Search

Hepatitis C virus (HCV) variability affects viral-host interactions. We analysed HCV 5′untranslated region (5′UTR) in sera and peripheral blood mononuclear cells (PBMC) from chronic hepatitis C patients undergoing antiviral treatment. We studied 139 patients treated with pegylated interferon and ribavirin. The primary endpoint was a sustained virological response (SVR) defined as negative HCV RNA level 24 weeks after the end of therapy. 5′UTR was analysed by single-strand conformational polymorphism (SSCP) and sequencing. The pretreatment SSCP pattern in serum and PBMC differed in 26 (18.7%) patients. During therapy, the SSCP pattern remained stable in 65 (60.8%) patients, number of bands declined in 16 (15.0%), and in 18 (16.8%) patients, changes were qualified as 'shift' indicating change in band positions. In univariate analysis, there was a significant ( P ≤ 0.05) positive association between SVR and pretreatment serum and PBMC dissimilarities, initial viral load <106 IU/mL, IL-28B CC genotype of the rs12979860 single nucleotide polymorphism and change in the SSCP band pattern (either 'shift' or decline) In multivariable analysis, only low initial viral load, IL-28B genotype, and changes in the SSCP band pattern were independent factors associated with SVR. In conclusion, stability of 5′UTR correlated with infection persistence, while changes correlated with SVR. [ABSTRACT FROM AUTHOR]

Purpose: Genetic variability of hepatitis C virus (HCV) is considered to be an important factor defining viral pathogenesis, [persistence and resistance to treatment. The aim of the present study was to characterize HCV genetic heterogeneity within a hypervariable region 1 (HVR-1) before and during the early period of pegylated interferon alfa (PEG-IFN-α) and ribavirin treatment in correlation with treatment outcome. Material and Methods: The study involved 24 patients treated with PEG-IFN-α and ribavirin whose sera were collected before (baseline) and at 7,14, 21 28 and 56 day of treatment. HCV HVR-1 region was amplified by nested RT-PCR and subjected to SSCP (single strand conformational polymorphism) analysis. SSCP changes of HCV HVR-1 over time in each patient were : compared to treatment outcome results. Results: In 2/11 (18%) SVR+ and 8/13 (62%) SVR- treated patients, HVR-1 genetic changes manifested by new SSCP bands (new genetic variants) and were significantly more frequent in nonresponders (P <0.05). Conclusions: Our results indicate that HCV HVR-1 variability during the early phase of PEG-IFN-α and ribavirin therapy may be predictive of treatment outcome. [ABSTRACT FROM AUTHOR]