Shifting hepatitis B virus genotypes of acute hepatitis B patients in northeast Japan

Abstract

It has been reported that acute hepatitis B (AHB) patients with genotype A HBV (HBV/A) have been increasing since the 1990s in metropolitan areas in Japan. However, little is known about the trends of HBV genotypes in AHB patients in northeast Japan where genotype B HBV (HBV/B) prevails more than in other areas. In this study, we aimed to clarify the changes in the HBV genotypes and clinical characteristics of AHB patients in this area. HBV genotypes were determined by direct sequencing (n = 125) or enzyme immunoassay (n = 9) using serum samples from AHB patients including fulminant hepatitis in 1987-2014. Among 134 patients, 26 (19%), 33 (25%), and 75 (56%) patients were infected with HBV of genotypes A, B, and C, respectively. HBV/A emerged from 2001 and the percentage was increased gradually up to 48% in 2010-2014, whereas HBV/B was reduced from 40% in 1987-1994 to 10% in 2010-2014. Phylogenetic analysis showed that three major subgenotype A2 strains had come into this area serially. The levels of HBV DNA and prothrombin time were higher in HBV/A patients than other genotypes. This study could not show significant difference in the HBsAg-positive period among genotypes nor the effect of nucleoside analogues to shorten the HBsAg-positive period. A higher level of initial HBV DNA was associated with late disappearance of HBsAg. In conclusion, the percentage of HBV/A in AHB patients has been increasing in northeast Japan since 2001, which is later than metropolitan areas, whereas that of HBV/B is decreasing.

Comparison of hepatitis B virus genotypes B and C among chronically hepatitis B virus‐infected patients who received nucleos(t)ide analogs: A multicenter retrospective study

“…Such people who moved to this area might have been younger than those living in this area for a long time, and we therefore speculate that such a flow of people is one of the reasons for the age difference among HBV genotypes. Similar changes in the HBV genotype distribution have been observed in HBV acute infection and HBV/A has increased in this area later than in metropolitan areas …”

“…To determine the subgenotypes of HBV/B, HBV partial sequences were determined as described previously . Total DNA was extracted from serum samples using SMITEST EX‐R&D (Genome Science, Tokyo, Japan) and subjected to nested PCR with PrimeSTAR HS DNA Polymerase (Takara Bio, Shiga, Japan) using primers HB095 and HB184 for the first round amplification, and HB097 and S2–2 for the second round.…”

“…27 HBV genotype B (HBV/B) is found frequently in northeast Japan (Tohoku district). 28 Patients with HBV/B are known to have a more favorable clinical courses than those with HBV/C, but the frequency of HBV/B is generally low in Japan, and the results were based on a relatively small number of patients. 29 Therefore, the long-term outcome of patients with HBV/B has not been clarified enough yet.…”

“…In Japan, the HBV genotype C (HBV/C) is the most prevalent in chronically infected patients, but there are differences in the distribution . HBV genotype B (HBV/B) is found frequently in northeast Japan (Tohoku district) . Patients with HBV/B are known to have a more favorable clinical courses than those with HBV/C, but the frequency of HBV/B is generally low in Japan, and the results were based on a relatively small number of patients .…”

Hepatitis B virus strains from Rwandan blood donors are genetically similar and form one clade within subgenotype A1

“…Patients infected with these mutants often have active liver disease with elevated HBV DNA levels in serum also after seroconversion to anti-HBe [15, 16]. The pre-core mutation occurs in almost all genotypes and subgenotypes of HBV, but rarely in subgenotypes A2, C1, F2, F3 and H [1, 16–18], and the basal pre-core mutations have been described from most genotypes [19, 20]. …”