Spatial and chronological differences in hepatitis B virus genotypes from patients with acute hepatitis B in Japan

Genotypes of hepatitis B virus (HBV) were determined in 485 patients with acute hepatitis B from all over Japan. They were A in 92 (19%), Ba in 26 (5%), Bj in 32 (7%), C in 330 (68%) and D in 5 (1%). Sexual contacts were the main route of transmission in them. Overall, HBV persisted in only 5 of the 464 (1%) followed patients. Genotypes C accounted for more than 68% in northern as well as southern areas, contrasting with genotype A accounting for 34% in and around the Metropolitan areas. During 24 years from 1982 to 2005, genotype A increased from 5% to 33%, while genotype B gradually decreased from 26% to 8%. Fulminant hepatitis was significantly more frequent in infection with genotype Bj (41%) than those with the other genotypes (p<0.01). The core-promoter double mutation (T1762/A1764) and precore stop-codon mutation (A1896) were more frequent in patients with fulminant than acute self-limited hepatitis (57% versus 15% and 58% versus 10%, respectively, p<0.01 for both). In conclusion, genotype A distributes unevenly over Japan, prevails in younger patients through sexual transmission and has increased with years. Furthermore, fulminant outcome was more frequent in patients with genotype Bj than those with the other genotypes.