Hepatitis C virus may have an entero-hepatic cycle which could be blocked with ezetimibe

Abstract Hepatitis C virus can lead to chronic infection, cirrhosis and hepatocellular carcinoma. With more than 170 million people infected worldwide, eradication remains a challenge even with the revolutionary current direct antiviral agents (DAAs). The risk of resistance, the safety profile in some populations, the genotype specificity and the high price of current DAAs explain why there is still interest in developing host targeting agents (HTA) that may help overcome some of these difficulties. Specifically, targeting the entry of HCV to the cell seems like a promising strategy. Recently it has been shown that the cholesterol transporter NPC1L1, a protein located in the small bowel epithelium and in the canalicular membrane of the hepatocyte is also an HCV receptor. Just as this protein is key in the entero-hepatic cycle of cholesterol, we hypothesize that there is an entero-hepatic cycle of HCV that could be disrupted by blocking NPC1L1 with ezetimibe, an already approved and readily available safe drug. Ezetimibe, either alone or in combination with DAAs, could decrease relapse rates, reduce resistance and even make treatments cheaper.