Drug-induced acute liver failure in children and adults: Results of a single-centre study of 128 patients.

Abstract

Drugs producing acute liver failure (ALF) are uncommon and vary geographically. Here we review the implicated drugs, clinical features, laboratory characteristics and outcome of patients with drug-induced ALF (DIALF). We analysed the predictors of mortality and their relationship with MELD, King's College criteria (KCC) and ALFSG prognostic index. We identified DIALF patients from our drug-induced liver injury (DILI) registry (1997-2017). RUCAM was used for case adjudication. Patients who fulfilled criteria for acute liver failure and drug-induced liver injury were included. Primary outcome measure was spontaneous survival or death. There were 128 cases of DIALF (14%) among 905 patients with DILI. Mean age was 38years, 68 (53%) female and 21(16.4%) children <18years. Combination anti-TB drugs (ATD) (n=92, 72.4%) accounted for a majority of DIALF. Others were anti-epileptic drugs (AED, n=11, 10%), dapsone (n=7, 5.5%), hormones (n=2), ferrous sulphate overdose (n=2), acetaminophen (APAP) (n=2), antiretroviral (n=2), CAM (N=2), chemotherapy agents (N=3), amoxicillin-clavulanic acid (n=2) and others (n=3). Forty-four patients (34%) recovered spontaneously and 84(66%) including 13 children (62%) died. Females, ascites, albumin, bilirubin, INR and MELD were significantly associated with mortality. Mortality was 79% for ATD and 100% for APAP and iron overdose. Area under ROC was 0.76 for MELD and ALFSG index and 0.51 for KCC. Fourteen percent of DILI resulted in DIALF. ATD, AED, dapsone and antiretroviral drugs are most common agents. Spontaneous survival was only 34% with an even higher mortality with ATD. Non-ATD and non-APAP drugs had a better survival (51%).INR and MELD predicted mortality.