DOI: http://dx.doi.org/10.18203/2349-3259.ijct20193213

N-acetylcysteine treatment in viral-induced acute liver failure

Tauseef Nabi, Nadeema Rafiq

Abstract


Background: Acute liver failure (ALF) is characterized by acute derangement of liver function and carries high mortality. Viral hepatitis is still one of the main causes of ALF in the India as well in world. A prospective case control study was carried with the aim to determine the effect of N-acetylcysteine (NAC) on survival of viral-ALF patients.

Methods: 37 patients with a diagnosis of viral-ALF were included in the study. 18 patients received NAC infusion for 72 hrs whereas 19 patients in control group received placebo. The variables evaluated were demographic, biochemical, outcome and length of hospital stay.

Results: Out of 37 viral-ALF patients, acute HEV-induced ALF (48.6%) was most common followed by HBV (24.3%) and HAV (21.6%). The two groups were comparable for the various baseline characteristics (age, INR, bilirubin, ALT, creatinine, albumin, grade of encephalopathy, mean grade of coma etc.). Use of NAC was associated with a shorter length of hospital stay of survived patients (p=0.024). A total of 20 of 37 (54.1%) patients died with ALF complications; 7 (38.9%) patients belonged to NAC group and 13 (68.4%) patients to control group (p=0.079). HEV induced ALF showed significant improved in survival than Non HEV induced ALF with NAC administration (p=0.022).

Conclusions: HEV was the most frequently cause of viral-ALF. Overall survival was not improved by NAC. HEV induced ALF showed significant improved in survival than Non HEV induced ALF with NAC administration. NAC reduced duration of hospital stay.


Keywords


Acute liver failure, Viral-ALF, Hepatic encephalopathy, Hepatitis E virus, N-acetylcysteine

Full Text:

PDF

References


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. Hepatology. 1995;21(1):240–52.

Bower WA, Johns M, Margolis HS, Williams IT, Bell BP. Population-based surveillance for acute liver failure. Am J Gastroenterol. 2007;102:2459-63.

Rockville. Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; 2007.

Lee WM, Squires Jr RH, Nyberg SL, Doo E, Hoofnagle JH. Acute liver failure: summary of a workshop. Hepatology. 2008;47(4):1401-15.

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

Ostapowicz G, Fontana R J, Schiodt F V. 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.

Lee WM. Etiologies of acute liver failure. Semin Liver Dis. 2008;28(2):142-52.

Sugawara K, Nakayama N, Mochida S. Acute liver failure in Japan: definition, classification, and prediction of the outcome. J Gastroenterol. 2012;47(8):849-61.

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. Hepatology. 1996;23:1448-55.

Tibbs C, Williams R. Viral causes and management of acute liver failure. J Hepatol. 1995;22(Suppl.1):68-73.

Fagan EA, Williams R. Fulminant viral hepatitis. Br Med Bull. 1990; 46: 462-80.

Khuroo MS, Kamili S. Aetiology and prognostic factors in acute liver failure in India. J Viral Hepat. 2003; 10: 224–31.

Khuroo MS, Teli MR, Skidmore S, Sofi MA, Khuroo MI. Incidence and severity of viral hepatitis in pregnancy. Am J Med. 1981;70:252–5.

Yoshiba M, Dehara K, Inoue K, Okamoto H, Mayumi M. Contribution of hepatitis C virus to non-A, non-B fulminant hepatitis in Japan. Hepatology. 1994;19:829–35.

Farci P, Alter HJ, Shimoda A, Govindarajan S, Cheung LC, Melpolder JC, et al. Hepatitis C virus-associated fulminant hepatic failure. N Engl J Med. 1996;335:631–4.

Govindarajan S, Chin KP, Redeker AG, Peters RL. Fulminant B viral hepatitis: Role of delta agent. Gastroenterology. 1984;86:1417–20.

Peters DJ, Greene WH, Ruggiero F, McGarrity TJ. Herpes simplex-induced fulminant hepatitis in adults. Dig Dis Sci. 2000;45(12):2399-404.

Farr RW, Short S, Weissman D. Fulminant hepatitis during herpes simplex virus infection in apparently immunocompetent adults: Report of two cases and review of the literature. Clin Infect Dis. 1997;24:1191–4.

Mellinger JL, Rossaro L, Naugler WE, Nadig SN, Appelman H, Lee WM, et al. Epstein–Barr virus (EBV) related acute liver failure: a case series from the US Acute Liver Failure Study Group. Dig Dis Sci. 2014;59(7):1630-7.

Srivastava P. Acute Liver Failure: due to Epstein Barr Virus infection-A Case Report. J Hep. 2015;2:1.

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

Schiodt FV, Atillasoy E, Shakil AO, Schiff ER, Caldwell C, Kowdley KV. Etiology and outcome for 295 patients with acute liver failure in the United States. Liver Transpl Surg. 1999;5(1):29-34.

Polson J, Lee WM. American Association for the Study of Liver Disease. AASLD position paper: the management of acute liver failure. Hepatology. 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.

Lee WM, Hynan LS, Rossaro L Fontana RJ, Stravitz RT, Larson AM, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137:856–64.

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.

Cotgreave IA. N-acetylcysteine pharmacological considerations and experimental and clinical applications. Adv Pharmacol. 1997;38:205-27.

Kharazmi A, Nielsen H, Schiotz PO. N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism. Int J Immunopharmacol. 1988;10:39-46.

Harrison P, Wendon J, Williams R. Evidence of increased guanylate cyclase activation by acetylcysteine in fulminant hepatic failure. Hepatology. 1996;23(5):1067–72.

Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med. 1991;324(26):1852–7.

Rank N, Michel C, Haertel C. N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study. Crit Care Med. 2000;28:3799–807.

Bémeur C, Vaquero J, Desjardins P, Butterworth RF. N-acetylcysteine attenuates cerebral complications of non-acetaminophen-induced acute liver failure in mice: antioxidant and anti-inflammatory mechanisms. Metab Brain Dis. 2010;25(2):241-9.

Lee WM, Larson AM, Stravitz RT. AASLD Position Paper: The Management of Acute Liver Failure: Update 2011. http://www. aasld.org/practiceguidelines/ Documents/AcuteLiverFailureUpdate2011.pdf. Accessed Jan 2019.

European Association for the Study of the Liver. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017;66(5):1047-81.

Khuroo MS, Duermeyer W, Zargar SA, Ahanger MA, Shah MA. Acute sporadic hepatitis in India. Am J Epidemiology. 1983:118:360–4.

Ramalingaswami V, Purcell RH. Waterborne Non-A, non-B hepatitis. Lancet. 1988;1:571–3.

Das AK, Begum T, Kar P, Dutta A. Profile of Acute liver failure from North-east India and its differences from other parts of country. Eurosian Journal of Hepato-Gastroenterology. 2016;6(2):111–5.

Ben-Ari Z, Vaknin H, Tur-Kaspa R. N-acetylcysteine in acute hepatic failure (non-paracetamol-induced). Hepatogastroenterology. 2000;47(33):786–9.

Sklar GE, Subramaniam M. Acetylcysteine treatment for non–acetaminophen-induced acute liver failure. Annals of Pharmacotherapy. 2004;38(3):498-501.

Mumtaz K, Azam Z, Hamid S, Abid S, Memon S, Shah HA, et al. Role of N‑Acetylcysteine in adults with non‑acetaminophen‑induced acute liver failure in a center without the facility of liver transplantation. Hepatol Int. 2009;3:563‑70.