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Effect of N-Acetylcysteine on Mortality and Liver Transplantation Rate in Non-Acetaminophen-Induced Acute Liver Failure: A Multicenter Study

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Abstract

Introduction and Aim

Previous studies and systematic reviews have not provided conclusive evidence on the effect of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). We aimed to study the value of intravenous NAC in reducing liver transplantation and mortality in NAI-ALF.

Patients and Methods

In a prospective, multicenter, observational study, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were enrolled. NAC infusion (in empirical dose) was given as 150 mg/kg in 100 ml dextrose 5% over half an hour, then 70 mg/kg in 500 ml dextrose 5% over 4 h, then 70 mg/kg in 500 ml dextrose 5% over 16 h. Thereafter continuous infusion was administered over 24 h of 150 mg/kg in 500 ml dextrose 5% until up to two consecutive normal international normalized ratios (INRs) were obtained. Our endpoints were recovery, transplantation, or death. The primary outcome of the study was to assess reduction in mortality or liver transplantation. The secondary outcome was the evaluation of other clinical outcomes (length of ICU and hospital stays, organ system failure, and hepatic encephalopathy).

Results

The study included a total of 155 adults; the NAC group (n = 85) were given NAC between January 2011 to December 2013 and the control group (n = 70) were not given NAC and were included from files dating between 2010 and 2011. Both groups (before NAC) were comparable with regard to etiology, age, sex, smoking, presence of co-morbidities, encephalopathy, liver profile, and INR. The success rate (transplant-free survival) in the NAC group was 96.4%. While in the control group, 17 patients (23.3%) recovered and 53 (76.6%) did not recover, of these 37 (53.3%) had liver transplantation and 16 (23.3%) died (p < 0.01). The NAC group had significantly shorter hospital stays (p < 0.001), less encephalopathy (p = 0.02), and less bleeding (p < 0.01) than the control group. The control group reported a higher ICU admission (p = 0.01) rate and abnormal creatinine and electrolytes (p = 0.002, p < 0.01, respectively). Liver profile and INR (after NAC infusion) differed significantly between the two groups with regard to bilirubin (increased in controls, p = 0.02), AST and INR (decreased in NAC group, p < 0.001 for both), but the ALT decrease showed no statistical significance between the two groups.

Conclusions

When administered on admission, intravenous NAC caused a reduction in NAI-ALF mortality and need for transplantation. NAC decreased encephalopathy, hospital stay, ICU admission, and failure of other organs.

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Acknowledgements

The authors thank Prof. Dr. Wafaa Al-Akel who provided the statistics for this study.

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Authors and Affiliations

  1. Hepato-Gastroenterology and Tropical Medicine Department, Faculty of Medicine, Cairo University, 63 Abo Dawood El-Thahery St., Nasr City, Cairo, Egypt

    Samar K. Darweesh

  2. Anesthesiology and ICU Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Mona F. Ibrahim

  3. Internal Medicine and Hepatology Department, National Liver Institute, Menoufya University, Al Minufya, Shibin El Kom, Menoufya Governorate, Egypt

    Mahmoud A. El-Tahawy

Authors
  1. Samar K. Darweesh
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  2. Mona F. Ibrahim
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  3. Mahmoud A. El-Tahawy
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Correspondence to Samar K. Darweesh.

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This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

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The authors declare no conflicts of interest.

Ethical approval

All procedures in this study were in accordance with the 1964 Declaration of Helsinki (and its amendments), and the requirements of the ethics committee or institutional review board that approved the study.

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Written informed consent obtained from patients, parents, or care givers.

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Darweesh, S.K., Ibrahim, M.F. & El-Tahawy, M.A. Effect of N-Acetylcysteine on Mortality and Liver Transplantation Rate in Non-Acetaminophen-Induced Acute Liver Failure: A Multicenter Study. Clin Drug Investig 37, 473–482 (2017). https://doi.org/10.1007/s40261-017-0505-4

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  • DOI: https://doi.org/10.1007/s40261-017-0505-4

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