAAs).

Methods: This study identified 9679 patients who completed DAA treatment and achieved sustained virologic response (SVR) from the Taiwan Nationwide Real-World HCV Registry Program, and their risk of HCC was analyzed.

Results: Multivariable Cox regression analyses identified diabetes mellitus (DM), alpha-fetoprotein (AFP) level, and FIB-4 score as independent predictors of HCC in both Model 1 (baseline) and Model 2 (SVR).

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.

Air Pollution Associated With Mortality Among Chronic Hepatitis B Patients Treated With Nucleotide/Nucleoside Analogues.

Background And Aims: Air pollution is associated with advanced liver fibrosis in patients with chronic liver diseases, including chronic hepatitis B (CHB). This study aimed to investigate the association between air pollution and mortality in patients with CHB treated with nucleotide/nucleoside analogues.

Methods: We enrolled 697 patients with CHB treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for mortality.

Air pollution causes abnormal alanine aminotransferase levels in patients with chronic hepatitis B.

Background: To investigate the association between air pollution and abnormal alanine aminotransferase levels in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs (NAs).

Methods: This cross-sectional study enrolled 1275 patients with chronic hepatitis B treated with nucleotide/NAs from 2019 to 2022 in Kaohsiung and analyzed the incidence and risk factors for abnormal alanine aminotransferase levels. Daily air pollutant concentrations were estimated for the year before enrollment.

Real-world efficacy and safety of universal 8-week glecaprevir/pibrentasvir in patients with chronic hepatitis C with early chronic kidney disease or pre-end-stage renal disease: Insights from a nationwide hepatisis C virus registry in Taiwan.

An 8-week regimen of glecaprevir/pibrentasvir is recommended for treatment-naïve patients with chronic hepatitis C (CHC). In alignment with the Taiwanese government's objective to eliminate hepatitis C by 2025, this study aimed to provide real-world evidence on the use of this regimen in treatment-naïve patients with chronic kidney disease (CKD) by using data from the Taiwan Association for the Study of the Liver HCV Registry (TACR). CKD was defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.

Hepatitis C virus-free endoscope procedures project: An in-hospital elimination approach.

Hepatitis C virus (HCV) elimination in the care cascades for patients receiving invasive procedures remains elusive. This study aimed to evaluate the efficacy of HCV-free Endoscope Procedures Project (CEPP) in the effort toward hospital HCV micro-elimination in Taiwan. An electronic medical record (EMR)-based remind system was introduced into gastrointestinal, surgical, urological, and gynecological departments prior to the endoscopy procedures.