三联疗法治疗难治性原发性胆汁性胆管炎的临床研究

Clinical study of triple therapy for intractable primary biliary cholangitis

目的探讨熊去氧胆酸(ursodeoxycholic acid,UDCA)联合泼尼松龙、免疫抑制剂治疗难治性原发性胆汁性胆管炎(primary biliary cholangitis,PBC)的临床疗效。方法选取2017年6月至2019年6月于温州医科大学附属平阳医院就诊的难治性PBC患者59例,所有患者在原有UDCA治疗的基础上加用泼尼松龙和免疫抑制剂(硫唑嘌呤或吗替麦考酚酯),记录患者在基线和治疗3、6、12、18、24个月时的实验室检查、免疫指标、肝纤维化无创性评估数据,探讨影响难治性PBC患者预后的因素。结果所有患者基线时谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)、γ-谷氨酰转移酶(γ-glutamyl transferase,GGT)、总胆红素(total bilirubin,TBiL)、免疫球蛋白(immunoglobulin,Ig)G和IgM均高于正常值范围,白蛋白(albumin,ALB)均低于正常值;肝脏病理分期以Ⅱ~Ⅲ期为主。谷草转氨酶-血小板比率指数(aspartate aminotransferase-to-plateletratio index,APRI)、基于4因子的纤维化指数(fibrosis index based on the four factors,FIB-4)显示肝纤维化进展与肝脏病理一致。抗线粒体抗体(anti-mitochondrial antibody,AMA)阳性率为72.88%,抗核抗体(antinuclear antibody,ANA)阳性率为96.61%。随访24个月,结果显示ALT、AST、ALP、GGT、TBiL、IgG、IgM、APRI和FIB-4呈下降趋势(P<0.05),ALB呈上升趋势(P<0.05);治疗3个月后AMA阳性率和ANA阳性率均为0。多因素分析结果显示基线ALB降低是难治性PBC患者预后不良的危险因素(P<0.05)。结论UDCA联合泼尼松龙、免疫抑制剂的三联疗法治疗难治性PBC患者可明显改善各项指标,值得临床推荐应用;基线ALB降低是造成难治性PBC患者预后不良的危险因素,应密切监测。

Objective To investigate the clinical efficacy of ursodeoxycholic acid(UDCA)combined with prednisolone and immunosuppressant in the treatment of intractable primary biliary cholangitis(PBC).Methods A total of 59 patients with intractable PBC treated in Pingyang Hospital Affiliated to Wenzhou Medical University from June 2017 to June 2019 were selected.All patients were treated with prednisolone and immunosuppressant(azathioprine or mycophenolate mofetil)in addition to the original UDCA therapy.Laboratory tests,immune indicators,and non-invasive evaluation data of hepatic fibrosis were recorded at baseline and at 3,6,12,18,and 24 months of treatment,and explored the factors affecting the prognosis of intractable PBC patients.Results In all patients,alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),γ-glutamyl transferase(GGT),total bilirubin(TBiL),immunoglobulin(Ig)G,and IgM levels were found to be higher than the normal range,while albumin(ALB)levels were lower than normal.Liver pathology stages were predominantly stageⅡ-Ⅲ.Aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis index based on the four factors(FIB-4)showed that the progression of hepatic fibrosis was consistent with liver pathology.The positive rate of anti-mitochondrial antibody(AMA)was 72.88%,and antinuclear antibody(ANA)was 96.61%.After 24 months of follow-up,ALT,AST,ALP,GGT,TBiL,IgG,IgM,APRI and FIB-4 showed a decreasing trend(P<0.05),ALB showed an increasing trend(P<0.05).The positive rates of AMA and ANA were zero after 3 months of treatment.Multivariate analysis showed that baseline ALB reduction was a risk factor for poor prognosis in patients with intractable PBC(P<0.05).Conclusion Triple therapy of UDCA combined with prednisolone and immunosuppressant can significantly improve various indexes in the treatment of intractable PBC patients,and is worthy of clinical recommendation.Baseline ALB reduction is a risk factor for poor prognosis in patients with intractable PBC and should be closely monitored.