1114 The Effect of Metabolic Syndrome on Acetaminophen-Induced Acute Liver Injury/Failure - Morbidity and Mortality: A Single Liver Transplant Center Experience

Abstract

INTRODUCTION: Acetaminophen (N-acetyl-p-aminophenol; APAP) toxicity is a major cause of acute liver injury in USA. Several risk factors could increase the risk and severity of APAP-induced acute liver injury/failure (APAP-ALI/ALF), including malnutrition, chronic hepatitis C, alcoholism, hepatic cytochrome P450-inducing medications, and pre-existing liver disease. Whether metabolic syndrome affects the risk or the severity of APAP-ALI/ALF has not been definitively confirmed. Clinical and animal studies show conflicting results. We aim to assess the effect of pre-existing metabolic syndrome on the natural history of APAP-ALI/ALF, including morbidity and mortality METHODS: This was a retrospective study performed at a tertiary care liver transplant center. A collective database of all patients with APAP-ALI/ALF from 2001-2012 was reviewed. Primary outcomes were 28-day mortality and the need for liver transplantation. Secondary outcomes were the degree of liver injury and elevation of biochemical markers RESULTS: A total of 327 patients were evaluated with APAP-ALI/ALF. A subset of 219 patients who had a recorded BMI in the medical record were included for analysis. There were 151 females and 68 males, with a mean age of 39.1 years old. Benzodiazepine or opioid co-ingestion occurred in 116 patients. A total of 60 patients were obese (BMI > 30 Kg/m2) with a mean BMI of 38.3 Kg/m2, and 21 were morbidly obese (BMI > 40 Kg/m2). 58 patients died (24 obese and 34 non-obese). Liver transplantation was performed in 4 out of the 7 patients who were listed. There was a statistically significant association between obesity and the 28-day mortality, OR 2.451 (95% CI 1.291-4.651) and P 0.005. No significant association was found between obesity and either listing for liver transplantation or liver transplantation (P 0.351 and 0.916 respectively). Maximum total bilirubin and INR were slightly higher in obese patients; however, this was not statistically significant (P 0.08 and 0.823, respectively). Pearson correlation showed a weak association between rising BMI and a higher maximum total bilirubin and INR, but this was not statistically significant (r 0.08, P 0.201 for total bilirubin and r 0.07, P 0.307 for INR) CONCLUSION: Our study demonstrates that obesity is associated with a higher mortality in patients with APAP-ALI/ALF. Preexisting hepatocyte lipid accumulation, CYP2E1 induction, reduced hepatic glutathione stores as well as mitochondrial dysfunction have been proposed as risk factors that may be contributing.