Sunil Kumar Nanjegowda, Remalayam Bhavith, Thomas Varghese, Ramachandran Thazhath M, Sunil Kumar Kandiyil
Department of Gastroenterology, Government Medical College, Kozhikode, India.
J Clin Exp Hepatol. 2021 Mar-Apr;11(2):163-170. doi: 10.1016/j.jceh.2020.08.008. Epub 2020 Aug 20.
Drug-induced liver injury (DILI) is an important cause of acute liver failure with significant morbidity and mortality. The outcome of DILI varies widely according to the drug implicated and the type of liver injury. Owing to the heterogeneous nature of liver injury, knowledge on clinical course and prognosis of DILI is limited. We had undertaken this study to determine the clinical characteristics, outcomes, and predictors of mortality in patients with DILI.
This prospective study was conducted from January 2015 through December 2018. We analyzed the drugs implicated, clinical course, and the outcome. Causality assessment was performed by using Roussel Uclaf Causality Assessment Method scoring. Patients were followed for 6 months until recovery/death or liver transplantation.
There were 133 cases with DILI. The mean age was 47.6 years, and 51.9% of them were men. Drugs causing DILI were antitubercular drugs (37.5%) followed by neuropsychiatric drugs (16.5%), antibiotics/antifungals (12%), complementary and alternative medicine (10.5%), immunomodulatory/chemotherapeutic drugs (10.5%), and nonsteroidal antiinflammatory drugs (7.5%). Eighty-two (61.6%) patients were classified as hepatocellular, 30 (22.5%) as mixed and 21 (15.7%) as cholestatic type of injury. There was no significant difference in the mortality and morbidity between the three types of liver injury. There were 18 deaths (13.5%), of which antitubercular drugs constituted the majority (55.5%) followed by neuropsychiatric drugs (27.7%) and complementary and alternative medicine (16.6%). Based on receiver operating characteristic curve analysis, model for end-stage liver disease (MELD) score >28, mean international normalized ratio (INR) >1.97, mean bilirubin level >15.6 mg/dl, and creatinine level >1.35 mg/dl were associated with mortality.
Although DILI is uncommon, it has significant morbidity and mortality. Antitubercular drugs were the most common cause for DILI and DILI-related mortality in our study. Variables such as MELD, INR, bilirubin, albumin, and creatinine help in predicting severity of liver injury and may help in triaging the patient for referral for liver transplantation.
药物性肝损伤(DILI)是急性肝衰竭的重要病因,具有较高的发病率和死亡率。DILI的结局因所涉及的药物和肝损伤类型而异。由于肝损伤的异质性,关于DILI临床病程和预后的知识有限。我们开展这项研究以确定DILI患者的临床特征、结局及死亡预测因素。
这项前瞻性研究于2015年1月至2018年12月进行。我们分析了所涉及的药物、临床病程及结局。采用鲁塞尔·优克福因果关系评估法评分进行因果关系评估。对患者随访6个月,直至康复/死亡或进行肝移植。
共有133例DILI患者。平均年龄为47.6岁,其中51.9%为男性。导致DILI的药物依次为抗结核药物(37.5%)、神经精神药物(16.5%)、抗生素/抗真菌药物(12%)、补充和替代医学药物(10.5%)、免疫调节/化疗药物(10.5%)及非甾体抗炎药(7.5%)。82例(61.6%)患者被归类为肝细胞型损伤,30例(22.5%)为混合型损伤,21例(15.7%)为胆汁淤积型损伤。三种类型的肝损伤在死亡率和发病率方面无显著差异。有18例死亡(13.5%),其中抗结核药物导致的死亡占多数(55.5%),其次是神经精神药物(27.7%)和补充和替代医学药物(16.6%)。基于受试者工作特征曲线分析,终末期肝病模型(MELD)评分>28、平均国际标准化比值(INR)>1.97、平均胆红素水平>15.6mg/dl及肌酐水平>1.35mg/dl与死亡率相关。
尽管DILI并不常见,但具有较高的发病率和死亡率。在我们的研究中,抗结核药物是DILI及DILI相关死亡的最常见原因。诸如MELD、INR、胆红素、白蛋白和肌酐等变量有助于预测肝损伤的严重程度,并可能有助于对患者进行分类以便转诊进行肝移植。