Hepatitis B virus (HBV) subgenotypes C2 and B2 differ in lamivudine- and adefovir-resistance-associated mutational patterns in HBV-infected Chinese patients

Abstract

We aimed to study the prevalence and clinical implications of hepatitis B virus (HBV) subgenotypes in Chinese patients. A total of 4,300 patients, mainly from northern China, were enrolled, including 182 patients with acute hepatitis B and 4,118 patients with chronic HBV infection who had been exposed to nucleoside or nucleotide analogs. HBV genotypes/subgenotypes were determined by direct sequencing of the HBV S/Pol region. The prevalence rates were 0.40% for HBV/B1, 14.30% for HBV/B2, 0.25% for HBV/B3, 0.35% for HBV/B4, 1.05% for HBV/C1, 81.72% for HBV/C2, 0.93% for HBV/C3, 0.16% for HBV/C4, and 0.84% for HBV/D. In chronic HBV infection, patients with HBV/B2 were younger and had lower ΗBeAg positive rates than patients with HBV/C2. The incidence of lamivudine-resistant mutations was significantly higher in HBV/C2 compared to HBV/B2 (27.9% versus 19.8%; P<0.01), and the significant difference was observed only for rtM204I and not rtM204V. In addition, compensatory mutations were more frequently detected in HBV/C2. The incidence of adefovir-resistant mutations was similar between the two subsets, but HBV/C2 inclined to show rtA181V (3.6% for C2 versus 0.9% for B2; P<0.01), while HBV/B2 inclined to show rtN236T (4.5% for versus 2.5% for C2; P<0.01). The ratios of HBV/B2 to HBV/C2 infection were 1.7 (110/65), 5.7 (2,653/463), 7.5 (520/69), 8.0 (48/6), and 15.3 (183/12) for acute hepatitis B, chronic hepatitis B, liver cirrhosis, acute-on-chronic liver failure, and hepatocellular carcinoma, respectively. In conclusion, HBV/C2 and HBV/B2, two prevalent subgenotypes, differ in lamivudine- and adefovir-resistance-associated mutational patterns. HBV/C2-infected patients are more likely to have disease progression than HBV/B2-infected ones.

FIG. 1.

Neighbor-joining phylogenetic tree based on the 38 representative analyzed HBV genetic sequences with GenBank accession numbers. Standard reference sequences are marked by circles.