Faculty Bibliography

Standard therapy with pegylated interferon and ribavirin for chronic hepatitis C is effective in 40% to 50% of individuals with genotype 1 hepatitis C virus (HCV) infection and is associated with significant treatment-related toxicities. Newly developed small molecules that target key enzymes essential for HCV replication are in development. Telaprevir, a peptidomimetic inhibitor of the HCV NS3/4A protease, has shown great promise in early trials and is currently in advanced stages of clinical development. In treatment-naive patients and those with previous treatment failure, the addition of telaprevir to standard interferon and ribavirin therapy is well tolerated and enhances rates of sustained virologic response while shortening the treatment duration. In this report, the current experience using telaprevir to treat chronic HCV infection as monotherapy and in combination with other agents is reviewed.

BACKGROUND: CXCR3-associated chemokines CXCL9-CXCL11 promote histologic progression in chronic hepatitis C virus (HCV) infection, as indicated by elevated intrahepatic levels of messenger RNA in patients with advanced inflammation and fibrosis. We evaluated the potential of peripheral chemokine levels to discriminate among patients with chronic HCV infection who had different stages of fibrosis. METHODS: Peripheral levels of CXCR3-associated chemokines were measured by enzyme-linked immunosorbent assay of plasma samples obtained from 93 patients with chronic HCV infection. Of the subjects, 79 (85%) were white, and 68 (73%) were infected with HCV genotype 1. RESULTS: Expression of all 3 chemokines, when analyzed as a group, was significantly associated with intrahepatic inflammation and fibrosis. Plasma levels of CXCL10 were significantly elevated in patients with advanced fibrosis, whereas CXCL9 levels were significantly elevated in patients with advanced inflammation. By proportional odds multivariate modeling, we observed an association between fibrosis and CXCL10 (P< .002) as well as between fibrosis and inflammation (P<.001). Of the individual parameters, the CXCL10 level was most useful in identifying patients with more-severe (stage 3-4) fibrosis. Discriminatory ability was improved by the combination of CXCL10 and CXCL9. CONCLUSIONS: The strong association between CXCR3-associated chemokines and fibrosis suggests that they may have promise as noninvasive markers of hepatic fibrosis in a predominantly white HCV genotype 1-infected population