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

日本主要的乙肝病毒基因分型为B和C。然而，在日本西部的爱媛地区，发现了广泛存在的乙肝病毒D型(HBVD)。这项研究的目的是阐明其起源、传播时间和在该地区的传播。对509例慢性乙肝患者进行了HBVDNA基因分型。对20株HBVD毒株的全基因组序列进行了分析，其中2株是从单个携带者那里获得的，间隔19年。计算进化率、最近共同祖先的日期和有效的乙肝病毒/D感染数。在509例患者中，14.3%的患者感染了HBVD，感染的患者大多出生于70年代。在系统进化树中，20株HBVD毒株产生了一个明确的聚类群，其进化速率为5.4×10-5个核苷酸替换/位/年。这棵树的根大约在1900年，从20世纪40年代开始传播，导致在20世纪70年代迅速增长。从这些结果可以推测，大约100年前，乙肝病毒/丁型肝炎病毒可能传播到调查过的地区，然后在20世纪70年代广泛传播。根据该地区的历史和基因分析，推测该地区的HBVD可能起源于俄罗斯。同时对48例急性乙型病毒性肝炎患者的基因分型和临床特征进行了研究。10例(21.7%)患者存在HBVD。29例乙肝病毒携带者中有1例进展为慢性肝炎，10例乙肝病毒携带者中有1例进展为慢性肝炎。急性肝炎患者的主要感染途径是性传播，与HBV型无关。这些结果表明有必要进一步努力防止性传播。

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.