Evidence for immune activation in patients with residual hepatitis C virus RNA long after successful treatment with IFN and ribavirin

J Gen Virol. 2014 Sep;95(Pt 9):2004-2009. doi: 10.1099/vir.0.064709-0. Epub 2014 Jun 11.

Abstract

Low-level hepatitis C virus (HCV) RNA may persist in PBMCs after successful treatment of chronic hepatitis C, but the consequences of this phenomenon are unclear. Forty-nine patients who achieved a sustained virological response (SVR) after pegylated IFN and ribavirin therapy were analysed 52-66 months after the SVR. HCV RNA was detected in PBMCs from 18 patients (47.4 %), and PBMCs in two patients stained positive for non-structural protein 3 (NS3). Quantification of various cytokine and chemokine transcripts in PBMCs revealed that levels of IL-6, IL-8, IL-12, TNF-α and macrophage inflammatory protein 1β were significantly higher in HCV-positive patients than in HCV-negative individuals. In conclusion, persistence of HCV RNA in PBMCs of patients with a SVR appears to be associated with immune activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use
  • Chemokine CCL4 / genetics
  • Drug Therapy, Combination
  • Female
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interleukin-12 Subunit p35 / genetics
  • Interleukin-6 / genetics
  • Interleukin-8 / genetics
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • RNA, Viral / blood
  • RNA, Viral / genetics
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics
  • Viral Load
  • Viral Nonstructural Proteins / genetics

Substances

  • Antiviral Agents
  • CXCL8 protein, human
  • Chemokine CCL4
  • IL12A protein, human
  • IL6 protein, human
  • Interferon-alpha
  • Interleukin-12 Subunit p35
  • Interleukin-6
  • Interleukin-8
  • NS3 protein, hepatitis C virus
  • RNA, Viral
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Viral Nonstructural Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Alanine Transaminase
  • peginterferon alfa-2a