title: Association of HIV, hepatitis C virus and liver fibrosis severity with interleukin-6 and C-reactive protein levels.
abstract: BACKGROUND
  Hepatitis C virus (HCV) infection is associated with chronic inflammation; yet studies show greater interleukin (IL)-6, but lower C-reactive protein (CRP) levels. We determined whether liver fibrosis severity and HCV replication affect the ability of IL-6 to stimulate the production of CRP from the liver.
  
  
  METHODS
  We used multivariable generalized linear regression to examine the association of HIV, HCV and transient elastography-measured liver stiffness with IL-6 and CRP in participants (164 HIV-monoinfected; 10 HCV-monoinfected; 73 HIV/HCV-coinfected; 59 neither infection) of the Women's Interagency HIV Study. Significant fibrosis was defined as liver stiffness greater than 7.1 kPa.
  
  
  RESULTS
  IL-6 was positively correlated with CRP levels in all women, but CRP levels were lower in HCV-infected women (with and without HIV infection) at all levels of IL-6. HCV-infected women with fibrosis had nearly 2.7-fold higher IL-6 levels compared to controls [95% confidence interval (CI 146%, 447%]; HCV-infected women without fibrosis had IL-6 levels that were similar to controls. By contrast, CRP was 28% lower in HCV-infected women with fibrosis (95% CI -55%, 15%) and 47% lower in HCV-infected women without fibrosis (95% CI -68%, -12%). Among the HCV-infected women, higher HCV-RNA levels were associated with 9% lower CRP levels per doubling (95% CI -18%, 0%).
  
  
  CONCLUSIONS
  Liver fibrosis severity is associated with greater IL-6 levels, but the stimulatory effect of IL-6 on CRP appears to be blunted by HCV replication rather than by liver fibrosis severity. Investigation of the potential CRP rebound after HCV-RNA eradication and persistent liver fibrosis on organ injury is needed.
authors: aDepartment of Medicine bDepartment of Pediatrics, University of California cMedical Service, Department of Veteran Affairs Medical Center, San Francisco, California dDepartment of Medicine, Stroger Hospital and Rush University, Chicago, Illinois eDepartment of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors: Shailja
authors: S
authors: Shah
authors: Yifei
authors: Y
authors: Ma
authors: Rebecca
authors: R
authors: Scherzer
authors: Greg
authors: G
authors: Huhn
authors: Audrey L
authors: AL
authors: French
authors: Michael
authors: M
authors: Plankey
authors: Marion G
authors: MG
authors: Peters
authors: Carl
authors: C
authors: Grunfeld
authors: Phyllis C
authors: PC
authors: Tien
mesh_terms: D000328:Adult; D060085:Coinfection; D054459:Elasticity Imaging Techniques; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D016014:Linear Models; D008103:Liver Cirrhosis / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011971:Receptors, Immunologic / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: C071581:CRP protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D011971:Receptors, Immunologic