肝移植患者术后14天内胆汁中胆汁酸水平变化及其对缺血性胆管损伤发生的预测价值
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摘要
目的观察肝移植患者术后14天内胆汁中胆汁酸水平变化,探讨其对缺血性胆管损伤(ITBL)发生的预测价值。方法选取原位肝移植手术患者39例,采用液相色谱串联质谱法检测术后第1、3、7、14天胆汁中6种胆汁酸水平变化,即甘氨胆酸(GCA)、牛磺胆酸(TCA)、牛磺石胆酸(TLCA)、甘氨鹅脱氧胆酸(GCDCA)、甘氨酸结合脱氧胆酸(GDCA)、牛磺酸结合脱氧胆酸(TDCA)。术后随访3个月,以胆道造影结果为金标准判定是否发生ITBL,比较发生ITBL者(ITBL组)与未发生者(N-ITBL组)术后第1、3、7、14天各胆汁酸水平,采用ROC曲线评价各胆汁酸对术后发生ITBL的预测价值。结果术后第1天,ITBL组胆汁中GDCA水平较N-ITBL组降低;术后第7天,ITBL组胆汁中GCA、GDCA水平较N-ITBL组升高;术后第14天,ITBL组胆汁中TLCA、GCDCA、GDCA水平较N-ITBL组升高;组间比较P均<0.05。ROC曲线分析显示,术后第14天胆汁中GCDCA水平对判断肝移植术后发生ITBL的AUC为0.751、TLCA的AUC为0.764,术后第7天GCA水平对判断肝移植术后发生ITBL的AUC为0.717。结论肝移植术后14天内胆汁中GCDCA、GCA、TLCA水平升高,三者对肝移植患者术后3个月内发生ITBL具有预测价值。
Objective To detect the levels of bile acids in the bile of patients within 14 days after liver transplantation and to investigate their predictive value for the occurrence of ischemic-type biliary lesion( ITBL). Methods Thirty-nine orthotopic liver transplant patients were selected. Using LC-MSMS to detect the contents of six kinds of bile acids including glycocholic acid( GCA),taurocholic acid( TCA),TLCA,glycochenodeoxycholic acid( GCDCA),glycine combined with deoxycholic acid( GDCA) and taurine combined with deoxycholic acid( TDCA) on day 1,3,7 and 14. They were followed up for three months after surgery,and then we determined whether ITBL occurred according to cholangiography results which served as gold standard,and compared the content of each bile acid on day 1,3,7 and 14 between patients with ITBL( ITBL group) and patients without ITBL( N-ITBL group). We used ROC curve to assess the predictive value of bile acids for the occurrence of ITBL. Results On day 1,the content of GDCA was lower in the ITBL group than that in the NITBL group; on day 7,the contents of GCA and GDCA were higher in the ITBL group than those in the N-ITBL group; on day 14,the contents of TLCA,GCDCA and GDCA were higher in the ITBL group than those in the N-ITBL group,and significant difference was found between these two groups( all P < 0. 05). Analysis results of ROC carve showed that the AUC of GCDCA on day 14 for the occurrence of ITBL was 0. 751,AUC of GCA on day 7 was 0. 717,and AUC of TLCA on day14 was 0. 764. Conclusion The contents of GCDCA,GCA and TLCA within 14 days after liver transplantation are increased and they all can be used as reliable indexes to predict whether ITBL occurs within 3 months after surgery.
Objective To detect the levels of bile acids in the bile of patients within 14 days after liver transplantation and to investigate their predictive value for the occurrence of ischemic-type biliary lesion( ITBL). Methods Thirty-nine orthotopic liver transplant patients were selected. Using LC-MSMS to detect the contents of six kinds of bile acids including glycocholic acid( GCA),taurocholic acid( TCA),TLCA,glycochenodeoxycholic acid( GCDCA),glycine combined with deoxycholic acid( GDCA) and taurine combined with deoxycholic acid( TDCA) on day 1,3,7 and 14. They were followed up for three months after surgery,and then we determined whether ITBL occurred according to cholangiography results which served as gold standard,and compared the content of each bile acid on day 1,3,7 and 14 between patients with ITBL( ITBL group) and patients without ITBL( N-ITBL group). We used ROC curve to assess the predictive value of bile acids for the occurrence of ITBL. Results On day 1,the content of GDCA was lower in the ITBL group than that in the NITBL group; on day 7,the contents of GCA and GDCA were higher in the ITBL group than those in the N-ITBL group; on day 14,the contents of TLCA,GCDCA and GDCA were higher in the ITBL group than those in the N-ITBL group,and significant difference was found between these two groups( all P < 0. 05). Analysis results of ROC carve showed that the AUC of GCDCA on day 14 for the occurrence of ITBL was 0. 751,AUC of GCA on day 7 was 0. 717,and AUC of TLCA on day14 was 0. 764. Conclusion The contents of GCDCA,GCA and TLCA within 14 days after liver transplantation are increased and they all can be used as reliable indexes to predict whether ITBL occurs within 3 months after surgery.
引文
[1]王学浩,钱晓峰.肝移植术术后并发症及其防治:胆道系统并发症[J].山东医药,2005,45(17):62.
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[6]Song GW,Lee SG,Hwang S,et al.Biliary stricture is the only concern in ABO-incompatible adult living donor liver transplantation in the rituximab era[J].J Hepatol,2014,61(3):575-582.
[7]董辉,丛文铭.肝移植后抗体介导性排斥反应的进展[J].中华器官移植杂志,2014,35(8):509-511.
[8]Farid WR,de Jonge J,Slieker JC,et al.The importance of portal venous blood flow in ischemic-type biliary lesions after liver transplantation[J].Am J Transplant,2011,11(4):857-862.
[9]Farid WR,de Jonge J,Zondervan PE,et al.Relationship between the histological appearance of the portal vein and development of ischemic-type biliary lesions after liver transplantation[J].Liver Transpl,2013,19(10):1088-1098.
[10]Hofmann AF.The continuing importance of bile acids in liver and intestinal disease[J].Arch Intern Med,1999,159(22):2647-2658.
[11]Trauner M,Fickert P,Wagner M.MDR3(ABCB4)defects:a paradigm forthe genetics of adult cholestatic syndromes[J].Semin Liver Dis,2007,27(1):77-98.
[12]Rolo AP,Palmeira CM,Wallace KB.Mitochondrially mediated synergistic cell killing by bile acids[J].Biochim Biophys Acta,2003,1637(1):127-132.
[13]Li D,Sun J,Sun H,et al.Bile salt induces apoptosis of hepatocytes:the mechanism of hepatic function injury during obstructive jaundice[J].Zhonghua Wai Ke Za Zhi,1998,36(10):624-626,117.
[14]Faubion WA,Guicciardi ME,Miyoshi H,et al.Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas[J].J Clin Invest,1999,103(1):137-145.
[15]Rust C,Gores GJ.Apoptosis and liver disease[J].Am J Med,2000,108(7):567-574.
[2]Nakamura N,Nishida S,Neff GR,et al.Intrahepatic biliary strictures without hepatic artery thrombosis after liver transplantation:an analysis of 1,113 liver transplantations at a single center[J].Transplantation,2005,79(4):427-432.
[3]陈光,刘英秀,王健,等.肝移植术后非肝动脉性缺血性胆管损伤的早期胆管造影诊断[J].中华放射学杂志,2008,42(8):835-839.
[4]Moench C,Moench K,Lohse AW,et al.Prevention of ischemictype biliary lesions by arterial back-table pressure perfusion[J].Liver Transpl,2003,9(3):285-289.
[5]Pirenne J,Van Gelder F,Coosemans W,et al.Type of donor aortic preservation solution and not cold ischemia time is a major determinant of biliary strictures after liver transplantation[J].Liver Transpl,2001,7(6):540-545.
[6]Song GW,Lee SG,Hwang S,et al.Biliary stricture is the only concern in ABO-incompatible adult living donor liver transplantation in the rituximab era[J].J Hepatol,2014,61(3):575-582.
[7]董辉,丛文铭.肝移植后抗体介导性排斥反应的进展[J].中华器官移植杂志,2014,35(8):509-511.
[8]Farid WR,de Jonge J,Slieker JC,et al.The importance of portal venous blood flow in ischemic-type biliary lesions after liver transplantation[J].Am J Transplant,2011,11(4):857-862.
[9]Farid WR,de Jonge J,Zondervan PE,et al.Relationship between the histological appearance of the portal vein and development of ischemic-type biliary lesions after liver transplantation[J].Liver Transpl,2013,19(10):1088-1098.
[10]Hofmann AF.The continuing importance of bile acids in liver and intestinal disease[J].Arch Intern Med,1999,159(22):2647-2658.
[11]Trauner M,Fickert P,Wagner M.MDR3(ABCB4)defects:a paradigm forthe genetics of adult cholestatic syndromes[J].Semin Liver Dis,2007,27(1):77-98.
[12]Rolo AP,Palmeira CM,Wallace KB.Mitochondrially mediated synergistic cell killing by bile acids[J].Biochim Biophys Acta,2003,1637(1):127-132.
[13]Li D,Sun J,Sun H,et al.Bile salt induces apoptosis of hepatocytes:the mechanism of hepatic function injury during obstructive jaundice[J].Zhonghua Wai Ke Za Zhi,1998,36(10):624-626,117.
[14]Faubion WA,Guicciardi ME,Miyoshi H,et al.Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas[J].J Clin Invest,1999,103(1):137-145.
[15]Rust C,Gores GJ.Apoptosis and liver disease[J].Am J Med,2000,108(7):567-574.