An Association Between Core Mutations in Hepatitis B Virus Genotype F1b and Hepatocellular Carcinoma in Alaskan Native People

Abstract

We have identified a novel association between Alaska specific core mutations and HCC development in AN people infected with genotype F1b. Accumulation of these core mutations during the course of chronic infection with genotype F1b would contribute to HCC development in AN people earlier in life. This article is protected by copyright. All rights reserved.

Hepatitis B Virus Core Variants, Liver Fibrosis, and Hepatocellular Carcinoma

“…Core T1938C (V13A) and A2051C (N51H) mutations had accumulated together with BCP and PC mutations, suggesting a functional association between these variants and hepatocarcinogenesis. (9) The N-terminal part of core protein is crucial for self-assembly, and the C-terminal part is essential for nucleocapsid formation. Interestingly, T1938C and A2051C mutations are located in the capsid assembly domain of the core protein.…”

“…Using an expression cloning approach An accumulation of Core T1938C and A2051C mutations together with BCP (A1762T/G1764A) and PC (G1896A) mutations were observed in Alaskan Native patients with HCC. (9) The mutations, leading to an increased viral replication, are indicated by stars on the genome. (B) Effects of HBV core mutants on the HBV life cycle and host cell pathways in liver chimeric mice as observed by Hayashi et al (9) Following viral entry mediated by HSPG and NTCP, the HBV genome is released into the nucleus where rcDNA is converted into cccDNA.…”

“…(9) The mutations, leading to an increased viral replication, are indicated by stars on the genome. (B) Effects of HBV core mutants on the HBV life cycle and host cell pathways in liver chimeric mice as observed by Hayashi et al (9) Following viral entry mediated by HSPG and NTCP, the HBV genome is released into the nucleus where rcDNA is converted into cccDNA. cccDNA serves as template for viral transcripts including pgRNA, which is encapsidated and reverse transcribed into de novo HBV genomic DNA before assembly and release of the viral particle.…”

Comparison of hepatitis B virus genotypes B and C among chronically hepatitis B virus‐infected patients who received nucleos(t)ide analogs: A multicenter retrospective study

“…[5][6][7][8][9][10][11][12] As viral factors from nucleotide sequencing analyses, core promoter mutations, precore mutations, core mutations, and Pre-S deletions have been reported. 10,13,14 Recently, the hepatitis B X protein genotype was reported to be associated with HCC development and HCC proliferation in vitro and in vivo. 15 Additionally, some single-nucleotide polymorphisms in several genes including HLA class I and II have been shown to be associated with HBV-related HCC.…”

“…Several cohorts have identified the risk factors for HBV‐related HCC, such as age, male sex, albumin, platelet counts (PLT), advanced fibrosis/liver cirrhosis, HBV DNA, and hepatitis B core‐related antigen (HBcrAg) . As viral factors from nucleotide sequencing analyses, core promoter mutations, precore mutations, core mutations, and Pre‐S deletions have been reported . Recently, the hepatitis B X protein genotype was reported to be associated with HCC development and HCC proliferation in vitro and in vivo .…”