原发性胆汁性胆管炎治疗应答的影响因素及预后预测作用研究

Response to Primary Biliary Cholangitis Treatment:Influencing Factors and the Role in Prognosis Prediction

目的探索血脂异常的原发性胆汁性胆管炎(primary biliary cholangitis,PBC)患者对熊去氧胆酸(ursodeoxycholic acid,UDCA)治疗应答不佳的影响因素、预后特点。方法回顾性收集2009年1月-2022年3月在四川大学华西医院治疗的512例确诊为PBC的患者。根据UDCA治疗应答情况分为完全应答组(n=305)和UDCA应答不佳组(n=207),对比两组患者的资料,预测影响应答的不利因素。受试者工作特征(receiver operating characteristic,ROC)曲线下面积(area under the curve,AUC)确定血清总胆固醇(total cholesterol,TC)的临界值,分析患者基线实验室检查指标、治疗后应答的差异。根据临界值将患者分为TC≥5.415 mmol/L组与TC<5.415 mmol/L组,并使用UK-PBC、GLOBE评分评估两组预后的差异。结果UDCA应答不佳组的基线谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TB)、碱性磷酸酶(alkaline phosphatase,ALP)、γ-谷氨酰转肽酶(gammaglutamyl transferase,GGT)、甘油三酯(triglyceride,TG)、TC、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)和低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)较完全应答组升高(P均<0.05),白蛋白水平下降(P=0.012)。logistic回归模型多因素分析提示TC[比值比(odds ratio,OR)=1.501,95%置信区间(confidence interval,CI):1.275~1.767,P<0.01]和ALP(OR=1.005,95%CI:1.003~1.006,P<0.01)是影响应答的独立风险因素。ROC曲线分析提示TC≥5.415 mmol/L的PBC患者预后更差(AUC:0.727,95%CI:0.680~0.775,敏感性63.8%,特异性76.4%)。另外,高TC组(TC≥5.415 mmol/L)治疗1年时的UK-PBC风险评分高于低TC组(TC<5.415 mmol/L),差异有统计学意义(P<0.01)。结论高胆固醇血症是PBC患者对UDCA应答不佳的一个独立风险因素。当基线血清TC≥5.415 mmol/L时,PBC患者对UDCA治疗的应答及预后较差。

Objective To examine the influencing factors and prognostic features of poor response to ursodeoxycholic acid(UDCA)treatment in primary biliary cholangitis(PBC)patients with dyslipidemia.Methods A retrospective study was conducted,covering 512 patients who had a confirmed diagnosis of PBC,and who received treatment at West China Hospital,Sichuan University between January 2009 and March 2022.According to their actual response to UDCA treatment,patients were divided into two groups,UDCA full-response group(n=305)and UDCA non-responding group(n=207).The data from the two groups were compared to predict the adverse factors influencing patient response and the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,identify the cut-off value of total cholesterol(TC),and analyze the differences in baseline laboratory test findings and the rate of responses to treatment.According to the TC cut-off value,patients were divided into a group with TC≥5.415 mmol/L and another group with TC<5.415 mmol/L.In addition,differences in the prognosis of the two groups were assessed by comparing the UK-PBC and GLOBE scores.Results The baseline data,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TB),alkaline phosphatase(ALP),gamma-glutamyl transpeptidase(GGT),triglycerides(TG),TC,high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C),were significantly increased in the UDCA non-responding group compared to those in the full-response group(all P<0.005),while the albumin level of the UDCA non-responding group was decreased compared to that of the full-response group(P=0.012).Findings of multi-factor logistic regression analysis suggested that TC(odds ratio[OR]=1.501,95%confidence interval[CI]:1.275-1.767,P<0.01)and ALP(OR=1.005,95%CI:1.003-1.006,P<0.01)were independent risk factors influencing patient response.The ROC curve analysis suggested worse prognosis for patients with TC≥5.415 mmol/L(AUC:0.727,95%CI:0.680-0.775,63.8%sensitivity,76.4%specificity).In addition,the UK-PBC risk score at 1 year of treatment was higher in the high-TC group(TC≥5.415 mmol/L)than that in the low-TC group(TC<5.415 mmol/L)(P<0.05).Conclusions Hypercholesterolemia is an independent risk factor for poor response to UDCA in PBC patients.When the baseline TC is equal to or higher than 5.415 mmol/L,PBC patients have a relatively poor response to UDCA and poor prognosis.