title: Natural killer cell activity and function in chronic HCV-infected patients during peg interferon and ribavirin: early effects of active substance use.
abstract: In Western countries, chronic hepatitis C virus (HCV)-infection mostly affects former and active substance users. The effect of active substance use on interferon (IFN)-responsiveness and therapy efficacy is not well understood. In this study, we compared natural killer (NK) cell activity and function in healthy controls and chronic HCV-infected patients with and without active substance use, as well as the early effects of antiviral therapy with peg-IFN and ribavirin. No differences were observed between chronic HCV patients and healthy individuals in the number and frequencies of CD56(dim) and CD56(bright) NK cells. Also, IL-12/18-induced IFN-gamma production by NK cells was comparable between all groups, whereas the cytotoxic ability of NK cells (granzyme and CD107a levels) was more potent in HCV-infected patients as compared to healthy controls, and highest in non-substance users. Moreover, at baseline, the activation of NK cells was significantly lower in HCV-infected patients who used substances, when compared to healthy individuals. Therapy-induced viral load reduction assessed early at day 7 showed a similar decline in substance users and non-substance use HCV patients, with 25% substance users and 17% non-substance users testing HCV-RNA negative at day 7. Furthermore, early during IFN-based therapy, NK cells from HCV patients remained responsive to IFN, and only a minor decline in the degree of STAT-1 phosphorylation was observed irrespective of substance use. These findings were further supported by comparable in vitro p-STAT-1 induction in all three experimental groups. Despite subtle differences at baseline between healthy individuals and chronic HCV patients, we observed that active substance use in chronic HCV-infected patients did not affect the immune responsiveness to IFN early after start of treatment, and thus, we found no evidence - from an immunological point of view - that antiviral therapy of our cohort of HCV-infected patients with active substance use is less efficient.
authors.affiliation: Liver Unit, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Daphne M
authors.initials: DM
authors.lastname: Hotho
authors.forename: Kim
authors.initials: K
authors.lastname: Kreefft
authors.forename: Zwier M A
authors.initials: ZM
authors.lastname: Groothuismink
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.forename: André
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D000328:Adult; D055030:Drug Users / Q000706:statistics & numerical data; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000627:therapeutic use*; D019966:Substance-Related Disorders / Q000150:complications / Q000188:drug therapy / Q000276:immunology*
chemical_list: D016898:Interferon-alpha; D012254:Ribavirin