2004-005, and the National Undergraduate Innovative Test Program, No. YA07059 and No. 081054239 Peer reviewer: Francesco Feo, Professor, Dipartimento di Scienze Biomediche, Sezione di Patologia Sperimentale e Oncologia, selleckbio Universit�� di Sassari, Via P, Manzella 4, 07100 Sassari, Italy S- Editor Cheng JX L- Editor Wang XL E- Editor Yin DH
Hepatitis B virus (HBV), a member of the Hepadnaviridae, is a circular, partially double-stranded DNA virus and is one of the major causes of chronic liver diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). The HBV genome is composed of approximately 3,200 nucleotides. HBV is classified into eight genotypes, designated A to H, based on an intergroup divergence of 8% or more in the complete nucleotide sequence (3, 23, 26, 37).
They have distinct geographical distributions and are associated with differences in clinical and virological characteristics, such as severity of liver disease and response to antiviral therapies (7, 8, 12, 13, 22, 28). Furthermore, subgenotypes have been reported for HBV/A, -B, and -C and named A1 to -3 (17, 38), B1 to -6 (31, 32, 40), and C1 to -6 (20, 31, 45). Equally, other genotypes are classified into subgenotypes. There have been increasing lines of evidence to indicate influences of HBV subgenotypes on the outcome of liver disease and the response to antiviral therapies (1, 39, 44). In 2001, we reported the geographic distribution of HBV genotypes in Japan (27). Of the 720 Japanese patients with chronic HBV infection (CHB), 12 (1.7%) harbored HBV/A, 88 (12.
2%) HBV/B, 610 (84.7%) HBV/C, 3 (0.4%) HBV/D, and 7 (1.0%) mixed genotypes. HBV/C was detected in over 94% of patients on the Japanese mainland, while HBV/B was found in 64% of those in Okinawa, the southernmost islands, and 44% of those in the Tohoku area in the northern part of the mainland. Recently, acute HBV infection (AHB) has been increasing in Japan, predominantly through promiscuous sexual contacts. In addition, it was reported that HBV/A was more frequent in patients with acute hepatitis than in those with chronic hepatitis (29, 41, 49). Recent studies suggest that the chances for progression to chronic disease may differ among patients acutely infected with HBV of distinct genotypes (21, 25); patients infected with HBV/A run an increased risk of becoming HBV carriers.
Hence, it is of utmost concern Brefeldin_A whether chronic HBV/A infection is increasing in Japan. In the present study, we compared the geographic distribution of HBV genotypes in Japan during 2005 and 2006 with 2000 and 2001, with special attention to changes in the proportion of HBV/A. Furthermore, we investigated the clinical characteristics of each genotype and examined the genomic characteristics of HBV/A isolates by molecular evolutionary analyses. MATERIALS AND METHODS Patients.