Role of FXR in Hepatitis C Virus Replication

Study of the Role of the Biliary Salts Nuclear Receptor FXR in Hepatitis C Virus Replication

In vitro in the hepatitis C virus (HCV) replicon system, modulation of the biliary salts nuclear receptor FXR by either agonists or antagonists respectively increases or decreases the replication of HCV (J Hepatol, 2008, 48: 192-9). One antagonist of FXR is a vegetal sterol, guggulsterone, that is extracted from the Commiphora mukul tree and that has already been given safely to hyper cholesterolemic patients in a clinical trial (JAMA 2003, 290: 765-72). The aim of this trial is to test the effect of the FXR antagonist guggulsterone given orally, three times a day, on the viral load in 15 HCV genotype 1 chronically infected patients.

Inclusion Criteria:

• Male patients infected by HCV genotype 1, with anti-HCV antibodies, non responders to at least one first line of therapy
• Viral load > 1 x 105 UI/mL for more than 6 months and not treated for at least the last two months.
• METAVIR score < F4

Exclusion Criteria:

• Alcohol intake > 20 g/day
• Immuno - suppressive therapy
• Obesity BMI > 30, diabetes
• Dyslipidemia requiring specific therapy
• Liver cirrhosis or carcinoma
• HIV or HBV co-infections
• Other liver diseases
• Major organ failures
• Therapy with cytochrome P450 metabolized drugs