原发性胆汁性肝硬化患者III型前胶原氨基端前肽与透明质酸：原发性胆汁性肝硬化的纤维化标志物

Aminoterminal propeptide of type III procollagen and hyaluronan in patients with primary biliary cirrhosis: markers of fibrosis in primary biliary cirrhosis.

作者信息

Remmel T, Remmel H, Salupere V

机构信息

Department of Internal Medicine, University of Tartu, Estonia.

出版信息

J Gastroenterol Hepatol. 1996 Nov;11(11):1016-20. doi: 10.1111/j.1440-1746.1996.tb00024.x.

DOI:10.1111/j.1440-1746.1996.tb00024.x

PMID:8985819

Abstract

The aminoterminal propeptide of type III procollagen (PIIINP) and hyaluronan have previously been studied in different liver diseases. The results of these studies are controversial. The aim of the present study was to examine the relationship between PIIINP and hyaluronan levels and the clinical, biochemical and histological features of primary biliary cirrhosis (PBC) and its prognosis. Fifty-five PBC patients were studied at the time of diagnosis of PBC and were followed up for a mean of 58 months. During the follow-up period 21 patients died. In addition, 30 healthy subjects were examined in the present study. Hyaluronan and PIIINP were measured by radioimmunoassay and the levels of both PIIINP and hyaluronan were higher in PBC patients than in healthy volunteers (P < 1.8 x 10(-6) and 1.6 x 10(-9), respectively). Hyaluronan and PIIINP levels were above normal values in 82 and 84% of PBC patients, respectively. There were correlations between PIIINP and hyaluronan and the histological stage of PBC (r = 0.44, P < 0.004 and r = 0.56, P < 0.00001, respectively). The correlation between PIIINP and hyaluronan was 0.46 (P < 0.0035). In symptomatic patients, both PIIINP and hyaluronan values were higher than in controls (P < 0.002 and P < 0.006, respectively). The levels of PIIINP correlated significantly with bilirubin (r = 0.43, P < 0.006), while hyaluronan was correlated with age (r = 0.33, P < 0.015), pruritus (r = 0.32, P < 0.02), fatigue (r = 0.41, P < 0.003), hepatomegaly (r = -0.46, P < 0.0008), the presence of oesophageal varices (r = 0.34, P < 0.002), weight loss (r = 0.29, P < 0.05), bilirubin (r = 0.54, P < 0.0001), albumin (r = -0.30, P < 0.04), extent of fat excretion (r = 0.53, P < 0.009) and length of symptomatic period before diagnosis of PBC (r = 0.43, P < 0.002). Using Cox's logistic regression analysis, survival was found to be influenced by bilirubin concentration but not by hyaluronan, PIIINP, age, albumin or histological stage. Therefore, hyaluronan is a more sensitive marker for predicting advanced PBC than is PIIINP. However, neither hyaluronan nor PIIINP gave any indication of prognostic outcome.

摘要

III型前胶原氨基端前肽（PIIINP）和透明质酸此前已在不同肝病中进行过研究。这些研究结果存在争议。本研究的目的是探讨PIIINP和透明质酸水平与原发性胆汁性肝硬化（PBC）的临床、生化和组织学特征及其预后之间的关系。55例PBC患者在确诊时接受了研究，并进行了平均58个月的随访。随访期间有21例患者死亡。此外，本研究还检查了30名健康受试者。采用放射免疫分析法测定透明质酸和PIIINP，PBC患者的PIIINP和透明质酸水平均高于健康志愿者（分别为P < 1.8×10⁻⁶和1.6×10⁻⁹）。82%和84%的PBC患者透明质酸和PIIINP水平高于正常值。PIIINP和透明质酸与PBC的组织学分期之间存在相关性（分别为r = 0.44，P < 0.004和r = 0.56，P < 0.00001）。PIIINP与透明质酸之间的相关性为0.46（P < 0.0035）。有症状的患者中，PIIINP和透明质酸值均高于对照组（分别为P < 0.002和P < 0.006）。PIIINP水平与胆红素显著相关（r = 0.43，P < 0.006），而透明质酸与年龄（r = 0.33，P < 0.015）、瘙痒（r = 0.32，P < 0.02）、疲劳（r = 0.41，P < 0.003）、肝肿大（r = -0.46，P < 0.0008）、食管静脉曲张的存在（r = 0.34，P < 0.002）、体重减轻（r = 0.29，P < 0.05）、胆红素（r = 0.54，P < 0.0001）、白蛋白（r = -0.30，P < 0.04）、脂肪排泄程度（r = 0.53，P < 0.009）以及PBC诊断前有症状期的时长（r = 0.43，P < 0.002）相关。使用Cox逻辑回归分析发现，生存受胆红素浓度影响，但不受透明质酸、PIIINP、年龄、白蛋白或组织学分期影响。因此，与PIIINP相比，透明质酸是预测晚期PBC更敏感的标志物。然而，透明质酸和PIIINP均未给出任何预后结果的指示。