A single center analysis of long-term outcomes and survival related risk factors in liver retransplantation

Background:Liver retransplant is the only option to save a patient with liver graft failure.However,it is controversial due to its poor survival outcome compared to primary transplantation.Insufficient deceased organ donation in Taiwan leads to high waitlist mortality.Hence,living-donor grafts offer a valuable alternative for retransplantation.This study aims to analyze the single center’s outcome in living donor liver retransplantation(re-LDLT)and deceased donor liver retransplantation(re-DDLT)as well as the survival related confounding risk factors.Methods:This is a single center retrospective study including 32 adults who underwent liver retransplantation(re-LT)from June 2002 to April 2020.The cohort was divided into a re-LDLT and a re-DDLT group and survival outcomes were analyzed.Patient outcomes over different periods,the effect of timing on survival,and multivariate analysis for risk factors were also demonstrated Results:Of the 32 retransplantations,the re-LDLT group(n=11)received grafts from younger donors(31.3 vs.43.75 years,P=0.016),with lower graft weights(688 vs.1,457.2 g,P<0.001)and shorter cold ischemia time(CIT)(45 vs.313 min,P<0.001).The 5-year survival was significantly better in the re-LDLT group than in the re-DDLT group(100%vs.70.8%,P=0.02).This difference was adjusted when only retransplantation after 2010 was analyzed.Further analysis showed that the timing of retransplantation(early vs.late)did not affect patient survival.Multivariate analysis revealed that prolonged warm ischemia time(WIT)and intraoperative blood transfusion were related to poor long-term survival.Conclusions:Retransplantation with living donor graft demonstrated good long-term outcomes with acceptable complications to both recipient and donor.It may serve as a choice in areas lacking deceased donors.The timing of retransplantation did not affect the long-term survival.Further effort should be made to reduce WIT and massive blood transfusion as they contributed to poor survival after retransplantation.

Liver retransplantation: indications and outcomes

BACKGROUND: Liver transplantation is a life-saving the- rapeutic modality for patients with end-stage liver diseases. After liver transplantation, however, more than 10% pa- tients may lose the grafts caused by a variety of reasons. This review covers the most frequent indications for liver retransplantation as well as the results and specific problems with each indication. DATA RESOURCES: Searching MEDLINE (1997-2003) for articles on liver retransplantation. RESULTS: The most frequent indications of liver retrans- plantation are primary non-function, hepatic artery throm- bosis, graft rejection and recurrent diseases. The results af- ter liver retransplantation remain inferior to those after first transplantation. CONCLUSION: Liver retransplantation, which is the only means of prolonging survival in those patients whose initial graft has failed, makes an important contribution to overall survival.

Preliminary clinical experience in liver retransplantation

BACKGROUND: The past several decades have witnessed increasingly successful rates of liver transplantation. However, retransplantation remains the only choice for patients with irreversible graft failure after primary transplantation. This article aimed to summarize our clinical experience in liver retransplantation. METHODS: From June 2002 to December 2005, a total of 185 cases of liver transplantation including 8 cases of retransplantation were performed in our hospital. The clinical data were analyzed retrospectively. RESULTS: The rate of liver retransplantation was 4.32%. Retransplantation was indicated for the following reasons: biliary complication (3 cases), chronic rejection (2), hepatic artery thrombosis (1), uncontrollable acute rejection (1) and hepatitis B recurrence (1). The mean model of end-stage liver disease (MELD) scores before primary transplantation and retransplantation were 15.6 and 23.9, respectively (P < 0.05). The MELD score reflected the severity of liver disease more precisely than the Child classification. The mean interval between the first and second transplantation was 316 days (78-725 days). The first three patients, with mean interval of 101 days, died of severe infection combined with multiple organ failure after retransplantation. The patients who underwent retransplantation more than six months after the first transplant had better outcomes. The one-year survival rate for retransplantation in our group was 62.5%. CONCLUSIONS: Liver retransplantation is the only means of saving the patient with hepatic allograft failure. Understanding of the indications for retransplantation, careful selection of operation timing, excellent surgical skills and meticulous postoperative management all contribute to the success of each case of retransplantation.

Retransplantation for graft failure in chronic hepatitis C infection: A good use of a scarce resource?

AIM: To investigate the outcome of patients with hepatitis C virus (HCV) infection undergoing liver retransplantation. METHODS: Using the UK National Registry, patients undergoing liver transplantation for HCV-related liver disease were identified. Data on patient and graft characteristics, as well as transplant and graft survival were collected to determine the outcome of HCV patients undergoing retransplantation and in order to identify factors associated with transplant survival. RESULTS: Between March 1994 and December 2007, 944 adult patients were transplanted for HCV-related liver disease. At the end of follow-up, 617 of these patients were alive. In total, 194 (21%) patients had first graft failure and of these, 80 underwent liver retransplantation, including 34 patients where the first graft failed due to recurrent disease. For those transplanted for HCV-related disease, the 5-year graft survival in those retransplanted for recurrent HCV was 45% [95% confidence interval (CI): 24%-64%] compared with 80% (95% CI: 62%-90%) for those retransplanted for other indications (P = 0.01, log-rank test); the 5-year transplant survival after retransplantation was 43% (95% CI: 23%-62%) and 46% (95% CI: 31%-60%), respectively (P = 0.8, log-rank test). In univariate analysis of all patients retransplanted, no factor analyzed was significantly associated with transplant survival. CONCLUSION: Outcomes for retransplantation in patients with HCV infection approach agreed criteria for minimum transplant benefit. These data support selective liver retransplantation in patients with HCV infection.

Predictive factors for survival and score application in liver retransplantation for hepatitis C recurrence

AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus(HCV) recurrence and to apply a survival score to this population.METHODS: We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers(seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis(FCH) post-first graft presenting with hepatic decompensation. RESULTS: Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease(MELD) score < 25 when replaced on the waiting list, and a retransplantation donor age < 60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patientswho underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andrés score was applied to 102 patients for whom all score variables were available, producing a mean score of 43.4(SD = 6.6). Survival rates after the date of the first decompensation post-first liver transplantation(LT1) in the liver retransplantation(re LT) group(94 patients decompensated) at 3, 5, and 10 years were 62%, 59%, and 51%, respectively, among 78 retransplanted individuals with advanced cirrhosis, and 42%, 32%, and 16% among 16 retransplanted individuals with FCH. In the non-re LT group with hepatic decompensation, survival rates were 27%, 18%, and 9% at 3, 5, and 10 years, respectively(P < 0.0001). Compared with non-retransplanted patients, retransplanted patients were younger at LT1(mean age 48 ± 8 years compared to 53 ± 9 years in the no re LT group, P < 0.0001), less likely to have human immunodeficiency virus(HIV) co-infection(4% vs 14% among no re LT patients, P = 0.005), more likely to have received corticosteroid bolus therapy after LT1(25% in re LT vs 12% in the no re LT group, P = 0.01), and more likely to have presented with sustained virological response(SVR) after the first transplantation(20% in the re LT group vs 7% in the no re LT group, P = 0.028).CONCLUSION: Antiviral therapy before and after retransplantation had a substantial impact on survival in the context of retransplantation for HCV recurrence, and with the new direct-acting antivirals now available, outcomes should be even better in the future.

Complex liver retransplantation to treat graft loss due to long-term biliary tract complication after liver transplantation: A case report

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.

Different modalities of arterial reconstruction in hepatic retransplantation using right partial graft

Though split-liver and living-related transplantation are routinely performed,they are done almost exclusively for primary liver transplantation because of potential surgical difficulties.These difficulties are generally related to arterial revascularization,particularly if there is hepatic artery thrombosis.According to UNOS data,of the hepatic retransplantations performed between 1996 and 2007,only 8.7% were done using right or extended right grafts from deceased donors,and 14.3% using right grafts from live donors.Here we report our experience with 5 hepatic retransplantations in which right partial grafts resulting from conventional in situ splits,and one right lobe resulting from an adult-toadult living-related transplant,were successfully used with different modalities of graft arterialization.

Report of 8 cases of liver retransplantation

BACKGROUND: Retransplantation of the liver is required for several complications of primary grafting, such as primary allograft non-function, hepatic artery thrombosis, biliary problems, or chronic ductopenic rejection. Surgeons usually take regrafting as the only pathway to treat those patients who are considered to have a poor outcome after the first operation. Whether the retransplantation is early or late, further attempts at rescue with a second or more grafts are associated with higher mortality and morbidity. However, retransplantation plays a role in improving survival of the patients. Therefore, it is necessary to summarize the experiences in liver retransplantation, as well as the factors influencing operative effects. METHOD: The clinical data of 8 patients who received liver retransplantation in our center were analyzed retrospectively. RESULTS: Complications of the biliary tract occurred in 5 of the 8 patients, chronic rejection in 2, and embolism in the hepatic artery in 1. Infections occurred in 7 patients before engraftment. Patient I had developed renal failure before the surgery, and he died of severe infection and multi-organ failure after transplantation. Patient 4 had a massive hemorrhage during the operation and also died of multi-organ failure after transplantation. Patient 7 developed intracranial hemorrhage and abdominal infection and died soon after transplantation. The other 5 patients recovered and discharged from the hospital. CONCLUSIONS: Liver retransplantation is the only measure that can be taken to save the lives of patients whose liver allograft fails to function. It is very important that the indications and time of retransplantation are carefully selected. Factors leading to harmful effects on retransplantation include the preoperative condition of the recipient, a difficult and prolonged operation, massive hemorrhage during the operation, and severe complications after the surgery.

Liver retransplantation:report of 80 cases and review of literature

BACKGROUND: Because the orthotopic liver transplantation (OLT) was performed widely in recent 5 years throughout China, the proportion of recipients whose graft function deteriorated to be retransplantation candidates increased gradually. This study was undertaken to analyze clinical experience of orthotopic liver retransplantation (re-OLT) at our center. METHODS: The medical records of 80 patients who had undergone liver retransplantation at our center from January 1999 to July 2005 were analyzed retrospectively, including indications and timing of retransplantation, surgical techniques, and the causes of death. RESULTS: The commonest cause leading to hepatic graft loss and subsequent retransplantation was biliary complications in 36 patients (45%). The patients underwent retransplantation more than 30 days after their primary transplant recovered better than those who underwent retransplantation within 8-30 days after primary transplantation (peri-operative mortality 19.6% versus 70%). Sepsis (12 of 22 patients, 54.5%) and multiple organ failure (4 of 22 patients, 18.2%) were leading causes of re-OLT recipient deaths. CONCLUSIONS: Proper indications and optimal operative time, surgical procedures, perioperative monitoring and appropriate postoperative treatment contribute to the improvement of the survival rate of patients after liver retransplantation.

Analysis of critical issues in case management for liver retransplantation

We report a case of a patient who underwent successful combined liver-kidney transplant after two prior liver transplantations. The topic of liver retransplantation is very controversial. Given the critical organ shortage, the question arises as to whether hepatic retransplantation should be offered liberally despite its greater cost, and inevitable denial of access to primary transplantation for the other patients on the waiting list. We suggest that careful selection of the retransplant candidates will improve outcomes and allow rational use of the limited organ supply. Analysis of the available literature allows us to identify the main predictors of morbidity and mortality for this patient population. It also enables development of a detailed plan for perioperative management. The role of transesophageal echocardiography (TEE) as a monitor in the complex liver transplant cases is also discussed. Our report is a significant contribution to the very limited data available on the subject of multiple liver retransplants.

Hepatic artery complications after orthotopic liver transplantation： interventional treatment or retransplantation？

Background The main therapeutic treatments for hepatic artery complications after orthotopic liver transplantation （OLT） include thrombolysis, percutaneous transluminal angioplasty, stent placement, and liver retransplantation. The prognosis of hepatic artery complications after OLT is not only related to the type, extent, and timing but also closely associated with the selection and timing of the therapeutic methods. However, there is no consensus of opinion regarding the treatment of these complications. The aim of this study was to determine optimal treatment for hepatic artery complications after OLT. Methods The clinical data of 25 patients diagnosed with hepatic artery thrombosis （HAT） and hepatic artery stenosis （HAS） between October 2003 and March 2007 were retrospectively reviewed. Treatments included liver retransplantation and interventions which contain thrombolysis, percutaneous transluminal angioplasty and stent placement. Results Among five patients with HAT, 3 were treated with thrombolysis. One recovered, one died after thrombolysis and another one died of multi-organ failure after retransplantation because of recurrent HAT. The remaining 2 patients underwent successful retransplantation and have survived after that. Among 12 patients presented with HAS within 1 month postoperatively, 2 patients underwent retransplantation due to irreversible liver failure and another 10 patients were treated with interventions. The liver function failed to improve in 3 patients and retransplantations were performed in 4 patients after stent placement because of ischemic cholangitis. Among 6 patients undergoing liver retransplantations, two died of intracranial hemorrhage and infection respectively. Eight patients presented with HAS after 1 month postoperatively, 5 patients were treated with interventional management and recovered after stent placement. Among another 3 patients presented with HAS, 2 patients’ liver function was stable and one patient received late liver retransplantation due to ischemic bile duct lesion. Conclusions Individualized therapeutic regimens should be adopted in treating hepatic artery complications after OLT, according to postoperative periods, types and whether ischemic bile duct lesion exists or not. Liver retransplantation is the best treatment for patients with hepatic artery thrombosis. Interventional treatments of late HAS without irreversible liver failure or bile duct ischemia are appropriate, whereas retransplantation is recommended for early HAS.

Liver retransplantation： a single-centre experience

Background The curative effect of liver transplantation for patients with end-stage liver disease was encouraging in recent years and the 5-year patient survival rate can reach up to 70%. However, some patients might lose grafts due to a variety of reasons, including bile duct complications, vascular complications, primary non-function, graft rejection and disease recurrence etc. Liver retransplantation （re-LT） was the only available means for those patients whose initial grafts had failed, but the inferior outcomes of re-LT compared to primary liver transplantation （PLT） continue to be a major concern. This study aimed to analyze the indications for re-LT, optimal timing of re-LT, and strategies to improve the survival rate after re-LT.Methods From January 2001 to December 2006, we performed 738 liver transplants and 39 re-LT （5.3%） at our center. A retrospective analysis was performed to identify factors （indication for re-LT, preoperative score of model for end-stage liver disease （MELD）, interval to re-LT from primary liver transplantation, methods of vascular and biliary reconstruction and common causes of death） associated with survival.Results Mean follow-up period was 1.8 years （1 to 5 years）. Patients with MELD score less than 20 were better than those whose MELD score was 〉20 and MELD score〉30 （1-year survival, 80.0% versus 50.0% and 3/5）. The perioperative survival rate of patients who received re-LT at an interval of more than 30 days and less than 8 days after the initial transplantation was higher than those who received retransplantation between 8 to 30 days following the first operation （88.5% and 74.3% versus 50.0%）. The main causes of death were infection （60.0%）, multiple organ failure （20.0%）, vascular complications （10.0%） and biliary fistula （10.0%） in perioperative period. The overall patient survival rate of 1-month, 6-month and 1-year was 80.0%, 76.7% and 66.7%, respectively.Conclusions Our study suggested the favorable results after re-LT. The analysis also showed optimal timing of operation, refined surgical techniques, individualized immunosuppressive regimen and effective prophylaxis and treatment of perioperative infection play an important role in achieving a higher survival after re-LT.

Early liver retransplantation versus late liver retransplantation： analysis of a single-center experience

Background Orthotopic liver retransplantation （re-OLT） is the only effective therapy for irreversible failure of a liver graft. Early and late graft failure gives way to two different clinical conditions that should be discussed separately. This study was designed to compare early and late re-OLT for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT. Methods The clinical data of 31 re-OLTs at our center from January 2004 to February 2007 were analyzed retrospectively, consisting of the first group with 14 cases of early re-OLT and the second group with 17 cases of late re-OLT.Results Biliary tract complications were the main indications for early re-OLT （57.1%） and late re-OLT （52.9%）. Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration, and perioperative mortality; except for the model of end-stage liver disease （MELD） score. Outcome was fatal for 7 patients in early re-OLT and 9 patients in late re-OLT. Two deaths were due to multiple organ failure with 3 deaths due to severe sepsis-related disease in early re-OLT, and 4 deaths were due to severe sepsis-related disease with 3 deaths due to recurrence of hepatocellular carcinoma （HCC） in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 55.2% and 36.9%, respectively, for patients in early re-OLT, and 65.1% and 52% respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups. Conclusions Similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, adequate preoperative preparation, experienced surgical procedures, and effective perioperative anti-infection strategy contribute to the improvement of overall survival rates of patients after re-OLT.

Predictors of graft function and survival in second kidney transplantation: A single center experience

BACKGROUND The increasing kidney retransplantation rate has created a parallel field of research,including the risk factors and outcomes of this advanced form of renal replacement therapy.The presentation of experiences from different kidney transplantation centers may help enrich the literature on kidney retransplantation,as a specific topic in the field of kidney transplantation.AIM To identify the risk factors affecting primary graft function and graft survival rates after second kidney transplantation(SKT).METHODS The records of SKT cases performed between January 1977 and December 2014 at a European tertiary-level kidney transplantation center were retrospectively reviewed and analyzed.Beside the descriptive characteristics,the survivals of patients and both the first and second grafts were described using Kaplan-Meier curves.In addition,Kaplan-Meier analyses were also used to estimate the survival probabilities at 1,3,5,and 10 post-operative years,as well as at the longest followup duration available.Moreover,bivariate associations between various predictors and the categorical outcomes were assessed,using the suitable biostatistical tests,according to the predictor type.RESULTS Out of 1861 cases of kidney transplantation,only 48 cases with SKT were eligible for studying,including 33 men and 15 women with a mean age of 42.1±13 years.The primary non-function(PNF)graft occurred in five patients(10.4%).In bivariate analyses,a high body mass index(P=0.009)and first graft loss due to acute rejection(P=0.025)were the only significant predictors of PNF graft.The second graft survival was reduced by delayed graft function in the first(P=0.008)and second(P<0.001)grafts.However,the effect of acute rejection within the first year after the first transplant did not reach the threshold of significance(P=0.053).The mean follow-up period was 59.8±48.6 mo.Censored graft/patient survival rates at 1,3,5 and 10 years were 90.5%/97.9%,79.9%/95.6%,73.7%/91.9%,and 51.6%/83.0%,respectively.CONCLUSION Non-immediate recovery modes of the first and second graft functions were significantly associated with unfavorable second graft survival rates.Patient and graft survival rates of SKT were similar to those of the first kidney transplantation.

Liver retransplants using living donors:An approach for management

Background and aims:Many centers do not offer living donor transplants for patients in need of a liver retransplant.We aimed to study our liver retransplant outcomes using living donors and compared them with those of retransplants performed using deceased donors.Methods:This study retrospectively analyzed all retransplants performed at our center between 2009 and 2023,and outcomes of living donor retransplants were compared with deceased donor retransplants using standard statistical tests.Results:Between January 2009 and March 2023,a total of 77 retransplants,60 with deceased donors and 17 with living donors,were performed.Important demographic differences between the two groups included a higher model for end-stage liver disease score in the deceased donor group(32.1±6.1 vs.19.4±5.7,P<0.001)and a higher number of early retransplants(within 3 months of the initial transplant),which accounted for 35% of deceased donor transplants but 0 of living donor transplants(P<0.01).Overall,the patient and graft survival rates were comparable between the two groups.The patient survival rates at 1 and 3 years after transplant were 73% and 67% in the deceased donor group and 84% and 73% in the living donor group,respectively(P=0.57).The hospital length of stay and blood product use were both better in the living donor group.Biliary complications did not show significant different between the two groups(P=0.33).Conclusions:Living donors can provide acceptable outcomes for those in need of a retransplant,with results comparable to those seen with deceased donors.A systematic approach to the patient in the pre-,peri-,and post-transplantation period is important in these complicated cases.

Study of the Effects of the Chinese Herbal Prescription Combinedwith Copper and Ferum on the Malignancy ot Cancer Cells

As compared with normal cells, cancer cells or malignant cells were morphologically abnor-mal : their contact inhibition and normal growth order were lost, the DNA content and ploid increased and suchkind of cells were transplantable. It the malignancy should be decreased or the malignant cells reversed, theabove abnormal changes could be reduced or disappear. BALB/c mice bearing ascites liver cancer wereused, Chinese herbal prescription combined with copper and ferrum (CHPCCF) was given by gavage for 10days, and then some cell-biological parameters were measured; further , the ascites cancer cells (controland treatment) were removed and retransptanted to another mice and observed. The results showed that inCHPCCF treatment group, DNA content of the cancer cells was decreased, and the proliferation index wasreduced (control : 83 . 4 ± 2 . 6, CHPCCF group : 78. 8 ± 1 . 5 ; or control : 67. 2 ± 1 . 3 , CHPCCF group : 64. 2 ±l . 6, P < 0. 02) , the number of the cancer cells in Gl phase increased obviously, but, those of S + G2Mphases decreased ( P < 0. 05 ￣ 0. 01 ) ; on the DNA histogram, the diploid peak became higher and bigger,but aneuploid or multiploid peaks became smaller. Furthermore, retransplanted experiments showed that in2/10 animals, the tumors did not grow, and in other 8/10 animals , the tumors grew, but the tumors' sizewere smaller than that of the control ; the growth inhibition rate was 71 . 7% ￣ 88. 3% ; and tumors ' grewslowly ; the growth curve of the tumors in CHPCCF group was considerably lower than that of the control ; thesurvival period of retransplanted animals was prolonged significantly (from 26. 1 ± 11 . 8 to 38. 1 ± 9. 6, or to39 . 6 ± 7 . 2 days, P<0 . 01 ); the increase in life span was 46% and 52% respectively. The results suggestedthat CHPCCF could reduce the malignancy of mice liver cancer cells.