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

J Viral Hepat. 2014 Aug;21(8):551-9. doi: 10.1111/jvh.12182. Epub 2013 Oct 13.

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.

Keywords: 5′untranslated region; hepatitis C; hepatitis C virus; interferon; ribavirin; treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use*
  • Female
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Polymorphism, Single-Stranded Conformational
  • RNA, Viral / blood
  • Sequence Analysis, DNA
  • Treatment Outcome
  • Young Adult

Substances

  • 5' Untranslated Regions
  • Antiviral Agents
  • RNA, Viral