Natural IFN-alpha was administered to 22 patients with chronic hepatitis C due to HCV subtype 1b and their serum HCV-RNA levels were examined using the reverse-transcription polymerase chain reaction (RT-PCR). The HCV 5′UTR sequence was determined by direct sequencing, and variations of the putative secondary structure were detected by analyzing single-strand confirmation polymorphisms (SSCP) in the patient's sera.Results:
Five of the 22 patients (22%) were complete responders to IFN and eradicated HCV-RNA from their sera and 17/22 (78%) were nonresponders in whom HCV-RNA persisted. The SSCP electrophoretic results predicted the efficacy of IFN therapy: the complete responders showed greater pattern diversity than the nonresponders. The serum HCV-RNA level correlated with the SSCP electrophoretic pattern: patients with the IFN-resistant SSCP electrophoretic pattern had higher levels than the others (10.1±2.4 vs 1.2±0.4 Meq/ml; p<0.001). Sequencing analysis suggested three one-point mutations influence alteration of the secondary structure.Conclusions:
Analysis of the secondary structure of the HCV 5′UTR contributes to predicting viremia severity and the efficacy of IFN therapy in patients with chronic hepatitis C.