2351 NAC of All Trades: Use of N-acetylcysteine in Cocaine-Induced Acute Liver Failure

Abstract

INTRODUCTION: Among patients with acute liver failure (ALF), drug-induced liver injury (DILI) presents a challenging clinical syndrome with limited therapeutic options. N-acetylcysteine (NAC) is a mainstay of treatment in acetaminophen-induced ALF, acting as an antioxidant, a vasodilator and a glutathione precursor. However, it has been used with success in other toxic ingestions causing ALF, and its beneficial effects do not seem to be unique to acetaminophen-induced hepatotoxicity. We present a case of ALF after acute cocaine ingestion with rapid recovery after administration of IV NAC. CASE DESCRIPTION/METHODS: A 58 year-old-male with a past medical history of chronic hepatitis C without cirrhosis and polysubstance abuse presented with acute psychosis. On arrival he was tachycardic but hemodynamically stable, with psychomotor agitation and fear delusions. He endorsed recent heavy cocaine ingestion. Initial labs demonstrated acute kidney injury, rhabdomyolysis and mild transaminitis; AST 59, ALT 56. Toxicology workup was positive for cocaine with undetectable acetaminophen, ethanol and salicylate levels. The following day however, he developed fulminant hepatic failure, AST >7000, ALT 2,568 (Figure 1) with progressive coagulopathy, INR 2.14, albumin 2.9, platelets 120. Of note, despite chronic hepatitis C, there was no evidence of cirrhosis and preserved liver synthetic function at presentation, INR 1.10, albumin 4.7, platelets 254. Our patient was not a candidate for liver transplant (LT), and decision was made to initiate IV NAC therapy, 140 mg/kg bolus followed by 70 mg/kg daily. Transaminases rapidly normalized after only 3 days of therapy, and he was discharged in stable condition. DISCUSSION: ALF is a rare but challenging syndrome, for which LT is the only curative treatment available. NAC is well established as an antidote in acetaminophen ALF, yet its mechanisms are applicable to other forms of DILI as well. Cocaine hepatotoxicity has been reported in humans, and is well studied in animal models. Studies in mice suggest toxic metabolites play a critical role, much like acetaminophen ALF. These species deplete glutathione, decrease hepatic blood flow, generate reactive oxygen species and cause lipid peroxidation of membranes. We present a case of ALF secondary to cocaine ingestion in the setting of underlying chronic hepatitis C, with rapid recovery after fluid resuscitation and IV NAC. NAC therapy has minimal adverse effects, and may be lifesaving in patients with ALF who are not candidates for LT.