Integrated DNA estimation in tissue biopsy and detection in liquid biopsy by HBV-targeted NGS assay.

Background & Aims: Integrated HBV DNA (iDNA) plays a critical role in HBV pathogenesis, particularly in predicting treatment response and HCC. This study aimed to use an HBV hybridization-capture next-generation sequencing (HBV-NGS) assay to detect HBV-host junction sequences (HBV-JS) in a sensitive nonbiased manner to detect and estimate the iDNA fraction in tissue biopsies and HBV genetics by liquid biopsy.

Methods: HBV DNA from plasmid monomers, HBV-HCC cell line (SNU398, Hep3B, and PLC/PRF/5), tissue biopsies of patients with serum HBV DNA <4 log IU/ml, and matched urine and plasma of HBV patients were assessed by HBV-NGS.

Agalactosyl IgG induces liver fibrogenesis via Fc gamma receptor 3a on human hepatic stellate cells.

The relevance of aberrant serum IgG N-glycosylation in liver fibrosis has been identified; however, its causal effect remains unclear. Because hepatic stellate cells (HSCs) contribute substantially to liver fibrosis, we investigated whether and through which mechanisms IgG N-glycosylation affects the fibrogenic properties of HSCs. Analysis of serum IgG N-glycome from 151 patients with chronic hepatitis B or liver cirrhosis revealed a positive correlation between Ishak fibrosis grading and IgG with agalactosyl N-glycoforms on the crystallizable fragment (Fc).

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients.

Background/aims: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection.

Methods: Patients with HBsAg detectable at screening and at least 6 months previously were eligible.

Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients.

Background/aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.

Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α).

Novel urine cell-free DNA methylation markers for hepatocellular carcinoma.

An optimized hepatocellular carcinoma (HCC)-targeted methylation next generation sequencing assay was developed to discover HCC-associated methylation markers directly from urine for HCC screening. Urine cell-free DNA (ucfDNA) isolated from a discovery cohort of 31 non-HCC and 30 HCC was used for biomarker discovery, identifying 29 genes with differentially methylated regions (DMRs). Methylation-specific qPCR (MSqPCR) assays were developed to verify the selected DMRs corresponding to 8 genes (GRASP, CCND2, HOXA9, BMP4, VIM, EMX1, SFRP1, and ECE).

The B56γ3-containing protein phosphatase 2A attenuates p70S6K-mediated negative feedback loop to enhance AKT-facilitated epithelial-mesenchymal transition in colorectal cancer.

Background: Protein phosphatase 2A (PP2A) is one of the major protein phosphatases in eukaryotic cells and is essential for cellular homeostasis. PP2A is a heterotrimer comprising the dimeric AC core enzyme and a highly variable regulatory B subunit. Distinct B subunits help the core enzyme gain full activity toward specific substrates and contribute to diverse cellular roles of PP2A.

Hepatic arterial infusion chemotherapy and immune checkpoint inhibitors, alone or in combination, in advanced hepatocellular carcinoma with macrovascular invasion: a single-centre experience in Taiwan.

Background: The presence of vascular invasion is associated with poor survival in advanced hepatocellular carcinoma (HCC). We compared the effectiveness of hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs), alone or in combination, in patients with advanced HCC.

Methods: We retrospectively reviewed medical records of adult patients with unresectable HCC and macrovascular invasion (MVI) who were treated with HAIC or ICIs alone or in combination at a single centre in Taiwan.

Real-World Effectiveness of Sorafenib versus Lenvatinib Combined with PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma.

Immune checkpoint inhibitors (ICIs) combined with multitarget tyrosine kinase inhibitors (MTKIs) exert a synergistic effect and are effective in unresectable hepatocellular carcinoma (uHCC). However, precise data regarding the real-world clinical applications of these combination therapies in uHCC are lacking. This study compared the treatment efficacy of sorafenib versus lenvatinib in combination with programmed cell death protein-1 (PD-1) inhibitors in patients with uHCC in a clinical setting.

Real-World Comparative Effectiveness of Nivolumab versus Pembrolizumab in Patients with Unresectable Hepatocellular Carcinoma.

Purpose: Immune checkpoint inhibitors are effective therapies for advanced hepatocellular carcinoma (HCC); however, comparisons of the clinical efficacy and safety profile for these drugs are still scarce. Thus, the aims of this study were to investigate the differences in efficacy and safety between nivolumab and pembrolizumab in unresectable HCC patients in a real-world setting.

Patients And Methods: A total of 115 patients who received treatment with nivolumab (n = 73) or pembrolizumab (n = 42) in combination with or without tyrosine kinase inhibitors was enrolled.

The Predictive Role of Hepatitis B Biomarkers on HBV Reactivation following Direct-Acting Antiviral Therapy in HBV/HCV Coinfected Patients.

Hepatitis B and C (HBV/HCV) coinfected patients have a potential risk of hepatitis B reactivation (HBVr) after direct-acting antivirals (DAAs) treatment. The study intends to investigate the predictive role of HBV biomarkers in HBVr. Forty-six HBV/HCV coinfected patients receiving DAAs were enrolled.

Impact of HCV viremia on HBV biomarkers in patients coinfected with HBV and HCV.

Backgrounds: Hepatitis B virus (HBV) biomarkers reflect the status of HBV infection; however, their role in patients with chronic hepatitis B and C (HBV/HCV) coinfection remains unknown. This study evaluated the characteristics of HBV biomarkers in patients with chronic HBV/HCV coinfection.

Methods: One hundred untreated HBV/HCV coinfected patients were enrolled.

Urine DNA biomarkers for hepatocellular carcinoma screening.

Background: Hepatocellular carcinoma (HCC) occurs in a well-defined high-risk patient population, but better screening tests are needed to improve sensitivity and efficacy. Therefore, we investigated the use of urine circulating tumour DNA (ctDNA) as a screening test.

Methods: Candidate markers in urine were selected from HCC and controls.

Ledipasvir/Sofosbuvir for Patients Coinfected With Chronic Hepatitis C and Hepatitis B in Taiwan: Follow-up at 108 Weeks Posttreatment.

Background: For patients coinfected with hepatitis C virus (HCV) and hepatitis B virus (HBV), HCV treatment with direct-acting antivirals can lead to HBV reactivation. We evaluated HBV reactivation during ledipasvir/sofosbuvir treatment and 108-week follow-up.

Methods: In Taiwan, 111 patients with HCV genotype 1 or 2 and HBV received ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks.

Risk scores to predict HCC and the benefits of antiviral therapy for CHB patients in gray zone of treatment guidelines.

Backgrounds: ALT ≥ 80 U/L and HBV DNA ≥ 2000 IU/ml are treatment criteria of APASL guidelines for chronic hepatitis B (CHB) patients. The need of antiviral therapy for patients in gray zone (ALT < 80 U/L or HBV DNA < 2000 IU/ml) is controversial. This study aimed to develop a scoring system to predict hepatocellular carcinoma (HCC) and evaluate the benefit of antiviral therapy in these patients.

Clinical characteristics and outcomes of drug-induced liver injury in Taiwan: With emphasis on the impact of chronic hepatitis B infection.

Background: Whether hepatitis B virus (HBV) infection can affect the outcomes of drug-induced liver injury (DILI) is controversial. This study aimed to evaluate the characteristics and outcomes of DILI in Taiwan, with an emphasis on the impact of HBV infection.

Methods: We prospectively recruited patients with DILI from multiple centers in Taiwan from 2010 to 2018.

Detection of Hepatitis B Virus-Host Junction Sequences in Urine of Infected Patients.

Integrated hepatitis B virus (HBV) DNA, found in more than 85% of HBV-associated hepatocellular carcinomas (HBV-HCCs), can play a significant role in HBV-related liver disease progression. HBV-host junction sequences (HBV-JSs), created through integration events, have been used to determine HBV-HCC clonality. Here, we investigate the feasibility of analyzing HBV integration in a noninvasive urine liquid biopsy.

Detection of Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. The beta-catenin gene, is among the most frequently mutated in HCC tissues. However, mutational analysis of HCC tumors is hampered by the difficulty of obtaining tissue samples using traditional biopsy.

Herbal and dietary supplement-induced liver injury in Taiwan: comparison with conventional drug-induced liver injury.

Background And Aims: Whether herbal and dietary supplements (HDS) are safer than Western conventional drugs is controversial. The aim of this study was to explore the characteristics and risk factors for HDS-induced liver injury (HILI) in Taiwan.

Methods: This is a 9-year multi-center prospective study conducted in Taiwan from 2011 to 2019.

Drug-induced liver injury associated with severe cutaneous adverse drug reactions: A nationwide study in Taiwan.

Background & Aims: Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are high-mortality adverse drug reactions. The risk factors and prognosis of drug-induced liver injury (DILI) concomitant with SCAR warrant clarification. We aimed to evaluate the characteristics and outcomes of DILI with SCAR.

Clinical Implications of Serum Hepatitis B Virus Pregenomic RNA Kinetics in Chronic Hepatitis B Patients Receiving Antiviral Treatment and Those Achieving HBsAg Loss.

Serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) is correlated with covalently closed circular DNA. We aimed to investigate the utility of serum HBV pgRNA in chronic hepatitis B patients receiving nucleos(t)ide analogue treatment and those achieving HBsAg loss. One hundred and eighty-five patients were enrolled for studying long-term HBV pgRNA kinetics during treatment.

Recurrent HBV Integration Targets as Potential Drivers in Hepatocellular Carcinoma.

Chronic hepatitis B virus (HBV) infection is the major etiology of hepatocellular carcinoma (HCC), frequently with HBV integrating into the host genome. HBV integration, found in 85% of HBV-associated HCC (HBV-HCC) tissue samples, has been suggested to be oncogenic. Here, we investigated the potential of HBV-HCC driver identification via the characterization of recurrently targeted genes (RTGs).

Real-world outcome of immune checkpoint inhibitors for advanced hepatocellular carcinoma with macrovascular tumor thrombosis.

Programmed cell death protein-1 (PD-1) inhibitors have shown promising results for treating advanced hepatocellular carcinoma (HCC). However, the clinical utility of such inhibitors in HCC patients with vascular tumor thrombosis remains unclear. This study investigated PD-1 inhibitor efficacy in advanced HCC with macrovascular invasion in a clinical setting.