Early prediction of response in interferon monotherapy and in interferon-ribavirin combination therapy for chronic hepatitis C: HCV RNA at 4 weeks versus ALT

Background/Aims: There is consensus that interferon for hepatitis C should be stopped if alanine aminotransferase (ALT) remains elevated after 12 week s; however, this may lead to unjust treatment withdrawal in around 20% of p otential sustained responders. No consensus exists for interferon-ribavirin combination therapy The aim of this study was to assess the predictive val ue of an HCV RNA test at 4 weeks in comparison with ALT, both in interferon monotherapy and in interferon-ribavirin combination therapy. Methods: Plasma HCV RNA was tested at 4 weeks in 149 naive patients undergo ing 6 months and 187 undergoing up to 12 months of interferon monotherapy, and in 40 non-responders treated for 6 months with interferon-ribavirin com bination therapy. Results: For 6 and up to 12 months of interferon monotherapy, the predictiv e value for non-response was 99% resp, 97% for a positive HCV RNA at week 4 , versus 97% resp, 91% for an elevated ALT at week 12, Using a positive HCV RNA at week 4 as a stopping rule would lead to missing 5% resp, 12% of pot ential sustained responders, versus 10% resp, 28% for an elevated ALT at we ek 12. In interferon-ribavirin combination therapy the predictive value for non-response was 100% for week 4 HCV RNA versus 95% for week 12 ALT, and 0 % potential sustained responders mere missed by a test for week 3 HCV RNA v ersus 20% for week 12 ALT, The overall sensitivity and specificity of a wee k 1 HCV RNA test,vas significantly better (area under ROC 0.85) as compared to testing ALT at week 4 (0.78, p<0.001), week 8 (0.76, p<0.001) or week 1 2 (0.78, p<0.001). Conclusion: A positive HCV RNA test (greater than or equal to 10(3) copies/ ml) at 4 weeks is highly predictive for non-response and leads to significa ntly less misidentification of potential sustained responders than ALT at w eek 4, 8 or 12, both in 6 or up to 12 months interferon monotherapy and in 6 months interferon-ribavirin combination therapy of chronic hepatitis C.