印度药物性肝损伤网络：1288例患者的病因、临床特征、结局及预后标志物

The Indian Network of Drug-Induced Liver Injury: Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients.

作者信息

Devarbhavi Harshad, Joseph Tarun, Sunil Kumar Nanjegowda, Rathi Chetan, Thomas Varghese, Prasad Singh Shivaram, Sawant Prabha, Goel Ashish, Eapen Chundamannil E, Rai Prakash, Arora Anil, Leelakrishnan Venkatakrishnan, Gopalakrishnan Gayathri, Vardhan Reddy Vishnu, Singh Rajvir, Goswami Bhabadev, Venkataraman Jayanthi, Balaraju Girisha, Patil Mallikarjun, Patel Rakesh, Taneja Sunil, Koshy Abraham, Nagaraja Rao Padaki, Kumar Sarin Shiv, Rathi Pravin, Dhiman Radhakrishna, Duseja Ajay K, Vargese Joy, Kumar Jain Ajay, Wadhawan Manav, Ranjan Piyush, Karanth Dheeraj, Ganesh Panchapakesan, Nijhawan Sandeep, Krishna Dhali Gopal, Adarsh Channagiri K, Jhaveri Ajay, Nagral Aabha, Rao Prasanna

机构信息

Department of Gastroenterology, St. John's Medical College Hospital, Bangalore, India.

Department of Gastroenterology, Government Medical College, Kozhikode, India.

出版信息

J Clin Exp Hepatol. 2021 May-Jun;11(3):288-298. doi: 10.1016/j.jceh.2020.11.002. Epub 2020 Nov 17.

DOI:10.1016/j.jceh.2020.11.002

PMID:33994711

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8103312/

Abstract

BACKGROUND

Etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI) vary geographically. We conducted a prospective study of DILI in India, from 2013 to 2018 and summarize the causes, clinical features, outcomes and predictors of mortality.

METHODS

We enrolled patients with DILI using international DILI expert working group criteria and Roussel Uclaf causality assessment method. Follow-up was up to 3 months from onset of DILI or until death. Multivariate logistics regression was carried out to determine predictors of non-survival.

RESULTS

Among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Concomitant features of skin reaction, ascites, and encephalopathy (HE) were seen in 19.5%, 16.4%, and 10% respectively. 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in those with HE, 17.6% in patients who fulfilled Hy's law, and 16.6% in those that developed jaundice. Combination anti-TB drugs (ATD) 46.4%, complementary and alternative medicines (CAM) 13.9%, anti-epileptic drugs (AED) 8.1%, non-ATD antimicrobials 6.5%, anti-metabolites 3.8%, anti-retroviral drugs (ART)3.5%, NSAID2.6%, hormones 2.5%, and statins 1.4% were the top 9 causes. Univariate analysis identified, ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score (p < 0.001), transaminases (p < 0.04), and anti-TB drugs (p = 0.02) as predictors of non-survival. Only serum creatinine (p = 0.017), INR (p < 0.001), HE (p < 0.001), and ascites (p = 0.008), were significantly associated with mortality on multivariate analysis. ROC yielded a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. More than 50 different agents were associated with DILI. Mortality varied by drug class: 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics.

CONCLUSION

In India, ATD, CAM, AED, anti-metabolites and ART account for the majority of cases of DILI. The 3-month mortality was approximately 12%. Hy's law, presence of jaundice or MELD were predictors of mortality.

摘要

背景

特异质性药物性肝损伤（DILI）的病因及预后存在地域差异。我们于2013年至2018年在印度开展了一项DILI的前瞻性研究，总结其病因、临床特征、预后及死亡预测因素。

方法

我们采用国际DILI专家工作组标准及鲁塞尔·优克福因果关系评估法纳入DILI患者。随访至DILI发病后3个月或直至死亡。进行多因素逻辑回归分析以确定非生存的预测因素。

结果

在1288例特异质性DILI患者中，51.4%为男性，68%出现黄疸，68%需要住院治疗，8.2%合并HIV感染。皮肤反应、腹水和肝性脑病（HE）的伴随特征分别见于19.5%、16.4%和10%的患者。32.4%患有严重疾病。就诊时平均终末期肝病模型（MELD）评分18.8±8.8。总体死亡率为12.3%；HE患者中为65%，符合Hy法则的患者中为17.6%，出现黄疸的患者中为16.6%。联合抗结核药物（ATD）占46.4%，补充和替代药物（CAM）占13.9%，抗癫痫药物（AED）占8.1%，非ATD抗菌药物占6.5%，抗代谢药物占3.8%，抗逆转录病毒药物（ART）占3.5%，非甾体抗炎药（NSAID）占2.6%，激素占2.5%，他汀类药物占1.4%，是前9大病因。单因素分析确定腹水、HE、血清白蛋白、胆红素、肌酐、国际标准化比值（INR）、MELD评分（p<0.001）、转氨酶（p<0.04）和抗结核药物（p=0.02）为非生存的预测因素。多因素分析显示，仅血清肌酐（p=0.017）、INR（p<0.001）、HE（p<0.001）和腹水（p=0.008）与死亡率显著相关。MELD评分曲线下面积（C统计量）为0.811，血清肌酐、INR、腹水和HE联合的C统计量为0.892。超过50种不同药物与DILI相关。死亡率因药物类别而异：ATD为15%，CAM为13.6%，AED为15.5%，抗生素为5.8%。