title: Tissue inhibitor of matrix-metalloprotease-1 predicts risk of hepatic fibrosis in human Schistosoma japonicum infection.
abstract: BACKGROUND
  Schistosomes infect 200 million individuals annually and cause significant hepatic fibrosis in up to 20%. Little is known regarding the mechanisms of schistosome-associated hepatic fibrosis in humans, and few biomarkers for risk of fibrosis have been identified.
  
  
  METHODS
  We treated 611 Schistosoma japonicum-infected Filipinos with praziquantel (PZQ) and performed ultrasound to quantify hepatic fibrosis at baseline and 12 months after PZQ treatment. We developed a multiplexed assay (FibroPlex) that quantifies predictors and effect modifiers of fibrosis. We measured FibroPlex analytes produced by peripheral blood mononuclear cells stimulated with schistosome egg antigen 4 weeks after PZQ treatment and related these levels to risk of fibrosis 1 year after PZQ treatment.
  
  
  RESULTS
  After adjusting for potential confounders, including baseline grade of fibrosis, individuals with detectable tissue inhibitor of matrix-metalloprotease-1 (TIMP-1) had a 3.5-fold greater risk of fibrosis 1 year after PZQ treatment, compared with individuals with undetectable levels (odds ratio, 3.48; 95% confidence interval, 1.41-8.43; P = .007).
  
  
  CONCLUSIONS
  Because TIMP-1 inhibits most matrix metalloproteases, which are responsible for collagen degradation, these data suggest that schistosome-associated hepatic fibrosis results, in part, from excessive inhibition of collagen remodeling. These data further suggest that TIMP-1 is a promising biomarker for assessing risk of hepatic fibrosis in schistosomiasis and, potentially, other infectious and noninfectious causes of liver disease.
authors.affiliation: Department of Medicine, Memorial Hospital of Rhode Island, Brown University Medical School, Providence, RI, USA. valeria_fabre@brown.edu
authors.forename: Valeria
authors.initials: V
authors.lastname: Fabre
authors.forename: Haiwei
authors.initials: H
authors.lastname: Wu
authors.forename: Sunthorn
authors.initials: S
authors.lastname: PondTor
authors.forename: Hannah
authors.initials: H
authors.lastname: Coutinho
authors.forename: Luz
authors.initials: L
authors.lastname: Acosta
authors.forename: Mario
authors.initials: M
authors.lastname: Jiz
authors.forename: Remigio
authors.initials: R
authors.lastname: Olveda
authors.forename: Ling
authors.initials: L
authors.lastname: Cheng
authors.forename: Eric S
authors.initials: ES
authors.lastname: White
authors.forename: Blanca
authors.initials: B
authors.lastname: Jarilla
authors.forename: Stephen T
authors.initials: ST
authors.lastname: McGarvey
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Friedman
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kurtis
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002648:Child; D015331:Cohort Studies; D003094:Collagen / Q000378:metabolism; D005243:Feces / Q000469:parasitology; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000469:parasitology*; D008297:Male; D010679:Philippines; D011223:Praziquantel / Q000627:therapeutic use; D011379:Prognosis; D012044:Regression Analysis; D012307:Risk Factors; D012549:Schistosoma japonicum; D012554:Schistosomiasis japonica / Q000097:blood* / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D000871:Anthelmintics; D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D011223:Praziquantel; D003094:Collagen