Clinical Profile of Patients with Antituberculous Drug-induced Hepatotoxicity

Abstract

© 2011, INASL 42 Clinical Profile of Patients with Antituberculous Drug-induced Hepatotoxicity R Kavitha, TM Ramachandran, V Thomas Department of Gastroenterology, Medical College Calicut, Calicut, Kerala Aim: To assess the clinical profile of patients with antituberculous drug-induced hepatotoxicity in a tertiary care institution. Materials and Methods: From January 2009 to January 2011, details of 22 consecutive patients with suspected anti-TB drug-induced hepatotoxicity who were admitted in the gastroenterology department of Calicut Medical College were analyzed. The tests done were HBsAg, anti-HCV, IgM HAV, IgM HEV, LFT, ANA and USG abdomen. Results: Total number of cases: 22. Male to female ratio (9/13) = 0.69:1. Mean age 45.09 years (18–65). The indication for ATT was pulmonary tuberculosis 9, lymph node tuberculosis 2, GI tuberculosis 5, disseminated 1, and other sites in 6 cases. In 6 (27.27%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. Sixteen (72.72%) patients took treatment under DOTS and 6 (27.27%) patients took daily regimen. Five (22.72%) patients had cirrhosis. Transaminase elevation alone was seen in 4/22 (18.18%), acute on chronic liver failure in 5 (22.7%), fulminant failure in 4/22 (18.18%). None had any evidence of acute viral hepatitis. The median duration of ATT to hepatotoxicity was 80 (5–175) days; the median icterus encephalopathy interval was 8.6 (5–20) days. Sepsis and acute renal failure were documented in 6 (27.27%), and 5 (22.72%) patients respectively. The mortality rate among patients with ATT hepatotoxicity was 7 (31.8%), and rest recovered with medical treatment. The mean recovery time from ATT hepatotoxicity was 51 days. Slow rechallenge with rifampicin and INH was attempted in 6 patients and was successful. Three were given alternative regimen with second line drugs. All those who had underlying cirrhosis and acute kidney injury expired. Conclusion: Incidence of ATT-hepatotoxicity at our center in the past 2 years is rising with a high mortality rate. All those who had underlying cirrhosis and acute kidney injury expired. A proportion of patients had consumed ATT empirically. Increased physician awareness about complications is needed, and ATT should not be prescribed without objective evidence of tuberculosis. Conflict of Interest: None Drug Induced Liver Injury (DILI) with Hypersensitivity Features Has a Better Outcome—A Single Center Experience of 39 Children with DILI H Devarbhavi, D Karanth, KS Prasanna, CK Adarsh, M Patil, B Girisha Department of Gastroenterology, St John’s Medical College Hospital, Bangalore Background: Drug-induced liver injury (DILI) is rare in children and adolescents and consequently data is remarkably limited. We have one of the largest single center registries of DILI. Aims: We analyzed the causes, clinical and biochemical features, natural history and outcome of children with DILI. Methods: Consecutive children with DILI from 1997 to 2004 (retrospective) and 2005 to 2010 (prospective) were studied based on International Consensus Criteria. Results: Thirty-nine children constituted 8.7% of 450 cases of DILI. We excluded 10 children for other competing causes (hepatitis A = 3, B = 1, E = 1, others = 5). There were 22 boys and 17 girls. The median age was 16 years (range 2.6–17). Combination antituberculous (AT) drugs were the commonest cause (n = 22), followed by anticonvulsants phenytoin (n = 10) and carbamazepine (n = 6). Sixteen children (41%) developed hypersensitivity features such as skin rashes, fever, lymphadenopathy, and/or eosinophilia including 3 with Stevens Johnson Syndrome; all of them survived. Presentation in those with hypersensitivity was earlier (43 days vs. 93 days, p = 0.24), less severe (MELD 15 vs. 26, p = 0.01) and with no mortality (0/16 vs. 12/23, p < 0.001) compared to those without hypersensitivity. The 12 fatalities were largely due to AT DILI (n = 11). Presence of encephalopathy and ascites were associated with mortality along with hyperbilirubinemia, high INR (international normalized ratio) and serum creatinine. Chronicity was noted in 3 children. According to Roussel Uclaf Causality Assessment Method (RUCAM) 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. The overall mortality is high (30.7%), largely accounted by antituberculous drugs. DILI with hypersensitivity features present early, are less severe and have consequently a better prognosis compared to those without and are often associated with anticonvulsants or sulfonamides. Conflict of Interest: None 03_JCEH-Abstract.indd 42 3/18/2011 11:13:05 AM