Association of hepatitis B virus subgenotypes and basal core promoter/ precore region variants with the clinical features of patients with acute hepatitis

Background: In endemic areas, including Japan, basal core promoter (BCP) and precore (PC) variants of hepatitis B virus (HBV) have been reported to be associated with the clinical outcome of acute hepatitis B patients. However, the associations of BCP/PC variants with clinical outcomes have not been observed in nonendemic areas. HBV subgenotypes, which show geographic variations in prevalence, may underlie this discrepancy in clinical outcomes. Little is known about the differences in the clinical and virological features of HBV subgenotypes and BCP/PC variants. The aim of this study was to investigate the distributions of subgenotypes and BCP/PC variants to identify clinical differences in acute hepatitis B patients. Methods: One hundred thirty-nine patients with acute hepatitis were enrolled. Nested polymerase chain reaction was used to amplify the pre-S region of HBV for genotyping and the BCP/PC regions for variant screening. Results: HBV subgenotypes A1 (n = 3), A2 (n = 28), B1 (n = 3), B2 (n = 9), C1 (n = 5), C2 (n = 84), C variant (n = 1), D2 (n = 3), and H (n = 3) were detected. BCP/PC variants were not associated with progression to chronic hepatitis. Patients infected with subgenotype C2 who progressed to fulminant hepatic failure frequently carried variants at nucleotides non-T1753 and non-T1754 and T1762, A1764, and A1896. Conclusions: BCP/PC variants would be associated with progression to fulminant hepatitis in subgenotype C2. Knowledge of HBV subgenotypes and BCP/PC variants is useful for developing strategies to treat acute hepatitis B patients.