Hepatitis C virus 5' untranslated region variability correlates with treatment outcome

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 <10(6) 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.