Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and im...Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and immunosuppression,there is better patient and graft survival following LT,and assessment of the liver allograft in long-term survivors is becoming increasingly important.Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults.However,no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients,as they have been transplanted for non-recurrent liver diseases.Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes.Pathological findings are frequently present in liver biopsies obtained after a year post LT.The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters.This narrative review summaries the factors predisposing to long-term liver allograft fibrosis,highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.展开更多
BACKGROUND Use of liver allograft with hepatic hemangioma after in vivo resection of hemangioma in living donor liver transplantation(LDLT)has been previously reported.However,there are few reports describing ex vivo ...BACKGROUND Use of liver allograft with hepatic hemangioma after in vivo resection of hemangioma in living donor liver transplantation(LDLT)has been previously reported.However,there are few reports describing ex vivo backtable resection of hemangioma from liver allografts in LDLT.CASE SUMMARY A 55-year-old male was evaluated as a donor for an 8-month-year old patient with acute hepatic failure due to biliary atresia.Pre-operative contrast enhanced computed tomography revealed a 9 cm hemangioma in segment 4 with vascular variations in the donor.During LDLT,an intra-operative intrahepatic cholangiography was performed to ensure no variation in the anatomy of the intrahepatic bile duct.After intra-operative pathological diagnosis,ex vivo backtable resection of the hemangioma was performed and the liver allograft was transplanted into the recipient.The donor’s and recipient’s post-operative course were uneventful.At the 2-year follow-up,the liver allograft showed good regeneration without any recurrence of hemangioma.CONCLUSION Liver allografts with hemangiomas are an acceptable alternative strategy for LDLT.Ex vivo backtable resection of hemangioma from the donor liver during pediatric LDLT is safe and feasible,and can effectively reduce the operative time and intra-operative bleeding for the donor.展开更多
To observe the effect of gene transfer of huCTLA4-Ig to inhibit the acute rejection of liver allograft in rats.Methods With AdEasy vector system,the recombinant adenovirus containing huCTLA4-Ig gene was constructed.Us...To observe the effect of gene transfer of huCTLA4-Ig to inhibit the acute rejection of liver allograft in rats.Methods With AdEasy vector system,the recombinant adenovirus containing huCTLA4-Ig gene was constructed.Using ex vivo gene transfer technique,exogenous gene was introduced to the liver graft during cold preservation and expressed locally in the graft.The effect of inhibition of acute rejection and inducing liver graft tolerance was observed.Results No recipients in group A (without any treatment,n=5) or group B (treated with Ad-GFP,n=4) died within 3 weeks after transplantation and severe acute rejection (massive periportal infiltration,endothelilitis,damage to biliary epithelium and severe tissue destruction) was confirmed pathologically in the graft.In contrast,all recipients in group C (treated with Ad-huCTLA4-Ig,n=5) achieved long-term liver allograft survival (>150 days).Histological examination of Ad-huCTLA4-Ig transduced allografts demonstrated a mild to moderate periportal inflammation and mild injury to liver graft on day 8 posttransplant.A mild mononuclear infiltration was observed;however,there was complete preservation of the bild ducts and no evidence of vascular injury on day 150 posttransplant.The mean IL-2 concentration in serum was (362.09±45.84) ng/L at day 1 pretransplant.In control animals (groups A and B),serum IL-2 concentration was elevated to a high level within 7 days posttransplant,which was about 1.5 to 2.5 times as much as that before transplant.In contrast,in huCTLA4-Ig-treated animals (groups C),IL-2 concentration in serum was maintained at a relative low level,which was near or less than that before transplant (P<0.01).Conclusion Using ex vivo gene transfer technique,huCTLA4-Ig gene can be introduced to the liver graft during cold preservation.The modified graft can express and excrete immunoregulatory protein locally,which can suppress acute alloimmune response and is responsible for prolongation of graft survival without using routine immunosuppressive drugs.These findings provide some experimental evidence that gene delivery of sequences encoding immunoregulatory proteins can be applied to clinical liver transplantation for inhibiting the acute alloimmune response and achieving graft tolerance.7 refs,2 tabs.展开更多
Antibody-mediated rejection(AMR) in liver transplantation has long been underestimated. The concept of the liver as an organ susceptible to AMR has emerged in recent years, not only in the context of the major histoco...Antibody-mediated rejection(AMR) in liver transplantation has long been underestimated. The concept of the liver as an organ susceptible to AMR has emerged in recent years, not only in the context of the major histocompatibility complex with the presence of HLA donor-specific antibodies, but also with antigens regarded as "minor", whose role in AMR has been demonstrated. Among them, antibodies against glutathione S-transferase T1 have been found in 100% of patients with de novo autoimmune hepatitis(dn AIH) when studied. In its latest update, the Banff Working Group for liver allograft pathology proposed replacing the term dn AIH with plasma cell(PC)-rich rejection. Antibodies to glutathione S-transferase T1(GSTT1) in null recipients of GSTT1 positive donors have been included as a contributory but nonessential feature of the diagnosis of PC-rich rejection. Also in this update, non-organ-specific anti-nuclear or smooth muscle autoantibodies are no longer included as diagnostic criteria. Although initially found in a proportion of patients with PC-rich rejection, the presence of autoantibodies is misleading since they are not diseasespecific and appear in many different contexts as bystanders. The cellular types and proportions of the inflammatory infiltrates in diagnostic biopsies have been studied in detail very recently. PC-rich rejection biopsies present a characteristic cellular profile with a predominance of T lymphocytes and a high proportion of PCs, close to 30%, of which 16.48% are Ig G4+. New data on the relevance of GSTT1-specific T lymphocytes to PC-rich rejection will be discussed in this review.展开更多
BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation...BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation after brain death(DBD) and donation after cardiac death(DCD) allograft recipients.METHODS:We reviewed our prospectively entered database for all DBD(n=377) and DCD(n=38) liver transplantations between January 1,2006 and October 30,2011.The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups.RESULTS:EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients,but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD(11.5%) compared with those without EAD(16.7%)(P=0.664) or in the rate of death in recipients with EAD(3.8%) compared with those without EAD(8.3%)(P=0.565).The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7(P=0.022).CONCLUSIONS:The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts.On initial assessment,it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts,however a study with a larger sample size of DCD allografts is needed to confirm these findings.The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure.An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.展开更多
BACKGROUND Early allograft dysfunction(EAD)after liver transplantation(LT)is an important cause of morbidity and mortality.To ensure adequate graft function,a critical hepatocellular mass is required in addition to an...BACKGROUND Early allograft dysfunction(EAD)after liver transplantation(LT)is an important cause of morbidity and mortality.To ensure adequate graft function,a critical hepatocellular mass is required in addition to an appropriate blood supply.We hypothesized that intraoperative measurement of portal venous and hepatic arterial flow may serve as a predictor in the diagnosis of EAD.AIM To study whether hepatic flow is an independent predictor of EAD following LT.METHODS This is an observational cohort study in a single institution.Hepatic arterial blood flow and portal venous blood flow were measured intraoperatively by transit flow.EAD was defined using the Olthoff criteria.Univariate and multivariate analyses were used to determine the intraoperative predictors of EAD.Survival analysis and prognostic factor analysis were performed using the Kaplan-Meier and Cox regression models.RESULTS A total of 195 liver transplant procedures were performed between January 2008 and December 2014 in 188 patients.A total of 54(27.7%)patients developed EAD.The median follow-up was 39 mo.Portal venous flow,hepatic arterial flow(HAF)and total hepatic arterial flow were associated with EAD in both the univariate and multivariate analyses.HAF is an independent prognostic factor for 30-d patient mortality.CONCLUSION Intraoperative measurement of blood flow after reperfusion appears to be a predictor of EAD;Moreover,HAF should be considered a predictor of 30-d patient mortality.展开更多
Objective:To investigate the mechanism of action of emodin for suppressing acute allograft rejection in a rat model of liver transplantation.Methods:Brown Norway(BW) recipient rats of orthotopic liver transplantat...Objective:To investigate the mechanism of action of emodin for suppressing acute allograft rejection in a rat model of liver transplantation.Methods:Brown Norway(BW) recipient rats of orthotopic liver transplantation(OLT) were divided into three groups,Group A receiving isografting(with BW rats as donor), Group B receiving allografting(with Lewis rats as donor),Group C receiving allografting and emodin treatment (50 mg/kg daily).They were sacrificed on day 7 of post-transplantation,and their hepatic histology,plasma cytokine levels,and T-cell subset expression were detected.Results:Compared with those in Group A,rats in Group B exhibited severe allograft rejection with a rejection activity index(RAI) of 7.67±0.98,extensive hepatocellular apoptosis with an apoptosis index(Al) of 35.83±2.32,and elevated plasma levels of interleukin-2 (IL-2),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),CD4^+ and CD4^+/CD8^+ ratio.However,recipients in Group C showed a decrease in histological grade of rejection and hepatocellular apoptosis,as well as a decrease in plasma levels of IL-2,TNF-α,CD4^+ and CD4^+/CD8^+ ratio,but elevated levels of IL-10 as compared with the allograft group.Conclusion:Post-OLT acute rejection could be attenuated by emodin,its mechanism of action may be associated with protecting hepatocytes from apoptosis,polarizing the Th 1 paradigm to Th2,and inhibiting the proliferation of CD4^+ T cell in plasma.展开更多
OBJECTIVE: To assess the immune status of auxiliary liver transplantation and to clarify the immune protection of auxiliary liver to other allograft. METHODS: Immunological markers and pathological changes in 3 patien...OBJECTIVE: To assess the immune status of auxiliary liver transplantation and to clarify the immune protection of auxiliary liver to other allograft. METHODS: Immunological markers and pathological changes in 3 patients undergoing auxiliary liver transplantation were analysed. RESULTS: The lower the concentration of immunosuppressive agent, the less the rejection and the milder the intensity in the 3 patients. The function of allograft after auxiliary liver transplantation was excellent. CONCLUSIONS: Patients are in a low immune reaction state after auxiliary liver transplantation. Auxiliary liver can protect other allografts by related immunological mechanisms. The side-effects of low-concentration immunosuppressive agents on auxiliary liver and other allografts are mild.展开更多
The role of plasmapheresis in liver failure and hepatic encephalopathy is undefined and its use as a strategy to salvage patients with severe allograft dysfunction after liver transplantation remains investigational. ...The role of plasmapheresis in liver failure and hepatic encephalopathy is undefined and its use as a strategy to salvage patients with severe allograft dysfunction after liver transplantation remains investigational. We present a case of early allograft dysfunction following deceased donor liver transplantation(DDLT) where plasmapheresis was effective as a bridge to recovery and possibly avoiding a retransplantation. A 16 years old boy, known to have decompensated Wilson's disease underwent DDLT at our Public Sector Hospital. He received a healthy liver from a brain-dead donor, whose liver was considered too large for the boy. The graft was reduced in situ to a left lobe graft. Surgery was uneventful and the recipient was well for the initial 96 h. On Doppler and further computed tomography scan, a partial portal vein thrombus was noted. He was reexplored and a Fogarty endothombecteomy was performed. Following the second surgery, he developed severe allograft dysfunction with a peak bilirubin of 40 mg/d L. He underwent imaging to rule out technical causes for the dysfunction, followed by a liver biopsy, which revealed acute cellular rejection. Multiple cycles of plasmapheresis were initiated. Over the next two weeks, the graft demonstrated a gradual recovery. He was discharged on the 30 th postoperative day, with a serum bilirubin of 5.5 mg/d L. He remains well on follow-up, with the liver function tests improving further. Our report demonstrates the beneficial effect of plasmapheresis, which appears to be an effective treatment option for early allograft dysfunction following liver transplantation and may obviate the need for retransplantation.展开更多
Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse ou...Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1<sup>th</sup> and the 5<sup>th</sup> day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.展开更多
BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the po...BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation.METHODS:Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis(MiS):MiS <30%(n=27), MiS 30%-60%(n=41) and MiS >60%(n=26).The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction(EAD) and primary nonfunction(PNF). RESULTS:The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF,one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group.CONCLUSION:Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.展开更多
AbstractAIM: To investigate the impact of minimum tacrolimus(TAC) on new-onset diabetes mellitus (NODM) afterliver transplantation (LT).METHODS: We retrospectively analyzed the data of973 liver transplant reci...AbstractAIM: To investigate the impact of minimum tacrolimus(TAC) on new-onset diabetes mellitus (NODM) afterliver transplantation (LT).METHODS: We retrospectively analyzed the data of973 liver transplant recipients between March 1999and September 2014 in West China Hospital LiverTransplantation Center. Following the exclusion ofineligible recipients, 528 recipients with a TAC-dominantregimen were included in our study. We calculatedand determined the mean trough concentration ofTAC (cTAC) in the year of diabetes diagnosis in NODMrecipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value forpredicting NODM 6 mo after LT was identified usinga receptor operating characteristic curve. TAC-relatedcomplications after LT was evaluated by χ^2 test, andthe overall and allograft survival was evaluated usingthe Kaplan-Meier method. Risk factors for NODM afterLT were examined by univariate and multivariate Cox regression.RESULTS: Of the 528 transplant recipients, 131(24.8%) developed NODM after 6 mo after LT, andthe cumulative incidence of NODM progressivelyincreased. The mean cTAC of NODM group recipientswas significantly higher than that of recipients in thenon-NODM group (7.66 ± 3.41 ng/mL vs 4.47 ± 2.22ng/mL, P 〈 0.05). Furthermore, NODM group recipientshad lower 1-, 5-, 10-year overall survival rates (86.7%,71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P 〈0.05) and allograft survival rates (92.8%, 84.6%, and75.7% vs 96.1%, 91%, and 86.1%, P 〈 0.05) thanthe others. The best cutoff of mean cTAC for predictingNODM was 5.89 ng/mL after 6 mo after LT. Multivariateanalysis showed that old age at the time of LT (〉 50years), hypertension pre-LT, and high mean cTAC (≥5.89 ng/mL) after 6 mo after LT were independent riskfactors for developing NODM. Concurrently, recipientswith a low cTAC (〈 5.89 ng/mL) were less likely tobecome obese (21.3% vs 30.2%, P 〈 0.05) or todevelop dyslipidemia (27.5% vs 44.8%, P 〈0.05),chronic kidney dysfunction (14.6% vs 22.7%, P 〈 0.05),and moderate to severe infection (24.7% vs 33.1%, P〈 0.05) after LT than recipients in the high mean cTACgroup. However, the two groups showed no significantdifference in the incidence of acute and chronicrejection, hypertension, cardiovascular events and newonsetmalignancy.CONCLUSION: A minimal TAC regimen can decreasethe risk of long-term NODM after LT. Maintaining a cTACvalue below 5.89 ng/mL after LT is safe and beneficial.展开更多
BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve th...BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 ℃ University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT. METHODS: From June 2007 to January 2008, 11 adult LDLT patients received modified right liver grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were preserved and reconstructed using cadaveric interposition vein allografts that had been stored for 1 to 10 days in 4 ℃ UW solution. The regeneration of the paramedian sector of the grafts and the patency of the interposition vein allografts were examined by Doppler ultrasonography after the operation. RESULTS: MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of renal failure and severe pulmonary infection on day 9 after transplantation without any hemiliver venous outflow obstruction. The other 8 recipients achieved long-term survival with a median follow-up of 30 months. The cumulative patency rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and 36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the paramedian sectors was equivalent.CONCLUSION: The cadaveric venous allograft preserved in 4 ℃ UW solution within 10 days serves as a useful alternative for interposition veins in facilitating implantation of a right lobe graft and guarantees outflow of the MHV.展开更多
Hepatic venous drainage in liver transplantation may be reduced to the level of caval anastomosis producing an obstruction degree and leading to serious vascular complication such as the acute Budd-Chiari syndrome, wh...Hepatic venous drainage in liver transplantation may be reduced to the level of caval anastomosis producing an obstruction degree and leading to serious vascular complication such as the acute Budd-Chiari syndrome, which may result in organ loss. Outflow obstruction may be caused by lack of technique in caval anastomosis or by allograft malposition as a consequence of anatomical graft and recipient conditions. Fixation of the round ligament, placement of bowel loops and use of tissue expanders have been described to stabilize graft position during liver transplantation with related procedure complications. We report our experience of a simple homemade device using a surgical glove expander that allowed us to successfully avoid outflow obstruction in all of nine treated patients. No device related complications occurred. In malposed liver allografts, we strongly suggest the use of this simple and safe device to avoid hepatic venous outflow obstruction on condition that the device is early removed within 48 hours.展开更多
文摘Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and immunosuppression,there is better patient and graft survival following LT,and assessment of the liver allograft in long-term survivors is becoming increasingly important.Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults.However,no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients,as they have been transplanted for non-recurrent liver diseases.Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes.Pathological findings are frequently present in liver biopsies obtained after a year post LT.The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters.This narrative review summaries the factors predisposing to long-term liver allograft fibrosis,highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.
文摘BACKGROUND Use of liver allograft with hepatic hemangioma after in vivo resection of hemangioma in living donor liver transplantation(LDLT)has been previously reported.However,there are few reports describing ex vivo backtable resection of hemangioma from liver allografts in LDLT.CASE SUMMARY A 55-year-old male was evaluated as a donor for an 8-month-year old patient with acute hepatic failure due to biliary atresia.Pre-operative contrast enhanced computed tomography revealed a 9 cm hemangioma in segment 4 with vascular variations in the donor.During LDLT,an intra-operative intrahepatic cholangiography was performed to ensure no variation in the anatomy of the intrahepatic bile duct.After intra-operative pathological diagnosis,ex vivo backtable resection of the hemangioma was performed and the liver allograft was transplanted into the recipient.The donor’s and recipient’s post-operative course were uneventful.At the 2-year follow-up,the liver allograft showed good regeneration without any recurrence of hemangioma.CONCLUSION Liver allografts with hemangiomas are an acceptable alternative strategy for LDLT.Ex vivo backtable resection of hemangioma from the donor liver during pediatric LDLT is safe and feasible,and can effectively reduce the operative time and intra-operative bleeding for the donor.
文摘To observe the effect of gene transfer of huCTLA4-Ig to inhibit the acute rejection of liver allograft in rats.Methods With AdEasy vector system,the recombinant adenovirus containing huCTLA4-Ig gene was constructed.Using ex vivo gene transfer technique,exogenous gene was introduced to the liver graft during cold preservation and expressed locally in the graft.The effect of inhibition of acute rejection and inducing liver graft tolerance was observed.Results No recipients in group A (without any treatment,n=5) or group B (treated with Ad-GFP,n=4) died within 3 weeks after transplantation and severe acute rejection (massive periportal infiltration,endothelilitis,damage to biliary epithelium and severe tissue destruction) was confirmed pathologically in the graft.In contrast,all recipients in group C (treated with Ad-huCTLA4-Ig,n=5) achieved long-term liver allograft survival (>150 days).Histological examination of Ad-huCTLA4-Ig transduced allografts demonstrated a mild to moderate periportal inflammation and mild injury to liver graft on day 8 posttransplant.A mild mononuclear infiltration was observed;however,there was complete preservation of the bild ducts and no evidence of vascular injury on day 150 posttransplant.The mean IL-2 concentration in serum was (362.09±45.84) ng/L at day 1 pretransplant.In control animals (groups A and B),serum IL-2 concentration was elevated to a high level within 7 days posttransplant,which was about 1.5 to 2.5 times as much as that before transplant.In contrast,in huCTLA4-Ig-treated animals (groups C),IL-2 concentration in serum was maintained at a relative low level,which was near or less than that before transplant (P<0.01).Conclusion Using ex vivo gene transfer technique,huCTLA4-Ig gene can be introduced to the liver graft during cold preservation.The modified graft can express and excrete immunoregulatory protein locally,which can suppress acute alloimmune response and is responsible for prolongation of graft survival without using routine immunosuppressive drugs.These findings provide some experimental evidence that gene delivery of sequences encoding immunoregulatory proteins can be applied to clinical liver transplantation for inhibiting the acute alloimmune response and achieving graft tolerance.7 refs,2 tabs.
基金Supported by Andalusian government,Proyecto de Excelencia,No.CTS-7846Spanish Ministry of Economy,Instituto de Salud Carlos Ⅲ,No.11/857 and No.17/1403
文摘Antibody-mediated rejection(AMR) in liver transplantation has long been underestimated. The concept of the liver as an organ susceptible to AMR has emerged in recent years, not only in the context of the major histocompatibility complex with the presence of HLA donor-specific antibodies, but also with antigens regarded as "minor", whose role in AMR has been demonstrated. Among them, antibodies against glutathione S-transferase T1 have been found in 100% of patients with de novo autoimmune hepatitis(dn AIH) when studied. In its latest update, the Banff Working Group for liver allograft pathology proposed replacing the term dn AIH with plasma cell(PC)-rich rejection. Antibodies to glutathione S-transferase T1(GSTT1) in null recipients of GSTT1 positive donors have been included as a contributory but nonessential feature of the diagnosis of PC-rich rejection. Also in this update, non-organ-specific anti-nuclear or smooth muscle autoantibodies are no longer included as diagnostic criteria. Although initially found in a proportion of patients with PC-rich rejection, the presence of autoantibodies is misleading since they are not diseasespecific and appear in many different contexts as bystanders. The cellular types and proportions of the inflammatory infiltrates in diagnostic biopsies have been studied in detail very recently. PC-rich rejection biopsies present a characteristic cellular profile with a predominance of T lymphocytes and a high proportion of PCs, close to 30%, of which 16.48% are Ig G4+. New data on the relevance of GSTT1-specific T lymphocytes to PC-rich rejection will be discussed in this review.
文摘BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation after brain death(DBD) and donation after cardiac death(DCD) allograft recipients.METHODS:We reviewed our prospectively entered database for all DBD(n=377) and DCD(n=38) liver transplantations between January 1,2006 and October 30,2011.The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups.RESULTS:EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients,but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD(11.5%) compared with those without EAD(16.7%)(P=0.664) or in the rate of death in recipients with EAD(3.8%) compared with those without EAD(8.3%)(P=0.565).The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7(P=0.022).CONCLUSIONS:The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts.On initial assessment,it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts,however a study with a larger sample size of DCD allografts is needed to confirm these findings.The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure.An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.
文摘BACKGROUND Early allograft dysfunction(EAD)after liver transplantation(LT)is an important cause of morbidity and mortality.To ensure adequate graft function,a critical hepatocellular mass is required in addition to an appropriate blood supply.We hypothesized that intraoperative measurement of portal venous and hepatic arterial flow may serve as a predictor in the diagnosis of EAD.AIM To study whether hepatic flow is an independent predictor of EAD following LT.METHODS This is an observational cohort study in a single institution.Hepatic arterial blood flow and portal venous blood flow were measured intraoperatively by transit flow.EAD was defined using the Olthoff criteria.Univariate and multivariate analyses were used to determine the intraoperative predictors of EAD.Survival analysis and prognostic factor analysis were performed using the Kaplan-Meier and Cox regression models.RESULTS A total of 195 liver transplant procedures were performed between January 2008 and December 2014 in 188 patients.A total of 54(27.7%)patients developed EAD.The median follow-up was 39 mo.Portal venous flow,hepatic arterial flow(HAF)and total hepatic arterial flow were associated with EAD in both the univariate and multivariate analyses.HAF is an independent prognostic factor for 30-d patient mortality.CONCLUSION Intraoperative measurement of blood flow after reperfusion appears to be a predictor of EAD;Moreover,HAF should be considered a predictor of 30-d patient mortality.
基金Supported by the National Natural Science Foundation of China (No.30572395,No.30973815).
文摘Objective:To investigate the mechanism of action of emodin for suppressing acute allograft rejection in a rat model of liver transplantation.Methods:Brown Norway(BW) recipient rats of orthotopic liver transplantation(OLT) were divided into three groups,Group A receiving isografting(with BW rats as donor), Group B receiving allografting(with Lewis rats as donor),Group C receiving allografting and emodin treatment (50 mg/kg daily).They were sacrificed on day 7 of post-transplantation,and their hepatic histology,plasma cytokine levels,and T-cell subset expression were detected.Results:Compared with those in Group A,rats in Group B exhibited severe allograft rejection with a rejection activity index(RAI) of 7.67±0.98,extensive hepatocellular apoptosis with an apoptosis index(Al) of 35.83±2.32,and elevated plasma levels of interleukin-2 (IL-2),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),CD4^+ and CD4^+/CD8^+ ratio.However,recipients in Group C showed a decrease in histological grade of rejection and hepatocellular apoptosis,as well as a decrease in plasma levels of IL-2,TNF-α,CD4^+ and CD4^+/CD8^+ ratio,but elevated levels of IL-10 as compared with the allograft group.Conclusion:Post-OLT acute rejection could be attenuated by emodin,its mechanism of action may be associated with protecting hepatocytes from apoptosis,polarizing the Th 1 paradigm to Th2,and inhibiting the proliferation of CD4^+ T cell in plasma.
文摘OBJECTIVE: To assess the immune status of auxiliary liver transplantation and to clarify the immune protection of auxiliary liver to other allograft. METHODS: Immunological markers and pathological changes in 3 patients undergoing auxiliary liver transplantation were analysed. RESULTS: The lower the concentration of immunosuppressive agent, the less the rejection and the milder the intensity in the 3 patients. The function of allograft after auxiliary liver transplantation was excellent. CONCLUSIONS: Patients are in a low immune reaction state after auxiliary liver transplantation. Auxiliary liver can protect other allografts by related immunological mechanisms. The side-effects of low-concentration immunosuppressive agents on auxiliary liver and other allografts are mild.
文摘The role of plasmapheresis in liver failure and hepatic encephalopathy is undefined and its use as a strategy to salvage patients with severe allograft dysfunction after liver transplantation remains investigational. We present a case of early allograft dysfunction following deceased donor liver transplantation(DDLT) where plasmapheresis was effective as a bridge to recovery and possibly avoiding a retransplantation. A 16 years old boy, known to have decompensated Wilson's disease underwent DDLT at our Public Sector Hospital. He received a healthy liver from a brain-dead donor, whose liver was considered too large for the boy. The graft was reduced in situ to a left lobe graft. Surgery was uneventful and the recipient was well for the initial 96 h. On Doppler and further computed tomography scan, a partial portal vein thrombus was noted. He was reexplored and a Fogarty endothombecteomy was performed. Following the second surgery, he developed severe allograft dysfunction with a peak bilirubin of 40 mg/d L. He underwent imaging to rule out technical causes for the dysfunction, followed by a liver biopsy, which revealed acute cellular rejection. Multiple cycles of plasmapheresis were initiated. Over the next two weeks, the graft demonstrated a gradual recovery. He was discharged on the 30 th postoperative day, with a serum bilirubin of 5.5 mg/d L. He remains well on follow-up, with the liver function tests improving further. Our report demonstrates the beneficial effect of plasmapheresis, which appears to be an effective treatment option for early allograft dysfunction following liver transplantation and may obviate the need for retransplantation.
文摘Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1<sup>th</sup> and the 5<sup>th</sup> day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.
文摘BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation.METHODS:Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis(MiS):MiS <30%(n=27), MiS 30%-60%(n=41) and MiS >60%(n=26).The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction(EAD) and primary nonfunction(PNF). RESULTS:The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF,one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group.CONCLUSION:Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.
基金Supported by Key Technology Support Program of Sichuan ProvinceNo.2013SZ0023
文摘AbstractAIM: To investigate the impact of minimum tacrolimus(TAC) on new-onset diabetes mellitus (NODM) afterliver transplantation (LT).METHODS: We retrospectively analyzed the data of973 liver transplant recipients between March 1999and September 2014 in West China Hospital LiverTransplantation Center. Following the exclusion ofineligible recipients, 528 recipients with a TAC-dominantregimen were included in our study. We calculatedand determined the mean trough concentration ofTAC (cTAC) in the year of diabetes diagnosis in NODMrecipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value forpredicting NODM 6 mo after LT was identified usinga receptor operating characteristic curve. TAC-relatedcomplications after LT was evaluated by χ^2 test, andthe overall and allograft survival was evaluated usingthe Kaplan-Meier method. Risk factors for NODM afterLT were examined by univariate and multivariate Cox regression.RESULTS: Of the 528 transplant recipients, 131(24.8%) developed NODM after 6 mo after LT, andthe cumulative incidence of NODM progressivelyincreased. The mean cTAC of NODM group recipientswas significantly higher than that of recipients in thenon-NODM group (7.66 ± 3.41 ng/mL vs 4.47 ± 2.22ng/mL, P 〈 0.05). Furthermore, NODM group recipientshad lower 1-, 5-, 10-year overall survival rates (86.7%,71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P 〈0.05) and allograft survival rates (92.8%, 84.6%, and75.7% vs 96.1%, 91%, and 86.1%, P 〈 0.05) thanthe others. The best cutoff of mean cTAC for predictingNODM was 5.89 ng/mL after 6 mo after LT. Multivariateanalysis showed that old age at the time of LT (〉 50years), hypertension pre-LT, and high mean cTAC (≥5.89 ng/mL) after 6 mo after LT were independent riskfactors for developing NODM. Concurrently, recipientswith a low cTAC (〈 5.89 ng/mL) were less likely tobecome obese (21.3% vs 30.2%, P 〈 0.05) or todevelop dyslipidemia (27.5% vs 44.8%, P 〈0.05),chronic kidney dysfunction (14.6% vs 22.7%, P 〈 0.05),and moderate to severe infection (24.7% vs 33.1%, P〈 0.05) after LT than recipients in the high mean cTACgroup. However, the two groups showed no significantdifference in the incidence of acute and chronicrejection, hypertension, cardiovascular events and newonsetmalignancy.CONCLUSION: A minimal TAC regimen can decreasethe risk of long-term NODM after LT. Maintaining a cTACvalue below 5.89 ng/mL after LT is safe and beneficial.
文摘BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 ℃ University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT. METHODS: From June 2007 to January 2008, 11 adult LDLT patients received modified right liver grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were preserved and reconstructed using cadaveric interposition vein allografts that had been stored for 1 to 10 days in 4 ℃ UW solution. The regeneration of the paramedian sector of the grafts and the patency of the interposition vein allografts were examined by Doppler ultrasonography after the operation. RESULTS: MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of renal failure and severe pulmonary infection on day 9 after transplantation without any hemiliver venous outflow obstruction. The other 8 recipients achieved long-term survival with a median follow-up of 30 months. The cumulative patency rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and 36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the paramedian sectors was equivalent.CONCLUSION: The cadaveric venous allograft preserved in 4 ℃ UW solution within 10 days serves as a useful alternative for interposition veins in facilitating implantation of a right lobe graft and guarantees outflow of the MHV.
文摘Hepatic venous drainage in liver transplantation may be reduced to the level of caval anastomosis producing an obstruction degree and leading to serious vascular complication such as the acute Budd-Chiari syndrome, which may result in organ loss. Outflow obstruction may be caused by lack of technique in caval anastomosis or by allograft malposition as a consequence of anatomical graft and recipient conditions. Fixation of the round ligament, placement of bowel loops and use of tissue expanders have been described to stabilize graft position during liver transplantation with related procedure complications. We report our experience of a simple homemade device using a surgical glove expander that allowed us to successfully avoid outflow obstruction in all of nine treated patients. No device related complications occurred. In malposed liver allografts, we strongly suggest the use of this simple and safe device to avoid hepatic venous outflow obstruction on condition that the device is early removed within 48 hours.