Outcome Of Retransplantation Research Articles

Histological recurrent hepatitis C after liver transplantation: Outcome and role of retransplantation

Impact of hepatitis C virus (HCV) recurrence on long-term outcome after orthotopic liver transplantation (OLT) is highly variable, and the role of retransplantation is still debated. From 1996 to 2003, 131 OLT with histologically proven HCV recurrence and 6 months of follow-up were retrospectively reviewed. One and 5-yr overall survivals were 90.7 and 81.3%, respectively. The mean time of HCV recurrence was 10.1 +/- 6.2 months in patients whose donor's age was less than 70 yr old, and 6.6 +/- 4.7 in patients whose donor's age was more than 70 (P < 0.01). The mean time between OLT and HCV recurrence was 10.7 +/- 8.2 months among patients still alive, and 5 +/- 4.2 among the 20 who died (P = 0.02). In 16 (12.2%) patients, retransplantation was required for severe HCV recurrence; 5 are still alive and 11 (68.7%) died. The mean survival time was 16.2 +/- 6 months if re-OLT was performed within 12 months from first OLT, and it was 45.9 +/- 10 months if re-OLT was performed later (P < 0.01). In conclusion, donors older than 70 yr are at high risk of early HCV recurrence; expectancy of life is significantly reduced in case of histologically proven recurrence within 6 months. Outcome is quite dismal in patients with early HCV recurrence requiring retransplantation within 1 yr of first OLT.

Survival Outcome After Hepatic Retransplantation for Hepatitis C Virus–Positive and –Negative Recipients

Introduction Hepatitis C virus (HCV)–related liver disease is the most common indication for liver transplantation in the United States. Recurrence of HCV infection in these recipients is almost uniform. The currently available antiviral treatment is known to cause significant side effects, and the rate of sustained viral response is low. There is still controversy about whether such patients should undergo subsequent transplantations for HCV disease. This study compared outcomes for hepatic retransplantation performed in HCV(+) and HCV(−) recipients at a single center. Patients and methods From December 1994 through November 2003, 68 patients at our institution received a second liver allograft. Nineteen of the recipients were HCV(+) (group A) and 49 were HCV(−) (group B). All patients were followed until January 2004. The mean follow-up time after initial retransplantation was 37 ± 29 months. Patient and graft survival for the two groups were compared. Results Seven recipients in group A (36.8%) and 22 recipients in group B (44.9%) died during follow-up. The actuarial 3-year patient survival after initial retransplantation for groups A and B were 61.7% and 51.6%, respectively. Nine patients required a second retransplantation, 3 (15.8%) in group A and 6 (12.2%) in group B. The actuarial 3-year graft survival from initial retransplantation for groups A and B were 56.3% and 45.7%, respectively. Conclusion We observed slightly better patient and graft survivals at 3 years from initial retransplantation in HCV(+) recipients compared to HCV(−) recipients. This may be due to younger donor age and better selection of HCV(+) recipients in this series.

Efficacy of MELD score in predicting survival after liver retransplantation

Objective We retrospectively investigated the efficacy of the MELD score to predict the outcome of liver retransplantation and serve as selection criteria. Materials and methods From 1987 to 2003, the 765 liver transplantations included 87 patients (11.4%) who received a second graft. In addition to graft and patient survivals, ROC curves were used to establish the best MELD score to select cases with poor outcomes. Results Indications for retransplantation were: 38 (43.7%) surgical complications; 12 (13.8%) chronic rejections; 15 (17.2%) disease recurrences; and 22 (15.3%) primary graft nonfunction. Overall patient survivals at 1, 3, and 5 years were 62.4%, 50.7%, and 49.1%, respectively. A MELD score of 25, calculated by ROC curves, significantly predicted graft and patient survival (44.2% vs 22.5%, P < .05 and 58.6% vs 27.8%, P < .005). During the first 30 postoperative days, patients with a MELD higher than 25 lost the second graft in 48% of cases compared to 16% in the other group ( P < .005). Patients retransplanted for primary graft nonfunction showed significant lower 5-year survival rates than those for other indications (28.6% vs 54.5%, P < .05) and higher mean MELD score (30.7 vs 21.9, P < .05). Conclusion A MELD score of 25 is a valid cut-off to predict the outcome of retransplantations, it may be useful to select patients among those who require a second graft. Cases with primary graft nonfunction displayed lower survival, because of their compromised clinical status as evidenced by their high MELD scores.

Hepatology highlights

Hepatology highlights

Retransplantation for recurrent hepatitis C: Positive aspects

1. The prevalence of retransplantation for hepatitis C (HCV) patients is stable (around 40%). 2. Survival models to predict outcome of retransplantation do not show that HCV is an independent variable with poor outcomes. 3. Using Model for End-Stage Liver Disease (MELD) scores from the United Network for Organ Sharing (UNOS) database from 1996-2002, retransplantation for HCV had similar outcomes to other causes of retransplantation. 4. Poorer outcomes were noted for retransplantation with MELD scores greater than 25. 5. Minimal survival thresholds need to be developed for retransplantation for all causes of retransplantation.

Liver retransplantation in children in Poland

An average of 15% of patients require retransplantation due to irreversible liver graft failure due to primary graft nonfunction, chronic rejection, vascular and biliary complications, or infections. The survival of patients and grafts after retransplantation is inferior to that after primary transplantation. The purpose of the present study was to examine the incidence, indications, and outcome of retransplantation in children. In our center 169 liver transplantations had been performed in 154 patients, and 14 patients (9%) required 15 retransplantations: nine in the early postoperative period, five late after primary transplantation, and one late after the second transplantation. One-year patient survival after primary transplantation was 82%, but after early retransplantation it was 55%.

Retransplantation of liver: Primary graft nonfunction and hepatitis C virus are associated with worse outcome

It is not known whether the outcome of liver retransplantation (re-LT) is dependent on the indication for re-LT or cause of liver disease. In this study, our aim is to compare the outcome of re-LT in adults with that of primary liver transplantation (PLT) and determine whether the outcome of re-LT is dependent on its indication. United Network for Organ Sharing data from 1988 to 2001 were used for the study. Of 34,267 patients who met our inclusion criteria, 761 patients underwent re-LT for primary graft nonfunction (PGNF; group 1), 3,428 patients underwent re-LT for other reasons (group 2), and 30,078 patients underwent PLT (group 3). There was a greater incidence of PGNF (9.4% v 4.0%; P < .001) and regrafting (23.1% v 7.4%; P < .001) in the re-LT groups compared with the PLT group. Kaplan-Meier analysis and Cox regression analysis, after adjusting for confounding risk factors, showed significantly lower short- and long-term patient and graft survival in the re-LT groups compared with the PLT group. Kaplan-Meier survival showed lower patient and graft survival in group 1 compared with group 2. However, only graft, not patient, survival was lower in group 1 by Cox regression analysis when adjusted for other risk factors. Patients with hepatitis C virus (HCV) infection who underwent re-LT had lower patient and graft survival compared with those without HCV infection, and HCV was an independent predictor of mortality after re-LT. Re-LT was associated with a greater rate of complications and lower patient and graft survival compared with PLT. Re-LT for PGNF and HCV infection was associated with lower patient and graft survival compared with re-LT for other causes. (Liver Transpl 2003;9:897-904.)

Outcome of Re-transplantation in hepatitis C is independent of the outcome after the first transplant

Outcome of Re-transplantation in hepatitis C is independent of the outcome after the first transplant

Severe recurrent hepatitis C after liver retransplantation for hepatitis C virus–related graft cirrhosis

An increase in the number of hepatitis C virus (HCV)-infected transplant recipients at need for repeated liver transplantation is anticipated. To date, there is a certain reluctance to accept these patients because of an increased organ shortage, early reports suggesting a poor outcome, and uncertainty regarding the natural history of recurrent hepatitis C in the second graft. The aim of this study is to determine the outcome of patients undergoing retransplantation for HCV-related graft cirrhosis. Of 49 transplant recipients with HCV-related allograft cirrhosis, 31 patients developed decompensation with criteria for retransplantation. Thirteen patients were denied this option. Of the 18 patients accepted, 6 patients died while on the waiting list (5 patients died of graft cirrhosis at a median of 3.2 months of listing), and 12 patients have undergone retransplantation (median, 10 months since HCV cirrhosis). After retransplantation, 8 patients (67%) died at a median of 8 months, and 4 patients (33%) remain alive after 1.9 years of follow-up. Causes and times of death from retransplantation were: surgical complications, n = 3 (perioperative period); HCV cirrhosis of the second graft, n = 2 (at 9 and 54 months); fibrosing cholestatic hepatitis, n = 1 (at 2 years); lymphoproliferative disorder, n = 1 (at 7 months); and endocarditis, n = 1 (at 3.5 years, with underlying cirrhosis). Of the 4 patients alive, fibrosis stages in the last biopsy specimens are stage 1 (n = 1), stage 3 (n = 1), and stage 4 or cirrhosis (n = 1; one patient has not undergone biopsy), despite antiviral therapy. The outcome of retransplantation for HCV cirrhosis of the first graft is very poor because of multiple complications. The severity of recurrent HCV disease in the second graft seems to be related to that observed in the first graft. (Liver Transpl 2003;9:228-235.)

Long-term outcome of liver retransplantation in children.

Retransplantation of the liver is the only means of prolonging survival in children whose initial graft has failed. Patient and graft survival rates after retransplantation in most series have been inferior to rates after first transplantation. Of 450 pediatric liver transplantations performed between January 1990 and March 2001, 50 were first retransplantations, 9 were second retransplantations, and 1 was a third retransplantation. The overall retransplantation rate was 13.3% (median age at retransplantation 4 years and median weight 15 kg). The median post-retransplantation follow-up was 73 (range, 6-139) months. Kaplan-Meier patient survival rates for the group (n=50) were 71.7%, 64.7%, and 64.7% at 1, 3, and 5 years, respectively. Graft survival rates were 65.6%, 56.7%, and 56.7% at 1, 3, and 5 years, respectively. This is significantly worse than rates for children undergoing first liver transplantation. There were 17 deaths, of which 9 occurred in the first month. Biliary complications occurred in 5 (10%) patients and vascular complications in 6 (12%). Improved patient and graft survival rates were observed in the later phase of the program, although the difference was not significant. Higher preoperative serum creatinine (P=0.001) and serum bilirubin (P=0.02) levels were associated with a higher postoperative mortality. Results of retransplantation in children remain inferior to those after first transplantation. There is a trend toward improving results. Liver retransplantation makes an important contribution to overall survival in children.

Liver transplantation for chronic hepatitis C: long-term results, role of antiviral therapy, and outcome of retransplantation

Hepatitis C virus (HCV)–related liver disease is the leading indication for orthotopic liver transplantation (OLT) worldwide. Recurrent HCV infection—defined by viremia after transplantation—is nearly universal, with histologic evidence of recurrent hepatitis present in the majority of patients. Although short-term survival is similar for patients transplanted for other causes of liver failure, approximately 20 to 25% of HCV-positive patients develop allograft cirrhosis by 5 years. Currently, there are no proven antiviral therapies that prevent HCV recurrence or development of allograft cirrhosis. Therefore, retransplantation is often the only viable option for patients with recurrent HCV-related liver disease. However, the outcome after retransplantation for HCV recurrence is poor, and whether organs should be offered to patients whose first allograft is failing because of recurrent HCV disease remains highly controversial. This review will highlight recent information regarding the long-term results of liver transplantation for HCV-related liver disease, the role of antiviral therapy, and the outcome after retransplantation.

Retransplantation of the liver in children.

Because of the poor outcome of hepatic retransplantation, it is still debated whether this procedure should be performed in an era of donor organ scarcity. The aim of this study was to analyze outcome of hepatic retransplantation in children, to identify risk factors influencing this outcome, and to assess morbidity and causes of death. A series of 97 children after a single transplantation and 34 children with one retransplantation was analyzed. The 1-, 3-, and 5-year survival of children with a retransplantation was 70, 63, and 52%, respectively, compared with 85, 82, and 78%, respectively, for children after a single transplantation (P=0.009). Survival of children with a retransplantation within 1 month after primary transplantation was worse (P=0.007) and survival of children with a late retransplantation was comparable (P=0.66) with single transplantation. In early retransplantations, the Child-Pugh score was higher, donors were older and weighed more, and more technical variant liver grafts were used compared with single transplantations. Biliary atresia and a high Child-Pugh score were associated with decreased patient survival after retransplantation. Sepsis was the most important complication and cause of death after retransplantation. Retransplantation is a significant event after pediatric liver transplantation. Outcome after hepatic retransplantation in children is inferior compared with single transplantation. This difference is explained by low survival after early retransplantation and can be explained by the poor clinical condition of the children at time of retransplantation, especially in children with biliary atresia, and by the predominant use of technical variant liver grafts in retransplantations.

Survival after acute graft failure in pediatric thoracic organ transplant recipients.

Survival among recipients of repeat thoracic organ transplantation, particularly in the setting of acute graft failure (AGF), is lower than survival after a primary transplant. This has created controversy over the fair allocation of scarce organs. We reviewed our experience to assess the effectiveness of aggressive therapy and retransplantation in pediatric patients with AGF. Between November 1994 and March 1998, 52 patients aged 49 days to 16.9 years (median age 4.7 years) underwent thoracic organ transplantation (32 primary and 4 repeat heart, 16 primary and 4 repeat lung, and 3 primary heart-lung transplants). Acute graft failure occurred in nine (4 heart, 3 lung, 2 heart-lung transplants), six of whom were supported with extracorporeal membrane oxygenation (ECMO), and four of whom underwent repeat transplant. Six of the nine survived, including all of those who were retransplanted, and five of the nine were alive 1 year later. The average postoperative hospital stay after receiving a second organ was 46.5 days vs. a postoperative 22-day stay in recipients without AGF (p = 0.07). We conclude that the decision to allocate institutional and professional resources to the aggressive support of patients with AGF must be made at the level of the individual transplant center. However, we feel that the outcome of aggressive support and retransplantation justifies the allocation of organs to these patients and suggests that the current policies governing organ allocation for patients with early graft failure should be re-examined.

POLYOMA VIRUS INFECTION IN THE RENAL ALLOGRAFT: A SINGLE CENTER EXPERIENCE

136 Introduction: Polyoma virus renal allograft infection (PVI) is a known cause of renal allograft dysfunction and loss. The clinical features of 12 kidney transplant (KTX) or simultaneous kidney-pancreas transplant (SPK) recipients with PVI at a single institution were reviewed. Materials and Methods: From 12/92 to 10/98, 12 patients were diagnosed with PVI by immunoperoxidase stain and electron microscopy. We reviewed these cases analyzing preoperative characteristics, immunosuppression, disease presentation and treatment. Results: Mean patient age was 35 (range 13-66 years). Follow-up ranged from 5 to 78 months. Of the 12 transplants performed, 5 were cadaveric KTX, 3 SPK, 1 pediatric en-bloc transplant, and 3 were living related. Immunosuppression consisted of triple drug therapy in all patients. At the time of diagnosis, 67% of patients were taking tacrolimus, 33% were taking cyclosporine. Concurrently, 83% were taking mycophenolate mofetil and all patients were taking prednisone. Latency of infection ranged from 57 to 625 days with a median of 232 days. 7 patients (58%) had been treated or hospitalized for recent infections, including pneumonia (3/7), UTI (2/7), line sepsis (1/7), and CMV antigenemia (1/7). Symptoms at presentation were nonspecific and included fatigue and myalgias. Patients presented with an acute rise in creatinine ranging from 0.5 to 2.2 mg/dL (mean 1.2 mg/dL). These symptoms and findings mimicked acute rejection leading to allograft biopsy which revealed characteristic histology for polyoma. PVI was typically managed by reduction in immunosuppression. However in two patients, empiric treatment with daclizumab or steroids had been initiated prior to final tissue diagnosis. Graft loss occurred in 5 (42%) patients, and partial to full recovery of renal function occurred in 7 (58%) patients. Of those patients who suffered graft loss, two underwent re-transplant with living related kidneys. Follow-up at 6 months shows excellent graft function. Conclusion: Polyoma virus infection of the renal allograft can cause significant graft dysfunction and loss. Presentation may mimic rejection, and the diagnosis of polyoma infection should be considered on review of biopsy specimens. Decreasing immunosuppression was not completely effective in salvaging kidney function. The impact of newer immunosuppression protocols on the occurrence of polyoma, as well as the long-term outcome of re-transplantation remains to be elucidated.

Long-term survival after cardiac retransplantation: A twenty-year single-center experience

Objective: To identify risk factors for survival after cardiac retransplantation and compare the survival after retransplantation with that after primary cardiac transplantation. Methods: A retrospective analysis of 952 patients undergoing cardiac transplantation for the treatment of end-stage heart disease at a single center between 1977 and October 1997. Of these, 43 patients (4.5%) underwent cardiac retransplantation for cardiac failure resulting from transplant-related coronary artery disease, rejection, and early graft failure. Results: No significant difference in actuarial patient survival was found by Kaplan-Meier analysis at 1, 2, and 5 years between patients undergoing primary transplantation and those undergoing retransplantation—76%, 71%, and 60% versus 66%, 66%, and 51%, respectively ( P = .2). Multivariable analysis identified a shorter interval between transplants and an initial diagnosis of ischemic cardiomyopathy as significant risk factors for death after retransplantation ( P = .04 and .03, respectively). Since 1993, when our criteria for patient selection for retransplantation were revised on the basis of earlier experience to exclude patients with allograft dysfunction as a result of primary graft failure and those with intractable acute rejection occurring less than 6 months after transplantation, the survival has been significantly better (<1993 = 45%, 45%, and 33% versus ≥1993 = 94%, 94%, and 94% at 1, 2, and 4 years, respectively, P = .003). Conclusion: The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation, especially in patients with transplant-related coronary artery disease. Patient characteristics and other preoperative variables should assist in the rational application of retransplantation to ensure optimal use of donor organs. (J Thorac Cardiovasc Surg 1999;117:543-55)

An analysis of hepatic retransplantation in children.

The limited supply of organ donors has led some groups to reconsider the role of retransplantation. Historically, except for children with malignancies, extrahepatic sources of sepsis, or severe irreversible neurologic injuries, our institution has offered all children with failing liver grafts the option of retransplantation regardless of their current severity of illness. The purpose of this study was to examine the outcome of hepatic retransplantation in children in an attempt to identify factors predictive of outcome and to assess the results of our approach to retransplantation. Between October 1984 and December 1995, 314 children less than 15 years of age underwent a total of 441 liver transplants. Data were obtained retrospectively by review of hospital records. With a mean follow-up period of 5.3+/-2.7 years, the overall patient survival rates at 1 and 5 years were 77.1% and 67.1%, respectively. Primary allograft survival rates were 65.6% and 56.5%, respectively. Of the 137 patients who developed failure of their primary allograft, 92 underwent retransplantation (29.3% of all primary transplants). Both patient and allograft survival rates were significantly decreased after retransplantation (P<0.0001 versus primary transplants). Univariate and multivariate analysis of retransplanted patients revealed only two factors that were statistically related to patient and graft survival: age at the time of retransplantation (P<0.02 univariate and P<0.05 multivariate) and retransplantation with a reduced-size allograft (P<0.005 univariate and P<0.05 multivariate). In this series, the effect on patient survival of differences in medical condition as reflected by United Network for Organ Sharing (UNOS) status approached, but did not achieve, significance (P=0.08 for UNOS 1 versus UNOS 2 and 3). UNOS status did not affect graft survival. Neither the cause of primary allograft loss or the timing of retransplantation relative to the first transplant were related to outcome. These data demonstrate that the failure of primary hepatic allografts remains a major problem in pediatric liver transplantation and that the overall results of retransplantation were significantly worse than those associated with primary transplants. We have identified a group of children who experienced a significantly worse outcome after retransplantation. This group consisted of children less than 3 years of age retransplanted using reduced-size grafts. Based on this finding, we now attempt to avoid retransplanting young children with reduced-size grafts. By using this approach, we hope to be able to offer children the option of retransplantation with improved results and simultaneously minimize the negative impact on patients awaiting primary transplants.

SURVIVAL AFTER ACUTE GRAFT FAILURE IN PEDIATRIC THORACIC ORGAN TRANSPLANT RECIPIENTS.

Survival among recipients of repeat thoracic organ transplantation, particularly in the setting of acute graft failure (AGF), is lower than survival after a primary transplant. This has created controversy over the fair allocation of scarce organs. We reviewed our experience to assess the effectiveness of aggressive therapy and retransplantation in pediatric patients with AGF. Between November 1994 and March 1998, 52 patients aged 49 days to 16.9 years (median age 4.7 years) underwent thoracic organ transplantation (32 primary and 4 repeat heart, 16 primary and 4 repeat lung, and 3 primary heart-lung transplants). Acute graft failure occurred in nine (4 heart, 3 lung, 2 heart-lung transplants), six of whom were supported with extracorporeal membrane oxygenation (ECMO), and four of whom underwent repeat transplant. Six of the nine survived, including all of those who were retransplanted, and five of the nine were alive 1 year later. The average postoperative hospital stay after receiving a second organ was 46.5 days vs. a postoperative 22-day stay in recipients without AGF (p = 0.07). We conclude that the decision to allocate institutional and professional resources to the aggressive support of patients with AGF must be made at the level of the individual transplant center. However, we feel that the outcome of aggressive support and retransplantation justifies the allocation of organs to these patients and suggests that the current policies governing organ allocation for patients with early graft failure should be re-examined.

Outcome of liver retransplantation (ReOLTx) for recurrent hepatitis C infection: [formula omitted] Pittsburgh Transplantation Institute, University of Pittsburgh, Pittsburgh, PA

Outcome of liver retransplantation (ReOLTx) for recurrent hepatitis C infection: [formula omitted] Pittsburgh Transplantation Institute, University of Pittsburgh, Pittsburgh, PA

Second Renal Transplantations

To determine whether the appropriate use of scarce donor resources has been accomplished by renal retransplantation by reviewing the initial and long-term outcomes of second-renal transplant recipients at the Massachusetts General Hospital, Boston. With a mean follow-up of nearly 5 years following transplantation, 54 (68%) of 80 second-transplant recipients had functioning allografts (allograft failure was defined by patient death or a return to dialysis). Rejection was the most common cause of failure (14 [54%] of 26 patients). The 1-, 3-, and 5-year actuarial allograft survival rates were 86%, 78%, and 69%, respectively, which were not significantly different from the survival rates of primary allografts at this center. These results support the continued approach of providing both cadaver-donor and living-donor renal allografts for recipients whose primary renal allograft has failed. The antiglobulin crossmatch may have contributed to the successful outcome by accurately determining compatibility and by averting early rejection failures. Health care policy reviewers should clearly distinguish the prospects for successful second renal transplants from the outcomes of extrarenal retransplantation. Moreover, because excellent second-renal allograft survival is attainable and comparable to primary-renal allograft survival and because the costs are comparable, restricting suitable patients to subsequent lifelong dialysis becomes unethical.

Survival in End‐stage Diabetic Renal Disease

The results of renal transplantation in patients with diabetes mellitus were studied in 100 consecutive patients transplanted between Dec. 1972 and June 1982. The study period was divided into two parts, 1972-76 (era I, 21 patients, 18 with juvenile onset diabetes) and 1977-82 (era II, 79 patients, 72 with juvenile onset diabetes). A group of 168 non-diabetic patients, aged 20-54 years, receiving primary grafts during the same period served as controls to the 72 juvenile onset diabetics from era II. The three-year actuarial patient survival of transplanted diabetics improved from 48% during era I to 76% during era II and was then not significantly inferior to that of the non-diabetic controls. The three-year actuarial graft survival rate was significantly higher for recipients of kidneys from living related donors than for those who had received kidneys from cadaveric donors (CD) among both diabetic and non-diabetic patients. However, the three-year graft survival rate was significantly higher (56%) for non-diabetic than diabetic CD recipients (37%). The overall survival in diabetes mellitus was strongly influenced by the outcome of retransplantation during era II (12 patients). Thus, 69 patients were alive, 64 with a functioning graft, at the end of the observation period.