Monitoring response during a randomised controlled trial of escalating interferon dose for chronic hepatitis C infection: predictive value of quantitative and qualitative HCV RNA assays

Background: In chronic hepatitis C infection, raising the interferon dose i n initial non-responders may increase the generally poor sustained response rates. Monitoring virological response is essential in this kind of indivi dual patient based approach. Quantitative HCV RNA assays are increasingly u sed for this purpose. However, their additional value as compared to strict ly qualitative HCV RNA assays should be evaluated before they are implement ed as a routine measurement, since these assays are more expensive and time consuming than qualitative assays. Objectives: Goals of this study were (1 ) to test the hypothesis that increasing interferon dose in initial non-res ponders results in permanent viral clearance in more patients and (2) evalu ation of the predictive value of quantitative versus qualitative HCV RNA as says before and during: treatment. Study design: 63 patients were treated i n a randomised controlled trial of escalating interferon dose. In the stand ard treatment group patients received 6 MU alpha-2a thrice weekly for 3 mon ths followed by 3 MU thrice weekly for 3 months. In the experimental group interferon dose was escalated at 6 weeks to 9 MU if I-ICV RNA was still det ectable at 4 weeks. Predictors of response were analyzed at various time po ints before and during treatment and the predictive value of quantitative H CV RNA measurements was compared to that of qualitative HCV RNA assays. Res ults: No significant difference in sustained response rate was found betwee n the treatment groups at the end of follow-up. At baseline, the strongest independent predictor for a sustained response was a viral load level below 10(6) copies/ml and age younger than 40 years. During treatment a negative HCV RNA status at week 4 was the strongest predictor of a sustained respon se. Viral load levels during treatment did not independently predict a sust ained response. Conclusions: While on treatment, qualitative HCV RNA assays should be used to monitor response. (C) 2001 Elsevier Science B.V. All rig hts reserved.