title: Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection.
abstract: Chronic hepatitis C virus (HCV) and HIV viral infections are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined.
  
  
  
  Seventy-nine HIV-infected patients who had been receiving antiretroviral therapy (ART) for more than 2 years and who had suppressed plasma HIV levels (< 50 HIV-1 RNA copies/mL) were included in the study. Two patient groups, HCV-positive/HIV-positive and HCV-negative/HIV-positive, and a control group comprised of healthy volunteers (n = 20) were examined. Markers of systemic inflammation [interleukin (IL)-6, interferon gamma-induced protein (IP)-10, soluble tumour necrosis factor receptor-I (sTNF-RI) and sTNF-RII], monocyte/macrophage activation [soluble CD163 (sCD163), soluble CD14 and neopterin], intestinal epithelial barrier loss [intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide (LPS)] and coagulation (d-dimers) were analysed. CD4 naïve T cells and CD4 recent thymic emigrants (RTEs) were enumerated.
  
  
  
  Plasma levels of IP-10, neopterin and sCD163 were higher in HCV/HIV coinfection than in HIV monoinfection and were positively correlated with indices of hepatic damage [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the AST to platelet ratio index (APRI)]. Levels of I-FABP were comparably increased in HIV monoinfection and HIV/HCV coinfection but LPS concentrations were highest in HCV/HIV coinfection, suggesting impaired hepatic clearance of LPS. Plasma HCV levels were not related to any inflammatory indices except sCD163. In coinfected subjects, a previously recognized relationship of CD4 naïve T-cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163.
  
  
  
  Hepatocellular injury in HCV/HIV coinfection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. A related decrease in CD4 naïve T cells and RTEs also merits further exploration.
authors.affiliation: Institute of Ecology and Genetics of Microorganisms UB RAS, Perm, Russia.|Perm State University, Perm, Russia.
authors.forename: K V
authors.initials: KV
authors.lastname: Shmagel
authors.affiliation: Institute of Ecology and Genetics of Microorganisms UB RAS, Perm, Russia.|Perm State University, Perm, Russia.
authors.forename: E V
authors.identifier: 0000-0002-4342-5362
authors.initials: EV
authors.lastname: Saidakova
authors.affiliation: Perm State University, Perm, Russia.|Perm Regional Center for Protection against AIDS and Infectious Diseases, Perm, Russia.
authors.forename: N G
authors.initials: NG
authors.lastname: Shmagel
authors.affiliation: Institute of Ecology and Genetics of Microorganisms UB RAS, Perm, Russia.|Perm State University, Perm, Russia.
authors.forename: L B
authors.initials: LB
authors.lastname: Korolevskaya
authors.affiliation: Institute of Ecology and Genetics of Microorganisms UB RAS, Perm, Russia.|Perm State University, Perm, Russia.|Institute of Immunology and Physiology UB RAS, Yekaterinburg, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Chereshnev
authors.affiliation: Case Western Reserve University, Cleveland, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Robinson
authors.affiliation: National Institute of Child Health and Development, Bethesda, MD, USA.
authors.forename: J-C
authors.initials: JC
authors.lastname: Grivel
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Douek
authors.affiliation: National Institute of Child Health and Development, Bethesda, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Margolis
authors.affiliation: Case Western Reserve University, Cleveland, OH, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Anthony
authors.affiliation: Case Western Reserve University, Cleveland, OH, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D060085:Coinfection / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000473:pathology*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008099:Liver / Q000473:pathology*; D008297:Male
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: CD31; HIV infections; antigens; hepatitis C; highly active antiretroviral therapy; inflammation mediators