囊性纤维化肝病中肝纤维化的血清标志物。

Serum markers of hepatic fibrogenesis in cystic fibrosis liver disease.

作者信息

Pereira Tamara N, Lewindon Peter J, Smith Jeffery L, Murphy Therese L, Lincoln Douglas J, Shepherd Ross W, Ramm Grant A

机构信息

The Hepatic Fibrosis Group, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Qld 4029, Australia.

出版信息

J Hepatol. 2004 Oct;41(4):576-83. doi: 10.1016/j.jhep.2004.06.032.

DOI:10.1016/j.jhep.2004.06.032

PMID:15464237

Abstract

BACKGROUND/AIMS: Hepatic fibrosis contributes to adverse outcome in cystic fibrosis (CF). Early detection of CF liver disease (CFLD) may identify patients at risk of significant complications. To evaluate the utility of serum markers to detect hepatic fibrosis in children with CFLD vs. CF patients without liver disease (CFnoLD) and controls.

METHODS

Sera from 36 CFLD, 30 CFnoLD and 39 controls were assessed for tissue inhibitor of matrix metalloproteinase (MMP) (TIMP)-1, collagen (CL)-IV, MMP-2, hyaluronic acid (HA) and prolyl hydroxylase (PH) by enzyme immunoassay and were correlated with hepatic fibrosis score in CFLD.

RESULTS

TIMP-1, PH and CL-IV were increased in CFLD vs. CFnoLD and controls. Fibrosis score was negatively correlated with TIMP-1 (r=-0.34, P=0.06) and PH (r=-0.48, P=0.008). Receiver-operating characteristics analysis showed CL-IV (AUC 0.785, P<0.0001) and TIMP-1 (AUC 0.765, P<0.0001) differentiated CFLD from CFnoLD and controls, while PH (AUC 0.814, P<0.0001) predicted early fibrogenesis. Diagnostic accuracy improved using logistic regression combining (i) CL-IV, TIMP-1, PH to identify CFLD (AUC 0.831, P<0.0001) and (ii) TIMP-1, PH to identify CFLD patients with no fibrosis (AUC 0.852, P<0.02).

CONCLUSIONS

Elevated TIMP-1, CL-IV, PH may be indicators of hepatic fibrogenesis in CF. Increased TIMP-1, PH may be early markers of CFLD.

摘要

背景/目的：肝纤维化会导致囊性纤维化（CF）出现不良后果。早期检测囊性纤维化肝病（CFLD）可能会识别出有严重并发症风险的患者。为了评估血清标志物在检测CFLD患儿与无肝病的CF患者（CFnoLD）及对照组肝纤维化方面的效用。

方法

采用酶免疫分析法对36例CFLD患者、30例CFnoLD患者和39例对照者的血清进行基质金属蛋白酶（MMP）组织抑制剂（TIMP）-1、IV型胶原（CL）-IV、MMP-2、透明质酸（HA）和脯氨酰羟化酶（PH）检测，并将其与CFLD患者的肝纤维化评分进行相关性分析。

结果

与CFnoLD患者和对照组相比，CFLD患者的TIMP-1、PH和CL-IV升高。纤维化评分与TIMP-1（r=-0.34，P=0.06）和PH（r=-0.48，P=0.008）呈负相关。受试者工作特征分析显示，CL-IV（曲线下面积[AUC]0.785，P<0.0001）和TIMP-1（AUC 0.765，P<0.0001）可将CFLD与CFnoLD及对照组区分开来，而PH（AUC 0.814，P<0.0001）可预测早期纤维化形成。使用逻辑回归联合（i）CL-IV、TIMP-1、PH来识别CFLD（AUC 0.831，P<0.0001）以及（ii）TIMP-1、PH来识别无纤维化的CFLD患者，诊断准确性得到提高（AUC 0.852，P<0.02）。