The Role of Hepatic Steatosis in Acetaminophen Hepatotoxicity
A Manuyakorn, N Logan, D Gjertson, JC Hong, S French. Siriraj Hospital, Bangkok, Thailand; UCLA, Los Angeles
Background: Acetaminophen, is the leading cause of drug induced acute liver failure in the United States. There are some potential factors such as heavy alcohol use, antitubercular agents, antiepileptic medications, and malnutrition that may render the liver more susceptible to injury from acetaminophen. Nonalcoholic fatty liver disease (NAFLD) has been associated with elevated liver tests, fibrosis and cirrhosis. The histologic similarity between fatty liver due to metabolic syndrome and heavy alcohol use raises the possibility that patients with NAFLD may be more susceptible to acetaminophen toxicity. We sought to determine if there was an association between steatosis and extent of liver injury at the time of transplantation.
Design: Patients who underwent liver transplantation for liver failure secondary to acetaminophen toxicity between 1992 and 2008 were identified from the UCLA pathology database. Pathologic evaluation included extent of hepatocellular necrosis and extent of steatosis. The clinical records of the patients were reviewed for: body mass index, liver function tests (LFTs), acetaminophen levels, hepatotrophic viral serologies, history of diabetes, hypertension and heavy alcohol use. The hepatocellular necrosis and steatosis were compared by Fisher's exact test.
Results: 37 patients (27 female) with mean age of 34 years (range 17-57) were identified and grouped by extent of necrosis. The majority (81%) had submassive hepatic necrosis (necrosis beyond zone 3) whereas seven patients had necrosis limited to zone 3. There was no correlation between extent of steatosis and extent of necrosis (p value=0.65). 86% of the group with submassive necrosis and 70% with zone 3 necrosis had moderate to severe steatosis (>33%). There was no obvious difference in LFTs, acetaminophen level and the other clinical parameters listed in the designs.
Conclusions: Here we demonstrate that the majority of patients suffering from acetaminophen induced acute liver failure show moderate to severe steatosis at the time of transplantation. There is no correlation between extent of steatosis and extent of hepatic necrosis. Clinical parameters that would indicate metabolic syndrome also appear to be unrelated to the extent of necrosis. This study suggests that patient's with metabolic syndrome may not have increased sensitivity to acetaminophen toxicity as is seen with heavy alcohol use. Further studies with a larger number of patients may provide statistical significance to this observation.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 159, Tuesday Morning