Mutations in the HBV PreS/S gene related to hepatocellular carcinoma in Vietnamese chronic HBV-infected patients

PLoS One. 2022 Apr 7;17(4):e0266134. doi: 10.1371/journal.pone.0266134. eCollection 2022.

Abstract

Background: Chronic hepatitis B virus (CHB) infection is a major health problem and leading cause of hepatocellular carcinoma (HCC) worldwide. Several point and deletion mutations on the PreS/S gene have been intensively considered associated with HCC. This study aimed to describe the characteristics of HBV PreS/S mutations in Vietnamese CHB-infected patients and their association with HCC.

Methods: This cross-sectional study was conducted from 02/2020 to 03/2021, recruited Vietnamese CHB-infected patients with HBV-DNA >3 log10-copies/mL and successful PreS/S gene sequencing. Mutations were detected by direct Sanger sequencing.

Results: 247 CHB-infected patients were recruited, characterized by 68.8% males, 54.7% HBV genotype B, 57.5% HBeAg positive, 23.1% fibrosis score ≥F3 and 19.8% HCC. 61.8% amino acid replacements were detected throughout the PreS1/PreS2/S genes. The most common point-mutations included N/H51Y/T/S/Q/P (30.4%), V68T/S/I (44.9%), T/N87S/T/P (46.2%) on PreS1 gene; T125S/N/P (30.8%), I150T (42.5%) on PreS2 gene; S53L (37.7%), A184V/G (39.3%), S210K/N/R/S (39.3%) on S gene. The rates of case(s) with any point-mutation on the Major Hydrophylic Region (MHR) and the "a" determinant region were 63.6% and 39.7%, respectively. Most of S point-mutations were presented with low rates such as T47A/E/V/K (9.3%), P120S/T (8.5%), G145R (2%). On multivariable analysis, males (OR = 4.51, 95%CI 1.78-11.4, p = 0.001), age≥40 (OR = 5.5, 95%CI 2.06-14.68, p = 0.001), W4P/R/Y on PreS1 (OR = 11.56, 95%CI 1.99-67.05, p = 0.006) and 4 S point-mutations as: T47A/E/V/K (OR = 3.67, 95%CI 1.19-11.29, p = 0.023), P120S/T (OR = 3.38, 95%CI 1.09-10.49, p = 0.035), S174N (OR = 29.73, 95%CI 2.12-417.07, p = 0.012), P203R (OR = 8.45, 95%CI 1.43-50.06, p = 0.019) were associated with HCC.

Conclusions: We detected 61% amino acid changes on PreS/S regions in Vietnamese CHB patients. One point-mutation at amino acid 4 on PreS1 gene and 4 point-mutations at amino acids 47, 120, 174, and 203 on S gene were associated with HCC. Further investigations are recommended to further clarify the relationship and interaction between mutations in HBV genome and HCC progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acids / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Carcinoma, Hepatocellular* / virology
  • Cross-Sectional Studies
  • DNA, Viral / genetics
  • Female
  • Genotype
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B virus* / genetics
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / pathology
  • Humans
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / virology
  • Male
  • Mutation
  • Vietnam
  • Viral Envelope Proteins* / genetics

Substances

  • Amino Acids
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • S envelope protein, hepatitis B virus
  • Viral Envelope Proteins

Grants and funding

This study was funded for the PreS/S gene Sequencing by the grant of research from the University of Medicine and Pharmacy at Ho Chi Minh city. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.