Published: 2019-03-25

Clinical features, laboratory characteristics and outcome of patients with drug-induced acute liver failure

Tauseef Nabi, Nadeema Rafiq, Imran Jamil, Quratul Ain Arifa


Background: Acute liver failure (ALF) is a rare medical emergency. Its rapid progression and high mortality demand early diagnosis and expert management. Drug-induced ALF (DI-ALF) remains the uncommon cause of ALF in India. Clinical and etiological profile varies with geographical area and time. A prospective study of DI-ALF was carried with the aim to determine the clinical features, laboratory characteristics, outcome and hospital course.

Methods: A total of 15 patients with a diagnosis of DI-ALF were included in the study. The variables evaluated were demographic, signs and symptoms, biochemical parameters [bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), internal normalization ratio (INR) etc.], outcome and course during hospitalization.

Results: Out of 15 DI-ALF patients, 12 had Anti-tuberculosis therapy (ATT) induced ALF and 3 patients had ayurvedic induced ALF. Majority of the patients were females (73.3%) and middle-aged (42.60±14.30 years). Coma grade at the time of admission showed that majority of patients (66.8%) had grade I and II encephalopathy. Depending on the pattern of liver injury, hepatocellular pattern was most common (53.3%) followed by mixed and cholestatic pattern. 40% of patients died with DI-ALF complications of which ATT induced ALF contributed 41.7%. Mean AST was more increased as compared to ALT. Development of ascites (P = 0.030) and mannitol use (P = 0.025) was significantly more common in non survived group than survived group. Length of hospital stay was significantly more in non survived group than survived group (P = 0.009).

Conclusions: ATT was the class of drugs most frequently associated with DI-ALF. DI-ALF disproportionately affected middle-aged women. Most DILI ALF patients had hepatocellular injury pattern. 40% of patients died with DI-ALF complications. Development of ascites, mannitol use and length of hospital stay was significantly more in non survived group than survived group.


Acute Liver failure, Anti-tuberculosis therapy induced ALF, Drug-induced liver injury, Drug-induced ALF, Hepatic encephalopathy

Full Text:



Trey C, Davidson CS. The management of fulminant hepatic failure. Prog Liver Dis. 1970;3:282-98.

Hoofnagle JH, Carithers RL Jr, Shapiro C, Ascher N. Fulminant hepatic failure: summary of a workshop. Hepatol. 1995;21(1):240-52.

Ostapowicz G, Fontana RJ, Schiodt FV. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137:947-54.

Acharya SK, Dasarathy S, Kumer TL, Sushma S, Prasanna KS, Tandon A, et al. Fulminant hepatitis in tropical population: clinical course, cause, and early predictors of outcome. Hepatol. 1996;23:1448-55.

Kaplowitz N. Drug-induced liver injury. Clin Infect Dis. 2004;38(Suppl 2):44-8.

Bernal W, Wendon J. Acute liver failure. N Engl J Med. 2013;369:2525-34.

Lee WM. Acute liver failure in the United States. Semin Liver Dis. 2003;23:217-26.

Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterol. 2015;148(7):1340-52.

Reuben A, Koch DG, Lee WM. Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a US multicenter, prospective study. Hepatol. 2010;52:2065-76.

Andrade RJ, Lucena MI, Fernandez MC, Pelaez G, Pachkoria K, García-Ruiz E, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterol. 2005;129(2):512-21.

Bjornsson E, Olsson R. Suspected drug-induced liver fatalities reported to the WHO database. Dig Liver Dis. 2006;38:33-8.

Wai CT, Tan BH, Chan CL, Sutedja DS, Lee YM, Khor C, et al. Drug-induced liver injury at an Asian center: a prospective study. Liver Int. 2007;27:465-74.

Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006;354:731-39.

Woolf GM, Redeker AG. Treatment of fulminant hepatic failure with insulin and glucagon: a randomized, controlled trial. Dig Dis Sci. 1991;36:92-6.

Sinclair SB, Greig PD, Blendis LM, Abecassis M, Roberts EA, Phillips MJ, et al. Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E: a preliminary report. J Clin Invest. 1989;84:1063-9.

O’Grady JG, Gimson AE, O’Brien CJ, Pucknell A, Hughes RD, Williams R. Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterol. 1988;94(1):1186-92.

Redeker AG, Yamahiro HS. Controlled trial of exchange-transfusion therapy in fulminant hepatitis. Lancet. 1973;1:3-6.

Randomised trial of steroid therapy in acute liver failure. Report from the European Association for the Study of the Liver (EASL). Gut. 1979;20:620-3.

Karkhanis J, Verna EC, Chang MS, Stravitz RT, Schilsky M, Lee WM, et al. Steroid use in acute liver failure. Hepatol. 2014;59:612-21.

Polson J, Lee WM. American Association for the Study of Liver Disease. AASLD position paper: the management of acute liver failure. Hepatol. 2005;41:1179-97.

Nabi T, Nabi S, Rafiq N, Shah A. Role of N-acetylcysteine treatment in non-acetaminophen-induced acute liver failure: A prospective study. Saudi J Gastroenterol. 2017;23(3):169-75.

Chughlay MF, Kramer N, Spearman CW, Werfalli M, Cohen K. N‐acetylcysteine for non‐paracetamol drug‐induced liver injury: a systematic review. Br J Clin Pharmacol. 2016;81(6):1021-9.

Darweesh SK, Ibrahim MF, El-Tahawy MA. Effect of N-Acetylcysteine on mortality and liver transplantation rate in non-acetaminophen-induced acute liver failure: a multicenter study. Clin Drug Investig. 2017;37(5):473-82.

Danan G, Benichou C. Causality assessment of adverse reactions to drugs-I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol. 1993;46:1323-30.

Lee WM, Larson AM, Stravitz RT. AASLD Position Paper: The Management of Acute Liver Failure: Update, 2011. Available at: http://www. Accessed on January 2019.

Rolando N, Harvey F, Brahm J, Howard JP, Alexander G, Gimson A, et al. Prospective study of bacterial infections in acute liver failure: an analysis of fifty patients. Hepatol. 1990;11:49-53.

Bernal W, Lee WM, Wendon J, Larsen FS, Williams R. Acute liver failure: a curable disease by 2024? J Hepatol. 2015;62(Suppl 1):112-20.

Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl. 2004;10:1018-23.

Mindikoglu AL, Magder LS, Regev A. Outcome of liver transplantation for drug induced acute liver failure in the US. Analysis of the UNOS database. Liver Transpl. 2009;15:719-29.

Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol. 2010;105:2396-404.

Devarbhavi H. Acute liver failure induced by anti-infectious drugs: causes and management. Curr Hepatol Rep. 2017;16(4):276-85.

Devarbhavi H, Patil M, Reddy VV, Singh R, Joseph T, Ganga D. Drug-induced acute liver failure in children and adults: Results of a single-centre study of 128 patients. Liver Int. 2018;38(7):1322-9.

Kumar R, Bhatia V, Khanal S, Sreenivas V, Gupta SD, Panda SK, Acharya SK. Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome. Hepatology. 2010;51(5):1665-74.

Rathi C, Pipaliya N, Patel R, Ingle M, Phadke A, Sawant P. Drug induced liver injury at a tertiary hospital in India: etiology, clinical features and predictors of mortality. Ann Hepatol. 2017;16(3):442-50.

Andrade RJ, Lucena MI, Ferna´ndez MC, Kaplowitz N. Drug-induced liver disease. Chapter 1. In: Kaplowtiz N, DeLeve LD, editors. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare; 2007:1-11.

Spanish Group for the Study of Drug-Induced Liver Disease. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish Registry over a 10-year period. Gastroenterology; 2005;129:512-21.

Devarbhavi H, Dierkhising R, Kremers WK. Antituberculosis therapy drug-induced liver injury and acute liver failure. Hepatol. 2010;52(2):798-9.

O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet. 1993;342:273-5.

Tost JR, Vidal R, Caylà J, Diaz-Cabanela D, Jimenez A, Broquetas JM. Severe hepatotoxicity due to anti-tuberculosis drugs in Spain. Int J Tuberc Lung Dis. 2005;9:534-40.