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

酒精性肝硬化和癌症的发病机制和病理生理学研究。

基本信息

批准号：
02304040
负责人：
TAKADA Akira
金额：
$ 9.28万
依托单位：
KANAZAWA MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

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.

为了分析酒精性肝病（ALD）的病理生理学，必不可少的ALD诊断标准。首先，我们获得了ALD的可靠诊断标准，尤其是与乙型肝炎病毒（HCV）感染有关的病因诊断。有了新的标准，重饮者中的肝病可以分为3个病因：仅酒精（AL），酒精和病毒合并（Al+HCV）等（可能单独使用病毒）。基于这些标准，日本对ALD的全国调查使用询问信显示，在60％的患者中发现了AL类型，其余40％发现了AL+HCV类型。慢性肝炎和肝细胞癌（HCC）患者AL+HCV类型的患病率很高。分类为AL或AL+HCV类型的患者肝脏的组织学特征截然不同。 Al+HCV类型中Al类型的纤维化和圆细胞浸润是特征的。在后续研究中，HCC在HCV标记阳性患者中的发展频率比在阴性患者中更频繁，这表明HCV标记阳性患者的HCC发生高风险。在具有不同病因和不同年龄的肝硬化患者中，对HCC的发展进行了多种逻辑回归分析。 AL+HCV类型的估计相对风险明显高于AL类型。 HCV与酒精之间用于HCC开发的相互作用在统计上是显着的，表明酒精滥用可能会增加与HCV感染相关的HCC的发展。醛脱氢酶-2基因的杂合子患者发生少量饮酒引起的ALD。在所有ALD患者中都发现了细胞色素P4502E1基因的C2基因，但在没有ALD的任何重型饮酒者中都没有发现。这些结果表明，ALD的发展受到遗传控制。