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用于监测非肝硬化原发性胆汁性肝硬化患者接受熊去氧胆酸治疗时疾病进展的血清学标志物。

Serological markers for monitoring disease progression in noncirrhotic primary biliary cirrhosis on ursodeoxycholic acid therapy.

作者信息

Färkkilä Martti, Rautiainen Henna, Kärkkäinen Päivi, Karvonen Anna-L, Nurmi Heimo, Niemelä Onni

机构信息

Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland.

出版信息

Liver Int. 2008 Jul;28(6):787-97. doi: 10.1111/j.1478-3231.2008.01722.x.

Abstract

BACKGROUND/AIM: Liver biopsy has so far been the only method to accurately follow the progression of primary biliary cirrhosis (PBC). The stage and the severity of lymphocytic piecemeal necrosis (LPN) have been shown to be an independent factor for the development of cirrhosis. In this 3-year prospective study, we evaluated the diagnostic value of several liver function tests, surrogate markers of fibrogenesis, hyaluronic acid (HA), procollagen III N-terminal peptide (S-PIIINP), cholestanol and plant sterols in noncirrhotic PBC patients treated with ursodeoxycholic acid (UDCA) or with UDCA and budesonide to assess the stage, inflammation and fibrosis.

METHODS

Seventy-seven stage I-III PBC patients were included into the study, with control biopsy at 36 months. Serum liver enzymes, bile acids (BA), HA, PIIINP, immunoglobulins, lipids and cholesterol precursors and plant sterols were measured at baseline and at 36 months.

RESULTS

Aspartate aminotransferase (AST), HA, BA and PIINP were significantly different between stages I to III and differentiated mild (F0F1) from moderate (F2F3) fibrosis. The combination of these variables (PBC score) exhibited best sensitivity and specificity, compared with AST/platelet ratio, Forns' score and fibrosis index. Using a cut-off value of 66 for the PBC score, the sensitivity was 81.4% and specificity was 65.2% for classifying the stage of PBC, regarding the stage the and fibrosis in noncirrhotic PBC.

CONCLUSIONS

Serum HA, BA, PIIINP and AST may serve as valuable simple tools to monitor the treatment response to UDCA in early stages of PBC. Combinations of these biomarkers into a single index further potentiate the diagnostic value of such measurements.

摘要

背景/目的:迄今为止,肝活检一直是准确跟踪原发性胆汁性肝硬化(PBC)进展的唯一方法。淋巴细胞性碎屑样坏死(LPN)的阶段和严重程度已被证明是肝硬化发展的独立因素。在这项为期3年的前瞻性研究中,我们评估了几种肝功能检查、纤维化形成的替代标志物、透明质酸(HA)、Ⅲ型前胶原N端肽(S-PIIINP)、胆甾烷醇和植物甾醇在接受熊去氧胆酸(UDCA)或UDCA与布地奈德治疗的非肝硬化PBC患者中的诊断价值,以评估疾病阶段、炎症和纤维化情况。

方法

77例I-III期PBC患者纳入研究,在36个月时进行对照活检。在基线和36个月时测量血清肝酶、胆汁酸(BA)、HA、PIIINP、免疫球蛋白、脂质、胆固醇前体和植物甾醇。

结果

I至III期之间,天冬氨酸转氨酶(AST)、HA、BA和PIINP存在显著差异,且能区分轻度(F0F1)和中度(F2F3)纤维化。与AST/血小板比值、Forns评分和纤维化指数相比,这些变量的组合(PBC评分)表现出最佳的敏感性和特异性。对于非肝硬化PBC的阶段和纤维化情况,使用PBC评分的临界值66来分类PBC阶段时,敏感性为81.4%,特异性为65.2%。

结论

血清HA、BA、PIIINP和AST可作为监测PBC早期阶段对UDCA治疗反应的有价值的简单工具。将这些生物标志物组合成单一指标可进一步提高此类测量的诊断价值。

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