title: Hepatitis C virus 5' untranslated region variability correlates with treatment outcome.
abstract: 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.
authors.affiliation: Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
authors.forename: I
authors.initials: I
authors.lastname: Bukowska-Ośko
authors.forename: M
authors.initials: M
authors.lastname: Radkowski
authors.forename: A
authors.initials: A
authors.lastname: Pawełczyk
authors.forename: M
authors.initials: M
authors.lastname: Rosinska
authors.forename: K
authors.initials: K
authors.lastname: Caraballo Cortés
authors.forename: R
authors.initials: R
authors.lastname: Płoski
authors.forename: H
authors.initials: H
authors.lastname: Berak
authors.forename: A
authors.initials: A
authors.lastname: Horban
authors.forename: J
authors.initials: J
authors.lastname: Stanczak
authors.forename: M
authors.initials: M
authors.lastname: Fic
authors.forename: T
authors.initials: T
authors.lastname: Laskus
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000097:blood; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; D000998:Antiviral Agents; D012367:RNA, Viral
keywords: 5′untranslated region; hepatitis C; hepatitis C virus; interferon; ribavirin; treatment