Umemura Takeji, Joshita Satoru, Sekiguchi Tomohiro, Usami Yoko, Shibata Soichiro, Kimura Takefumi, Komatsu Michiharu, Matsumoto Akihiro, Ota Masao, Tanaka Eiji
Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Am J Gastroenterol. 2015 Jun;110(6):857-64. doi: 10.1038/ajg.2015.118. Epub 2015 Apr 28.
Noninvasive markers of liver fibrosis in patients with primary biliary cirrhosis (PBC) are needed for predicting disease progression. As the Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA(+)-M2BP) was recently established as a liver fibrosis glycobiomarker in chronic hepatitis C, we assessed its efficacy in evaluating liver fibrosis stage and disease progression in PBC.
A total of 137 patients with PBC who underwent liver biopsy and serological tests for WFA(+)-M2BP were enrolled. All patients were treated with ursodeoxycholic acid. Clinical data were compared with those for other noninvasive markers (aspartate aminotransferase-to-platelet ratio, FIB-4 index, aspartate aminotransferase/alanine aminotransferase ratio, Forn's index, and Mayo score) for estimating liver fibrosis using receiver operating characteristic analysis. The association between WFA(+)-M2BP and clinical outcome (liver decompensation, liver transplantation, or death) was evaluated using the Cox proportional hazards model with stepwise method.
WFA(+)-M2BP was independently associated with liver fibrosis stage as determined by liver biopsy. The cutoff values of WFA(+)-M2BP for fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 0.7, 1.0, 1.4, and 2.0, respectively. The area under the receiver operating characteristic curve values for significant fibrosis, severe fibrosis, and cirrhosis were 0.979, 0.933, and 0.965, respectively. WFA(+)-M2BP was significantly superior to the other indices for the determination of significant and severe fibrosis stages. Furthermore, the WFA(+)-M2BP level at enrollment was strongly and independently associated with clinical outcome (hazard ratio 18.59, P=0.021).
Baseline measurements of WFA(+)-M2BP represent a simple and reliable noninvasive surrogate marker of liver fibrosis and prognosis in patients with PBC.
原发性胆汁性肝硬化（PBC）患者需要肝纤维化的非侵入性标志物来预测疾病进展。由于紫藤凝集素阳性Mac-2结合蛋白（WFA(+)-M2BP）最近被确立为慢性丙型肝炎的肝纤维化糖生物标志物，我们评估了其在评估PBC肝纤维化阶段和疾病进展中的作用。
共纳入137例接受肝活检及WFA(+)-M2BP血清学检测的PBC患者。所有患者均接受熊去氧胆酸治疗。使用受试者工作特征分析，将临床数据与其他用于评估肝纤维化的非侵入性标志物（天冬氨酸转氨酶与血小板比值、FIB-4指数、天冬氨酸转氨酶/丙氨酸转氨酶比值、Forn指数和梅奥评分）的数据进行比较。采用逐步法的Cox比例风险模型评估WFA(+)-M2BP与临床结局（肝失代偿、肝移植或死亡）之间的关联。
WFA(+)-M2BP与肝活检确定的肝纤维化阶段独立相关。纤维化阶段≥F1、≥F2、≥F3和F4时WFA(+)-M2BP的截断值分别为0.7、1.0、1.4和2.0。显著纤维化、严重纤维化和肝硬化的受试者工作特征曲线下面积值分别为0.979、0.933和0.965。在确定显著和严重纤维化阶段方面，WFA(+)-M2BP明显优于其他指标。此外，入组时的WFA(+)-M2BP水平与临床结局密切且独立相关（风险比18.59，P = 0.021）。
WFA(+)-M2BP的基线测量是PBC患者肝纤维化和预后的一种简单可靠的非侵入性替代标志物。
