Effect of atorvastatin and diet on non-alcoholic fatty liver disease activity score in hyperlipidemic chickens

Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), which includes from simple steatosis and steatohepatitis, to the most severe cirrhosis and carcinoma, which develops in the absence of excessive alcohol intake. NAFLD is the most common liver disorder in affluent societies. There is no proven treatment for NAFLD/NASH. One of the most frequent adverse effects of statins is an increase in hepatic aminotransferases. Studies that evaluate if the benefits of statins overcome the risks in NASH are lacking. The present study was conceived to explore the effect of both atorvastatin and diet on regression of steatohepatitis, using a chicken experimental model induced by a hyperlipidemic diet (HD). Plasma lipid levels, liver enzymes and hepatic histopathology, as well as image analysis were performed to determine changes in liver lipid deposits and inflammatory infiltration. Features of steatosis, cell-ballooning, and inflammation were scored to obtain the NAFLD activity score (NAS). A severe level of steatosis was found in animals fed on HD. Atorvastatin treated groups showed smaller size of lipid deposits and a lower level of inflammation than non-treated groups. Atorvastatin therapy induced a significant reduction of hepatocellular damage, even though in the animals which continuously received a hyperlipidemic diet. The combination of atorvastatin therapy and a standard diet produced the lowest decrease of NAS. Our results show that atorvastatin therapy not only decreased plasmatic levels of cholesterol and triglycerides, but also induced a reduction of liver steatosis, inflammation and hepatocellular damage, without increasing plasmatic amynotransferase levels.