| Project/Area Number |
02304040
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | KANAZAWA MEDICAL UNIVERSITY |
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Principal Investigator |
TAKADA Akira KANAZAWA MEDICAL UNIVERSITY, MEDICINE, PROFESSOR., 医学部, 教授 (30064497)
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| 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)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 1992: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1990: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Alcoholic liver disease / Alcoholic cirrhosis / Hepatocellular carcinoma / Diagnostic criteria / Course / prognosis / Hepatitis C virus / Genetic factor / Pathogenesis / 大酒家慢性肝炎 / アルコ-ル性肝硬変 / 肝癌 / C型肝炎ウイルス(HCV) / HCVーRNA / アルデヒド脱水素酵素(ALDH)2 / 遺伝子型 |
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| 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.
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