The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or earl...The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.展开更多
AIM:To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions(IITBLs).METHODS:A prospective study was conducted to investig...AIM:To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions(IITBLs).METHODS:A prospective study was conducted to investigate potential microthrombosis in biliary microcirculation when non-heart-beating cadaveric livers were under warm or cold ischemic conditions.The experimental group included 140 patients who underwent liver transplantation during the period of January 2006 to December 2007, and survived for more than 1 year.The control group included 220 patients who received liver transplantation between July 1999 and December 2005 and survived for more than 1 year.In the experimental group, the arterial system of the donor liver was perfused twice with urokinase during cold perfusion and after trimming of the donor liver.The incidence of IITBLs was compared between the two groups.RESULTS:In the control group, the incidence of IITBLs was 5.9%(13/220 cases) after 3-11 mo of transplantation.In the experimental group, two recipients(1.4%) developed IITBLs at 3 and 6 mo after transplantation, respectively.The difference in the incidence between the two groups was statistically signiflcant(P < 0.05).CONCLUSION:Double perfusion of cadaveric livers from non-heart-beating donors with urokinase mayreduce the incidence of IITBLs.展开更多
BACKGROUND: Ischemic-type biliary lesions (ITBLs) play an extremely important role in influencing the long-term survival and quality of life of recipients after orthotopic liver transplantation (OLT). Some patients ca...BACKGROUND: Ischemic-type biliary lesions (ITBLs) play an extremely important role in influencing the long-term survival and quality of life of recipients after orthotopic liver transplantation (OLT). Some patients can be cured by interventional therapies, however others lose their grafts at last and receive liver retransplantation (re-OLT). The aim of this study was to analyze the data of 66 patients who had received re-OLT at our center because of ITBL and to discuss the treatment of ITBL after OLT. METHODS: We retrospectively analyzed 66 re-OLT cases due to ITBL from September 2001 to February 2007 at our center. The Kaplan-Meier method and the Cox-Mantel test were used to identify factors associated with mortality for univariate analysis and multivariate analysis, respectively. RESULTS: Fifty-five of 66 ITBL cases underwent interventional therapies before re-OLT. The actuarial survival at I month and I year for these patients was 83% and 74%, respectively. Prognostic factors for mortality in univariate analysis were model of end-stage liver disease score (MELD) >16.5 (chi(2)=5.856, P=0.016), cold ischemia time >8 hours (chi(2)=6.539, P=0.011), infections (chi(2)=5.550, P=0.018) and complications (chi(2)=12.168, P=0.002) after re-OLT. In the multivariate analysis (Cox regression), the risk factors independently associated with mortality were MELD score >16.5 (RR: 3.140; P=0.035), cold ischemia time >8.2 hours (RR: 0.192; P=0.016) and complications (RR: 3.896, P=0.003). CONCLUSIONS: The incidence of ITBL in China is higher than in other countries. Based on our experience, MELD score, cold ischemia time and complications after re-OLT are risk factors independently associated with mortality in retransplanted ITBL patients.展开更多
AIM: To evaluate the risk factors for ischemic-type biliary lesion(ITBL) after ABO-incompatible(ABO-I) adult living donor liver transplantation(ALDLT).METHODS: Among 141 ALDLTs performed in our hospital between 2008 a...AIM: To evaluate the risk factors for ischemic-type biliary lesion(ITBL) after ABO-incompatible(ABO-I) adult living donor liver transplantation(ALDLT).METHODS: Among 141 ALDLTs performed in our hospital between 2008 and 2014, 27(19%) were ABO-I ALDLT and 114 were ABO-identical/compatible ALDLT. In this study, we extensively analyzed the clinico-pathological data of the 27 ABO-I recipients to determine the risk factors for ITBL after ABO-I ALDLT. All ABO-I ALDLT recipients underwent an identical B-cell depletion protocol with preoperative rituximab, plasma exchange(PE), and operative splenectomy. The median follow-up period after transplantation was 26 mo. The clinical outcomes of the 27 ABO-I ALDLT recipients were compared with those of 114 ABO-identical/compatible ALDLT recipients.RESULTS: ITBL occurred in four recipients(14.8%) between 45 and 112 d after ABO-I ALDLT. The overall survival rates were not different between ABO-I ALDLT and ABO-identical/compatible ALDLT(P = 0.303). Among the ABO-I ALDLT recipients, there was no difference between patients with ITBL and those without ITBL in terms of B-cell and T-cell count, serum isoagglutinin titers, number of PEs, operative time and transfusion, use of graft infusion therapy, or number of remnant B-cell follicles and plasma cells in the spleen. However, the perioperative NK cell counts in the blood of patients with ITBL were significantly higher than those in the patients without ITBL(P < 0.05). Preoperative NK cell count > 150/μL and postoperative NK cell count > 120/μL were associated with greater relative risks(RR) for development of ITBL(RR = 20 and 14.3, respectively, P < 0.05). CONCLUSION: High NK cell counts in a transplant recipient's blood are associated with ITBL after ABO-I ALDLT. Further research is needed to elucidate the molecular mechanism of NK cell involvement in the development of ITBL.展开更多
AIM:To explore a method to establish an animal model of ischemic type intrahepatic biliary lesion in rabbits. METHODS:Forty Japanese white rabbits of clean grade were divided randomly into four groups(10 rabbits per g...AIM:To explore a method to establish an animal model of ischemic type intrahepatic biliary lesion in rabbits. METHODS:Forty Japanese white rabbits of clean grade were divided randomly into four groups(10 rabbits per group)including sham operation(SO) group,and artery-bile obstruction(ABO)-1 h group, ABO-2 h group and ABO-3 h group.All the rabbits in this study underwent the same initial surgical procedure in which the liver was prepared as for graft removal during liver transplantation.Subsequently in the SO group,no additional vascular intervention was performed,while in groups ABO-1 h,ABO-2 h and ABO-3 h,the animals underwent combined clamping of the hepatic artery and common bile duct with microvascular clips for 1,2 and 3 h,respectively.After the scheduled occlusion time,the clip was removed to recover blood supply.The animals were killed 4 wk after operation.The survival rate,liver function, cholangiography and histopathological manifestation of the rabbits in each group were observed. RESULTS:The survival rate was 100%in groups SO,ABO-1 h and ABO-2 h,while it was 60%in group ABO-3 h.At each observation time,the change degree of the indexes of liver function was proportional to the clamping time(ABO-3 h>ABO-2 h>ABO-1 h> SO,P<0.05).Cholangiographical and histopathologic manifestations both showed that intrahepatic biliary lesion aggravated proportionally with the increase of the clamping time. CONCLUSION:An animal model of ischemic type intrahepatic biliary lesion in rabbits is successfully established,which may provide a reliable technique for basic and clinical research into the etiology, development and prophylaxis of ischemic type intrahepatic biliary lesion after liver transplantation.展开更多
BACKGROUND: The ischemic-type biliary lesion (ITBL) is one of the most serious biliary complications of liver transplantation. This study aimed to investigate the effects of autologous bone marrow mononuclear cell (BM...BACKGROUND: The ischemic-type biliary lesion (ITBL) is one of the most serious biliary complications of liver transplantation. This study aimed to investigate the effects of autologous bone marrow mononuclear cell (BM-MNC) implantation on neovascularization and the prevention of intrahepatic ITBL in a rabbit model. METHODS: The rabbits were divided into control, experimental model, and cell implantation groups, with 10 in each group. The model of intrahepatic ITBL was established by clamping the hepatic artery and common bile duct. Autologous BM-MNCs were isolated from the tibial plateau by density gradient centrifugation and were implanted through the common hepatic artery. Changes in such biochemical markers as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total bilirubin and direct bilirubin were measured. Four weeks after operation, cholangiography, histopathological manifestations, differentiation of BM-MNCs, microvessel density and the expression of vascular endothelial growth factor were assessed. RESULTS: Compared with the experimental model group, the BM-MNC implantation group showed superiority in the time to recover normal biochemistry. The microvessel density and vascular endothelial growth factor expression of the implantation group were significantly higher than those of the control and experimental model groups. The ITBL in the experimental model group was more severe than that in the implantation group and fewer new capillary blood vessels occurred around it. CONCLUSIONS: Implanted autologous BM-MNCs can differentiate into vascular endothelial cells, promote neovascularization and improve the blood supply to the ischemic bile duct, and this provides a new way to diminish or prevent intrahepatic ITBL after liver transplantation. (Hepatobiliary Pancreat Dis Int 2010; 9:593-599)展开更多
基金funding received in the form of the Catherine Marie Enright research scholarship from the Royal Australasian College of Surgeons to support his program of research
文摘The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.
文摘AIM:To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions(IITBLs).METHODS:A prospective study was conducted to investigate potential microthrombosis in biliary microcirculation when non-heart-beating cadaveric livers were under warm or cold ischemic conditions.The experimental group included 140 patients who underwent liver transplantation during the period of January 2006 to December 2007, and survived for more than 1 year.The control group included 220 patients who received liver transplantation between July 1999 and December 2005 and survived for more than 1 year.In the experimental group, the arterial system of the donor liver was perfused twice with urokinase during cold perfusion and after trimming of the donor liver.The incidence of IITBLs was compared between the two groups.RESULTS:In the control group, the incidence of IITBLs was 5.9%(13/220 cases) after 3-11 mo of transplantation.In the experimental group, two recipients(1.4%) developed IITBLs at 3 and 6 mo after transplantation, respectively.The difference in the incidence between the two groups was statistically signiflcant(P < 0.05).CONCLUSION:Double perfusion of cadaveric livers from non-heart-beating donors with urokinase mayreduce the incidence of IITBLs.
基金a grant from the China Medical Board in New York(No.06837).
文摘BACKGROUND: Ischemic-type biliary lesions (ITBLs) play an extremely important role in influencing the long-term survival and quality of life of recipients after orthotopic liver transplantation (OLT). Some patients can be cured by interventional therapies, however others lose their grafts at last and receive liver retransplantation (re-OLT). The aim of this study was to analyze the data of 66 patients who had received re-OLT at our center because of ITBL and to discuss the treatment of ITBL after OLT. METHODS: We retrospectively analyzed 66 re-OLT cases due to ITBL from September 2001 to February 2007 at our center. The Kaplan-Meier method and the Cox-Mantel test were used to identify factors associated with mortality for univariate analysis and multivariate analysis, respectively. RESULTS: Fifty-five of 66 ITBL cases underwent interventional therapies before re-OLT. The actuarial survival at I month and I year for these patients was 83% and 74%, respectively. Prognostic factors for mortality in univariate analysis were model of end-stage liver disease score (MELD) >16.5 (chi(2)=5.856, P=0.016), cold ischemia time >8 hours (chi(2)=6.539, P=0.011), infections (chi(2)=5.550, P=0.018) and complications (chi(2)=12.168, P=0.002) after re-OLT. In the multivariate analysis (Cox regression), the risk factors independently associated with mortality were MELD score >16.5 (RR: 3.140; P=0.035), cold ischemia time >8.2 hours (RR: 0.192; P=0.016) and complications (RR: 3.896, P=0.003). CONCLUSIONS: The incidence of ITBL in China is higher than in other countries. Based on our experience, MELD score, cold ischemia time and complications after re-OLT are risk factors independently associated with mortality in retransplanted ITBL patients.
基金Supported by An Academic-Grant for Scientific Research from Astellas Pharma Korea,Inc
文摘AIM: To evaluate the risk factors for ischemic-type biliary lesion(ITBL) after ABO-incompatible(ABO-I) adult living donor liver transplantation(ALDLT).METHODS: Among 141 ALDLTs performed in our hospital between 2008 and 2014, 27(19%) were ABO-I ALDLT and 114 were ABO-identical/compatible ALDLT. In this study, we extensively analyzed the clinico-pathological data of the 27 ABO-I recipients to determine the risk factors for ITBL after ABO-I ALDLT. All ABO-I ALDLT recipients underwent an identical B-cell depletion protocol with preoperative rituximab, plasma exchange(PE), and operative splenectomy. The median follow-up period after transplantation was 26 mo. The clinical outcomes of the 27 ABO-I ALDLT recipients were compared with those of 114 ABO-identical/compatible ALDLT recipients.RESULTS: ITBL occurred in four recipients(14.8%) between 45 and 112 d after ABO-I ALDLT. The overall survival rates were not different between ABO-I ALDLT and ABO-identical/compatible ALDLT(P = 0.303). Among the ABO-I ALDLT recipients, there was no difference between patients with ITBL and those without ITBL in terms of B-cell and T-cell count, serum isoagglutinin titers, number of PEs, operative time and transfusion, use of graft infusion therapy, or number of remnant B-cell follicles and plasma cells in the spleen. However, the perioperative NK cell counts in the blood of patients with ITBL were significantly higher than those in the patients without ITBL(P < 0.05). Preoperative NK cell count > 150/μL and postoperative NK cell count > 120/μL were associated with greater relative risks(RR) for development of ITBL(RR = 20 and 14.3, respectively, P < 0.05). CONCLUSION: High NK cell counts in a transplant recipient's blood are associated with ITBL after ABO-I ALDLT. Further research is needed to elucidate the molecular mechanism of NK cell involvement in the development of ITBL.
文摘AIM:To explore a method to establish an animal model of ischemic type intrahepatic biliary lesion in rabbits. METHODS:Forty Japanese white rabbits of clean grade were divided randomly into four groups(10 rabbits per group)including sham operation(SO) group,and artery-bile obstruction(ABO)-1 h group, ABO-2 h group and ABO-3 h group.All the rabbits in this study underwent the same initial surgical procedure in which the liver was prepared as for graft removal during liver transplantation.Subsequently in the SO group,no additional vascular intervention was performed,while in groups ABO-1 h,ABO-2 h and ABO-3 h,the animals underwent combined clamping of the hepatic artery and common bile duct with microvascular clips for 1,2 and 3 h,respectively.After the scheduled occlusion time,the clip was removed to recover blood supply.The animals were killed 4 wk after operation.The survival rate,liver function, cholangiography and histopathological manifestation of the rabbits in each group were observed. RESULTS:The survival rate was 100%in groups SO,ABO-1 h and ABO-2 h,while it was 60%in group ABO-3 h.At each observation time,the change degree of the indexes of liver function was proportional to the clamping time(ABO-3 h>ABO-2 h>ABO-1 h> SO,P<0.05).Cholangiographical and histopathologic manifestations both showed that intrahepatic biliary lesion aggravated proportionally with the increase of the clamping time. CONCLUSION:An animal model of ischemic type intrahepatic biliary lesion in rabbits is successfully established,which may provide a reliable technique for basic and clinical research into the etiology, development and prophylaxis of ischemic type intrahepatic biliary lesion after liver transplantation.
文摘BACKGROUND: The ischemic-type biliary lesion (ITBL) is one of the most serious biliary complications of liver transplantation. This study aimed to investigate the effects of autologous bone marrow mononuclear cell (BM-MNC) implantation on neovascularization and the prevention of intrahepatic ITBL in a rabbit model. METHODS: The rabbits were divided into control, experimental model, and cell implantation groups, with 10 in each group. The model of intrahepatic ITBL was established by clamping the hepatic artery and common bile duct. Autologous BM-MNCs were isolated from the tibial plateau by density gradient centrifugation and were implanted through the common hepatic artery. Changes in such biochemical markers as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total bilirubin and direct bilirubin were measured. Four weeks after operation, cholangiography, histopathological manifestations, differentiation of BM-MNCs, microvessel density and the expression of vascular endothelial growth factor were assessed. RESULTS: Compared with the experimental model group, the BM-MNC implantation group showed superiority in the time to recover normal biochemistry. The microvessel density and vascular endothelial growth factor expression of the implantation group were significantly higher than those of the control and experimental model groups. The ITBL in the experimental model group was more severe than that in the implantation group and fewer new capillary blood vessels occurred around it. CONCLUSIONS: Implanted autologous BM-MNCs can differentiate into vascular endothelial cells, promote neovascularization and improve the blood supply to the ischemic bile duct, and this provides a new way to diminish or prevent intrahepatic ITBL after liver transplantation. (Hepatobiliary Pancreat Dis Int 2010; 9:593-599)
