Micro-evolution of the hepatitis B virus genome in hepatitis B e-antigen-positive carriers: Comparison of genotypes B and C at various immune stages

Background and AimPatients with hepatitis B virus (HBV) genotype B infection experience hepatitis B e-antigen (HBeAg) seroconversion at an earlier stage than do patients with genotype C infection. Therefore, this study investigated whether the differential phenotypes are related to HBV genomic evolution. MethodsThirty-three HBeAg-positive patients with a mean follow-up of 3.1 years were enrolled: 16 at the immune tolerance stage (group I) and 17 at the immune clearance stage (group II). The evolution rates of paired viral genomes at enrollment and at the final follow-up in the full-length genome (f), nonoverlapping regions (synonymous [s] and nonsynonymous [a]), and overlapping regions () were calculated. The evolution rates were then compared according to serum alanine aminotransferase (ALT) levels and HBV genotype. ResultsThe overall f evolution rate was lower in group I than in group II (1.4x10(-5)3.3x10(-5)vs 1.2x10(-3)+/- 1.2x10(-3) nucleotide substitution/site/year, P<0.001). We observed similar results for the s, a, and evolution rates. All evolution parameters were comparable between genotypes B and C. We determined a positive correlation between a/y and the area under the average ALT time curve in genotype B (R-2=0.6935, P<0.0001), but not in genotype C (R-2=0.1606, P=0.124). ConclusionThe evolution rate of the HBV genome is higher at the immune clearance stage than at the immune tolerance stage. Host immune selection might play a role in triggering evolution of genotype B.