Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis

J Med Microbiol. 2016 Aug;65(8):703-712. doi: 10.1099/jmm.0.000272. Epub 2016 May 10.


Extra-hepatic compartments might contribute to hepatitis C virus (HCV) persistence and extra-hepatic manifestations. Therefore, we investigated HCV infection in colonic tissue in patients with chronic hepatitis C (CHC) and its relationship with HCV pathogenesis. Colonic biopsies were collected from three groups with CHC infection: treatment naïve (TN; n=12), non-responders (NR; n=10) to anti-HCV therapy (pegylated interferon-α and ribavirin) and sustained virologic response (SVR; n=10) and from a fourth healthy control group (n=10). Liver biopsies were examined to assess inflammation and fibrosis. HCV infection and colonic T regulatory (Treg) frequency were detected by immunohistochemistry. HCV core and NS3 proteins were detected in B cells and macrophage/monocytes of 42 % and 25 % of TN and 50 % and 30 % of NR, respectively, but not in SVR or control group. The numbers of cells expressing HCV proteins were positively correlated with both HCV viral load and colonic Treg frequency. A significant negative correlation between HCV-expressing cells with both liver inflammation and fibrosis was identified. Our study provides evidence that HCV can infect B cells and macrophages of the colon. The correlations between HCV infection in colonic tissue and HCV viral load and liver pathology underline the significance of this extra-hepatic infection in HCV pathogenesis and response to therapy.

MeSH terms

  • Adult
  • B-Lymphocytes / virology
  • Biopsy
  • Colon / virology*
  • Cross-Sectional Studies
  • Female
  • Hepacivirus / isolation & purification*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Immunohistochemistry
  • Liver / virology
  • Macrophages / virology
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology
  • Young Adult