Chronic Hepatitis C Virus Infection and the Proinflammatory Effects of Injection Drug Use

Martin Markowitz, Sherry Deren, Charles Cleland, Melissa La Mar, Evelyn Silva, Pedro Batista, Leslie St Bernard, Natanya Gettie, Kristina Rodriguez, Teresa H. Evering, Haekyung Lee, Saurabh Mehandru

Research output: Contribution to journalArticle

Abstract

Background. Chronic inflammation, as defined by persistent immune activation, is associated with adverse clinical outcomes. People who inject drugs (PWID) have evidence of persistent immune activation. Here, in a cohort of PWID with or without hepatitis C virus (HCV) infection, we sought to dissect out the contribution of chronic HCV infection (common in PWID) from the effects of injection drug use itself. Methods. Four groups of study volunteers were recruited: group 1 comprised active PWID; group 2, individuals who ceased injecting drugs 1-2 months before recruitment; group 3, individuals who ceased injecting drugs 3-4 months before recruitment; and group 4, healthy volunteers. Soluble and cell-associated markers of immune activation were quantified. Results. HCV-viremic PWID have elevated levels of immune activation when compared to healthy volunteers. Cessation of injection drug use results in a decline in immune activation in the absence of HCV viremia, while HCV-viremic individuals who previously were PWID continue to harbor elevated levels of immune activation, as defined by increased levels of soluble CD14 and tumor necrosis factor α and by the presence of CD38+HLA-DR+ CD4+ and CD8+ T cells. Conclusions. Immune activation, a well-defined surrogate of poor clinical outcome that is elevated in PWID, can regress to normal levels in former injection drug users who are HCV aviremic. Therefore, enhanced harm-reduction efforts should incorporate aggressive treatment of HCV infection. Clinical Trials Registration. NCT01831284.

Original languageEnglish (US)
Pages (from-to)1376-1382
Number of pages7
JournalJournal of Infectious Diseases
Volume214
Issue number9
DOIs
StatePublished - Nov 1 2016

Fingerprint

Chronic Hepatitis C
Virus Diseases
Hepacivirus
Injections
Pharmaceutical Preparations
Healthy Volunteers
Harm Reduction
Viremia
HLA-DR Antigens
Drug Users
Volunteers
Tumor Necrosis Factor-alpha
Biomarkers
Clinical Trials
Inflammation
T-Lymphocytes

Keywords

  • HCV infection
  • immune activation
  • injection drug use

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Markowitz, M., Deren, S., Cleland, C., La Mar, M., Silva, E., Batista, P., ... Mehandru, S. (2016). Chronic Hepatitis C Virus Infection and the Proinflammatory Effects of Injection Drug Use. Journal of Infectious Diseases, 214(9), 1376-1382. https://doi.org/10.1093/infdis/jiw373

Chronic Hepatitis C Virus Infection and the Proinflammatory Effects of Injection Drug Use. / Markowitz, Martin; Deren, Sherry; Cleland, Charles; La Mar, Melissa; Silva, Evelyn; Batista, Pedro; St Bernard, Leslie; Gettie, Natanya; Rodriguez, Kristina; Evering, Teresa H.; Lee, Haekyung; Mehandru, Saurabh.

In: Journal of Infectious Diseases, Vol. 214, No. 9, 01.11.2016, p. 1376-1382.

Research output: Contribution to journalArticle

Markowitz, M, Deren, S, Cleland, C, La Mar, M, Silva, E, Batista, P, St Bernard, L, Gettie, N, Rodriguez, K, Evering, TH, Lee, H & Mehandru, S 2016, 'Chronic Hepatitis C Virus Infection and the Proinflammatory Effects of Injection Drug Use', Journal of Infectious Diseases, vol. 214, no. 9, pp. 1376-1382. https://doi.org/10.1093/infdis/jiw373
Markowitz, Martin ; Deren, Sherry ; Cleland, Charles ; La Mar, Melissa ; Silva, Evelyn ; Batista, Pedro ; St Bernard, Leslie ; Gettie, Natanya ; Rodriguez, Kristina ; Evering, Teresa H. ; Lee, Haekyung ; Mehandru, Saurabh. / Chronic Hepatitis C Virus Infection and the Proinflammatory Effects of Injection Drug Use. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 9. pp. 1376-1382.
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