Molecular analysis of hepatitis D virus infection in Miyako Island, a small Japanese island

Abstract

The present investigation attempted to determine the exact prevalence of hepatitis D virus (HDV) infection among inhabitants of Miyako Island (a remote island in the Okinawa Prefecture) and the molecular characteristics of the HDV genome that was isolated. Among the 4728 inhabitants, 375 (7.9%) were hepatitis B surface antigen (HBsAg) positive. Antibody to HDV (anti-HDV) was present in 32 (8. 5%) of these 375 subjects, and liver function tests were normal in most subjects. The presence of HDV RNA was analysed by nested polymerase chain reaction (PCR). Thirteen out of the 32 anti-HDV antibody-positive subjects were HDV RNA positive. Thus, 3.5% of HBsAg-positive subjects on Miyako Island were HDV RNA positive. Among the HDV RNA-positive subjects, liver function tests were within normal limits or were mildly abnormal. Nucleotide sequence analysis revealed that the HDV genomes on Miyako Island were similar to the Japanese and Taiwan isolates of HDV genotype II. Taiwan is geographically close to Miyako Island. Even though the races are different, a geographical factor was revealed to be significant with regard to HDV infection, which was spread in a closed environment.

Hepatitis D Virus: Introduction and Epidemiology

“…The prevalence of anti-HD was only 0.32% in a mixed-hospital HBsAg population collected in the country from 2008 to 2010 (Kim et al 2011). There has been no report of significant HDValso, in Japan, except for a high prevalence in the Mikayo Islands, Okinawa (Abbas et al 2010), where up to 23% of the HBsAg carriers were found to be infected with HDV in the 1990s; the prevalence of HDV in the area had decreased to 8.5% in 2000 (Arakawa et al 2000).…”

Genotype Analysis, Using PCR with Type-Specific Primers, of Hepatitis B Virus Isolates from Patients Coinfected with Hepatitis Delta Virus Genotype II from Miyako Island, Japan

“…We determined the HBV genotype of HDV antibody-positive subjects on Miyako Island, and all were positive for HBV genotype B (data not shown). It has been reported that the pathogenesis of HBV genotype B is mild [4][5][6]. Therefore, although a case-control study of long-term outcome in patients with different HBV genotypes coinfected with HDV could not be performed because most of the HBV infection was genotype B, there is a possibility that the clinical profile of patients from Miyako Island with HDV is actually attributable to the coinfecting HBV genotype B, which is associated with a low percentage of FH cases and many asymptomatic carriers.…”

“…This study included three patients with chronic hepatitis who were positive for hepatitis B surface (HBs) antigen (HBsAg) (enzymelinked immunosorbent assay; ELISA; Abbott, Tokyo, Japan), HDV antibody (ELISA, Abbott) and HDV RNA by PCR [4]. The reason for the selection of these three patients for this study was as follows: the patients' full genome sequences of HDV could be determined and were determined to be HDV genotype IIb and IIc by phylogenetic analysis.…”

“…Miyako Island is the main island of the Miyako Islands. We previously reported a molecular epidemiological analysis of HDV infection on Miyako Island, a distant island in Okinawa Prefecture in Japan [4][5][6]. The molecular epidemiological and clinical features of HDV and HBV infection clustered on Miyako Island are as follows: we found that approximately 30% of the HDV RNA-positive cases were asymptomatic carriers, and that the two genetic subtypes of HDV genotype II were present, designated genotypes IIb and IIc [5,6].…”

The complete genomic sequence of hepatitis delta virus genotype IIb prevalent in Okinawa, Japan

“…Recently, Wu et al (1998) reported a novel strain of genotype II in Taiwan and proposed genotypes IIa and IIb. The Miyako Islands, which are located in the southernmost part of Japan, about 390 km east of Taiwan, are one of the areas in Japan that is endemic for HDV (Sakugawa et al, 1995(Sakugawa et al, , 1997a(Sakugawa et al, , b, 1999Nakasone et al, 1998;Arakawa et al, 2000). The majority of patients with chronic HDV-related liver disease in the Miyako Islands exhibit a relatively mild course of infection that evolves to a quiescent cirrhotic condition (Sakugawa et al, 1997a).…”