Tissue Inhibitor of Matrix-Metalloprotease-1 Predicts Risk of Hepatic Fibrosis in Human Schistosoma japonicum Infection
Tissue Inhibitor of Matrix-Metalloprotease-1 Predicts Risk of Hepatic Fibrosis in Human Schistosoma japonicum Infection
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DOI：
10.1093/infdis/jiq099
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发表时间：
2011-03-01
影响因子：
6.4
通讯作者：
Kurtis, Jonathan D.
中科院分区：
文献类型：
--
作者：
Fabre, Valeria;Wu, Haiwei;Kurtis, Jonathan D.
方法.我们用吡喹酮（PZQ）治疗了611例日本血吸虫感染的菲律宾人，并在基线和PZQ治疗后12个月进行了超声定量肝纤维化。我们开发了一种多重测定（Fibroblast），其定量纤维化的预测因子和效应调节因子。我们在PZQ治疗后4周测量了由外周血单个核细胞用卵抗原刺激产生的Fibroblast分析物，并将这些水平与PZQ治疗后1年的纤维化风险相关。在调整了潜在的混杂因素（包括纤维化的基线分级）后，与未检测到基质金属蛋白酶组织抑制剂-1（TIMP-1）的个体相比，PZQ治疗1年后，TIMP-1可检测的个体发生纤维化的风险高3.5倍（比值比，3.48; 95%可信区间，1.41-8.43; P = .007）。讨论由于TIMP-1抑制负责胶原降解的大多数基质金属蛋白酶，这些数据表明，在某种程度上，过度抑制胶原蛋白重塑这些数据进一步表明，TIMP-1是一个有前途的生物标志物，用于评估血吸虫病肝纤维化的风险，并可能评估其他感染性和非感染性肝病的原因。
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.