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

• Published in: PloS one 2022-04, Vol.17 (4), p.e0266134-e0266134
• Main Authors: Thi Cam Huong, Nguyen, Trung, Nguyen Quang, Luong, Bac An, Tram, Duong Bich, Vu, Hoang Anh, Bui, Hoang Huu, Pham Thi Le, Hoa
• Format: Article
• Language: English
• Subjects: Abdomen; Adult; Amino acid sequence; Amino acids; Amino Acids - genetics; Analysis; Antigens; Biology and Life Sciences; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Cell cycle; Chronic infection; Cross-Sectional Studies; Deoxyribonucleic acid; Diagnosis; DNA; DNA, Viral - genetics; Female; Fibrosis; Gastroenterology; Gene deletion; Gene mutations; Gene sequencing; Genetic aspects; Genomes; Genotype; Genotype & phenotype; Genotypes; Hepatitis B; Hepatitis B e antigen; Hepatitis B Surface Antigens - genetics; Hepatitis B virus - genetics; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - pathology; Hepatocellular carcinoma; Hepatoma; Humans; Infections; Infectious diseases; Liver cancer; Liver Neoplasms - pathology; Liver Neoplasms - virology; Male; Males; Medicine; Medicine and Health Sciences; Mutation; People and Places; Pharmacy; Physical Sciences; Proteins; S gene; Vietnam; Viral Envelope Proteins - genetics; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0266134

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. 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. 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. 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.