Increased risk of acute liver failure by pain killer drugs in NAFLD: Focus on nuclear receptors and their coactivators

Non-alcoholic fatty liver disease (NAFLD) is a global condition characterized by an accumulation of lipids in the hepatocytes. NAFLD ranges from simple steatosis, a reversible and relatively benign condition, to fibrosis with non-alcoholic steatohepatitis (NASH), potentially leading to cirrhosis and hepatocarcinoma. NAFLD can increase the susceptibility to severe liver injury with eventual acute liver failure induced by specific hepatotoxic drugs, including acetaminophen (APAP), which is commonly used as analgesic and antipyretic. Although several animal models have been used to clarify the predisposing role of hepatic steatosis to APAP intoxication, the exact mechanism is still not clear. Here, we shed a light into the association between NAFLD and APAP toxicity by examining the peculiar role of nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR alpha) and coactivator peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC-1 beta) in driving fatty acid metabolism, inflammation and mitochondria redox balance. The knowledge of the mechanism that exposes patients with NAFLD to higher risk of acute liver failure by pain killer drug is the first step to eventually claim for a reduction of the maximal diurnal dose of APAP for subjects with liver steatosis. (C) 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Automated summary

Non-alcoholic fatty liver disease (NAFLD) is a global condition characterized by the accumulation of lipids in hepatocytes, which can lead to cirrhosis and hepatocarcinoma. Research has shown that patients with NAFLD are at higher risk of acute liver injury induced by specific hepatotoxic drugs like acetaminophen, prompting further study to potentially reduce dosages of painkiller drugs for individuals with liver steatosis.