Department of Gastroenterology, St John's Medical College Hospital, Bangalore, India.
Am J Gastroenterol. 2010 Nov;105(11):2396-404. doi: 10.1038/ajg.2010.287. Epub 2010 Jul 20.
Although drug-induced liver injury (DILI) is rare, it may result in significant morbidity or death. The causes and outcome vary according to regions, with acetaminophen and complementary medicines common in the West and the Far East, respectively. This study evaluates the causes, outcomes, predictors, and models for 90-day mortality from DILI from India.
Consecutive patients with DILI from 1997 to 2008 based on International Consensus Criteria from a medical college hospital setting were studied.
Of the 313 patients, 58% were males. Leading causes were a combination of four anti-tuberculous drugs (ATDs) (58%), anti-epileptics (11%), olanzapine (5.4%), and dapsone (5.4%). The overall 90-day mortality of 17.3% was significantly higher for ATD hepatitis (21.5%) vs. those without (11.4%) (P=0.02). The highest mortality was for leflunomide (75%). Seventy-eight percent of patients received more than one drug. Fulminant hepatic failure developed more commonly in females than in males (23% vs. 17%). Of the 66% of cases with jaundice and/or icterus, mortality was 26%. Multivariable models for mortality using a combination of encephalopathy, ascites, and bilirubin, or a combination of albumin, prothrombin time, and white blood cell count yielded a C-statistic of at least 0.86 by recursive partitioning and 0.92 by logistic regression. Model for end stage liver disease (MELD) scores of 38 and 46 yield probabilities of death of 0.90 (confidence interval (CI): 0.71-0.97) and 0.99 (CI: 0.90-1.00), respectively.
DILI results in significant overall mortality (17.3%). ATDs, anti-convulsants, sulphonamides, and olanzapine are the leading causes of DILI. Although common in males, more females developed fulminant hepatic failure. High-MELD score or a combination of ascites, encephalopathy, high bilirubin, prothrombin time, and leukocyte count are predictive of mortality.
尽管药物性肝损伤（DILI）较为少见，但它可能导致严重的发病率或死亡率。其病因和结局因地区而异，在西方和远东地区，分别以对乙酰氨基酚和补充药物较为常见。本研究评估了来自印度的 DILI 患者 90 天死亡率的病因、结局、预测因素和模型。
本研究基于医学院医院环境中的国际共识标准，对 1997 年至 2008 年期间连续出现 DILI 的患者进行了研究。
在 313 例患者中，58%为男性。主要病因是四种抗结核药物（ATD）（58%）、抗癫痫药（11%）、奥氮平（5.4%）和氨苯砜（5.4%）的联合用药。总体 90 天死亡率为 17.3%，ATD 肝炎患者（21.5%）显著高于无 ATD 肝炎患者（11.4%）（P=0.02）。肝衰竭的死亡率最高，达 75%。78%的患者接受了不止一种药物。女性比男性更易发生暴发性肝衰竭（23%比 17%）。在 66%出现黄疸和/或黄疸的患者中，死亡率为 26%。使用脑病、腹水和胆红素组合，或白蛋白、凝血酶原时间和白细胞计数组合进行死亡率的多变量模型，通过递归分区可获得至少 0.86 的 C 统计量，通过逻辑回归可获得 0.92 的 C 统计量。MELD 评分分别为 38 和 46 时，死亡概率分别为 0.90（置信区间（CI）：0.71-0.97）和 0.99（CI：0.90-1.00）。
DILI 导致总体死亡率（17.3%）较高。ATD、抗惊厥药、磺胺类药物和奥氮平是 DILI 的主要病因。尽管在男性中较为常见，但更多的女性发生暴发性肝衰竭。高 MELD 评分或腹水、脑病、高胆红素、凝血酶原时间和白细胞计数的组合是死亡率的预测因素。
