Infection by hepatitis C virus (HCV) affects more than 170 million people in the World and 80.000 in Chile. It causes more deaths than HIV infection in the US and is a leading cause for liver transplantation in Chile. Even though treatments are evolving with new direct antiviral agents (DAAs) that are increasing response rates, there are several issues with these new approaches, including increased toxicity, need for using interferon and ribavirin, complex algorithms of treatment, high cost, limited effectivity in certain groups (liver transplant patients) and drug interactions. Treatments targeted at host factors required for the viral cycle are becoming increasingly explored as an alternative or complement to DAAs. It has been recently described that Niemann-Pick C1-like 1 (NPC1L1), the intestinal receptor of cholesterol, serves as an entry factor for HCV. NPC1L1 is, therefore, a key transporter in the enterohepatic cycle of cholesterol. NPC1L1 can be blocked with ezetimibe, which is an approved and generally safe drug used for the management of hypercholesterolemia. Our hypothesis posits that blocking HCV entry to the hepatocyte or intestinal HCV reabsorption with ezetimibe may have an antiviral effect. In the study, we will administer ezetimibe 20 mg/d to 20 patients with stable chronic hepatitis C for 12 weeks and assess changes in HCV RNA and core antigen in plasma, bile and feces.

Inclusion criteria:

• Chronic hepatitis C defined as detectable HCV RNA for more than 6 months.
• Age > 18 years old.
• Compensated liver disease (bilirubin < 3mg/dL, unless having Gilbert´s syndrome, albumin > 3 g/dL, INR < 2, no hepatic encephalopathy, no ascites or recent -1 month- history of variceal bleeding).
• HCV RNA level > 10.000 IU/mL.
• Signed informed consent document.

Exclusion criteria:

• History of cholecystectomy or known gallstones.
• Current HCV antiviral treatment.
• Medications for dyslipidemia in the preceding 2 months.
• Abdominal surgery that could alter biliary or intestinal anatomy.
• Evidence of sitosterolemia.
• Negative pregnancy test in urine (for females).