Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival in Patients with Cholestatic Liver Diseases.
Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival in Patients with Cholestatic Liver Diseases.
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DOI：
10.1038/srep30847
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发表时间：
2016-08-10
影响因子：
4.6
通讯作者：
Milkiewicz P
中科院分区：
文献类型：
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作者：
Wunsch E;Krawczyk M;Milkiewicz M;Trottier J;Barbier O;Neurath MF;Lammert F;Kremer AE;Milkiewicz P
自分泌运动因子（ATX）参与溶血磷脂酸的合成。两者最近都与胆汁淤积性瘙痒和肝损伤有关。我们的目的是研究ATX是否是胆汁淤积性肝损伤、健康相关生活质量（HRQoL）和预后的指标，基于一组233例患者，118例原发性胆汁性胆管炎（PBC）和115例原发性硬化性胆管炎（PSC）。随访1-60个月，计算累积生存率。ATX活性在两组中均显著高于103例对照组，特别是在肝硬化患者和病程较长的患者中。PBC的熊去氧胆酸（UDCA）无应答者表现出ATX活性增加。ATX活性与肝脏生化、MELD、马约风险评分相关，并与疾病特异性HRQoL方面较差相关。在两组中，考克斯模型分析表明ATX是生存率的负预测因子。ATX水平升高与PBC患者死亡/肝移植风险增加4倍相关，与PSC患者死亡/肝移植风险增加2.6倍相关。我们得出结论，在胆汁淤积性疾病患者中，ATX不仅与瘙痒相关，还表明其他HRQoL方面的损害、肝功能障碍，并可作为生存预测因子。
Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have recently been linked to cholestatic pruritus and liver injury. We aimed to investigate whether ATX is an indicator of cholestatic liver injury, health-related quality of life (HRQoL) and prognosis based on a group of 233 patients, 118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing cholangitis (PSC). Patients were followed for 1–60 months, cumulative survival rates were calculated. ATX activity was significantly higher in both groups than in the 103 controls, particularly in patients with cirrhosis and in patients with longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC exhibited increased ATX activity. ATX activity was correlated with liver biochemistry, MELD, Mayo Risk scores and was associated with worse disease-specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was a negative predictor of survival. Increased ATX levels were associated with a 4-fold higher risk of death/liver transplantation in patients with PBC and a 2.6-fold higher risk in patients with PSC. We conclude that in patients with cholestatic conditions, ATX is not only associated with pruritus but also indicates impairment of other HRQoL aspects, liver dysfunction, and can serve as a predictor of survival.