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
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
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 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
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 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
Major injuries of the pancreas may result in considerable morbidity and mortality when associated with vascular and visceral injuries. In such cases, a right diagnosis and a prompt surgical intervention are necessary ...Major injuries of the pancreas may result in considerable morbidity and mortality when associated with vascular and visceral injuries. In such cases, a right diagnosis and a prompt surgical intervention are necessary to give a chance to the patient. We herein describe a case of blunt abdominal trauma in a 29-year- old man whose pancreatic rupture was associated with hepatic artery, splenic vein and extrahepatic bile duct damage. Immediate surgery was performed after computer tomograghy (CT), the haemorrhagic lesions dictat the emergency transfer to the operating room. Spleno-pancreatic resection was done with reconstruction of the hepatic artery, ligation of the splenic vein and a Roux-en-Y bilio-jejunal diversion. The early post-operative course was complicated by stenosis of the arterial reconstruction, which was treated by endovascular angioplasty followed by percutaneous drainage of symptomatic pseudocyst, rest and antibiotics. Finally, the patient was discharged and was alive without clinical problems at the time when we wrote this case report. The present case underlines the clinical relevance of vascular and visceral injuries associated with pancreatic trauma and the problems arising in the diagnostic evaluation and the surgical strategy of complex multiple visceral and vascular lesions in blunt abdominal trauma.展开更多
Biliary complicationsfBC) are a major cause of morbidity in liver transplant recipients with an incidence of 10-30% following orthotopic liver transplantation(OLT), and a mortality rate of up to 10%. The most commo...Biliary complicationsfBC) are a major cause of morbidity in liver transplant recipients with an incidence of 10-30% following orthotopic liver transplantation(OLT), and a mortality rate of up to 10%. The most common biliary complications are bile leaks, biliary strictures, ampullary dysfunction, and stones. Leaks predominate in the early posttransplant period; while stricture formation typically develops gradually over time. Risk factors for biliary complications comprise technical failure, T-tube-related complications, hepatic artery thrombosis, bleeding, ischemia/reperfusion injury, primary diseases, and other immunological, non-immunological, and infectious complications. Cholangiography, such as endoscopic retrograde cholangiopancreatograpby(ERCP) or percutaneous transhepatic cholangiogram(PTC), is considered the gold standard for identifying post-transplant BC. The management of biliary complications after OLT requires a multidisciplinary approach, in which interventional radiology and endoscopic techniques are emerging as the preferred treatment option, but in a selected majority of patients, surgery is still necessary.展开更多
AIM: To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver transplantation.METHODS: We retrospectively reviewed 200 patients of our newly est...AIM: To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver transplantation.METHODS: We retrospectively reviewed 200 patients of our newly established liver transplantation(LT) program, who received full size liver graft. Biliary reconstruction was performed by side-to-side(SS), end-to-end(EE) anastomosis or hepeaticojejunostomy(HJ). Biliary complications(BC), anastomotic stenosis, bile leak, papillary stenosis, biliary drain complication, ischemic type biliary lesion(ITBL) were evaluated by studying patient records, corresponding radiologic imaging and reports of interventional procedures [e.g., endoscopic retrograde cholangiopancreatography(ERCP)]. Laboratory results included alanine aminotransferase(ALT), gammaglutamyltransferase and direct/indirect bilirubin with focus on the first and fifth postoperative day, six weeks after LT. The routinely employed external bile drain was examined by a routine cholangiography on the fifth postoperative day and six weeks after transplantation as a standard procedure, but also whenever clinically indicated. If necessary, interventional(e.g., ERCP) or surgical therapy was performed. In case of biliary complication, patients were selected, assigned to different complication-groups and subsequently reviewed in detail. To evaluate the patients outcome, we focussed on appearance of postoperative/post-interventional cholangitis, need for rehospitalisation, retransplantation, ITBL or death caused by BC.RESULTS: A total of 200 patients [age: 56(19-72), alcoholic cirrhosis: n = 64(32%), hepatocellular carcinoma: n = 40(20%), acute liver failure: n = 23(11.5%), cryptogenic cirrhosis: n = 22(11%), hepatitis B virus /hepatitis C virus cirrhosis: n = 13(6.5%), primary sclerosing cholangitis: n = 13(6.5%), others: n = 25(12.5%) were included. The median follow-up was 27 mo until June 2015. The overall biliary complication rate was 37.5%(n = 75) with anastomotic strictures(AS): n = 38(19%), bile leak(BL): n = 12(6%), biliary drain complication: n = 12(6%); papillary stenosis(PS): n = 7(3.5%), ITBL: n = 6(3%). Clinically relevant were only 19%(n = 38). We established a comprehensive classification for AS with four grades according to clinical relevance. The reconstruction techniques [SS: n = 164, EE: n = 18, HJ: n = 18] showed no significant impact on the development of BCs in general(all n < 0.05), whereas in the HJ group significantly less AS were found(P = 0.031). The length of donor intensive care unit stay over 6 d had a significant influence on BC development(P = 0.007, HR = 2.85; 95%CI: 1.33-6.08) in the binary logistic regression model, whereas other reviewed variables had not [warm ischemic time > 45 min(P = 0.543), cold ischemic time > 10 h(P = 0.114), ALT init > 1500 U/L(P = 0.631), bilirubin init > 5 mg/d L(P = 0.595), donor age > 65(P = 0.244), donor sex(P = 0.068), rescue organ(P = 0.971)]. 13%(n = 10) of BCs had no therapeutic consequences, 36%(n = 27) resulted in repeated lab control, 40%(n = 30) received ERCP and 11%(n = 8) surgical therapy. Fifteen(7.5%) patients developed cholangitis [AS(n = 6), ITBL(n = 5), PS(n = 3), biliary lesion BL(n = 1)]. One patient developed ITBL twelve months after LT and subsequently needed retransplantation. Rehospitalisation rate was 10.5 %(n = 21) [AS(n = 11), ITBL(n = 5), PS(n = 3), BL(n = 1)] with intervention or reinterventional therapy as main reasons. Retransplantation was performed in 5(2.5%) patients [ITBL(n = 1), acute liver injury(ALI) by organ rejection(n = 3), ALI by occlusion of hepatic artery(n = 1)]. In total 21(10.5%) patients died within the follow-up period. Out of these, one patient with AS developed severe fatal chologenic sepsis after ERCP.CONCLUSION: In our data biliary reconstruction technique and ischemic times seem to have little impact on the development of BCs.展开更多
AIM To review the clinical impact of machine perfusion(MP) of the liver on biliary complications post-transplantation, particularly ischaemic-type biliary lesions(ITBL). METHODS This systematic review was performed in...AIM To review the clinical impact of machine perfusion(MP) of the liver on biliary complications post-transplantation, particularly ischaemic-type biliary lesions(ITBL). METHODS This systematic review was performed in accordance with the Preferred Reporting Systematic Reviews and MetaAnalysis(PRISMA) protocol. The following databases were searched: PubMed, MEDLINE and Scopus. The keyword "liver transplantation" was used in combination with the free term "machine perfusion". Clinical studies reporting results of transplantation of donor human livers following ex situ or in situ MP were analysed. Details relating to donor characteristics, recipients, technique of MP performed and post-operative biliary complications(ITBL, bile leak and anastomotic strictures) were critically analysed.RESULTS Fifteen articles were considered to fit the criteria for this review. Ex situ normothermic MP was used in 6 studies, ex situ hypothermic MP in 5 studies and the other 4 studies investigated in situ normothermic regional perfusion(NRP) and controlled oxygenated rewarming. MP techniques which have per se the potential to alleviate ischaemia-reperfusion injury: Such as hypothermic MP and NRP, have also reported lower rates of ITBL. Other biliary complications, such as biliary leak and anastomotic biliary strictures, are reported with similar incidences with all MP techniques. There is currently less clinical evidence available to support normothermic MP as a mitigator of biliary complications following liver transplantation. On the other hand, restoration of organ to full metabolism during normothermic MP allows assessment of hepatobiliary function before transplantation, although universally accepted criteria have yet to be validated.CONCLUSION MP of the liver has the potential to have a positive impact on post-transplant biliary complications, specifically ITBL, and expand extended criteria donor livers utilisation.展开更多
AIM: To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation (OLT) biliary complications and to study their profile before and after endoscopic therapy. METHODS: Pa...AIM: To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation (OLT) biliary complications and to study their profile before and after endoscopic therapy. METHODS: Patients who developed biliary complications were analysed in detail for the clinical information,laboratory tests,treatment offered,response to it,follow up and outcomes. The profile of liver enzymes was determined. The safety,efficacy and outcomes of endoscopic retrograde cholangiography (ERC) were also analysed. RESULTS: 40 patients required ERC for 70 biliary complications. GGT was found to be > 3 times (388.1 ± 70.9 U/mL vs 168.5 ± 34.2 U/L,P = 0.007) and SAP > 2 times (345.1 ± 59.1 U/L vs 152.7 ± 21.4 U/L,P = 0.003) the immediate post OLT values. Most frequent complication was isolated anastomotic strictures in 28 (40%). Sustained success was achieved in 26 (81%) patients. CONCLUSION: Biliary complications still remain an important problem post OLT. SAP and GGT can be used as early,non-invasive markers for diagnosis and also to assess the adequacy of therapy. Endoscopic management is usually effective in treating the majority of these biliary complications.展开更多
BACKGROUND Loss of graft function after liver transplantation(LT) inevitably requires liver retransplant. Retransplantation of the liver(Re LT) remains controversial because of inferior outcomes compared with the prim...BACKGROUND Loss of graft function after liver transplantation(LT) inevitably requires liver retransplant. Retransplantation of the liver(Re LT) remains controversial because of inferior outcomes compared with the primary orthotopic LT(OLT).Meanwhile, if accompanied by vascular complications such as arterial and portal vein(PV) stenosis or thrombosis, it will increase difficulties of surgery. We hereby introduce our center’s experience in Re LT through a complicated case of ReLT.CASE SUMMARY We report a patient who suffered from hepatitis B-associated cirrhosis and underwent LT in December 2012. Early postoperative recovery was uneventful.Four months after LT, the patient’s bilirubin increased significantly and he was diagnosed with an ischemic-type biliary lesion caused by hepatic artery occlusion. The patient underwent percutaneous transhepatic cholangial drainage and repeatedly replaced intrahepatic biliary drainage tube regularly for 5 years.The patient developed progressive deterioration of liver function and underwent liver re-transplant in January 2019. The operation was performed in a classic OLT manner without venous bypass. Both the hepatic artery and PV were occluded and could not be used for anastomosis. The donor PV was anastomosed with the recipient’s left renal vein. The donor hepatic artery was connected to the recipient’s abdominal aorta. The bile duct reconstruction was performed in an end-to-end manner. The postoperative process was very uneventful and the patient was discharged 1 mo after retransplantation.CONCLUSION With the development of surgical techniques, portal thrombosis and arterial occlusion are no longer contraindications for ReLT.展开更多
AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland.METHODS Data on liver donors and recipients in Queensland between 2005...AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland.METHODS Data on liver donors and recipients in Queensland between 2005 and 2014 was obtained from an electronic patient data system.In addition,intra-operative and post-operative characteristics were collected and a logistical regression analysis was performed to evaluate their association with the development of biliary strictures.RESULTS Of 296 liver transplants performed,285(96.3%) were from brain dead donors.Biliary strictures developed in 45(15.2%) recipients.Anastomotic stricture formation(n = 25,48.1%) was the commonest complication,with 14(58.3%) of these occurred within 6-mo of transplant.A percutaneous approach or endoscopic retrograde cholangiography was used to treat 17(37.8%) patients with biliary strictures.Biliary reconstruction was initially or ultimately required in 22(48.9%) patients.In recipients developing biliary strictures,bilirubin was significantly increased within the first postoperative week(Day 7 total bilirubin 74 μmol/L vs 49 μmol/L,P = 0.012).In both univariate and multivariate regression analysis,Day 7 total bilirubin > 55 μmol/L was associated with the development of biliary stricture formation.In addition,hepatic artery thrombosis and primary sclerosing cholangitis were identified as independent risk factors.CONCLUSION In addition to known risk factors,bilirubin levels in the early post-operative period could be used as a clinical indicator for biliary stricture formation.展开更多
The cellular and molecular mechanisms that mediate hepatic fibrosis have provided a framework of different therapeutic foci to prevent, delay or in such case revert fibrosis and cirrhosis. The fundamental event in dev...The cellular and molecular mechanisms that mediate hepatic fibrosis have provided a framework of different therapeutic foci to prevent, delay or in such case revert fibrosis and cirrhosis. The fundamental event in development of hepatic fibrosis caused by secondary biliary cholestasis is based on activation of the hepatic stellar cells (HSC) which the primary function is forming fibrosis. The activated HSC cells transform into myofibroblasts with capacity to produce alpha smooth muscle actin (α-SMA). As a result, the HSC activates proliferation of the cholangiocytes and epithelial cells whose functions represent important anti-fibrotic objectives. Some strategies are described as targeting against molecule involved in fibrosis production;and some medications with anti-fibrotic functions that are actually available in the medical arsenal have been tested in experimental animal models and in few clinical studies, and their components act in relation to the fibrotic cascade. In the end, the treatment strategies for hepatic fibrosis can vary on an individual basis depending on the etiology, the risk of fibrosis progression and the predominant pathogenic medium, which indicates that a multi-factorial approach could be necessary. Orthotopic liver transplant continues being the last final alternative for hepatic insufficiency from any cause;however, in no way does it supersede healthy natural liver in survival and adequate function. The investigative arsenal continues to develop rapidly, giving rise to other possible objectives in pre-clinical studies of conceptual trials, such as the utilization of molecular, cellular, drugs therapy and Chinese herbs. Despite being aforementioned, there are no existing ideal alternatives that completely reverse fibrosis in humans. Future usefulness of the majority of management alternatives seems probable and could be feasible.展开更多
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.
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)
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 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 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Major injuries of the pancreas may result in considerable morbidity and mortality when associated with vascular and visceral injuries. In such cases, a right diagnosis and a prompt surgical intervention are necessary to give a chance to the patient. We herein describe a case of blunt abdominal trauma in a 29-year- old man whose pancreatic rupture was associated with hepatic artery, splenic vein and extrahepatic bile duct damage. Immediate surgery was performed after computer tomograghy (CT), the haemorrhagic lesions dictat the emergency transfer to the operating room. Spleno-pancreatic resection was done with reconstruction of the hepatic artery, ligation of the splenic vein and a Roux-en-Y bilio-jejunal diversion. The early post-operative course was complicated by stenosis of the arterial reconstruction, which was treated by endovascular angioplasty followed by percutaneous drainage of symptomatic pseudocyst, rest and antibiotics. Finally, the patient was discharged and was alive without clinical problems at the time when we wrote this case report. The present case underlines the clinical relevance of vascular and visceral injuries associated with pancreatic trauma and the problems arising in the diagnostic evaluation and the surgical strategy of complex multiple visceral and vascular lesions in blunt abdominal trauma.
文摘Biliary complicationsfBC) are a major cause of morbidity in liver transplant recipients with an incidence of 10-30% following orthotopic liver transplantation(OLT), and a mortality rate of up to 10%. The most common biliary complications are bile leaks, biliary strictures, ampullary dysfunction, and stones. Leaks predominate in the early posttransplant period; while stricture formation typically develops gradually over time. Risk factors for biliary complications comprise technical failure, T-tube-related complications, hepatic artery thrombosis, bleeding, ischemia/reperfusion injury, primary diseases, and other immunological, non-immunological, and infectious complications. Cholangiography, such as endoscopic retrograde cholangiopancreatograpby(ERCP) or percutaneous transhepatic cholangiogram(PTC), is considered the gold standard for identifying post-transplant BC. The management of biliary complications after OLT requires a multidisciplinary approach, in which interventional radiology and endoscopic techniques are emerging as the preferred treatment option, but in a selected majority of patients, surgery is still necessary.
文摘AIM: To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver transplantation.METHODS: We retrospectively reviewed 200 patients of our newly established liver transplantation(LT) program, who received full size liver graft. Biliary reconstruction was performed by side-to-side(SS), end-to-end(EE) anastomosis or hepeaticojejunostomy(HJ). Biliary complications(BC), anastomotic stenosis, bile leak, papillary stenosis, biliary drain complication, ischemic type biliary lesion(ITBL) were evaluated by studying patient records, corresponding radiologic imaging and reports of interventional procedures [e.g., endoscopic retrograde cholangiopancreatography(ERCP)]. Laboratory results included alanine aminotransferase(ALT), gammaglutamyltransferase and direct/indirect bilirubin with focus on the first and fifth postoperative day, six weeks after LT. The routinely employed external bile drain was examined by a routine cholangiography on the fifth postoperative day and six weeks after transplantation as a standard procedure, but also whenever clinically indicated. If necessary, interventional(e.g., ERCP) or surgical therapy was performed. In case of biliary complication, patients were selected, assigned to different complication-groups and subsequently reviewed in detail. To evaluate the patients outcome, we focussed on appearance of postoperative/post-interventional cholangitis, need for rehospitalisation, retransplantation, ITBL or death caused by BC.RESULTS: A total of 200 patients [age: 56(19-72), alcoholic cirrhosis: n = 64(32%), hepatocellular carcinoma: n = 40(20%), acute liver failure: n = 23(11.5%), cryptogenic cirrhosis: n = 22(11%), hepatitis B virus /hepatitis C virus cirrhosis: n = 13(6.5%), primary sclerosing cholangitis: n = 13(6.5%), others: n = 25(12.5%) were included. The median follow-up was 27 mo until June 2015. The overall biliary complication rate was 37.5%(n = 75) with anastomotic strictures(AS): n = 38(19%), bile leak(BL): n = 12(6%), biliary drain complication: n = 12(6%); papillary stenosis(PS): n = 7(3.5%), ITBL: n = 6(3%). Clinically relevant were only 19%(n = 38). We established a comprehensive classification for AS with four grades according to clinical relevance. The reconstruction techniques [SS: n = 164, EE: n = 18, HJ: n = 18] showed no significant impact on the development of BCs in general(all n < 0.05), whereas in the HJ group significantly less AS were found(P = 0.031). The length of donor intensive care unit stay over 6 d had a significant influence on BC development(P = 0.007, HR = 2.85; 95%CI: 1.33-6.08) in the binary logistic regression model, whereas other reviewed variables had not [warm ischemic time > 45 min(P = 0.543), cold ischemic time > 10 h(P = 0.114), ALT init > 1500 U/L(P = 0.631), bilirubin init > 5 mg/d L(P = 0.595), donor age > 65(P = 0.244), donor sex(P = 0.068), rescue organ(P = 0.971)]. 13%(n = 10) of BCs had no therapeutic consequences, 36%(n = 27) resulted in repeated lab control, 40%(n = 30) received ERCP and 11%(n = 8) surgical therapy. Fifteen(7.5%) patients developed cholangitis [AS(n = 6), ITBL(n = 5), PS(n = 3), biliary lesion BL(n = 1)]. One patient developed ITBL twelve months after LT and subsequently needed retransplantation. Rehospitalisation rate was 10.5 %(n = 21) [AS(n = 11), ITBL(n = 5), PS(n = 3), BL(n = 1)] with intervention or reinterventional therapy as main reasons. Retransplantation was performed in 5(2.5%) patients [ITBL(n = 1), acute liver injury(ALI) by organ rejection(n = 3), ALI by occlusion of hepatic artery(n = 1)]. In total 21(10.5%) patients died within the follow-up period. Out of these, one patient with AS developed severe fatal chologenic sepsis after ERCP.CONCLUSION: In our data biliary reconstruction technique and ischemic times seem to have little impact on the development of BCs.
基金supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trustthe University of Birmingham
文摘AIM To review the clinical impact of machine perfusion(MP) of the liver on biliary complications post-transplantation, particularly ischaemic-type biliary lesions(ITBL). METHODS This systematic review was performed in accordance with the Preferred Reporting Systematic Reviews and MetaAnalysis(PRISMA) protocol. The following databases were searched: PubMed, MEDLINE and Scopus. The keyword "liver transplantation" was used in combination with the free term "machine perfusion". Clinical studies reporting results of transplantation of donor human livers following ex situ or in situ MP were analysed. Details relating to donor characteristics, recipients, technique of MP performed and post-operative biliary complications(ITBL, bile leak and anastomotic strictures) were critically analysed.RESULTS Fifteen articles were considered to fit the criteria for this review. Ex situ normothermic MP was used in 6 studies, ex situ hypothermic MP in 5 studies and the other 4 studies investigated in situ normothermic regional perfusion(NRP) and controlled oxygenated rewarming. MP techniques which have per se the potential to alleviate ischaemia-reperfusion injury: Such as hypothermic MP and NRP, have also reported lower rates of ITBL. Other biliary complications, such as biliary leak and anastomotic biliary strictures, are reported with similar incidences with all MP techniques. There is currently less clinical evidence available to support normothermic MP as a mitigator of biliary complications following liver transplantation. On the other hand, restoration of organ to full metabolism during normothermic MP allows assessment of hepatobiliary function before transplantation, although universally accepted criteria have yet to be validated.CONCLUSION MP of the liver has the potential to have a positive impact on post-transplant biliary complications, specifically ITBL, and expand extended criteria donor livers utilisation.
文摘AIM: To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation (OLT) biliary complications and to study their profile before and after endoscopic therapy. METHODS: Patients who developed biliary complications were analysed in detail for the clinical information,laboratory tests,treatment offered,response to it,follow up and outcomes. The profile of liver enzymes was determined. The safety,efficacy and outcomes of endoscopic retrograde cholangiography (ERC) were also analysed. RESULTS: 40 patients required ERC for 70 biliary complications. GGT was found to be > 3 times (388.1 ± 70.9 U/mL vs 168.5 ± 34.2 U/L,P = 0.007) and SAP > 2 times (345.1 ± 59.1 U/L vs 152.7 ± 21.4 U/L,P = 0.003) the immediate post OLT values. Most frequent complication was isolated anastomotic strictures in 28 (40%). Sustained success was achieved in 26 (81%) patients. CONCLUSION: Biliary complications still remain an important problem post OLT. SAP and GGT can be used as early,non-invasive markers for diagnosis and also to assess the adequacy of therapy. Endoscopic management is usually effective in treating the majority of these biliary complications.
文摘BACKGROUND Loss of graft function after liver transplantation(LT) inevitably requires liver retransplant. Retransplantation of the liver(Re LT) remains controversial because of inferior outcomes compared with the primary orthotopic LT(OLT).Meanwhile, if accompanied by vascular complications such as arterial and portal vein(PV) stenosis or thrombosis, it will increase difficulties of surgery. We hereby introduce our center’s experience in Re LT through a complicated case of ReLT.CASE SUMMARY We report a patient who suffered from hepatitis B-associated cirrhosis and underwent LT in December 2012. Early postoperative recovery was uneventful.Four months after LT, the patient’s bilirubin increased significantly and he was diagnosed with an ischemic-type biliary lesion caused by hepatic artery occlusion. The patient underwent percutaneous transhepatic cholangial drainage and repeatedly replaced intrahepatic biliary drainage tube regularly for 5 years.The patient developed progressive deterioration of liver function and underwent liver re-transplant in January 2019. The operation was performed in a classic OLT manner without venous bypass. Both the hepatic artery and PV were occluded and could not be used for anastomosis. The donor PV was anastomosed with the recipient’s left renal vein. The donor hepatic artery was connected to the recipient’s abdominal aorta. The bile duct reconstruction was performed in an end-to-end manner. The postoperative process was very uneventful and the patient was discharged 1 mo after retransplantation.CONCLUSION With the development of surgical techniques, portal thrombosis and arterial occlusion are no longer contraindications for ReLT.
文摘AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland.METHODS Data on liver donors and recipients in Queensland between 2005 and 2014 was obtained from an electronic patient data system.In addition,intra-operative and post-operative characteristics were collected and a logistical regression analysis was performed to evaluate their association with the development of biliary strictures.RESULTS Of 296 liver transplants performed,285(96.3%) were from brain dead donors.Biliary strictures developed in 45(15.2%) recipients.Anastomotic stricture formation(n = 25,48.1%) was the commonest complication,with 14(58.3%) of these occurred within 6-mo of transplant.A percutaneous approach or endoscopic retrograde cholangiography was used to treat 17(37.8%) patients with biliary strictures.Biliary reconstruction was initially or ultimately required in 22(48.9%) patients.In recipients developing biliary strictures,bilirubin was significantly increased within the first postoperative week(Day 7 total bilirubin 74 μmol/L vs 49 μmol/L,P = 0.012).In both univariate and multivariate regression analysis,Day 7 total bilirubin > 55 μmol/L was associated with the development of biliary stricture formation.In addition,hepatic artery thrombosis and primary sclerosing cholangitis were identified as independent risk factors.CONCLUSION In addition to known risk factors,bilirubin levels in the early post-operative period could be used as a clinical indicator for biliary stricture formation.
文摘The cellular and molecular mechanisms that mediate hepatic fibrosis have provided a framework of different therapeutic foci to prevent, delay or in such case revert fibrosis and cirrhosis. The fundamental event in development of hepatic fibrosis caused by secondary biliary cholestasis is based on activation of the hepatic stellar cells (HSC) which the primary function is forming fibrosis. The activated HSC cells transform into myofibroblasts with capacity to produce alpha smooth muscle actin (α-SMA). As a result, the HSC activates proliferation of the cholangiocytes and epithelial cells whose functions represent important anti-fibrotic objectives. Some strategies are described as targeting against molecule involved in fibrosis production;and some medications with anti-fibrotic functions that are actually available in the medical arsenal have been tested in experimental animal models and in few clinical studies, and their components act in relation to the fibrotic cascade. In the end, the treatment strategies for hepatic fibrosis can vary on an individual basis depending on the etiology, the risk of fibrosis progression and the predominant pathogenic medium, which indicates that a multi-factorial approach could be necessary. Orthotopic liver transplant continues being the last final alternative for hepatic insufficiency from any cause;however, in no way does it supersede healthy natural liver in survival and adequate function. The investigative arsenal continues to develop rapidly, giving rise to other possible objectives in pre-clinical studies of conceptual trials, such as the utilization of molecular, cellular, drugs therapy and Chinese herbs. Despite being aforementioned, there are no existing ideal alternatives that completely reverse fibrosis in humans. Future usefulness of the majority of management alternatives seems probable and could be feasible.