Hepatitis B virus strains of subgenotype A2 with an identical sequence spreading rapidly from the capital region to all over Japan in patients with acute hepatitis B

Abstract

Objective To examine recent trends of acute infection with hepatitis B virus (HBV) in Japan by nationwide surveillance and phylogenetic analyses. Methods During 1991 through 2009, a sentinel surveillance was conducted in 28 national hospitals in a prospective cohort study. Genotypes of HBV were determined in 547 patients with acute hepatitis B. Nucleotide sequences in the preS1/S2/S gene of genotype A and B isolates were determined for phylogenetic analyses. Results HBV genotype A was detected in 137 (25% (accompanied by genotype G in one)) patients, B in 48 (9%), C in 359 (66%), and other genotypes in the remaining three (0.5%). HBV persisted in five with genotype A including the one accompanied by genotype G; another was co-infected with HIV type 1. The genotype was A in 4.8% of patients during 1991e1996, 29.3% during 1997e2002, and 50.0% during 2003e2008 in the capital region, as against 6.5%, 8.5% and 33.1%, respectively, in other regions. Of the 114 genotype A isolates, 13 (11.4%) were subgenotype A1, and 101 (88.6%) were A2, whereas of the 43 genotype B isolates, 10 (23.3%) were subgenotype B1, 28 (65.1%) were B2, two (4.7%) were B3, and three (7.0%) were B4. Sequences of 65 (64%) isolates of A2 were identical, as were three (23%) of A1, and five (18%) of B2, but none of the B1, B3 and B4 isolates shared a sequence. Conclusions Acute infection with HBV of genotype A, subgenotype A2 in particular, appear to be increasing, mainly through sexual contact, and spreading from the capital region to other regions in Japan nationwide. Infection persisted in 4% of the patients with genotype A, and HBV strains with an identical sequence prevailed in subgenotype A2 infections. This study indicates the need for universal vaccination of young people to prevent increases in HBV infection in Japan.Hepatitis B virus (HBV) has been classified into 10 genotypes, designated AeJ, based on a >8% divergence in the full-genome sequence. Significance of this studyWhat is already known about this subject?< In Japan, a national prevention programme was started in 1986 with selective vaccination of babies born to mothers who carry hepatitis B virus (HBV). Since then, the prevalence of hepatitis B surface antigen among younger generations has decreased sharply. < However, retrospective studies indicate that the frequency of HBV genotype A is increasing among patients with acute hepatitis B (AHB) within the capital region of Japan. < Infection with genotype A more often persists than infection with other genotypes. < Because there is no reliable and comprehensive surveillance system for AHB in Japan, the incidence of AHB and factors responsible for changes over many years are not known. What are the new findings?< This is a prospective cohort study for surveillance of AHB throughout Japan in a national research programme. < The incidence of AHB in Japan has not decreased, because genotype A infections have increased over time. < Genotype A infections started to increase in the capital region of Japan, and then spread to other r...

Hepatitis B virus genotypes: epidemiological and clinical relevance in Asia

“…In Shanghai, China, where genotypes B and C prevail, a population-based surveillance showed 8.50 % of the adult patients with AHB became chronic; in the 68 AHB patients with genotype data available, the only identified risk factor for chronicity was sub-genotype C2 [31]. In Japan, a large prospective cohort study showed that the proportion of AHB patients with genotype A (particularly sub-genotype A2, mainly through sexual contact) is increasing year by year, with a chronicity rate of 4 % [32]. A nationwide multicenter cohort study in Japan on 212 AHB patients revealed that genotype A was independently associated with viral persistence following AHB [33].…”

Molecular identification of hepatitis B virus genotypes/subgenotypes: Revised classification hurdles and updated resolutions

“…Nosocomial transmission and unsafe injection practices are considered responsible for more than 60% of HBV infections in Central Europe [87] . Though genotype E is transmitted by heterosexual relations in Africa, genotype A and particularly genotype G were isolated from men who have sex with men in Europe and Canada [81,88] . In West Asia and in the Middle East (where genotype D is dominant), the route of transmission and HBV seroprevalence depend on the region.…”

“…Some genotypes are more associated with particular kinds of prognoses, such as acute forms of disease [88] . Several reports showed that genotype A evolves more rapidly in patients than genotype D does, which poses problems for treatment [16] .…”

Recent Population Expansions of Hepatitis B Virus in the United States

“…Although locally circulating HBV strains may be expected to be genetically (20,21). As noted, rapid transmissions among acutely infected MSM in the Netherlands and Japan (25,26) were associated with genetically identical or closely related A2 strains. The data from Japan also indicate a greater propensity of primary infection with A2, compared to other genotypes, associated with persistent HBV infection (29,30).…”

“…In Europe, the majority of incident HBV strains belong to A2 (19,20), with specific strains identified in English prisons (21), in outbreaks of nosocomial HBV transmissions in Germany (22) and Belgium (23), and among MSM in The Netherlands (24). In Japan, HBV A2 has been observed to be spreading not only within the MSM community (25) but also from there to the general population (26). The National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study-II (REDS-II) of 34 million U.S. blood donations between 2006 and 2009 reported that the majority of 193 donor HBV strains (37%) consisted of A2, with incident donors carrying higher frequencies of A2 (67%) compared to those in prevalent donors (27%) (27).…”