药物性肝内胆管消失综合征的临床特征与转归

Clinical features and prognosis of drug-induced vanishing bile duct syndrome

目的分析药物性肝损伤(drug-induced liver injury,DILI)伴胆管消失(vanishing bile duct syndrome,VBDS)患者的临床特征及转归。方法 2010年1月至2016年12月首都医科大学附属北京佑安医院临床诊断为DILI患者1 010例,其中267例肝脏穿刺,病理符合VBDS患者19例,在无胆管损伤DILI患者中采用数字表法随机抽取54例作为对照。比较两组患者的临床资料及转归。结果 VBDS占7.12%(19/267),73.68%(14/19)临床表现为胆汁淤积,26.32%(5/19)患者无黄疸。与无VBDS组相比,大部分VBDS患者进展为慢性肝损伤(88.2%vs 35.2%)。涉及药物包括性激素2例(10.5%),非甾体抗炎药3例(16%),免疫调节剂3例(16%),抗生素3例(16%),中草药4例(21%),染发剂1例(5%),质子泵抑制剂1例(5%),抗精神药2例(10.5%)。VBDS患者与无VBDS患者比较,总胆固醇(cholesterol,CHOL)[(8.4±3.9) mmol/L vs (4.4±1.5) mmol/L]、碱性磷酸酶(alkaline phosphatase,ALP)[(613.6±544.4) U/L vs (151.8±70.4) U/L]、谷氨酰转肽酶(glutamyl transpeptidase,GGT)[(631.2±472.8) U/L vs (228.7±174.4) U/L]均升高,差异均有统计学意义(P <0.05)。结论大部分VBDS患者临床表现胆汁淤积,VBDS可能是慢性DILI患者的病理基础,预后较差。

Objective To analyze the clinical features and outcomes of the drug-induced liver injury(DILI)patients with vanishing bile duct syndrome(VBDS).Methods A total of 1010 patients with DILI were diagnosed clinically from January 2010 to December 2016.Of which,267 patients underwent liver biopsy,19 patients were diagnosed DILI with VBDS by histology.At the same time,54 patients without VBDS were randomly enrolled as a control.The clinical data and outcomes of the two groups of patients were compared.Results In this study,VBDS accounted for 7.12%(19/267).Of DILI patients with VBDS,73.68%(14/19)patients had cholestasis,26.32%(5/19)had no jaundice.The majority of VBDS patients were developed to chronic liver injury(88.2%vs 35.2%)compared to those without VBDS.Those drugs included sex hormones drugs(n=2),non-steroidal anti-inflammatory drugs(n=3),immunomodulators drugs(n=3),antibiotics(n=3),herbal products(n=4),hair dye(n=1),proton pump inhibitor(n=1),and antipsychotics(n=1).VBDS patients had significantly higher than those without VBDS serum cholesterol(CHOL)[(8.4±3.9)vs(4.4±1.5)mmol/L],alkaline phosphatase(ALP)[(613.6±544.4)U/L vs(151.8±70.4)U/L],and glutamyl transpeptidase(GGT)[(631.2±472.8)U/L vs(228.7±174.4)U/L](P<0.05).Conclusion Most DILI patients with VBDS have cholestasis.VBDS may be the pathological basis of patients development to chronic DILI with poor prognosis.