title: Chronic hepatitis delta virus infection with genotype IIb variant is correlated with progressive liver disease.
abstract: We determined the sequence of the hepatitis delta virus (HDV) genome in 40 Japanese patients, most of whom were from the Miyako Islands, Okinawa, Japan. Consensus sequences from 33 HDV full genomes out of a total of 40 patients were determined by directly sequencing four partially overlapping PCR products. Phylogenetic tree analysis classified these 33 complete HDV genomes as HDV genotype I (two patients), genotype IIa (one patient) and genotype IIb (30 patients). Among the 30 genotype IIb patients, there were two clusters of genetic variants. One group consisted of six isolates showing significant homology with genotype IIb, previously reported from Taiwan. The other group consisted of 24 isolates, whose sequences formed a new genetic subgroup (genotype IIb-Miyako; IIb-M). When the genetic structures were compared in detail between IIb and IIb-M, characteristic variations were found in the C-terminal sequence of the large delta antigen-conferring packaging signal as well as the RNA editing site. Determination of subclasses of genotype IIb in a total of 37 patients, including seven HDV patients whose partial HDV sequence was determined, revealed eight patients with IIb and 29 patients with IIb-M. Although there was no significant difference in the clinical background or virological state of hepatitis B virus between these two groups, patients with genotype IIb-M showed greater progression of chronic hepatitis and cirrhosis than those with genotype IIb (P=0.0009). These data indicate the existence of a genetic subgroup of HDV genotype IIb, which is associated with different clinical characteristics and which could be related to genetic variations in functionally important parts of the HDV genome.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Nagayama
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Chinzei
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamashiro
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.affiliation: Institute for Clinical Research, World Health Organization Collaborating Center for Reference and Research on Viral Hepatitis, National Nagasaki Medical Center, Nagasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, USA.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, USA.
authors.forename: Betty H
authors.initials: BH
authors.lastname: Robertson
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakasone
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakugawa
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D016384:Consensus Sequence; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D019701:Hepatitis D, Chronic / Q000175:diagnosis* / Q000473:pathology; D003698:Hepatitis Delta Virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D035923:Hepatitis delta Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment
chemical_list: D035923:Hepatitis delta Antigens