Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection

K. V. Shmagel, E. V. Saidakova, N. G. Shmagel, L. B. Korolevskaya, V. A. Chereshnev, J. Robinson, Jean-Charles B. Grivel, D. C. Douek, L. Margolis, D. D. Anthony, M. M. Lederman

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)581-589
Number of pages9
JournalHIV Medicine
Volume17
Issue number8
DOIs
Publication statusPublished - 1 Sep 2016
Externally publishedYes

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Coinfection
Hepacivirus
HIV
Inflammation
Liver
Neopterin
Lipopolysaccharides
Fatty Acid-Binding Proteins
Aspartate Aminotransferases
T-Lymphocytes
Macrophage Activation
Tumor Necrosis Factor Receptors
Wounds and Injuries
Chronic Hepatitis C
Virus Diseases
Alanine Transaminase
Interferon-gamma
HIV Infections
HIV-1
Monocytes

Keywords

  • antigens
  • CD31
  • hepatitis C
  • highly active antiretroviral therapy
  • HIV infections
  • inflammation mediators

ASJC Scopus subject areas

  • Health Policy
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Shmagel, K. V., Saidakova, E. V., Shmagel, N. G., Korolevskaya, L. B., Chereshnev, V. A., Robinson, J., ... Lederman, M. M. (2016). Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection. HIV Medicine, 17(8), 581-589. https://doi.org/10.1111/hiv.12357

Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection. / Shmagel, K. V.; Saidakova, E. V.; Shmagel, N. G.; Korolevskaya, L. B.; Chereshnev, V. A.; Robinson, J.; Grivel, Jean-Charles B.; Douek, D. C.; Margolis, L.; Anthony, D. D.; Lederman, M. M.

In: HIV Medicine, Vol. 17, No. 8, 01.09.2016, p. 581-589.

Research output: Contribution to journalArticle

Shmagel, KV, Saidakova, EV, Shmagel, NG, Korolevskaya, LB, Chereshnev, VA, Robinson, J, Grivel, J-CB, Douek, DC, Margolis, L, Anthony, DD & Lederman, MM 2016, 'Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection', HIV Medicine, vol. 17, no. 8, pp. 581-589. https://doi.org/10.1111/hiv.12357
Shmagel KV, Saidakova EV, Shmagel NG, Korolevskaya LB, Chereshnev VA, Robinson J et al. Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection. HIV Medicine. 2016 Sep 1;17(8):581-589. https://doi.org/10.1111/hiv.12357
Shmagel, K. V. ; Saidakova, E. V. ; Shmagel, N. G. ; Korolevskaya, L. B. ; Chereshnev, V. A. ; Robinson, J. ; Grivel, Jean-Charles B. ; Douek, D. C. ; Margolis, L. ; Anthony, D. D. ; Lederman, M. M. / Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection. In: HIV Medicine. 2016 ; Vol. 17, No. 8. pp. 581-589.
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abstract = "Objectives: 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. Methods: 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 na{\"i}ve T cells and CD4 recent thymic emigrants (RTEs) were enumerated. Results: 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 na{\"i}ve T-cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163. Conclusions: 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 na{\"i}ve T cells and RTEs also merits further exploration.",
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AU - Chereshnev, V. A.

AU - Robinson, J.

AU - Grivel, Jean-Charles B.

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