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15 February 1995 | Volume 122 Issue 4 | Pages 241-248
Objective: Fulminant hepatitis B can be induced by hepatitis B virus (HBV) strains with mutations in the precore region that cannot encode hepatitis B e antigen (HBeAg). Such mutations are rarely seen in HBV DNA clones from patients with fulminant hepatitis B in the United States and France. Thus, the other mutations in HBV strains causing fulminant hepatitis B need to be identified.
Design: Retrospective clinical, serologic, and molecular biological studies of patients with fulminant hepatitis B.
Setting: University and city hospitals in Japan.
Patients: 43 patients with fulminant hepatitis B.
Measurements: The precore region coding for a part of the HBeAg precursor and the core promoter regulating the transcription of precore messenger RNA were sequenced in HBV DNA clones.
Results: A point mutation from G to A at nucleotide 1896 in the precore region was detected in 519 (98%) of 529 HBV DNA clones from 38 patients. Two point mutations in the core promoter, from A to T at nucleotide 1762 and from G to A at nucleotide 1764, were detected in all 130 clones from the remaining 5 patients, who did not have mutations in the precore region, and in 20 (63%) of 32 clones from a patient with chronic hepatitis B who had transmitted HBV to 1 of these other 5 patients. Mutations in the core promoter were also detected in clones from 26 (68%) of the 38 patients with the precore mutation at nucleotide 1896. Neither HBeAg nor antibody to HBeAg was detected in 37 (90%) of the 41 patients tested.
Conclusions: In Japan, fulminant hepatitis B is closely associated with HBV strains that do not produce HBeAg because of mutations in the precore region, which affect translation of HBeAg, or because of mutations in the core promoter, which affect transcription of the HBeAg coding region.
Author and Article Information
From Iwate Medical University, Iwate-Ken, Japan. Yamanashi Medical University, Yamanashi-Ken, Japan. Ehime University School of Medicine, Ehime-Ken, Japan. Asahikawa Medical College, Hokkaido, Japan. Dokkyo University School of Medicine and Jichi Medical School, Tochigi-Ken, Japan. Toshiba General Hospital and Mita Institute, Tokyo, Japan. The Japanese Red Cross Saitama Blood Center, Saitama-Ken, Japan.
ARTICLE
Hepatitis B Virus Strains with Mutations in the Core Promoter in Patients with Fulminant Hepatitis
Requests for Reprints: Makoto Mayumi, MD, Immunology Division, Jichi Medical School, Tochigi-Ken 329-04, Japan.
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