• Discuss the potential for acetaminophen to cause drug-induced liver disease (LD)
• Describe common pathologic presentations of drug-induced LD
• List common clinical manifestations of drug-induced LD
• Describe a general approach to treatment of drug-induced LD

Donald H. Marks, MD, PhD
Director, Hepatitis Clinic
Pharmacy and Therapeutics Committee
Cooper Green Mercy Hospital

Clinical Assistant Professor
Division of General Internal Medicine
Department of Medicine
University of Alabama at Birmingham

Birmingham, Alabama

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Drug-induced liver disease (LD) is a relatively uncommon but severe cause of liver damage, and requires special consideration as a safety problem. There are approximately 2000 cases of acute liver failure each year in the U.S., and medications account for perhaps 25 - 50% of these. Thirty-nine percent are due to acetaminophen, and 13% are idiosyncratic reactions due to other medications. Drug-induced LD accounts for 2-5% of cases of patients hospitalized with jaundice, approximately 10% of all cases of acute hepatitis and up to a quarter of all cases of chronic hepatitis. Drug-induced LD has become the leading cause of acute liver failure among patients presenting for evaluation at liver transplant centers in the United States, and the leading single cause for having to remove approved drugs from the market.

In Part 1 of this two-part series, a variety of classification systems for drug-induced LD were presented, effects of medications on the liver were described, along with case-based discussions of factors that can affect susceptibility to liver disease. In the current module, we will further the discussion by presenting several cases, descriptions of possible pathologic presentations, common clinical presentations, and pathophysiologic mechanisms.

A previously healthy 2-year-old male has had a mild viral upper respiratory infection for the last 2 days, with rhinorrhea, no earache, a slight cough, no diarrhea, and a mild fever to 100.4 orally. His mother, a registered nurse, elects to give acetaminophen to her child, and she is absolutely certain that she is using the correct dose for age and weight, as listed on the labeling affixed to the bottle. The child persists in his viral symptoms, and over the next 1½ days becomes “fussy” and is not eating or drinking well. When he eats, he vomits the contents of his food within 30 minutes of ingestion. His mental and physical states continue to deteriorate over the next 24 hours, and he is taken to his family physician, who finds a rather listless child with slightly swollen and minimally tender abdomen especially in the right upper quadrant.