Macrophage Activation Marker Soluble CD163 Is a Dynamic Marker of Liver Fibrogenesis in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection

J Infect Dis. 2018 Sep 22;218(9):1394-1403. doi: 10.1093/infdis/jiy331.

Abstract

Background: Coinfection with human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV)-related liver fibrosis. Macrophages are triggered during both viral infections and are critical in liver inflammation/fibrogenesis. Liver fibrosis strongly associates with serum soluble CD163 (sCD163, a macrophage activation marker); comprehensive evaluation in HIV/HCV coinfection is lacking.

Methods: We retrospectively analyzed sCD163 (enzyme-linked immunosorbent assay) and hepatic CD163 (immunofluorescent CD163/CD68 costaining) in patients infected with HIV/HCV, HCV, or HIV, pre- and post-antiviral therapy.

Results: sCD163 was significantly higher in HIV/HCV compared to either monoinfection, and decreased following successful antiviral therapy, although did not fully normalize. In HIV/HCV, sCD163 was associated with necroinflammation, Ishak fibrosis scores, and noninvasive fibrosis scores. We observed a novel trend whereby sCD163 levels progressively increase with increasing Ishak fibrosis score, peaking at stage 4, above which levels plateaued. Periportal CD163+ macrophage frequency was also higher with increasing fibrosis score. When stratified by fibrosis stage, sCD163 levels were higher in HIV/HCV than HCV but only in individuals with mild to moderate fibrosis.

Conclusions: In HIV/HCV, increasing sCD163 levels accompanied periportal CD163+ macrophage enrichment in mild to moderate fibrosis, but not in established cirrhosis, suggesting that sCD163 is a dynamic biomarker of fibrogenesis rather than accumulated fibrosis. Our findings implicate HIV-related macrophage activation in accelerated fibrosis progression in HIV/HCV coinfection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Biomarkers / metabolism*
  • Coinfection / metabolism*
  • Coinfection / virology
  • Female
  • HIV / pathogenicity
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • Hepacivirus / pathogenicity
  • Hepatitis C, Chronic / metabolism*
  • Hepatitis C, Chronic / virology
  • Humans
  • Liver / metabolism
  • Liver / virology
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / virology
  • Macrophage Activation / physiology*
  • Macrophages / metabolism
  • Macrophages / virology
  • Male
  • Middle Aged
  • Receptors, Cell Surface / metabolism*
  • Retrospective Studies
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • Receptors, Cell Surface