药物性肝损伤与原发性胆汁性胆管炎引起胆管消失综合征的病理学特征比较
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摘要
目的比较药物性肝损伤(DILI)与原发性胆汁性胆管炎(PBC)引起的胆管消失综合征(VBDS)患者的病理学特征,总结临床鉴别特点。方法回顾性选取2003年1月-2018年1月于石家庄市第五医院经肝穿刺病理明确诊断合并VBDS的DILI患者(D-VBDS组) 42例、PBC患者(P-VBDS组) 43例,收集入选患者的一般资料、临床症状体征、血清学指标等数据,观察病理形态学特征。计量资料2组间比较采用Mann-Whitney U秩和检验;计数资料2组间比较采用X~2检验。结果 2组患者均以40～50岁女性多见。D-VBDS组发生皮肤巩膜黄染较P-VBDS组多见,差异有统计学意义(X~2=5. 683,P=0. 017)。肝生化各指标高峰值比较,D-VBDS组TBil(Z=-2. 020,P=0. 043)、DBil (Z=-2. 910,P=0. 004)明显高于P-VBDS组。病理形态学分析显示,P-VBDS组在汇管区炎症、汇管区纤维化、汇管区肉芽肿病理形态学评分高于D-VBDS组,差异均有统计学意义(Z值分别为-3. 136、-2. 710、-2. 913,P值分别为0. 002、0. 007、0. 005);肝小叶内形态学评分结果分析显示,D-VBDS组在小叶内炎症、毛细胆管胆栓、活化吞噬细胞的病理形态学评分高于P-VBDS组,差异均有统计学意义(Z值分别为-3. 255、-2. 455、-4. 398,P值分别为0. 001、0. 014、<0. 001)。结论肝组织病理形态特点是D-VBDS与P-VBDS较为客观准确的鉴别点,对明确诊断、了解病变损伤程度及判断预后具有重要意义。
Objective To investigate the clinical features of patients with drug-induced liver injury( DILI) and vanishing bile duct syndrome( VBDS) and patients with primary biliary cholangitis( PBC) and VBDS. Methods A retrospective analysis was performed for the clinical data of 42 DILI patients and 43 PBC patients who visited Shijiazhuang Fifth Hospital from January 2003 to January 2018 were diagnosed with VBDS by liver biopsy,including general information,clinical symptoms and signs,and serological markers,and pathomorphological features were observed. The Mann-Whitney U rank sum test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Most of the patients in the two groups were female patients aged 40-50 years. The D-VBDS group had a significantly higher incidence rate of yellow staining of skin and sclera than the P-VBDS group( X~2=5. 683,P = 0. 017). Comparison of the peak values of liver biochemical indices showed that compared with the P-VBDS group,the D-VBDS group had significantly higher total bilirubin( Z =-2. 020,P = 0. 043) and direct bilirubin( Z =-2. 910,P = 0. 004). According to the results of pathomorphological analysis and morphological scores of the portal area,the P-VBDS group had significantly higher morphological scores of portal inflammation,fibrosis,and granuloma than the D-VBDS group( Z =-3. 136,-2. 710,and-2. 913,P =0. 002,0. 007,and 0. 005). The morphological scores of the hepatic lobules showed that compared with the P-VBDS group,the D-VBDS group had significantly higher morphological scores of intralobular inflammation,bile thrombus in bile capillary,and activated phagocytes( Z =-3. 255,-2. 455,and-4. 398,P = 0. 001,0. 014,and < 0. 001). Conclusion Pathomorphological features of the liver are objective and accurate indices for the differentiation between DILI with VBDS and PBS with VBDS and have great significance in making a definite diagnosis,understanding the degree of injury,and predicting prognosis.
Objective To investigate the clinical features of patients with drug-induced liver injury( DILI) and vanishing bile duct syndrome( VBDS) and patients with primary biliary cholangitis( PBC) and VBDS. Methods A retrospective analysis was performed for the clinical data of 42 DILI patients and 43 PBC patients who visited Shijiazhuang Fifth Hospital from January 2003 to January 2018 were diagnosed with VBDS by liver biopsy,including general information,clinical symptoms and signs,and serological markers,and pathomorphological features were observed. The Mann-Whitney U rank sum test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Most of the patients in the two groups were female patients aged 40-50 years. The D-VBDS group had a significantly higher incidence rate of yellow staining of skin and sclera than the P-VBDS group( X~2=5. 683,P = 0. 017). Comparison of the peak values of liver biochemical indices showed that compared with the P-VBDS group,the D-VBDS group had significantly higher total bilirubin( Z =-2. 020,P = 0. 043) and direct bilirubin( Z =-2. 910,P = 0. 004). According to the results of pathomorphological analysis and morphological scores of the portal area,the P-VBDS group had significantly higher morphological scores of portal inflammation,fibrosis,and granuloma than the D-VBDS group( Z =-3. 136,-2. 710,and-2. 913,P =0. 002,0. 007,and 0. 005). The morphological scores of the hepatic lobules showed that compared with the P-VBDS group,the D-VBDS group had significantly higher morphological scores of intralobular inflammation,bile thrombus in bile capillary,and activated phagocytes( Z =-3. 255,-2. 455,and-4. 398,P = 0. 001,0. 014,and < 0. 001). Conclusion Pathomorphological features of the liver are objective and accurate indices for the differentiation between DILI with VBDS and PBS with VBDS and have great significance in making a definite diagnosis,understanding the degree of injury,and predicting prognosis.
引文
[1]BGORNSSON ES.Drug-induced liver injury due to antibiotics[J].Scand J Gastroenterol,2017,52(6-7):617-623.
[2]OPPENHEIMER AP,KOH C,MCLAUGHLIN M,et al.Vanishing bile duct syndrome in human immunodeficiency virus infected adults:A report of two cases[J].World J Gastroenterol,2013,19(1):115-121.
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[4]Chinese Society of Hepatology,Chinese Medical Association;Chinese Society of Gastroenterology,Chinese Medical Association;Chinese Society of Infectious Diseases,Chinese Medical Association.Consensus on the diagnosis and management of primary biliary cirrhosis(cholangitis)(2015)[J].J Clin Hepatol,2015,31(12):1980-1988.(in Chinese)中华医学会肝病学分会,中华医学会消化病学分会,中华医学会感染病学分会.原发性胆汁性肝硬化(又名原发性胆汁性胆管炎)诊断和治疗共识(2015)[J].临床肝胆病杂志,2015,31(12):1980-1988.
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[8]SUN Y,ZHAO XY,JIA JD.Etiological diagnosis and prognosis of vanishing bile duct syndrome[J].Liver,2014,19(2):137-139.(in Chinese)孙玥,赵新颜,贾继东.胆管消失综合征病因学诊断及预后进展[J].肝脏,2014,19(2):137-139.
[9]JGARCIA-CORTES M,ORTEGA-ALONSO A,LUCENA MI,et al.Drug-induced liver injury:A safety review[J].Expert Opin Drug Saf,2018,17(8):795-804.
[10]JBESSONE F,DIRCHWOLF M,RODIL MA,et al.Review article:Drug-induced liver injury in the context of nonalcoholic fatty liver diseasea physiopathological and clinical integrated view[J].Aliment Pharmacol Ther,2018,48(9):892-913.
[11]JPALOMO L,MLECZKO JE,AZARGORTA M,et al.Abundance of cytochromes in hepatic extracellular vesicles is altered by drugs related with drug-induced liver injury[J].Hepatol Commun,2018,2(9):1064-1079.
[12]WANG LF,LI YY,JIN L,et al.Epidemiology and natural history of primary biliary cirrhosis[J].J Clin Hepatol,2015,31(2):165-170.(in Chinese)王立峰,李元元,金磊,等.原发性胆汁性肝硬化的流行病学与自然史变迁[J].临床肝胆病杂志,2015,31(2):165-170.
[13]CHEN Y,HAN Y.Clinical features of primary biliary cholangitis and stratified treatment management[J].J Clin Hepatol,2017,33(11):2095-2100.(in Chinese)陈瑜,韩英.原发性胆汁性胆管炎的临床特征与治疗分层管理[J].临床肝胆病杂志,2017,33(11):2095-2100.
[14]VISENTIN M,LENQQENHAQER D,GAI Z,et al.Drug-induced bile duct injury[J].Biochim Biophys Mol Basis Dis,2018,1846(4 Pt B):1498-1506.
[15]CONRAD MA,CUI J,LIN HC.Sertraline-associated cholestasis and ductopenia consistent with vanishing bile duct syndrome[J].Am J Surg Pathol,2016,169(18):313-315.
[2]OPPENHEIMER AP,KOH C,MCLAUGHLIN M,et al.Vanishing bile duct syndrome in human immunodeficiency virus infected adults:A report of two cases[J].World J Gastroenterol,2013,19(1):115-121.
[3]The Study of Drug Induced Liver Disease of Chinese Medical Association.Diagnosis and treatment guideline on drug-induced liver injury[J].J Clin Hepatol,2015,31(11):1752-1769.(in Chinese)中华医学会肝病学分会药物性肝病学组.药物性肝损伤诊治指南[J].临床肝胆病杂志,2015,31(11):1752-1769.
[4]Chinese Society of Hepatology,Chinese Medical Association;Chinese Society of Gastroenterology,Chinese Medical Association;Chinese Society of Infectious Diseases,Chinese Medical Association.Consensus on the diagnosis and management of primary biliary cirrhosis(cholangitis)(2015)[J].J Clin Hepatol,2015,31(12):1980-1988.(in Chinese)中华医学会肝病学分会,中华医学会消化病学分会,中华医学会感染病学分会.原发性胆汁性肝硬化(又名原发性胆汁性胆管炎)诊断和治疗共识(2015)[J].临床肝胆病杂志,2015,31(12):1980-1988.
[5]GOSSARD AA,TALWALKAR JA.Cholestatic liver disease[J].Med Clin North Am,2014,98(1):73-85.
[6]JEON J,SONG SY,LEE KH,et al.Clinical significance and long-term outcome of incidentally found bile ductdilatation[J].Dig Dis Sci,2013,58(11):3293-3299.
[7]LIU YW,YANG S,CHEN J.Extrahepatic autoimmune diseases in primary biliary cholangitis[J/CD].Chin J Liver Dis:E-lectronic Edition,2017,9(4):27-30.(in Chinese)刘雨薇,杨松,成军.原发性胆汁性胆管炎合并肝外自身免疫性疾病研究进展[J/CD].中国肝脏病杂志:电子版,2017,9(4):27-30.
[8]SUN Y,ZHAO XY,JIA JD.Etiological diagnosis and prognosis of vanishing bile duct syndrome[J].Liver,2014,19(2):137-139.(in Chinese)孙玥,赵新颜,贾继东.胆管消失综合征病因学诊断及预后进展[J].肝脏,2014,19(2):137-139.
[9]JGARCIA-CORTES M,ORTEGA-ALONSO A,LUCENA MI,et al.Drug-induced liver injury:A safety review[J].Expert Opin Drug Saf,2018,17(8):795-804.
[10]JBESSONE F,DIRCHWOLF M,RODIL MA,et al.Review article:Drug-induced liver injury in the context of nonalcoholic fatty liver diseasea physiopathological and clinical integrated view[J].Aliment Pharmacol Ther,2018,48(9):892-913.
[11]JPALOMO L,MLECZKO JE,AZARGORTA M,et al.Abundance of cytochromes in hepatic extracellular vesicles is altered by drugs related with drug-induced liver injury[J].Hepatol Commun,2018,2(9):1064-1079.
[12]WANG LF,LI YY,JIN L,et al.Epidemiology and natural history of primary biliary cirrhosis[J].J Clin Hepatol,2015,31(2):165-170.(in Chinese)王立峰,李元元,金磊,等.原发性胆汁性肝硬化的流行病学与自然史变迁[J].临床肝胆病杂志,2015,31(2):165-170.
[13]CHEN Y,HAN Y.Clinical features of primary biliary cholangitis and stratified treatment management[J].J Clin Hepatol,2017,33(11):2095-2100.(in Chinese)陈瑜,韩英.原发性胆汁性胆管炎的临床特征与治疗分层管理[J].临床肝胆病杂志,2017,33(11):2095-2100.
[14]VISENTIN M,LENQQENHAQER D,GAI Z,et al.Drug-induced bile duct injury[J].Biochim Biophys Mol Basis Dis,2018,1846(4 Pt B):1498-1506.
[15]CONRAD MA,CUI J,LIN HC.Sertraline-associated cholestasis and ductopenia consistent with vanishing bile duct syndrome[J].Am J Surg Pathol,2016,169(18):313-315.