TY - JOUR
T1 - The Indian Network of Drug-Induced Liver Injury
T2 - Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients
AU - Devarbhavi, Harshad
AU - Joseph, Tarun
AU - Sunil Kumar, Nanjegowda
AU - Rathi, Chetan
AU - Thomas, Varghese
AU - Prasad Singh, Shivaram
AU - Sawant, Prabha
AU - Goel, Ashish
AU - Eapen, Chundamannil E.
AU - Rai, Prakash
AU - Arora, Anil
AU - Leelakrishnan, Venkatakrishnan
AU - Gopalakrishnan, Gayathri
AU - Vardhan Reddy, Vishnu
AU - Singh, Rajvir
AU - Goswami, Bhabadev
AU - Venkataraman, Jayanthi
AU - Balaraju, Girisha
AU - Patil, Mallikarjun
AU - Patel, Rakesh
AU - Taneja, Sunil
AU - Koshy, Abraham
AU - Nagaraja Rao, Padaki
AU - Kumar Sarin, Shiv
AU - Rathi, Pravin
AU - Dhiman, Radhakrishna
AU - Duseja, Ajay K.
AU - Vargese, Joy
AU - Kumar Jain, Ajay
AU - Wadhawan, Manav
AU - Ranjan, Piyush
AU - Karanth, Dheeraj
AU - Ganesh, Panchapakesan
AU - Nijhawan, Sandeep
AU - Krishna Dhali, Gopal
AU - Adarsh, Channagiri K.
AU - Jhaveri, Ajay
AU - Nagral, Aabha
AU - Rao, Prasanna
AU - Shalimar,
N1 - Publisher Copyright:
© 2020 Indian National Association for Study of the Liver
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jceh.2020.11.002
DO - 10.1016/j.jceh.2020.11.002
M3 - Article
AN - SCOPUS:85097685602
SN - 0973-6883
VL - 11
SP - 288
EP - 298
JO - Journal of Clinical and Experimental Hepatology
JF - Journal of Clinical and Experimental Hepatology
IS - 3
ER -