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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
Author(s) -
Liu ChunJen,
Chen TingChih,
Chen PeiJer,
Wang HurngYi,
Tseng TaiChung,
Cheng HueiRu,
Liu ChenHua,
Chen DingShinn,
Kao JiaHorng
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12654
Subject(s) - genotype , hepatitis b virus , immune system , hbeag , virology , seroconversion , hepatitis b , nonsynonymous substitution , medicine , viral load , hbsag , immunology , biology , virus , genome , genetics , gene
Background and Aim Patients 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. Methods Thirty‐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 (μf), nonoverlapping regions (synonymous [μs] and nonsynonymous [μa]), and overlapping regions (μ) were calculated. The evolution rates were then compared according to serum alanine aminotransferase ( ALT ) levels and HBV genotype. Results The overall μf evolution rate was lower in group I than in group II (1.4 × 10 −5 ± 3.3 × 10 −5 vs 1.2 × 10 −3 ± 1.2 × 10 −3 nucleotide substitution/site/year, P < 0.001). We observed similar results for the μs, μa, and μ evolution rates. All evolution parameters were comparable between genotypes B and C . We determined a positive correlation between μa/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). Conclusion The 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 .