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Intraoperative Hepatic Artery Blood Flow Predicts Early Hepatic Artery Thrombosis After Liver Transplantation
Intraoperative Hepatic Artery Blood Flow Predicts Early Hepatic Artery Thrombosis After Liver Transplantation L.M. Marín-Gómez, C. Bernal-Bellido, J.M. Álamo-Martínez, F.M. Porras-López, G. Suárez-Artacho, J. Serrano-Diaz-Canedo, J. Padillo-Ruiz, and M.A. Gómez-Bravo ABSTRACT Hepatic artery complications after orthotopic liver transplantation are associated with a high rate of graft loss and mortality (23% to 35%) because they can lead to liver ischemia. The reported incidence of hepatic artery thrombosis (HAT) after adult liver transplantation is 2.5% to 6.8%. Typically, these patients are treated with urgent surgical revascularization or emergent liver retransplantation. Since January 2007, we have recorded the postanastomotic hepatic artery flow after revascularization. The aim of this study was to assess the relationship between hepatic blood flow on revascularization and early HAT. Retrospectively, we reviewed perioperative variables from 110 consecutive liver transplantation performed at the Virgen del Rocío University Hospital (Seville, Spain) between January 2007 and October 2010. We evaluated the following preoperative (donor and recipient) and intraoperative variables: donor and recipient age, cytomegalovirus serology, ABO-compatibility, anatomical variations of the donor hepatic artery, number of arterial anastomoses, portal and hepatic artery flow before closure, cold ischemia time, and blood transfusion. These variables were included in a univariate analysis. Of the 110 patients included in the study, 85 (77.7%) were male. The median age was 52 years. ABO blood groups were identical between donor and recipient in all the patients. The prevalence of early HAT was 6.36% (7 of 110). Crude mortality with/without HAT was 22% versus 2% (P ⫽ .001), respectively. Crude graft loss rate with/without HAT was 27% versus 4% (P ⫽ .003), respectively. Early HAT was shown to be primarily associated with intraoperative hepatic artery blood flow (93.3 mL/min recipients with HAT versus 187.7 mL/min recipients without HAT, P ⬍ .0001). No retransplantation showed early HAT. In our experience, intraoperative hepatic artery blood flow predicts early HAT after liver transplantation. EPATIC artery complications after orthotopic liver transplantation (OLT) are associated with a high rate of graft loss and mortality (23% to 35%) because they can lead to liver ischemia.1 The reported incidence of hepatic artery thrombosis (HAT) after adult liver transplantation is 2.5% to 6.8%.2 Early HAT, occurring within days of transplantation, usually manifests as abnormal liver function test results and progresses to acute graft failure. Sufficient arterial blood flow is mandatory for liver regeneration and recovery of organ function after transplantation.3 Typically, these patients are treated with urgent surgical revascularization or emergent liver retransplantation.4,5 Several factors have been reported to predispose to HAT in full-size liver trans-
H
plantation, including technical aspects.6 Recent reports have assessed the relationship between the intraoperative vascular inflow and graft survival in liver transplantation recipients.7 Since January 2007, we have recorded the postanastomotic hepatic artery flow after revascularization. The aim of
From the Liver Transplant Unit (L.M.M.G., C.B.B., J.M.A.M., G.S.A., J.S.D.C., J.P.R., M.A.G.G.) and the Intensive Care Unit (F.M.P.L.), University Hospital “Virgen Del Rocío”, Seville, Spain. Address reprint requests to L.M. Marín-Gómez, C/La chiquita piconera, 19, San Juan de Aznalfarache, Sevilla, Spain 41920. E-mail: [email protected]
0041-1345/12/$–see front matter http://dx.doi.org/10.1016/j.transproceed.2012.07.077
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
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Transplantation Proceedings, 44, 2078 –2081 (2012)
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this study was to assess the relation between hepatic blood flow on revascularization and early HAT.
Table 2. Relationship Between Dichotomic Variables and Early Hepatic Thrombosis (chi Square) Early HAT
METHODS Retrospectively, we reviewed perioperative variables from 110 consecutive liver transplantations performed at the Virgen del Rocío University Hospital (Seville, Spain) between January 2007 and October 2010. We evaluated the following preoperative (donor and recipient) and intraoperative variables: donor and recipient age, cytomegalovirus serology, ABO-compatibility, anatomical variations of the donor hepatic artery, number of arterial anastomoses, portal and hepatic artery flow before closure, cold ischemia time, and blood transfusion. These variables were included in a univariate analysis. Portal and hepatic blood flow were measured by flowmeter at the end of surgery (Medi-Stim AS, Oslo, Norway). We defined early HAT as a thromboembolic occlusion of the hepatic artery occurring within 1 month after liver transplantation.8 Diagnosis of HAT was based on absence of intrahepatic arterial flow on duplex ultrasound, clinical identification of HAT at reexploration, or absence of hepatic arterial enhancement on computed tomographic angiogram or formal visceral angiogram. Overall actuarial survival was calculated from the date of OLT until death from any cause. Results are expressed as mean values ⫾ standard deviations for continuous variables and as percentages for qualitative variables. The optimal cut-off value for intraoperative blood flows with respect to hepatic artery thrombosis was established by receiver operating characteristic (ROC) curves. The Kaplan-Meier method and log-rank test were used to calculate the survival rates and differences in survival curves. All statistical tests were evaluated at the .05 significance level. Analyses were performed using commercially available software (SPSS 17.0; SPSS, Inc, Chicago, IL, United States).
RESULTS
Of the 110 patients included in the study, 85 (77.7%) were male. The median age was 52 years. ABO blood groups were identical between donor and recipient in all patients. The prevalence of early HAT was 6.36% (7 of 110). Crude mortality with/without HAT was 22% versus 2% (P ⫽ .001), respectively. Crude graft loss rate with/without HAT was 27% versus 4% (P ⫽ .003), respectively (Tables 1 and 2). The mean cumulative patient survival (Fig 1) was 52.7 Table 1. Relationship Between Continuous Variables and Early Hepatic Thrombosis (Student t) Early HAT Continuous Variables
No
Yes
P
n Recipient age Donor age MELD score No. anastomoses Portal flow Arterial flow Cold ischemia time PRC
103 52 ⫾ 9.7 52 ⫾ 17.8 17.8 ⫾ 6.5 1.2 ⫾ 0.4 1.8 ⫾ 0.8 188.3 ⫾ 3 398 ⫾ 111 4.3 ⫾ 3.6
7 51 ⫾ 7.5 57.6 ⫾ 16.5 16.1 ⫾ 6.1 1.3 ⫾ 0.5 1.3 ⫾ 0.4 93.3 ⫾ 28 415 ⫾ 68.4 6.6 ⫾ 3.3
NS NS NS NS .085 ⬍.001 NS NS
Abbreviations: HAT, hepatic artery thrombosis; MELD, Model for End-Stage Liver Disease; PRC, packed red blood cells; NS, not significant.
Dichotomic Variables
No
Yes
P
n CMV risk Anatomical variations Mortality Graft loss
103 6.8 22.3 2 4
7 0 42.8 22 27
— NS NS .001 .003
Abbreviations: HAT, hepatic artery thrombosis; CMV, cytomegalovirus; NS, not significant.
versus 37.1 months (no HAT versus HAT), P ⫽ .003. The mean cumulative graft survival (Fig 2) was 47.2 versus 26.8 months (no HAT versus HAT, respectively), P ⫽ .001. Early HAT was shown to be primarily associated with intraoperative hepatic artery blood flow (93.3 mL/min recipients with HAT versus 187.7 mL/min recipients without HAT, P ⬍ .0001). No retransplantation showed early HAT. We use ROC analysis to calculate the cut-off value of intraoperative hepatic artery blood flow related to the lack of HAT (Fig 3; Table 3). The area under curve was 0.831 (P ⫽ .003, confidence interval CI 95% [0.717– 0.944]). We selected 100.5 mL/min as cut-off point to predict the lack of HAT.
DISCUSSION
The success of liver transplantation depends on adequate inflow to the graft. Although HAT is not usual, its prevention and treatment represent a true primary endpoint in the outcome. Similar to Pratschke et al,7 we showed in our series the relationship between intraoperative hepatic artery blood flow and early HAT, as well as between early HAT and poor cumulative survival. No consensus exists on recommended arterial blood flow. Some authors consider that the minimum flow is 200 mL/min and when the value falls below this, they systematically rebuild a new arterial anastomosis with a graft directly from the aorta.9 Our series failed to reproduce these data because the arterial blood flow of the group without HAT was ⬍ 200 ml/min. In our experience, intraoperative hepatic artery blood flow predicts early HAT after liver transplantation. Table 3. Accuracy of Intraoperative Hepatic Artery Blood Flow to Predict the Lack of HAT After Liver Transplantation for Values > 100.5 mL/min Cut-off Arterial Flow (mL/min)
Value ⱖ100.5
CI 95%
Sensitivity (%) Specificity (%) PPV (%) NPV (%)
84.5 71.4 97.8 23.8
76.2–90.2 35.9–91.8 92.2–99.4 10.6–45.1
Abbreviations: CI, confidence interval; HAT, hepatic artery thrombosis; PPV, positive predictive value; NPV, negative predictive value.
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MARÍN-GÓMEZ, BERNAL-BELLIDO, ÁLAMO-MARTÍNEZ ET AL
Fig 1. Cumulative patient survival (months).
Fig 2. Cumulative graft survival (months).
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REFERENCES
Fig 3. ROC curve. Accuracy of intraoperative hepatic artery blood flow to predict the lack of HAT after liver transplantation for values ⱖ 100.5 mL/min.
ACKNOWLEDGMENT The authors thank Juan M. Praena for his assistance in statistical calculations.
1. Jain A, Costa G, Marsh W, et al: Thrombotic and nonthrombotic hepatic artery complications in adults and children following primary liver transplantation with long-term follow-up in 1000 consecutive patients. Transpl Int 19:27, 2006 2. Silva MA, Jambulingam PS, Gunson BK, et al: Hepatic artery thrombosis following orthotopic liver transplantation: a 10-year experience from a single centre in the United Kingdom. Liver Transpl 12:146, 2006 3. Reck T, Steinbauer F, Steinbauer M, et al: Impact of arterialization on hepatic oxygen supply, tissue energy phosphates, and outcome after liver transplantation in the rat. Transplantation 62:582, 1996 4. Pinna AD, Smith CV, Furukawa H, et al: Urgent revascularization of liver allografts after early hepatic artery thrombosis. Transplantation 15:1584, 1996 5. Bellido CB, Martínez JM, Gómez LM, et al: Indications and survival after liver retransplantation. Transplant Proc 42: 1281, 2010 6. Vivarelli M, Cucchetti A, LaBarba G, et al: Ischemic arterial complications after liver transplantation in the adult: multivariate analysis of risk factors. Arch Surg 139:1069, 2004 7. Pratschke S, Meimarakis G, Mayr S, et al: Arterial blood flow predicts graft survival in liver transplant patients. Liver Transpl 17:436, 2011 8. Pareja E, Cortes M, Navarro R, et al: Vascular complications after orthotopic liver transplantation: hepatic artery thrombosis. Transplant Proc 42:2970, 2010 9. Abbasoglu O, Levy M, Testa G, et al: Does intraoperative hepatic artery blood flow predict arterial complications after liver transplantation? Transplantation 66:598, 1998
H
plantation, including technical aspects.6 Recent reports have assessed the relationship between the intraoperative vascular inflow and graft survival in liver transplantation recipients.7 Since January 2007, we have recorded the postanastomotic hepatic artery flow after revascularization. The aim of
From the Liver Transplant Unit (L.M.M.G., C.B.B., J.M.A.M., G.S.A., J.S.D.C., J.P.R., M.A.G.G.) and the Intensive Care Unit (F.M.P.L.), University Hospital “Virgen Del Rocío”, Seville, Spain. Address reprint requests to L.M. Marín-Gómez, C/La chiquita piconera, 19, San Juan de Aznalfarache, Sevilla, Spain 41920. E-mail: [email protected]
0041-1345/12/$–see front matter http://dx.doi.org/10.1016/j.transproceed.2012.07.077
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2078
Transplantation Proceedings, 44, 2078 –2081 (2012)
HEPATIC ARTERY THROMBOSIS
2079
this study was to assess the relation between hepatic blood flow on revascularization and early HAT.
Table 2. Relationship Between Dichotomic Variables and Early Hepatic Thrombosis (chi Square) Early HAT
METHODS Retrospectively, we reviewed perioperative variables from 110 consecutive liver transplantations performed at the Virgen del Rocío University Hospital (Seville, Spain) between January 2007 and October 2010. We evaluated the following preoperative (donor and recipient) and intraoperative variables: donor and recipient age, cytomegalovirus serology, ABO-compatibility, anatomical variations of the donor hepatic artery, number of arterial anastomoses, portal and hepatic artery flow before closure, cold ischemia time, and blood transfusion. These variables were included in a univariate analysis. Portal and hepatic blood flow were measured by flowmeter at the end of surgery (Medi-Stim AS, Oslo, Norway). We defined early HAT as a thromboembolic occlusion of the hepatic artery occurring within 1 month after liver transplantation.8 Diagnosis of HAT was based on absence of intrahepatic arterial flow on duplex ultrasound, clinical identification of HAT at reexploration, or absence of hepatic arterial enhancement on computed tomographic angiogram or formal visceral angiogram. Overall actuarial survival was calculated from the date of OLT until death from any cause. Results are expressed as mean values ⫾ standard deviations for continuous variables and as percentages for qualitative variables. The optimal cut-off value for intraoperative blood flows with respect to hepatic artery thrombosis was established by receiver operating characteristic (ROC) curves. The Kaplan-Meier method and log-rank test were used to calculate the survival rates and differences in survival curves. All statistical tests were evaluated at the .05 significance level. Analyses were performed using commercially available software (SPSS 17.0; SPSS, Inc, Chicago, IL, United States).
RESULTS
Of the 110 patients included in the study, 85 (77.7%) were male. The median age was 52 years. ABO blood groups were identical between donor and recipient in all patients. The prevalence of early HAT was 6.36% (7 of 110). Crude mortality with/without HAT was 22% versus 2% (P ⫽ .001), respectively. Crude graft loss rate with/without HAT was 27% versus 4% (P ⫽ .003), respectively (Tables 1 and 2). The mean cumulative patient survival (Fig 1) was 52.7 Table 1. Relationship Between Continuous Variables and Early Hepatic Thrombosis (Student t) Early HAT Continuous Variables
No
Yes
P
n Recipient age Donor age MELD score No. anastomoses Portal flow Arterial flow Cold ischemia time PRC
103 52 ⫾ 9.7 52 ⫾ 17.8 17.8 ⫾ 6.5 1.2 ⫾ 0.4 1.8 ⫾ 0.8 188.3 ⫾ 3 398 ⫾ 111 4.3 ⫾ 3.6
7 51 ⫾ 7.5 57.6 ⫾ 16.5 16.1 ⫾ 6.1 1.3 ⫾ 0.5 1.3 ⫾ 0.4 93.3 ⫾ 28 415 ⫾ 68.4 6.6 ⫾ 3.3
NS NS NS NS .085 ⬍.001 NS NS
Abbreviations: HAT, hepatic artery thrombosis; MELD, Model for End-Stage Liver Disease; PRC, packed red blood cells; NS, not significant.
Dichotomic Variables
No
Yes
P
n CMV risk Anatomical variations Mortality Graft loss
103 6.8 22.3 2 4
7 0 42.8 22 27
— NS NS .001 .003
Abbreviations: HAT, hepatic artery thrombosis; CMV, cytomegalovirus; NS, not significant.
versus 37.1 months (no HAT versus HAT), P ⫽ .003. The mean cumulative graft survival (Fig 2) was 47.2 versus 26.8 months (no HAT versus HAT, respectively), P ⫽ .001. Early HAT was shown to be primarily associated with intraoperative hepatic artery blood flow (93.3 mL/min recipients with HAT versus 187.7 mL/min recipients without HAT, P ⬍ .0001). No retransplantation showed early HAT. We use ROC analysis to calculate the cut-off value of intraoperative hepatic artery blood flow related to the lack of HAT (Fig 3; Table 3). The area under curve was 0.831 (P ⫽ .003, confidence interval CI 95% [0.717– 0.944]). We selected 100.5 mL/min as cut-off point to predict the lack of HAT.
DISCUSSION
The success of liver transplantation depends on adequate inflow to the graft. Although HAT is not usual, its prevention and treatment represent a true primary endpoint in the outcome. Similar to Pratschke et al,7 we showed in our series the relationship between intraoperative hepatic artery blood flow and early HAT, as well as between early HAT and poor cumulative survival. No consensus exists on recommended arterial blood flow. Some authors consider that the minimum flow is 200 mL/min and when the value falls below this, they systematically rebuild a new arterial anastomosis with a graft directly from the aorta.9 Our series failed to reproduce these data because the arterial blood flow of the group without HAT was ⬍ 200 ml/min. In our experience, intraoperative hepatic artery blood flow predicts early HAT after liver transplantation. Table 3. Accuracy of Intraoperative Hepatic Artery Blood Flow to Predict the Lack of HAT After Liver Transplantation for Values > 100.5 mL/min Cut-off Arterial Flow (mL/min)
Value ⱖ100.5
CI 95%
Sensitivity (%) Specificity (%) PPV (%) NPV (%)
84.5 71.4 97.8 23.8
76.2–90.2 35.9–91.8 92.2–99.4 10.6–45.1
Abbreviations: CI, confidence interval; HAT, hepatic artery thrombosis; PPV, positive predictive value; NPV, negative predictive value.
2080
MARÍN-GÓMEZ, BERNAL-BELLIDO, ÁLAMO-MARTÍNEZ ET AL
Fig 1. Cumulative patient survival (months).
Fig 2. Cumulative graft survival (months).
HEPATIC ARTERY THROMBOSIS
2081
REFERENCES
Fig 3. ROC curve. Accuracy of intraoperative hepatic artery blood flow to predict the lack of HAT after liver transplantation for values ⱖ 100.5 mL/min.
ACKNOWLEDGMENT The authors thank Juan M. Praena for his assistance in statistical calculations.
1. Jain A, Costa G, Marsh W, et al: Thrombotic and nonthrombotic hepatic artery complications in adults and children following primary liver transplantation with long-term follow-up in 1000 consecutive patients. Transpl Int 19:27, 2006 2. Silva MA, Jambulingam PS, Gunson BK, et al: Hepatic artery thrombosis following orthotopic liver transplantation: a 10-year experience from a single centre in the United Kingdom. Liver Transpl 12:146, 2006 3. Reck T, Steinbauer F, Steinbauer M, et al: Impact of arterialization on hepatic oxygen supply, tissue energy phosphates, and outcome after liver transplantation in the rat. Transplantation 62:582, 1996 4. Pinna AD, Smith CV, Furukawa H, et al: Urgent revascularization of liver allografts after early hepatic artery thrombosis. Transplantation 15:1584, 1996 5. Bellido CB, Martínez JM, Gómez LM, et al: Indications and survival after liver retransplantation. Transplant Proc 42: 1281, 2010 6. Vivarelli M, Cucchetti A, LaBarba G, et al: Ischemic arterial complications after liver transplantation in the adult: multivariate analysis of risk factors. Arch Surg 139:1069, 2004 7. Pratschke S, Meimarakis G, Mayr S, et al: Arterial blood flow predicts graft survival in liver transplant patients. Liver Transpl 17:436, 2011 8. Pareja E, Cortes M, Navarro R, et al: Vascular complications after orthotopic liver transplantation: hepatic artery thrombosis. Transplant Proc 42:2970, 2010 9. Abbasoglu O, Levy M, Testa G, et al: Does intraoperative hepatic artery blood flow predict arterial complications after liver transplantation? Transplantation 66:598, 1998