Molecular epidemiologic study of the spread of hepatitis B virus genotype D in Japan.

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The major hepatitis B virus (HBV) genotypes in Japan are B and C. HBV genotype D (HBV/D), however, has been found to be widespread in Ehime area of Western Japan. The aim of the study was to elucidate its origin, time of transmission, and spread in this area. Genotyping of HBV-DNA was done in 509 patients with chronically HBV infection. The year of birth was checked in patients with HBV/D. The full genome sequences of 20 HBV/D strains, 2 of which were obtained from a single carrier with a 19-year-interval, were analyzed. An evolutionary rate, the date of the most recent common ancestor, and the effective number of HBV/D infections were calculated. HBV/D was found in 14.3% of the 509 patients, and majority of patients infected with HBV/D were born in 1970s. In a phylogenetic tree, the 20 HBV/D strains produced a definite cluster, and the evolutionary rate was calculated to be 5.4 x 10-5 nucleotide substitutions/site/year. The root of the tree was in approximately 1900 and began to spread from the 1940s, leading to a rapid increase in the 1970s. From these results, it is suspected that HBV/D was likely transmitted to the area investigated approximately 100 years ago and then spread widely in the 1970s. From the history of the area and the genetic analysis, HBV/D in this area was speculated to be of Russian origin. Genotypes and clinical features of 48 patients with acute hepatitis B in Ehime were also studied. HBV/D was found in 10 patients (21.7%). Progression to chronic hepatitis occurred in 1 of 29 patients with HBV/C and 1 of 10 patients with HBV/D. The major infectious route for patients with AH is sexual transmission, regardless of HBV genotype. These results indicate the necessity of the additional efforts to prevent sexual transmission.