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，可靠的 ALD 诊断标准至关重要。首先，我们获得了可靠的ALD诊断标准，特别是其与丙型肝炎病毒（HCV）感染相关的病因学诊断。根据新标准，重度饮酒者的肝病可分为3个病因类别：单纯酒精（AL）、酒精和病毒结合（AL+HCV）和其他（可能是单纯病毒）。基于这些标准，日本通过询问信对 ALD 进行了全国调查，结果显示 60% 的患者为 AL 型，其余 40% 的患者为 AL+HCV 型。慢性肝炎和肝细胞癌（HCC）患者中 AL+HCV 型的患病率非常高。 AL 型或 AL+HCV 型患者的肝脏组织学特征有很大不同。 AL型的纤维化和AL+HCV型的圆形细胞浸润是特征性的。在后续研究中，HCV 标志物阳性患者比阴性患者更容易发生 HCC，这表明 HCV 标志物阳性患者发生 HCC 的风险较高。对不同病因和不同年龄的肝硬化患者进行了 HCC 发展的多重逻辑回归分析。 AL+HCV 型的估计相对风险显着高于 AL 型。计算出的 HCV 和酒精对于 HCC 发展的相互作用具有显着的统计学意义，表明酗酒可能会增加与 HCV 感染相关的 HCC 的发展。少量饮酒引起的 ALD 发生在乙醛脱氢酶 2 基因杂合子患者中。细胞色素P4502E1基因的c2基因在所有ALD患者中均被发现，但在非ALD重度饮酒者中未发现。这些结果表明 ALD 的发展是受基因控制的。