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1992 Fiscal Year Final Research Report Summary

Studies on the pathogenesis and pathophysiology of alcoholic liver cirrhosis and cancer.

Research Project

Project/Area Number 02304040
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKANAZAWA MEDICAL UNIVERSITY

Principal Investigator

TAKADA Akira  KANAZAWA MEDICAL UNIVERSITY, MEDICINE, PROFESSOR., 医学部, 教授 (30064497)

Co-Investigator(Kenkyū-buntansha) ISHII Hiromasa  KEIO UNIVERSITY, MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (20051500)
TANIKAWA Kyuichi  KURUME UNIVERSITY, MEDICINE, PROFESSOR., 医学部, 教授 (10080649)
TSUJII Tadasu  NARA MEDICAL UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (30075064)
OHTA Yasuyuki  EHIME UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (40033055)
OKUDAIRA Masahiko  KITAZATO UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (50050331)
Project Period (FY) 1990 – 1992
KeywordsAlcoholic liver disease / Alcoholic cirrhosis / Hepatocellular carcinoma / Diagnostic criteria / Course / prognosis / Hepatitis C virus / Genetic factor / Pathogenesis
Research Abstract

For analysis of the pathophysiology of alcoholic liver disease (ALD), reliable criteria for the diagnosis of ALD are essential. First, we obtained reliable diagnostic criteria for ALD, especially for its etiological diagnosis related to hepatitis C virus (HCV) infection. With the new criteria, liver disease in heavy drinkers can be classified into 3 etiological categories: alcohol alone (AL), alcohol and virus combined (AL+HCV), and others(probably virus alone). Based on these criteria, a national survey of ALD in Japan using a letter of inquiry revealed that the AL type was found in 60 % of patients and the AL+HCV type was found in the remaining 40%. The prevalence of the AL+HCV type was very high in patients with chronic hepatitis and hepatocellular carcinoma (HCC). Histological features of livers in patients classified with the AL or AL+HCV type were quite different. Fibrosis in the AL type and round cell infiltration in the AL+HCV type were characteristic. In follow-up studies, HCC developed more frequently in HCV marker-positive patients than in negative patients, suggesting a high risk for development of HCC in HCV marker-positive patients. Multiple logistic-regression analysis for the development of HCC was performed in cirrhotic patients with different etiologies and different ages. The estimated relative risk was significantly higher in the AL+HCV type than in the AL type. The calculated interaction between HCV and alcohol for development of HCC was significant statistically, indicating that alcohol abuse may increase development of HCC related to HCV infection. ALD caused by smaller amounts of alcohol consumption occurred in patients heterozygous for the aldehyde dehydrogenase-2 gene. The c2 gene of cytochrome P4502E1 gene was found in all patients with ALD, but not in any heavy drinkers without ALD. These results indicate that the development of ALD is controlled genetically.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Shujiro Takase: "Different types of chronic hepatitis in alcoholic patients:Does chronic hepatitis induced by alcohol exist?" Hepatology. 13. 876-881 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nobuyuki Enomoto: "Alcoholic liver disease in heterozygotes of mutant and normal aldehyde dehydrogenade-2 genes." Hepatology. 13. 1071-1075 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshiro Matsuda: "Accumulation of glycoprotein in the Golgi apparatus of hepatocytes in alcoholic liver injury." Amer J Gastroenterol. 86. 854-860 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akira Takada: "Alcoholic liver disease:Its classification and pathogene-sis." J Kanazawa Med Univ. 16. 347-361 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shujiro Takase: "The alcohol-altered liver membrane antibode and hepatitis C virus infection in the progressin of alcoholic liver disease." Hepatology. 17. 9-13 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akira Takada: "Characteristic features of alcoholic liver disease in Japan:A review." Gastroenterol Jpn. 28. 137-148 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高瀬 修二郎: "アルコールと肝炎(発生機序を中心に).In:肝炎-増補C型肝炎." 鈴木宏編南江堂, 8 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akira Takada: "Alcohol and hepatic carcinogenesis.In:Alcohol,Immunity,and Cancer." R.Yirmiya & A.N.Taylor eds,CRC press, 23 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akira Takada, Mikihiro Tsutsumi, Jian-Song Wang, Yoshiro Matsuda, Shujiro Takase.: "Genetic polymorphisms of cytochrome P4502E1 related to the development of alcoholic liver disease." Lancet.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mikihiro Tsutsumi, Jian-Song Wang, Yoshiro Matsuda, Akira Takada.: "Hepatic messenger RNA contents of cytochrome P4502E1 in its different types." Int Hepatol Commun.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akira Takada, Shujiro Takase, Mikihiro Tsutsumi, Yuki Kobayashi.: "Genotypes of ALDH2 related to liver and pulmonary disease." Alcohol & Alcoholism.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mikihiro Tsutsumi, Yoshiro Matsuda, Shujiro Takase, Akira Takada.: "Genetic factors related to the development of carcinoma in digestive organs." Alcohol & Alcoholism.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1994-03-24  

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