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

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.

Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants

“…The likely cause of this is unknown, but it can be attributed to the growing interest in the HBV cohort, the high index of HBV mutations, and the likelihood that HBV will advance to liver cancer and cirrhosis. The latter is consistent with other people's reports [19,47,[83][84][85]. Each study design makes a significant contribu-tion to the overall prevalence while also providing unique viewpoints on the connection between HBV and HCC in the Southeast Asian context [86,87].…”

Genetic diversity, haplotype analysis, and prevalence of Hepatitis B virus MHR mutations among isolates from Kenyan blood donors

“…Based on influence of the observed mutations on antigen functionality, 19 mutations were traced to "a" determinant region of S antigen. The observed mutations in the "a" determinant region were more compared to mutations that were previously reported [32,37,56,57]. Key mutation observed in "a" determinant region included non-synonymous change T143M, that was present in 9 different samples, all belonging to HBV genotype A which is also reported by other studies [32,58].…”