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Review Article| Volume 53, ISSUE 1, P26-34, January 2021

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

      Abstract

      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 α (PPARα) and coactivator peroxisome proliferator-activated receptor gamma coactivator 1-β (PGC-1β) 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.

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      • Selecting an optimal prognostic model for advanced hepatocellular carcinoma: Any new ideas?
        Digestive and Liver DiseaseVol. 53Issue 9
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          We read with great interest the paper “Comparison of prognostic models in advanced hepatocellular carcinoma patients undergoing sorafenib: A multicenter study”, which was recently published in Digestive and Liver Disease [1]. It is an elegant study with a large patient cohort comparing different staging systems for advanced hepatocellular carcinoma (HCC) from Italy. While this is an important issue for HCC patients receiving sorafenib, a few concerns in study design and data interpretation may deserve the authors’ attention.
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