Acute Liver Failure in a 64-Year-Old Man

Gregory Taylor, DO; Adam M. Vieder, DO

Disclosures

March 29, 2019

Discussion

The patient in this case reportedly ingested 50 tablets of hydrocodone/acetaminophen (10-325 mg; 16.2 g of acetaminophen) approximately 6 hours before arrival at the initial outside hospital. Acetaminophen overdose accounts for approximately 50% of overdose-related liver failure cases and as many as 20% of all liver transplants, and acetaminophen is one of the most common pharmaceutical agents to cause drug-induced liver injury.[1]

Acetaminophen is considered the most widely utilized antipyretic and analgesic in the United States. The US Food and Drug Administration (FDA) advertises that up to 4000 mg of acetaminophen within a 24-hour period is safe, without toxic effects.[1] Toxic ingestions that result in liver failure usually exceed 150 mg/kg as a single dose. The patient in this case ingested beyond this toxic dose. Various risk prediction tools, including a paracetamol-aminotransferase multiplication product, are available to help identify patients who are likely to develop hepatotoxicity.[2]

Acetaminophen metabolism involves conjugation pathways to nontoxic metabolites, using a process called sulfation and glucuronidation, in addition to the cytochrome P450 CYP2E1 through the liver, forming a potentially toxic metabolite called NAPQ1. The body uses glutathione to convert NAPQ1 into nontoxic metabolites. However, with significant overdoses, the regular metabolic pathways are overwhelmed, glutathione stores are depleted, and NAPQ1 accumulates. The result is necrosis of the hepatocytes and fulminant liver failure.[3] Many patients may present with nonspecific symptoms (malaise, fatigue, abdominal pain, nausea/vomiting) similar to those of a viral syndrome at first.[1]

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