Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury
Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury
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DOI：
10.1111/j.1440-1746.2012.07279.x
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发表时间：
2013-01-01
影响因子：
4.1
通讯作者：
Balaraju, Girisha
中科院分区：
文献类型：
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作者：
Devarbhavi, Harshad;Singh, Rajvir;Balaraju, Girisha
背景与目的：在世界范围内，抗结核（TB）药物性肝病（DILI）是引起肝毒性和药物性急性肝衰竭（ALF）的重要原因。关于抗结核DILI的报道系列受到轻度转氨酶升高或适应的病例的限制。我们的目的是分析临床特征、实验室特征、结果，并确定90天死亡率的预测因素。方法：对1997-2011年联合抗结核药物暴露后抗结核DILI连续病例进行单中心分析。结果269例患者中黄疸191例（71%），ALF 69例（25.7%）。平均年龄41.3岁，治疗时间1.9个月；男性占55.7%。DILI发生在整个治疗过程中；四分之三发生在头两个月内。21例（7.8%）感染艾滋病毒。90天死亡率为22.7%。DILI合并黄疸（n = 191）、脑病（n = 69）和腹水（n = 69）的死亡率分别为30%、69.6%和50.7% （P < 0.001）。年龄、性别、转氨酶水平、HIV或乙型肝炎表面抗原（HBsAg）状态对生存率没有影响。治疗时间、脑病、腹水、胆红素、血清白蛋白、国际标准化比值（INR）、血清肌酐和白细胞计数与死亡率相关（P < 0.001）。死亡率的多变量logistic回归模型，包括脑病、白蛋白、胆红素、INR和肌酐，c统计量为97%。结论：1 / 4的患者在整个治疗期间发生抗结核DILI，进展为ALF。总死亡率为22.7%，当伴有黄疸、腹水或脑病时，死亡率更高。结合胆红素、INR、脑病、血清肌酐和白蛋白的抗结核DILI模型预测死亡率，c统计量为97%。
Background and Aim: Worldwide anti-tuberculosis (TB) drug-induced liver disease (DILI) is an important cause of hepatotoxicity, and drug-induced acute liver failure (ALF). Reported series on anti-TB DILI are limited by a mix of cases with mild transaminase elevation or adaptation. Our aim was to analyze the clinical features, laboratory characteristics, outcome, and determine predictors of 90-day mortality.Methods: Single center analysis of consecutive cases of anti-TB DILI following combination anti-TB drugs exposure from 1997-2011.Results: Of the 269 patients, 191 (71%) experienced jaundice and 69 (25.7%) accounted for ALF. The mean age and treatment duration was 41.3 years and 1.9 months, respectively; males constituted 55.7%. DILI occurred throughout the course of treatment; three-quarters occurred within the first 2 months. HIV infection was present in 21 (7.8%). The 90-day mortality was 22.7%. DILI accompanied by jaundice (n = 191), encephalopathy (n = 69) or ascites (n = 69) resulted in mortality in 30%, 69.6% and 50.7%, respectively (P < 0.001). Age, gender, transaminase levels, HIV or hepatitis B surface antigen (HBsAg) status did not influence survival. Treatment duration, encephalopathy, ascites, bilirubin, serum albumin, international normalized ratio (INR), serum creatinine and leukocyte count were associated with mortality (P < 0.001). Multivariate logistic regression model for mortality, incorporating encephalopathy, albumin, bilirubin, INR, and creatinine yielded a C-statistic of 97%.Conclusions: Anti-TB DILI occurs throughout treatment duration progressing to ALF in a quarter of patients. The overall mortality is 22.7%, which is higher when accompanied by jaundice, ascites or encephalopathy. An anti-TB DILI model, incorporating bilirubin, INR, encephalopathy, serum creatinine and albumin predicted mortality with C-statistic of 97%.