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). DISCUSSION: 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.
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). DISCUSSION: 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.
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Authors: E Doehring-Schwerdtfeger; G Mohamed-Ali; I M Abdel-Rahim; R Kardorff; D Franke; C Kaiser; M Elsheikh; J H Ehrich Journal: Am J Trop Med Hyg Date: 1989-07 Impact factor: 2.345
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Authors: Emily A McDonald; Ling Cheng; Blanca Jarilla; Marianne J Sagliba; Annaliza Gonzal; Amabelle J Amoylen; Remigio Olveda; Luz Acosta; David Baylink; Eric S White; Jennifer F Friedman; Jonathan D Kurtis Journal: Infect Immun Date: 2013-10-28 Impact factor: 3.441
Authors: Emily A McDonald; Jennifer F Friedman; Surendra Sharma; Luz Acosta; Sunthorn Pond-Tor; Ling Cheng; Eric S White; Jonathan D Kurtis Journal: PLoS Negl Trop Dis Date: 2013-06-06
Authors: Yasmina Bauer; Eric S White; Simon de Bernard; Peter Cornelisse; Isabelle Leconte; Adele Morganti; Sebastien Roux; Oliver Nayler Journal: ERJ Open Res Date: 2017-03-22