Impact of Duration of N-Acetylcysteine in Non-Acetaminophen–Induced Acute Liver Failure

Bass, Stephanie; Lumpkin, Mollie; Mireles-Cabodevila, Eduardo; Lindenmeyer, Christina C.; Dolan, Bridget; Pickett, Caleigh; Kapoor, Aanchal

doi:10.1097/cce.0000000000000411

Cited by 2 publications

(3 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the primary literature captured in these reviews, a 2021 retrospective analysis found improved transplant-free survival and reduced all-cause mortality with extended NAC treatment compared to 72 hours ( 66 ). Another retrospective analysis of pediatric data included 61 patients with non-acetaminophen induced liver injury etiologies were treated with NAC compared with 44 patients not receiving NAC; this analysis did not find significant differences in liver function values between the two groups ( 64 ).…”

Section: Resultsmentioning

confidence: 99%

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

Jerome,

Zahn,

Abner

et al. 2024

Transl Gastroenterol Hepatol

View full text Add to dashboard Cite

Background The World Health Organization (WHO)’s Essential Medicines List (EML) plays an important role in advocating for access to key treatments for conditions affecting people in all geographic settings. We applied our established drug repurposing methods to one EML agent, N-acetylcysteine (NAC), to identify additional uses of relevance to the global health community beyond its existing EML indication (acetaminophen toxicity). Methods We undertook a phenome-wide association study (PheWAS) of a variant in the glutathione synthetase ( GSS ) gene in approximately 35,000 patients to explore novel indications for use of NAC, which targets glutathione. We then evaluated the evidence regarding biologic plausibility, efficacy, and safety of NAC use in the new phenotype candidates. Results PheWAS of GSS variant R418Q revealed increased risk of several phenotypes related to non-acetaminophen induced acute liver failure (ALF), indicating that NAC may represent a therapeutic option for treating this condition. Evidence review identified practice guidelines, systematic reviews, clinical trials, retrospective cohorts and case series, and case reports. This evidence suggesting benefit of NAC use in this subset of ALF patients. The safety profile of NAC in this literature was also concordant with existing evidence on safety of this agent in acetaminophen-induced ALF. Conclusions This body of literature indicates efficacy and safety of NAC in non-acetaminophen induced ALF. Given the presence of NAC on the EML, this medication is likely to be available across a range of resource settings; promulgating its use in this novel subset of ALF can provide healthcare professionals and patients with a valuable and safe complement to supportive care for this disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

Jerome,

Zahn,

Abner

et al. 2024

Transl Gastroenterol Hepatol

View full text Add to dashboard Cite

show abstract

“…The clinical trials were double-blinded ( Lee et al, 2009 ; Moosa et al, 2021 ) or unknown blinded ( Nabi et al, 2017 ), and all of them were placebo-controlled ( Lee et al, 2009 ; Nabi et al, 2017 ; Moosa et al, 2021 ). In the majority of studies, the cohorts were formed by patients with ALF from a variety of different causes ( Lee et al, 2009 ; Mumtaz et al, 2009 ; Darweesh et al, 2017 ; Nabi et al, 2017 ; Bass et al, 2021 ), except for two studies conducted by Moosa et al (2021) and Borlak et al (2018) , in which the overall cohort was formed by DILI patients. In the RCTs, the total number of patients with non-acetaminophen-induced ALF (NAI-ALF) was 350, of whom 162 were DILI patients.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, Bass et al (2021) evaluated two dosing regimens of NAC intravenously in the management of NAI-ALF in an observational study. The standard duration of NAC was considered 72 h, whereas extended duration was defined as continuation beyond 72 h. In total, 53 patients were included retrospectively: 40 in the standard duration group and 13 in the extended duration group.…”

Section: Resultsmentioning

confidence: 99%

N-Acetylcysteine for the Management of Non-Acetaminophen Drug-Induced Liver Injury in Adults: A Systematic Review

et al. 2022

View full text Add to dashboard Cite

Introduction: Idiosyncratic drug-induced liver injury (DILI) is a rare adverse reaction to drugs and other xenobiotics. DILI has different grades of severity and may lead to acute liver failure (ALF), for which there is no effective therapy. N-acetylcysteine (NAC) has been occasionally tested for the treatment of non-acetaminophen drug-induced ALF. However, limited evidence for its efficacy and safety is currently available. Our aim was to elucidate the benefit and safety of NAC in DILI and evaluate its hepatoprotective effect.Methods: We conducted a systematic review to evaluate the management and prevention focused on NAC in idiosyncratic DILI. The main outcomes included mortality due to DILI, time to normalization of liver biochemistry, transplant-free survival, and adverse events. We included clinical trials and observational studies, either prospective or retrospective.Results: A total of 11 studies were included after literature screening. All studies had different methodologies, and some of them had important risk of bias that may lead to interpreting their findings with caution. The majority of the studies proved NAC efficacy in a cohort of patients with ALF due to different etiologies, where DILI represented a subgroup. NAC seemed to improve transplant-free survival; however, its benefit was inconclusive in terms of overall survival. With regard to safety, NAC showed an adequate safety profile. In prevention studies, NAC showed a possible hepatoprotective effect; however, this finding is limited by the lack of studies and presence of bias.Conclusion: NAC treatment seems to have some benefit in non-acetaminophen drug-induced liver failure patients with acceptable safety; however, due to the lack of evidence and limitations detected across studies, its benefit must be corroborated in clinical trials with adequate methodology.

show abstract

Impact of Duration of N-Acetylcysteine in Non-Acetaminophen–Induced Acute Liver Failure

Abstract: Supplemental Digital Content is available in the text.

Cited by 2 publications

References 13 publications

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

N-Acetylcysteine for the Management of Non-Acetaminophen Drug-Induced Liver Injury in Adults: A Systematic Review

Contact Info

Product

Resources

About