Department of Clinical and Experimental Medicine, Federico II University Medical School of Naples, Naples, Italy.
Hepatol Res. 2007 Jun;37(6):410-5. doi: 10.1111/j.1872-034X.2007.00072.x.
Liver damage due to facultative hepatotoxins is scarcely foreseeable. We evaluated the prevalence of acute drug-induced liver injury (DILI) in a specific setting, assessing eventual interactions with pre-existing hepatic illnesses.
The research was carried out in an Italian tertiary care hospital, by analyzing 248 patients with non-advanced liver disease, divided into two well-matched groups: 174 patients (median age 53, 94 females) with hepatitis C virus-related chronic hepatitis; and 74 (median age 55, 39 females) with non-alcoholic fatty liver disease (NAFLD).
Six patients (2.4% of the whole population) belonging to the NAFLD group (chi(2)-test, P = 0.004) suffered from acute hepatoxicity related to the following drugs, that is antihypertensive, acting on platelet aggregation, antimicrobial, non-steroidal anti-inflammatory and proton pump inhibitor. The NAFLD presence was an independent risk factor in determining drug-related acute hepatitis, with an odds ratio of 3.95 (95% confidence intervals: 11.48-1.35). Central obesity was relevant in every patient with acute toxicity. Alcohol consumption and drug association did not influence the acute drug-induced liver damage.
NAFLD conveys a nearly fourfold increase of DILI risk in obese middle-aged patients. NAFLD, characterized by mitochondrial dysfunction, could predispose to drug-induced hepatotoxicity that probably shares the same pathophysiological mechanism.
由于兼性肝毒物导致的肝损伤几乎是不可预见的。我们评估了特定环境下急性药物性肝损伤(DILI)的发生率,并评估了其与先前存在的肝疾病的潜在相互作用。
该研究在意大利的一家三级保健医院进行,对 248 例非晚期肝病患者进行分析,将其分为两组,匹配良好:174 例(中位年龄 53 岁,94 例女性)丙型肝炎病毒相关慢性肝炎;74 例(中位年龄 55 岁,39 例女性)非酒精性脂肪性肝病(NAFLD)。
NAFLD 组有 6 例(整个人群的 2.4%)患者发生与以下药物相关的急性肝毒性,即抗高血压药、抗血小板聚集药、抗菌药、非甾体抗炎药和质子泵抑制剂。NAFLD 的存在是导致药物相关急性肝炎的独立危险因素,其比值比为 3.95(95%置信区间:11.48-1.35)。每位急性毒性患者均存在中心性肥胖。饮酒和药物联合使用并未影响急性药物性肝损伤。
在肥胖的中年患者中,NAFLD 使 DILI 的风险增加近 4 倍。NAFLD 表现为线粒体功能障碍,可能易发生药物性肝毒性,其可能具有相同的病理生理机制。