血浆金属蛋白酶组织抑制剂-1和转化生长因子β1——慢性乙型和丙型肝炎患者肝纤维化可能的非侵入性生物标志物。

Plasma tissue inhibitor of metalloproteinases-1 and transforming growth factor beta 1--possible non-invasive biomarkers of hepatic fibrosis in patients with chronic B and C hepatitis.

作者信息

Flisiak Robert, Maxwell Paul, Prokopowicz Danuta, Timms Peter M, Panasiuk Anatol

机构信息

Department of Infectious Diseases, Liver Unit Medical Academy of Bialystok, Zurawia Str., 14, Bialystok 15-540, Poland.

出版信息

Hepatogastroenterology. 2002 Sep-Oct;49(47):1369-72.

PMID:12239944

Abstract

BACKGROUND/AIMS: The role of transforming growth factor-beta 1 (TGF-beta 1) in liver fibrosis is in part related to impairment of extracellular matrix breakdown by stimulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) gene. The aim of the study was to evaluate association between TGF-beta 1 and TIMP-1 in relation to liver injury in chronic viral hepatitis B and C.

METHODOLOGY

Association between plasma TGF-beta 1 and TIMP-1 was evaluated in 28 consecutive patients undergoing liver biopsy for chronic viral hepatitis B and C (CH-B, CH-C) and these tests were correlated with hepatic fibrosis, inflammation and liver function tests. Moreover carboxyterminal cross-linked telopeptide of type 1 procollagen (ICTP) and carboxyterminal propeptide of type 1 collagen (PICP) were also measured for assessment of extracellular matrix breakdown or synthesis, respectively.

RESULTS

Chronic viral hepatitis B and C resulted in a significant increase in plasma TIMP-1 levels but not TGF-beta 1. Among biochemical markers of liver injury, significant correlation with TGF-beta 1 and TIMP-1 was demonstrated in respect to aminotransferase activities in both groups. TIMP-1 showed significant correlation with ICTP levels in both CH-B (r = 0.59) and CH-C (r = 0.62), whereas TGF-beta 1 was correlated with ICTP only in CH-C patients (r = 0.75). PICP did not demonstrate any correlation with either TGF-beta 1 or TIMP-1. Hepatic fibrosis, but not inflammation, correlated significantly with TGF-beta 1 (CH-B: r = 0.73; CH-C: r = 0.79) and TIMP-1 (CH-B: r = 0.66; CH-C: r = 0.71) in both groups and there was a significant correlation between TIMP-1 and TGF-beta 1 in the CH-B group (r = 0.83) and CH-C group (r = 79).

CONCLUSIONS

These results support the role of TIMP-1 in a TGF-beta 1-dependent mechanism for liver fibrosis and suggest their plasma levels can be used as a possible early non-invasive marker of liver fibrosis useful for chronic hepatitis management.

摘要

背景/目的：转化生长因子-β1（TGF-β1）在肝纤维化中的作用部分与通过刺激金属蛋白酶组织抑制剂-1（TIMP-1）基因导致细胞外基质降解受损有关。本研究的目的是评估慢性乙型和丙型病毒性肝炎中TGF-β1与TIMP-1之间的关联及其与肝损伤的关系。

方法

对28例因慢性乙型和丙型病毒性肝炎（CH-B、CH-C）接受肝活检的连续患者评估血浆TGF-β1与TIMP-1之间的关联，并将这些检测结果与肝纤维化、炎症及肝功能检测结果进行相关性分析。此外，还分别检测了I型前胶原羧基末端交联肽（ICTP）和I型胶原羧基末端前肽（PICP），以评估细胞外基质的降解或合成情况。

结果

慢性乙型和丙型病毒性肝炎导致血浆TIMP-1水平显著升高，但TGF-β1水平未升高。在肝损伤的生化标志物中，两组患者的转氨酶活性均与TGF-β1和TIMP-1存在显著相关性。在CH-B组（r = 0.59）和CH-C组（r = 0.62）中，TIMP-1与ICTP水平均呈显著相关，而仅在CH-C患者中TGF-β1与ICTP相关（r = 0.75）。PICP与TGF-β1或TIMP-1均无相关性。在两组中，肝纤维化而非炎症与TGF-β1（CH-B：r = 0.73；CH-C：r = 0.79）和TIMP-1（CH-B：r = 0.66；CH-C：r = 0.71）显著相关，且在CH-B组（r = 0.83）和CH-C组（r = 0.79）中TIMP-1与TGF-β1之间存在显著相关性。