Objective: To clarify the value of autocrine motility factor (ATX) in predicting the disease progression of primary biliary cholangitis (PBC)-associated hepatocellular carcinoma (HCC). Methods: A prospective cohort of 179 newly diagnosed autoimmune liver disease (PBC) patients admitted to the Department of Hepatology at the Fifth Medical Center of the People's Liberation Army General Hospital from January 2016 to January 2018 was selected. All PBC patients received ursodeoxycholic acid (UDCA) treatment and were followed up.The endpoint of the follow-up was the occurrence of primary liver cancer. The relationship between ATX and the clinical characteristics of patients and its significance in predicting disease progression and HCC were analyzed. Results: The peripheral blood ATX level was significantly higher in PBC patients than that of alcoholic cirrhosis (t = 3.278, P = 0.001) and healthy controls (t = 6.594, P < 0.001), but there was no significant difference in ATX levels compared with patients with non-PBC- associated HCC (t = -0.240, P = 0.811). The expression of ATX in liver tissue of PBC patients was significantly higher than that of healthy individuals (Z = -3.633, P < 0.001) and patients with alcoholic cirrhosis (Z = -3.283, P < 0.001), while the expression of ATX in the advanced stage was significantly higher than that in early-stage PBC patients (Z = -2.018, P = 0.034). There was a significant difference in baseline ATX levels between PBC patients without HCC and PBC patients with HCC (228.451 ± 124.093 ng/ml vs. 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). Multivariate logistic regression analysis showed that ATX was an independent predictor of PBC progression to HCC (OR = 1.245, 95%CI 1.097-1.413). The baseline peripheral blood ATX level in predicting AUROC of PBC-associated HCC was 0.714, 95%CI 0.597-0.857 and the sensitivity and specificity were 84.6%, and 59.0%, respectively. The optimal cutoff value for predicting serum ATX levels in the occurrence of HCC was 235.254 ng/ml. Conclusion: Patients with PBC have significantly higher levels of ATX expression in their peripheral blood and liver tissue, which can be utilized to assess treatment effectiveness and predict disease progression.
目的： 明确自分泌运动因子（ATX）在预测原发性胆汁性胆管炎（PBC）疾病进展及相关肝细胞癌（HCC）中的价值。 方法： 选取解放军总医院第五医学中心肝病医学部自身免疫性肝病前瞻性队列中2016年1月至2018年1月期间收治的PBC初诊患者179例，所有PBC患者均接受熊去氧胆酸（UDCA）治疗，对入组PBC患者完成随访，随访终点事件为发生原发性肝癌，分析ATX与患者临床特征的关系及其在预测疾病进展和HCC中的意义。 结果： PBC患者外周血ATX水平显著高于酒精性肝硬化（t = 3.278，P = 0.001）和健康对照组（t = 6.594，P < 0.001），但与非PBC相关HCC患者相比，ATX水平差异无统计学意义（t = -0.240，P = 0.811)；PBC患者肝组织中ATX的表达显著高于健康人（Z = -3.633，P < 0.001）及酒精性肝硬化患者（Z = -3.283，P < 0.001)，而进展期ATX表达显著高于早期PBC患者（Z = -2.018，P = 0.034）。未发生HCC的PBC患者与发生HCC的PBC患者相比，基线ATX水平差异具有统计学意义[（228.451±124.093） ng/ml对比（301.583±100.512）ng/ml，t = 2.339，P = 0.021]；多因素logistic回归分析显示，ATX是PBC进展为HCC的独立预测因素（OR = 1.245, 95%CI为1.097~1.413）；基线外周血ATX水平在预测PBC相关肝癌的AUROC为0.714，95%CI为0.597~0.857，灵敏度为84.6%，特异度为59.0%，预测HCC发生的血清ATX水平的最佳临界值为235.254 ng/ml。 结论： ATX在PBC患者外周血水平及肝组织中的表达均显著升高，可用于PBC患者疗效评估和疾病进展预测。.
Keywords: Autotaxin; Hepatocellular carcinoma; Primary biliary cholangitis.