Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure

Lee, William M.; Hynan, Linda S.; Rossaro, Lorenzo; Fontana, Robert J.; Stravitz, R. Todd; Larson, Anne M.; Davern, Timothy J.; Murray, Natalie; McCashland, Timothy M.; Reisch, Joan; Robuck, Patricia R.

doi:10.1053/j.gastro.2009.06.006

Cited by 601 publications

(447 citation statements)

References 27 publications

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“…102 Nacetylcysteine has been extensively evaluated in paracetamol induced ALF and a recent report has demonstrated its utility although not unequivocally, in non-paracetamol druginduced ALF, particularly in early grade encephalopathy. 100 In another recent series in subjects older than 70 years, NAC showed minimal to no elevation in liver transaminases in patients exposed to TB drugs and simultaneously given oral NAC. 101 Further studies are needed to test its generalizability.…”

Section: Management Of Patients With Drug-induced Liver Injurymentioning

confidence: 92%

“…Results of transplantation are similar to those of other acute liver failure. 100 Once the liver function tests return to normal which usually occurs in days or weeks, considerations may be given for substituting the implicated drug with an alternative drug, particularly in those with immune-allergic DILI. With the widespread availability of newer antiepileptic drugs with good safety profile, there will be a declining use of the older drugs such as phenytoin, carbamazepine and phenobarbitone.…”

Section: Management Of Patients With Drug-induced Liver Injurymentioning

confidence: 99%

“…[100][101][102] Silymarin alone or silymarin combination with benzylpenicillin has been used in mushroom (Amanita phalloides) toxicity although there is no clear evidence about its efficacy. 102 Nacetylcysteine has been extensively evaluated in paracetamol induced ALF and a recent report has demonstrated its utility although not unequivocally, in non-paracetamol druginduced ALF, particularly in early grade encephalopathy.…”

Section: Management Of Patients With Drug-induced Liver Injurymentioning

confidence: 99%

See 2 more Smart Citations

An Update on Drug-induced Liver Injury

Devarbhavi

2012

Journal of Clinical and Experimental Hepatology

143

101

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Section: Management Of Patients With Drug-induced Liver Injurymentioning

confidence: 92%

Section: Management Of Patients With Drug-induced Liver Injurymentioning

confidence: 99%

Section: Management Of Patients With Drug-induced Liver Injurymentioning

confidence: 99%

See 1 more Smart Citation

An Update on Drug-induced Liver Injury

Devarbhavi

2012

Journal of Clinical and Experimental Hepatology

143

101

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“…Although most idiosyncratic DILIs improve after drug withdrawal, failure to recover after severe liver injury (DILI‐ALF) is unlikely 1. N‐acetyl cysteine has been shown to improve transplant‐free survival in adults with DILI‐ALF 22. However, the results are contradictory in the pediatric population23 and equivocal in a prospective cohort study 24.…”

Section: Discussionmentioning

confidence: 99%

Drug idiosyncrasy due to pirfenidone presenting as acute liver failure: Case report and mini‐review of the literature

Verma

Kumar

Mitra

et al. 2017

Hepatology Communications

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Idiosyncratic drug‐induced liver injury (DILI) is ranked among the top most common etiologies of acute liver failure (ALF). It carries poor transplant‐free survival. Pirfenidone is an anti‐inflammatory and antifibrotic drug that is commonly used for the treatment of idiopathic pulmonary fibrosis (IPF). Hepatotoxicity due to pirfenidone is rare and generally manifests as a mild rise in serum aminotransferases. In this mini‐review, we report an unusual case of idiosyncratic DILI due to pirfenidone presenting as ALF, with emphasis on the definition, classification, diagnostic criteria, histopathology, molecular markers, and treatment options for DILI and related ALF. A 77‐year‐old man with known Parkinson's disease and IPF presented with jaundice for 7 days and altered mental status for 4 days. His long‐term medications included a levodopa/carbidopa combination with a recent addition of pirfenidone over the previous 1 month; there was no monitoring of liver function tests. The evaluation suggested features of acute liver failure with grade III hepatic encephalopathy, acute kidney injury, and metabolic acidosis. The diagnostic workup ruled out viral, toxic, ischemic, and other etiologies for acute liver failure. Based on a Roussel Uclaf Causality Assessment Method score of 7 and possible DILI‐ALF, pirfenidone was withdrawn. He was evaluated for liver transplantation but was declined. Despite all supportive measures in intensive care, organ failure progressed and he succumbed to the illness on day 4. Postmortem liver biopsy revealed findings consistent with DILI (final Roussel Uclaf Causality Assessment score, 10). Conclusion: DILI‐ALF carries poor prognosis, and liver transplantation should be considered early in the course. Characterization, reporting, monitoring, and labeling of pirfenidone‐related hepatotoxicity is vital given its common use in IPF. (Hepatology Communications 2018;2:142–147)

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“…N‐Acetylcysteine (NAC), the proven antidote for APAP overdose, may also be considered in adults with early stage ALF, given its good safety profile and some evidence for its efficacy in early coma‐stage patients 30. For those with an etiology of DILI within the NAC trial,31 transplant‐free survival was 58% for those who received NAC versus 27% for those who did not receive NAC. However, the use of NAC in children with non‐APAP ALF demonstrated a lower rate of survival at 1 year; therefore, NAC is not recommended for children with severe iDILI leading to ALF 32.…”

Section: Management Of Idilimentioning

confidence: 99%

Idiosyncratic drug‐induced liver injury: A short review

Yamashita

Imai

Mima

et al. 2017

Hepatology Communications

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Idiosyncratic drug‐induced liver injury (iDILI) is a rare adverse drug reaction that occasionally leads to acute liver failure or even death. An aging population that uses more drugs, a constant influx of newly developed drugs, and a growing risk from herbal and dietary supplements of uncertain quality can lead to an increase in iDILI. Antimicrobials, central nervous system agents, and herbal and dietary supplements are the most common causes of iDILI in developed countries. iDILI is still a diagnosis of exclusion, and thus careful history taking and thorough work‐ups for competing etiologies, such as acute viral hepatitis, autoimmune hepatitis, and others, are essential. The pathogenesis of iDILI is not clear and includes a mix of host reactions, drug metabolites, and environmental factors. Immediate cessation of the suspected offending drug is key to preventing or minimizing progressive damage. No definitive therapies for iDILI are available, and the treatments remain largely supportive. (Hepatology Communications 2017;1:494–500)

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Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure

Abstract: Background-N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen related acute liver failure.

Cited by 601 publications

References 27 publications

An Update on Drug-induced Liver Injury

An Update on Drug-induced Liver Injury

Drug idiosyncrasy due to pirfenidone presenting as acute liver failure: Case report and mini‐review of the literature

Idiosyncratic drug‐induced liver injury: A short review

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