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

乙型肝炎病毒（HBV）在日本的主要基因型是B型和c型。HBV基因型D型（HBV/D）在日本西部爱媛地区广泛存在。该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HBV感染患者进行HBV- dna基因分型。检查HBV/D患者的出生年份。分析了20株HBV/D的全基因组序列，其中2株来自单个携带者，间隔19年。计算了进化速率、最近的共同祖先的日期以及HBV/D感染的有效数量。509例患者中HBV/D检出率为14.3%，以70后为主。在系统发育树中，20株HBV/D产生了一个明确的聚类，计算出进化速率为5.4 x 10-5个核苷酸取代/位点/年。这棵树的根大约在1900年，从20世纪40年代开始蔓延，导致20世纪70年代迅速增长。根据这些结果，怀疑HBV/D可能在大约100年前传播到所调查的地区，然后在20世纪70年代广泛传播。根据该地区的历史和遗传分析，推测该地区的HBV/D起源于俄罗斯。对48例爱希姆急性乙型肝炎患者的基因型和临床特征进行了研究。10例（21.7%）患者检出HBV/D。29例HBV/C患者中有1例进展为慢性肝炎，10例HBV/D患者中有1例。无论HBV基因型如何，AH患者的主要感染途径是性传播。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.