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.

Comparative Study of Community Acquired and Nosocomial Spontaneous Bacterial Peritonitis and its Variants in 150 Patients.

BACKGROUND: Nosocomial acquisition of spontaneous bacterial peritonitis (SBP) is debated as having a different microbial etiology and prognosis. Identification of clinical, laboratory predictors of mortality and appropriate empirical antimicrobial selection is necessary to prevent early mortality and morbidity. We aimed to find the clinical and bacteriological profile in nosocomial and community acquired SBP and its variants, and the predictors of mortality. MATERIAL AND METHODS: One hundred and fifty patients with 162 discrete episodes of different types of SBP were analyzed. Relevant clinical and laboratory data were analyzed. SBP was diagnosed according to standard criteria and classified as community acquired if the infection detected within 48 h of admission and as nosocomial after 48 h of admission to the hospital. RESULTS: Eighty seven percent had community acquired SBP (CSBP), 13% had nosocomial SBP (NSBP). Patients of NSBP were older, had more episodes of GI bleed and higher previous episodes of encephalopathy. Patients who died were older, had worse encephalopathy. NSBP had higher one month mortality. Age, serum sodium, encephalopathy and NSBP predicted mortality. Culture positivity was 22.22%. Escherichia coli was the commonest organism isolated. There was no difference in the bacteriological profile between CSBP and NSBP. E. coli showed up to 48% resistance to third generation cephalosporins. Overall sensitivity to aminoglycosides was more than 75%. CONCLUSIONS: Overall mortality was 59%. NSBP had significantly high one month mortality. Age, serum sodium, encephalopathy and NSBP were predictors of mortality. Bacteriological profile was similar between CSBP and NSBP.

Drug-Induced liver injury with hypersensitivity features has a better outcome: a single-center experience of 39 children and adolescents.

UNLABELLED: Drug-induced liver injury (DILI) is rare in children and adolescents, and, consequently, data are remarkably limited. We analyzed the causes, clinical and biochemical features, natural history, and outcomes of children with DILI. Consecutive children with DILI from 1997 to 2004 (retrospective) and 2005 to 2010 (prospective) were studied based on standard criteria for DILI. Thirty-nine children constituted 8.7% of 450 cases of DILI. There were 22 boys and 17 girls. Median age was 16 years (range, 2.6-17). Combination antituberculous drugs were the most common cause (n = 22), followed by the anticonvulsants, phenytoin (n = 10) and carbamazepine (n = 6). All of the 16 children (41%) who developed hypersensitivity features, such as skin rashes, fever, lymphadenopathy, and/or eosinophilia, including the 3 with Stevens-Johnson syndrome, survived. Those with hypersensitivity presented earlier (24.5 versus 35 days; P = 0.24) had less severe disease (MELD, 16 versus 29; P = 0.01) and had no mortality (0/16 versus 12/23; P < 0.001), compared to those without hypersensitivity. The 12 fatalities were largely the result of antituberculous DILI (n = 11). The presence of encephalopathy and ascites were associated with mortality, along with hyperbilirubinemia, high international normalized ratio, and serum creatinine. According to the Roussel Uclaf Causality Assessment Method, 18 were highly probable, 14 probable, and 7 possible. Thirty-two children were hospitalized. CONCLUSION: DILI is not uncommon in children and accounts for 8.7% of all patients with DILI. Antituberculous drugs and anticonvulsants are the leading causes of DILI in India. Overall mortality is high (30.7%), largely accounted by antituberculous drugs. Children with DILI and hypersensitivity features present early, have less severe disease, and, consequently, a better prognosis, compared to those without, and are often associated with anticonvulsants or sulfonamides.

HIV/AIDS cholangiopathy: clinical spectrum, cholangiographic features and outcome in 30 patients.

BACKGROUND AND AIMS: AIDS cholangiopathy is presently considered rare and has been reported mainly from the West. With the HIV epidemic in India, we have encountered an increasing number of patients. We aimed to study these patients and determine differences from earlier experiences. METHODS: We describe the clinical presentation, cholangiographic features, and outcome and determine differences reported in Western literature. RESULTS: From Jan 1999 to May 2009, 30 patients (27 men) with AIDS cholangiopathy were seen. The most common mode of transmission was heterosexual (n = 28) followed by blood transfusion (n = 2). Abdominal pain (n = 20) of biliary origin, was the commonest manifestation followed by an asymptomatic group (n = 6) and a third group (n = 3) with pain due to pancreatitis. Ultrasonography of the abdomen was abnormal in all patients. Papillary stenosis (n = 23) was the most common cholangiographic feature followed by sclerosing cholangitis (n = 5). Abdominal pain resolved reliably and promptly after endoscopic sphincterotomy. Cholangiographic abnormalities regressed during follow up on antiretroviral therapy in 10 patients. Seven patients on anti retroviral therapy developed de novo cholangiopathy, with a precipitous drop in CD4 count of whom two had a worse prognosis. None had Kaposi's sarcoma. CONCLUSIONS: In contrast to Western literature, HIV cholangiopathy was seen predominantly in patients who acquired HIV by heterosexual transmission. De novo development of cholangiopathy on antiretroviral therapy may indicate the occurrence of resistance. Papillary stenosis is the most common feature. Abdominal pain resolved with sphincterotomy. Regression of cholangiographic abnormality occurred with anti retroviral medications. Median survival following cholangiopathy diagnosis was 34 months, higher than reported in previous studies.

Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality.

OBJECTIVES: Although drug-induced liver injury (DILI) is rare, it may result in significant morbidity or death. The causes and outcome vary according to regions, with acetaminophen and complementary medicines common in the West and the Far East, respectively. This study evaluates the causes, outcomes, predictors, and models for 90-day mortality from DILI from India. METHODS: Consecutive patients with DILI from 1997 to 2008 based on International Consensus Criteria from a medical college hospital setting were studied. RESULTS: Of the 313 patients, 58% were males. Leading causes were a combination of four anti-tuberculous drugs (ATDs) (58%), anti-epileptics (11%), olanzapine (5.4%), and dapsone (5.4%). The overall 90-day mortality of 17.3% was significantly higher for ATD hepatitis (21.5%) vs. those without (11.4%) (P=0.02). The highest mortality was for leflunomide (75%). Seventy-eight percent of patients received more than one drug. Fulminant hepatic failure developed more commonly in females than in males (23% vs. 17%). Of the 66% of cases with jaundice and/or icterus, mortality was 26%. Multivariable models for mortality using a combination of encephalopathy, ascites, and bilirubin, or a combination of albumin, prothrombin time, and white blood cell count yielded a C-statistic of at least 0.86 by recursive partitioning and 0.92 by logistic regression. Model for end stage liver disease (MELD) scores of 38 and 46 yield probabilities of death of 0.90 (confidence interval (CI): 0.71-0.97) and 0.99 (CI: 0.90-1.00), respectively. CONCLUSIONS: DILI results in significant overall mortality (17.3%). ATDs, anti-convulsants, sulphonamides, and olanzapine are the leading causes of DILI. Although common in males, more females developed fulminant hepatic failure. High-MELD score or a combination of ascites, encephalopathy, high bilirubin, prothrombin time, and leukocyte count are predictive of mortality.