Hepatology International

, Volume 3, Issue 4, pp 563–570 | Cite as

Role of N-acetylcysteine in adults with non-acetaminophen-induced acute liver failure in a center without the facility of liver transplantation

  • Khalid Mumtaz
  • Zahid Azam
  • Saeed Hamid
  • Shahab Abid
  • Sadik Memon
  • Hasnain Ali Shah
  • Wasim Jafri
Original Article

Abstract

Purpose

We aimed to study the role of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF).

Methods

A total of 47 adult patients were prospectively enrolled with NAI-ALF (group 1 or NAC group) and oral NAC was given. The primary outcome was reduction in mortality with the use of NAC in NAI-ALF. The secondary outcomes were to evaluate safety of NAC and to assess factors predicting mortality. We compared these results with records of NAI-ALF patients admitted in our hospital from 2000 to 2003 (n = 44) who were not given NAC (group 2 or historical controls).

Results

The two groups were comparable for the etiology of ALF, prothrombin time (PT), alanine aminotransferase, creatinine, albumin, etc. The mean age in group 1 was 27.7 ± 11.8 years and in group 2 37.5 ± 18.8 years (P = 0.004). Bilirubin was 20.63 ± 11.03 and 14.36 ± 8.90 mg/dl in groups 1 and 2, respectively (P = 0.004). There were 8 (17%) and 1 (2.3%) pregnant ALF women with acute hepatitis E virus (HEV) infection in groups 1 and 2, respectively (P = 0.031). All patients were given supportive care, including mechanical ventilation. A total of 34 (37.36%) patients survived; 22 (47%) in group 1 (NAC group) and 12 (27%) in group 2 (controls) (P = 0.05). On multivariable regression analysis, patients not given NAC (odds ratio [OR] = 10.3, 95% confidence interval [CI] = 1.6–65.7), along with age older than 40 years (OR = 10.3, 95% CI = 2.0–52.5), PT more than 50 s (OR = 15.4, 95% CI = 3.8–62.2), patients requiring mechanical ventilation (OR = 20.1, 95% CI = 3.1–130.2), and interval between jaundice and hepatic encephalopathy (OR = 5.0, 95% CI = 1.3–19.1) were independent predictors of mortality.

Conclusions

The use of NAC causes reduction in NAI-ALF mortality and its use was safe.

Keywords

Liver failure Acute Mortality Acetylcysteine Prospective/retrospective studies Viral Survival rate 

References

  1. 1.
    O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993;342(8866):273–275CrossRefPubMedGoogle Scholar
  2. 2.
    O’Grady JG, Williams R. Classification of acute liver failure. Lancet 1993;342(8873):743CrossRefPubMedGoogle Scholar
  3. 3.
    Smilkstein MJ, Bronstein AC, Linden C, Augenstein WL, Kulig KW, Rumack BH. Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol. Ann Emerg Med 1991;20(10):1058–1063CrossRefPubMedGoogle Scholar
  4. 4.
    Burgunder JM, Varriale A, Lauterburg BH. Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration. Eur J Clin Pharmacol 1989;36(2):127–131CrossRefPubMedGoogle Scholar
  5. 5.
    Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci 2003;60(1):6–20CrossRefPubMedGoogle Scholar
  6. 6.
    Harrison P, Wendon J, Williams R. Evidence of increased guanylate cyclase activation by acetylcysteine in fulminant hepatic failure. Hepatology 1996;23(5):1067–1072CrossRefPubMedGoogle Scholar
  7. 7.
    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):1852–1857PubMedCrossRefGoogle Scholar
  8. 8.
    Ytrebo LM, Korvald C, Nedredal GI, Elvenes OP, Nielsen Grymyr OJ, Revhaug A. N-Acetylcysteine increases cerebral perfusion pressure in pigs with fulminant hepatic failure. Crit Care Med 2001;29(10):1989–1995CrossRefPubMedGoogle Scholar
  9. 9.
    Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 1988;319(24):1557–1562PubMedGoogle Scholar
  10. 10.
    Harrison PM, Keays R, Bray GP, Alexander GJ, Williams R. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet 1990;335(8705):1572–1573CrossRefPubMedGoogle Scholar
  11. 11.
    Ben-Ari Z, Vaknin H, Tur-Kaspa R. N-Acetylcysteine in acute hepatic failure (non-paracetamol-induced). Hepatogastroenterology 2000;47(33):786–789PubMedGoogle Scholar
  12. 12.
    Katoonizadeh A, Decaestecker J, Wilmer A, Aerts R, Verslype C, Vansteenbergen W, et al. MELD score to predict outcome in adult patients with non-acetaminophen-induced acute liver failure. Liver Int 2007;27(3):329–334CrossRefPubMedGoogle Scholar
  13. 13.
    Lee WM. Acute liver failure in the United States. Semin Liver Dis 2003;23(3):217–226CrossRefPubMedGoogle Scholar
  14. 14.
    Schiodt FV, Atillasoy E, Shakil AO, Schiff ER, Caldwell C, Kowdley KV, et al. Etiology and outcome for 295 patients with acute liver failure in the United States. Liver Transpl Surg 1999;5(1):29–34CrossRefPubMedGoogle Scholar
  15. 15.
    Escorsell A, Mas A, de la Mata M. Acute liver failure in Spain: analysis of 267 cases. Liver Transpl 2007;13(10):1389–1395CrossRefPubMedGoogle Scholar
  16. 16.
    Kortsalioudaki C, Taylor RM, Cheeseman P, Bansal S, Mieli-Vergani G, Dhawan A. Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-induced acute liver failure. Liver Transpl 2008;14(1):25–30CrossRefPubMedGoogle Scholar
  17. 17.
    Polson J, Lee WM. AASLD position paper: the management of acute liver failure. Hepatology 2005;41(5):1179–1197CrossRefPubMedGoogle Scholar
  18. 18.
    Jalan R, Olde Damink SW, Deutz NE, Hayes PC, Lee A. Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension. Gastroenterology 2004;127(5):1338–1346CrossRefPubMedGoogle Scholar
  19. 19.
    Khuroo MS, Kamili S. Aetiology and prognostic factors in acute liver failure in India. J Viral Hepat 2003;10(3):224–231CrossRefPubMedGoogle Scholar
  20. 20.
    Ellis A, Wendon J. Circulatory, respiratory, cerebral, and renal derangements in acute liver failure: pathophysiology and management. Semin Liver Dis 1996;16(4):379–388CrossRefPubMedGoogle Scholar
  21. 21.
    Hussaini SH, Skidmore SJ, Richardson P, Sherratt LM, Cooper BT, O’Grady JG. Severe hepatitis E infection during pregnancy. J Viral Hepat 1997;4(1):51–54CrossRefPubMedGoogle Scholar
  22. 22.
    O’Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989;97(2):439–445PubMedGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2009

Authors and Affiliations

  • Khalid Mumtaz
    • 1
  • Zahid Azam
    • 1
  • Saeed Hamid
    • 1
  • Shahab Abid
    • 1
  • Sadik Memon
    • 2
  • Hasnain Ali Shah
    • 1
  • Wasim Jafri
    • 1
  1. 1.Department of MedicineAga Khan University HospitalKarachiPakistan
  2. 2.Isra University HospitalHyderabadPakistan

Personalised recommendations