Double point mutation in the core promoter region of hepatitis B virus (HBV) genotype C may be related to liver deterioration in patients with chronic HBV infection

Hisashi Nakashima, Norihiro Furusyo, Norihiko Kubo, Kenichiro Kashiwagi, Yoshitaka Etoh, Seizaburou Kashiwagi, Jun Hayashi

Research output: Contribution to journalArticle

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Abstract

Background and Aim: Hepatitis B virus (HBV) genotype C has a more severe pathogenesis than gen-otype B in Japan. We retrospectively investigated the relationship between HBV genotype and the core promoter (CP) (nt 1762 and 1764) and precore (PreC) (nt 1896) mutations of the HBV genome. Methods: A total of 129 Japanese patients (42 genotype B and 87 genotype C) with chronic HBV infection, living in two different geographical areas in Japan, were evaluated (mean follow-up period 10.1 ± 3.8 years). In 2000, CP and PreC HBV mutations were analyzed by direct sequencing from sera. Hepatitis B e antigen (HBeAg), HBV DNA and serial alanine aminotransferase (ALT) changes were followed and determined using serological methods. Results: Genotype C patients had significantly higher rates of HBeAg (40.2% vs 2.4%), HBV DNA positivity (75.9% vs 7.1%) and ALT abnormality (71.3% vs 11.9%) than genotype B patients (all P < 0.05). Among genotype B patients, CP wild type (92.9%) was predominant and PreC mutation (88.1%) was predominant. However, among genotype C patients, CP mutation (75.9%) was predominant and PreC mutation (66.7%) was predominant. The CP mutation was found significantly more in genotype C than in genotype B (P < 0.05). Of the 67 patients with ALT abnormality, five (7.5%) genotype B and 62 (92.5%) genotype C patients (31 HBeAg positive and 31 negative) were found. Among the 31 genotype C patients who were HBeAg positive, the combination of CP mutation and PreC wild (54.8%) was predominant, while among the remaining 31 genotype C patients who were HBeAg negative, the combination of CP mutation and PreC mutant (71.0%) was predominant. Conclusion: Genotype C might be one of the worse prognostic markers in patients with chronic HBV infection, possibly because of mutation in the CP region.

Original languageEnglish
Pages (from-to)541-550
Number of pages10
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume19
Issue number5
DOIs
Publication statusPublished - Jan 1 2004

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Chronic Hepatitis B
Virus Diseases
Point Mutation
Genetic Promoter Regions
Hepatitis B virus
Genotype
Liver
Hepatitis B e Antigens
Mutation
Alanine Transaminase
Japan
DNA

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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Double point mutation in the core promoter region of hepatitis B virus (HBV) genotype C may be related to liver deterioration in patients with chronic HBV infection. / Nakashima, Hisashi; Furusyo, Norihiro; Kubo, Norihiko; Kashiwagi, Kenichiro; Etoh, Yoshitaka; Kashiwagi, Seizaburou; Hayashi, Jun.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 19, No. 5, 01.01.2004, p. 541-550.

Research output: Contribution to journalArticle

Nakashima, Hisashi ; Furusyo, Norihiro ; Kubo, Norihiko ; Kashiwagi, Kenichiro ; Etoh, Yoshitaka ; Kashiwagi, Seizaburou ; Hayashi, Jun. / Double point mutation in the core promoter region of hepatitis B virus (HBV) genotype C may be related to liver deterioration in patients with chronic HBV infection. In: Journal of Gastroenterology and Hepatology (Australia). 2004 ; Vol. 19, No. 5. pp. 541-550.
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abstract = "Background and Aim: Hepatitis B virus (HBV) genotype C has a more severe pathogenesis than gen-otype B in Japan. We retrospectively investigated the relationship between HBV genotype and the core promoter (CP) (nt 1762 and 1764) and precore (PreC) (nt 1896) mutations of the HBV genome. Methods: A total of 129 Japanese patients (42 genotype B and 87 genotype C) with chronic HBV infection, living in two different geographical areas in Japan, were evaluated (mean follow-up period 10.1 ± 3.8 years). In 2000, CP and PreC HBV mutations were analyzed by direct sequencing from sera. Hepatitis B e antigen (HBeAg), HBV DNA and serial alanine aminotransferase (ALT) changes were followed and determined using serological methods. Results: Genotype C patients had significantly higher rates of HBeAg (40.2{\%} vs 2.4{\%}), HBV DNA positivity (75.9{\%} vs 7.1{\%}) and ALT abnormality (71.3{\%} vs 11.9{\%}) than genotype B patients (all P < 0.05). Among genotype B patients, CP wild type (92.9{\%}) was predominant and PreC mutation (88.1{\%}) was predominant. However, among genotype C patients, CP mutation (75.9{\%}) was predominant and PreC mutation (66.7{\%}) was predominant. The CP mutation was found significantly more in genotype C than in genotype B (P < 0.05). Of the 67 patients with ALT abnormality, five (7.5{\%}) genotype B and 62 (92.5{\%}) genotype C patients (31 HBeAg positive and 31 negative) were found. Among the 31 genotype C patients who were HBeAg positive, the combination of CP mutation and PreC wild (54.8{\%}) was predominant, while among the remaining 31 genotype C patients who were HBeAg negative, the combination of CP mutation and PreC mutant (71.0{\%}) was predominant. Conclusion: Genotype C might be one of the worse prognostic markers in patients with chronic HBV infection, possibly because of mutation in the CP region.",
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T1 - Double point mutation in the core promoter region of hepatitis B virus (HBV) genotype C may be related to liver deterioration in patients with chronic HBV infection

AU - Nakashima, Hisashi

AU - Furusyo, Norihiro

AU - Kubo, Norihiko

AU - Kashiwagi, Kenichiro

AU - Etoh, Yoshitaka

AU - Kashiwagi, Seizaburou

AU - Hayashi, Jun

PY - 2004/1/1

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N2 - Background and Aim: Hepatitis B virus (HBV) genotype C has a more severe pathogenesis than gen-otype B in Japan. We retrospectively investigated the relationship between HBV genotype and the core promoter (CP) (nt 1762 and 1764) and precore (PreC) (nt 1896) mutations of the HBV genome. Methods: A total of 129 Japanese patients (42 genotype B and 87 genotype C) with chronic HBV infection, living in two different geographical areas in Japan, were evaluated (mean follow-up period 10.1 ± 3.8 years). In 2000, CP and PreC HBV mutations were analyzed by direct sequencing from sera. Hepatitis B e antigen (HBeAg), HBV DNA and serial alanine aminotransferase (ALT) changes were followed and determined using serological methods. Results: Genotype C patients had significantly higher rates of HBeAg (40.2% vs 2.4%), HBV DNA positivity (75.9% vs 7.1%) and ALT abnormality (71.3% vs 11.9%) than genotype B patients (all P < 0.05). Among genotype B patients, CP wild type (92.9%) was predominant and PreC mutation (88.1%) was predominant. However, among genotype C patients, CP mutation (75.9%) was predominant and PreC mutation (66.7%) was predominant. The CP mutation was found significantly more in genotype C than in genotype B (P < 0.05). Of the 67 patients with ALT abnormality, five (7.5%) genotype B and 62 (92.5%) genotype C patients (31 HBeAg positive and 31 negative) were found. Among the 31 genotype C patients who were HBeAg positive, the combination of CP mutation and PreC wild (54.8%) was predominant, while among the remaining 31 genotype C patients who were HBeAg negative, the combination of CP mutation and PreC mutant (71.0%) was predominant. Conclusion: Genotype C might be one of the worse prognostic markers in patients with chronic HBV infection, possibly because of mutation in the CP region.

AB - Background and Aim: Hepatitis B virus (HBV) genotype C has a more severe pathogenesis than gen-otype B in Japan. We retrospectively investigated the relationship between HBV genotype and the core promoter (CP) (nt 1762 and 1764) and precore (PreC) (nt 1896) mutations of the HBV genome. Methods: A total of 129 Japanese patients (42 genotype B and 87 genotype C) with chronic HBV infection, living in two different geographical areas in Japan, were evaluated (mean follow-up period 10.1 ± 3.8 years). In 2000, CP and PreC HBV mutations were analyzed by direct sequencing from sera. Hepatitis B e antigen (HBeAg), HBV DNA and serial alanine aminotransferase (ALT) changes were followed and determined using serological methods. Results: Genotype C patients had significantly higher rates of HBeAg (40.2% vs 2.4%), HBV DNA positivity (75.9% vs 7.1%) and ALT abnormality (71.3% vs 11.9%) than genotype B patients (all P < 0.05). Among genotype B patients, CP wild type (92.9%) was predominant and PreC mutation (88.1%) was predominant. However, among genotype C patients, CP mutation (75.9%) was predominant and PreC mutation (66.7%) was predominant. The CP mutation was found significantly more in genotype C than in genotype B (P < 0.05). Of the 67 patients with ALT abnormality, five (7.5%) genotype B and 62 (92.5%) genotype C patients (31 HBeAg positive and 31 negative) were found. Among the 31 genotype C patients who were HBeAg positive, the combination of CP mutation and PreC wild (54.8%) was predominant, while among the remaining 31 genotype C patients who were HBeAg negative, the combination of CP mutation and PreC mutant (71.0%) was predominant. Conclusion: Genotype C might be one of the worse prognostic markers in patients with chronic HBV infection, possibly because of mutation in the CP region.

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