2001 Fiscal Year Final Research Report Summary
Clinical significance of HBV mutation
| Project/Area Number |
11670540
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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 | Tokyo Women's Medical University |
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Principal Investigator |
HASEGAWA Kiyoshi Lecturer, Medical Department, Tokyo Women's Medical University, 医学部, 講師 (30172886)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Makio Professor, Medical Department, Tokyo Women's Medical University, 医学部, 教授 (80060086)
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| Project Period (FY) |
1999 – 2001
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| Keywords | hepatitis B virus / fulminant hepatitis / mutation |
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| Research Abstract |
(1) Different antibody response against hepatitis B surface antigen among mice strains transfected with mutant viral DNA
Purpose Rapid seroconversion from HBsAg to anti-HBs antibody is seen in most patients with fulminant hepatitis B. It is unclear whether viral mutation or host immune background is responsible for such enhanced host reaction to HBV. To investigate interaction between virus mutation and host immune background, we established a mouse model of hepatitis B using liposome-mediated gene transfer.
Methods A mixture of liposomes and full-length viral DNA derived from hepatitis B patients was injected into 3 strains of purebred mice intrahepatically. After injection, hepatitis B surface antigen and antibody in liver and serum were serially measured.
Results Three days after transfection, viral transcript and antigen were detected in the liver and serum. Ten days after transfection with wild-type DNA, hepatitis B surface antibody was detectable in 2 of the 3 strains. Mice that did
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not produce antibody after transfection with wild-type DNA produced a high amount of serum antibody against surface antigen when transfected with fulminant hepatitis-associated DNA.
Conclusion The present results are consistent with previous clinical observations of rapid HBsAg seroconversion in patients with fulminant hepatitis B. Further studies are needed to determine which mutations are responsible for differences in immunogenicity between HBV strains.
(2) Clinical features and viral sequences of various genotypes of hepatitis B virus compared among patients with acute hepatitis B
Clinical manifestations and viral sequences of core promoter and precore/core region were compared among various genotypes of hepatitis B virus in 25 patients with acute hepatitis. The genotype in patients with acute hepatitis was distributed differently from that among chronic hepatitis patients in Japan, which are predominantly genotypes B and C. Of 25 patients with acute hepatitis, 14 had genotype A, 5 genotype B and 6 genotype C. Serum total bilirubin levels were significantly higher in patients with genotype A than in those with genotype C. Prothrombin time was shorter in patients with genotype B than those with genotype A or C.
Total bilirubin was lower in patients with short duration of acute hepatitis. The serum ALT value remained above 1000 IU/L for over 10 days in 79% of patients with genotype A. This prolonged duration of hepatitis in patients with genotype A may contribute to hyperbilirubinemia. Sequence analysis revealed no difference in the number of mutations in precore/core regions among the three genotypes. Although the double mutation, A-T and G-A at 1762 and 1764, respectively, was found in 2 patients each with genotype A and C, these mutations were not related to the HBeAg/HBeAb phenotype. Two of 7 patients with thymidine at 1858 also had a G to A mutation at 1896. Thus, the difference in the genotype little influenced the HBeAg/HBeAb phenotype in acute hepatitis patients. Understanding the viral genotypes in acute HBV infection may be valuable in predicting the clinical course of acute hepatitis B. Less
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Research Products
(16 results)
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[Publications] Joh R, Hasegawa K, Torii N, Ogawa M, Kanai N, Naritomi T, Ishikawa K, lizuka A, Shizuma T, Hashimoto E, Hayashi N.: "Repeated jaundice due to YMDD mutant in a patient with prolonged lamivudine therapy for chronic hepatitis B under prednisolone treatment for Still's disease"Intern Med. 41. 701-705 (2002)
Description
「研究成果報告書概要(欧文)」より
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