Early changes in Hepatitis C Virus (HCV) RNA levels predict response to interferon treatment in noncirrhotic HCV patients

Abstract

The role of hepatitis C virus (HCV) RNA quantification in determining ideal interferon (IFN) treatment of noncirrhotic HCV liver disease is uncertain. The specific aim of this study was to determine whether measurement of baseline HCV RNA or changes in HCV RNA levels (ΔHCV RNA) early during therapy predict response to IFNa in noncirrhotic HCV patients. PATIENTS AND METHODS: Twenty-one noncirrhotic patients with chronic HCV were treated with 3 MU IFNα-Za three times per week. HCV RNA levels were determined at baseline and after two, four, six, eight and 12 weeks of treatment. Baseline HCV RNA and ΔHCV RNA during therapy were compared with treatment response results at six months. Data were expressed as mean ± SE, and differences were assessed using Student's t test. RESULTS: Twenty-one patients initiated IFNα therapy. Two patients were noncompliant and lost to follow-up. One patient discontinued IFNα due to side effects. Apart from age, where responders tended to be younger than nonresponders, the baseline clinical characteristics and alanine aminotransferase (ALT), aspartate aminotransferase, bilirubin and HCV RNA levels did not differ between IFNα responders and nonresponders. Levels of HCV RNA were significantly lower after both two and four weeks of therapy in IFNa responders compared with nonresponders (P<0.001). Changes in log HCV RNA levels after both two and four weeks of therapy were significantly greater in IFNα responders compared with nonresponders (P<0.001). Changes in log HCV RNA of more than 1.0 after two weeks of IFNα therapy identified all six-month responders, with a sensitivity of 100% and a specificity of 89%. Potential financial impact of these findings on patients' management was also calculated. Decisions regarding discontinuation of therapy based on early changes in HCV RNA levels would result in a 40% to 50% reduction in IFNα cost. CONCLUSIONS: In noncirrhotic HCV patients, the change in quantitative HCV RNA after the first two weeks of IFNα therapy identifies responders. This finding would result in a 40% to 50% cost savings if decisions about continuing IFNα were based on early changes in HCV RNA levels rather than ALT or HCV RNA assessment after the completion of three months of IFNα treatment.