2006 Fiscal Year Final Research Report Summary
Long-term outcome of patients co-infected with hepatitis B and D virus
| Project/Area Number |
16590608
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
HOKAMA Akira University of the Ryukyus, University Hospital, lecturer, 医学部附属病院, 講師 (00305202)
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| Co-Investigator(Kenkyū-buntansha) |
HIGA Futoshi University of the Ryukyus, University Hospital, lecturer, 医学部附属病院, 講師 (50291555)
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| Project Period (FY) |
2004 – 2006
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| Keywords | hepatitis B virus / hepatitis D virus / chronic hepatitis / hepatocellular carcinoma / molecular biology / genotype / long-term outcome / epidemiological study |
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| Research Abstract |
To clarify the correlation between HBV DNA levels and serum ALT levels in patients with chronic hepatitis HDV infection, sensitive HBV quantitative assays were used. Thirty-four consecutive patients with CLD who were positive for both HBsAg and anti-HDV, including 19 patients with CH, 8 patients with LC and 7 patients with HCC. All were negative for HBeAg and positive for antibody to HBeAg. HBV DNA was detected in 25 (73.5%) of the 34 patients using real-time detection PCR, and the HBV DNA levels of these patients were significantly lower compared with HBeAg status and ALT level-matched patients with CLD positive for HBsAg but negative for anti-HDV. There was no correlation between serum HBV DNA and ALT levels among the 34 patients with CLD positive for anti-HDV. ALT levels in anti-HDV-positive HBsAg carriers with HDV RNA were significantly higher than those without HDV RNA. Liver damage in patients with HDV infection may be caused mainly by ongoing HDV infection not by HBV replication
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We determined the sequence of HDV genome in 40 patients from the Miyako Islands, Okinawa. Consensus sequences from 33 HDV full genomes were determined by directly sequencing four partially overlapping PCR products. Phylogenetic tree analysis classified these 33 complete HDV genomes as HDV genotype I, IIa and IIb. 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). 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, including HDV patients whose partial HDV sequence was determined, revealed eight patients with IIb and 29 patients with IIb-M. Patients with genotype IIb-M showed greater progression of CH and LC than those with genotype IIb. 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. Less
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