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 in initial non-responders may increase the generally poor sustained response rates. Monitoring virological response is essential in this kind of individual patient based approach. Quantitative HCV RNA assays are increasingly used for this purpose. However, their additional value as compared to strictly qualitative HCV RNA assays should be evaluated before they are implemented as a routine measurement, since these assays are more expensive and time consuming than qualitative assays.


OBJECTIVE
Goals of this study were (1) to test the hypothesis that increasing interferon dose in initial non-responders results in permanent viral clearance in more patients and (2) evaluation of the predictive value of quantitative versus qualitative HCV RNA assays before and during treatment.


METHODS
63 patients were treated in a randomised controlled trial of escalating interferon dose. In the standard treatment group patients received 6 MU alpha-2a thrice weekly for 3 months followed by 3 MU thrice weekly for 3 months. In the experimental group interferon dose was escalated at 6 weeks to 9 MU if HCV RNA was still detectable at 4 weeks. Predictors of response were analyzed at various time points before and during treatment and the predictive value of quantitative HCV RNA measurements was compared to that of qualitative HCV RNA assays.


RESULTS
No significant difference in sustained response rate was found between 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 response. Viral load levels during treatment did not independently predict a sustained response.


CONCLUSIONS
While on treatment, qualitative HCV RNA assays should be used to monitor response.
Schinkel
J
J
Department of Medical Microbiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. c.j.schinkel@lumc.nl
Kroes
A C
AC
Wagtmans
M J
MJ
Lamers
C B
CB
van Hoek
B
B
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000032:analysis*; D011994:Recombinant Proteins; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins