Introduction: A set of genetic mutations to classify hepatocellular carcinoma (HCC) useful to clinical studies is an unmet need. Hepatitis B virus-related HCC (HBV-HCC) harbors a unique genetic mutation, namely, the HBV integration, among other somatic endogenous gene mutations. We explored a combination of HBV DNA integrations and common somatic mutations to classify HBV-HCC by using a capture-sequencing platform.
Methods: A total of 153 HBV-HCCs after surgical resection were subjected to capture sequencing to identify HBV integrations and three common somatic mutations in genomes. Three mutually exclusive mutations, HBV DNA integration into the TERT promoter, HBV DNA integration into MLL4, or TERT promoter point mutation, were identified in HBV-HCC.
Results: They were used to classify HBV-HCCs into four groups: G1 with HBV-TERT integration (25.5%); G2 with HBV-MLL4 integration (10.5%); G3 with TERT promoter mutation (30.1%); and G4 without these three mutations (34.0%). Clinically, G3 has the highest male-to-female ratio, cirrhosis rate, and associated with higher early recurrence and mortality after resection, but G4 has the best outcome. Transcriptomic analysis revealed a grouping different from the published ones and G2 with an active immune profile related to immune checkpoint inhibitor response. Analysis of integrated HBV DNA provided clues for HBV genotype and variants in carcinogenesis of different HCC subgroup. This new classification was also validated in another independent cohort.
Conclusion: A simple and robust genetic classification was developed to aid in understanding HBV-HCC and in harmonizing clinical studies.
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http://dx.doi.org/10.1159/000530699 | DOI Listing |
Virol J
December 2024
Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China.
Background: Oxidative stress plays a crucial role in the pathogenesis of HBV. This study aimed to investigate the value of fibroblast growth factor 21 (FGF21) promoter methylation in the occurrence and development of chronic hepatitis B (CHB) oxidative stress.
Methods: A total of 241 participants including 221 patients with CHB and 20 healthy controls (HCs) were recruited.
J Viral Hepat
January 2025
Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Zanzibar, a low-resource semiautonomous region of Tanzania, has an estimated prevalence of hepatitis B virus (HBV) infections of 3.6%. To assess the feasibility of care and treatment, a 5-year hepatitis B demonstration project was implemented in Zanzibar during January 2017-December 2021, following the 2015 WHO HBV care and treatment guidelines.
View Article and Find Full Text PDFVirol J
December 2024
Department of Hepatology, Center of Infectious Disease and Pathogen Biology, The First Hospital of Jilin University, Changchun, China.
In preclinical studies, GST-HG141, a novel hepatitis B virus (HBV) capsid assembly modulator displayed potent anti-HBV activity in vitro and strong efficacy in HBV animal models. A randomized, double-blind, ascending phase 1b trial assessed the pharmacokinetics, safety, and efficacy of GST-HG141 in chronic hepatitis B (CHB) individuals. Thirty treatment-naïve CHB patients were enrolled in three cohorts (25, 50, and 100 mg twice orally after meals daily) over 28 days, with 10 subjects per cohort (8:2 ratio for GST-HG141 and placebo).
View Article and Find Full Text PDFJ Ethnopharmacol
December 2024
Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China. Electronic address:
Ethnopharmacological Relevance: Chronic hepatitis B virus (HBV) infection is still a widespread global health issue. HuaganJiedu Decoction (HGJDD) is a common prescription for treating HBV in China, which has the effect of enhancing antiviral efficacy and improving clinical efficacy. However, its precise mechanism of action remains unclear, warranting further investigation to elucidate its therapeutic potential and integration into standard medical practices.
View Article and Find Full Text PDFBioorg Chem
December 2024
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China. Electronic address:
The inhibition of HBV DNA and elimination of HBsAg has already been established as an indicator for HBV clinic cure, and a novel dual-targeting inhibitors of HBV polymerase/entry are designed and synthesized in this study. Pentacyclic triterpenes (PTs) scaffold of exhibiting a high affinity to NTCP, including glycyrrhitinic acid (GA), oleanolic acid (OA), ursolic acid (UA), and betulinic acid (BA) were linked neatly with the nucleoside drug zidovudine (AZT) through a molecular hybrid strategy to synthesize twenty of PTs-AZT conjugates for targeting HBV polymerase as well as sodium taurocholate cotransporting polypeptide (NTCP). The conjugates showed significant inhibitory effects on the secretion of HBsAg and HBeAg in HepG2.
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