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

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: There were 128 cases of DIALF (14%) among 905 patients with DILI. Mean age was 38 years, 68 (53%) female and 21(16.4%) children <18 years. 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. CONCLUSIONS: 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.

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

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.

Virilizing ovarian steroid cell tumor in a 40 year old South Indian female: a case report.

Virilism is the masculinization and enhancement of male secondary sexual characteristics in females. The etiology is usually of adrenal or ovarian origin. Here we report a case of virilizing Leydig cell type, steroid cell tumor of the left ovary, in a 40 year old female who presented with clinical signs and symptoms of virilization: deepening of voice, hirsutism (Ferriman-Gallwey score 26), clitoromegaly, and androgenic alopecia. On further evaluation, laboratory investigations revealed hyperandrogenism in the male range. Basal testosterone values were elevated. Folicle Stimulating Hormone and Luteinising Hormone levels were within normal limits. Dexamethasone suppression test did not alter cortisol or testosterone levels. An ovarian mass was confirmed radiologically. Following a total abdominal hysterectomy with bilateral salpingoophorectomy, histopathological studies confirmed a left sided steroid-cell ovarian tumor, Leydig cell type (stage T(1)N(0)M(0)), which proved to the etiology of virilization in this patient. Post-operatively her serum testosterone levels declined with near-complete reversal of symptoms over time.