title: Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers.
abstract: OBJECTIVE
  Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade extracellular matrix (ECM) proteins into small soluble fragments, which reflect hepatic remodeling processes. This study used these novel biomarkers to investigate the effect of HIV and cART on hepatic fibrosis remodeling.
  
  
  METHODS
  In 249 patients with HIV monoinfection and 55 healthy controls, the serum levels of MMP-degraded collagen type III (C3M), biglycan (BGM), elastin (ELM), as well as the formation marker 7S (P4NP 7S), and MMP-degraded collagen type IV (C4M) were determined using specific ELISAs. Sixty-eight patients underwent a follow-up visit 3 years later including assessment of ECM markers and fibrosis using transient elastography (Fibroscan).
  
  
  RESULTS
  C3M, BGM, C4M and P4NP 7S were significantly elevated in HIV patients compared to controls and correlated to HIV viral loads and inversely to cART duration. C4M, P4NP 7S and ELM were lower in patients under cART therapy and in patients without HIV viremia, indicating that lowering of the HIV load by cART attenuates remodeling of ECM. The levels of C3M, C4M, P4NP 7S and ELM correlated significantly with the progression of fibrosis in these patients.
  
  
  CONCLUSIONS
  Specific therapy of patients with HIV monoinfection also beneficially influences liver fibrosis. These novel markers of liver fibrosis remodeling may help to monitor the hepatic effects by HIV therapy.
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.forename: Evrim
authors.initials: E
authors.lastname: Anadol
authors.forename: Robert
authors.initials: R
authors.lastname: Schierwagen
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.forename: Inger
authors.initials: I
authors.lastname: Byrjalsen
authors.forename: Mette Juul
authors.initials: MJ
authors.lastname: Nielsen
authors.forename: Carolyn
authors.initials: C
authors.lastname: Schwarzer-Zander
authors.forename: Christoph
authors.initials: C
authors.lastname: Boesecke
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
authors.forename: Søren
authors.initials: S
authors.lastname: Møller
authors.forename: Christian P
authors.initials: CP
authors.lastname: Strassburg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Aleksander
authors.initials: A
authors.lastname: Krag
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rockstroh
authors.forename: Jonel K
authors.initials: JK
authors.lastname: Trebicka
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D058578:Biglycan / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D060085:Coinfection; D024061:Collagen Type III / Q000097:blood; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004359:Drug Therapy, Combination; D054459:Elasticity Imaging Techniques; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D006526:Hepatitis C / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010449:Peptide Mapping
chemical_list: D000998:Antiviral Agents; D058578:Biglycan; D015415:Biomarkers; D024061:Collagen Type III; D004549:Elastin