Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study

Abstract

Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen-induced ALF at 22 tertiary care centers in the United States. Detailed prospective data were gathered on 662 consecutive patients over a 6-year period fulfilling standard criteria for ALF (coagulopathy and encephalopathy), from which 275 (42%) were determined to result from acetaminophen liver injury. The annual percentage of acetaminophen-related ALF rose during the study from 28% in 1998 to 51% in 2003. Median dose ingested was 24 g (equivalent to 48 extra-strength tablets). Unintentional overdoses accounted for 131 (48%) cases, intentional (suicide attempts) 122 (44%), and 22 (8%) were of unknown intent. In the unintentional group, 38% took two or more acetaminophen preparations simultaneously, and 63% used narcotic-containing compounds. Eighty-one percent of unintentional patients reported taking acetaminophen and/or other analgesics for acute or chronic pain syndromes. Overall, 178 subjects (65%) survived, 74 (27%) died without transplantation, and 23 subjects (8%) underwent liver transplantation; 71% were alive at 3 weeks. Transplant-free survival rate and rate of liver transplantation were similar between intentional and unintentional groups. In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States. Susceptible patients have concomitant depression, chronic pain, alcohol or narcotic use, and/or take several preparations simultaneously. Education of patients, physicians, and pharmacies to limit high-risk use settings is recommended. (HEPATOLOGY 2005;42:1364-1372

Role of free radicals in liver diseases

“…However, an overdose can induce severe liver injury both in experimental animals and in humans [65]. In the past, researchers studying the toxic action mechanism of APAP focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI) to cellular proteins as the main cause of hepatic cell death [66].…”

An Update on Drug-induced Liver Injury

“…9 DILI is a leading cause of acute liver failure (ALF) in the Western world, with paracetamol being the commonest drug followed by antimicrobials. 12,13 In India antituberculosis drugs are the commonest cause of druginduced ALF in adults and children, [14][15][16] contributing to 5.7-22% of all cases of ALF. [14][15][16] Paradoxically, many could be preventable, as empirical treatment for tuberculosis in 43-60% drives most of the reasons for antituberculous ALF.…”

Risk of Unintentional Overdose with Non-Prescription Acetaminophen Products

“…[7][8][9][10] Acetaminophen overdose is the leading cause of acute liver failure. [11][12][13] In 2009, the FDA convened a panel to review the existing evidence and characterize the problem of acetaminophen overdose. The panel concluded that 1) limited evidence is available, 2) the majority of overdoses appear unintentional, and 3) OTC drug labeling is a likely root cause.…”