Liver transplantation for primary biliary cirrhosis: influence of primary immunosuppression on survival

INTRODUCTION: Liver transplantation is the only established curative therapy for end-stage primary biliary cirrhosis (PBC). However, the influence of primary immunosuppression on long-term patient and graft survival is still controversial. PATIENTS AND METHODS: Among 1372 patients who underwent liver transplantation from April 1989 to January 2001, 95 (6.9%) suffered from PBC. The primary immunosuppression consisted of cyclosporine (CyA; n = 56) and tacrolimus (FK; n = 39). RESULTS: The median survival of all PBC patients at 5 years was 92% and at 10 years, 90%. There was no difference between the two primary immunosuppression agents. Seven patients died, including five in the cyclosporine group (median = 25 months) and two in the tacrolimus cohort (median = 37 months). One CyA patient group died due to PBC recurrence. Seven patients underwent retransplantation without any difference in primary immunosuppression (CyA 7%; FK 10%). Fifty patients developed an acute rejection episode (CyA 57%; FK 46%); 2 patients, chronic rejection (CyA 2%; FK 4%). Fifty-five patients developed AMA titers after liver transplantation (CyA 66%; FK 46%). Patients presented cyclosporine-based regimens showed significantly (P = .001) more side effects. CONCLUSION: Long-term follow-up after liver transplantation for PBC shows excellent organ and patient survival. The choice of the primary immunsuppressant had no significant influence on patient survival, PBC-related graft loss, or development of acute or chronic rejection episodes.     

First‐Degree Living‐Related Donor Liver Transplantation in Autoimmune Liver Diseases

Liver transplantation (LT) is the treatment of choice for end‐stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first‐degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty‐three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post‐LT follow‐up, were included in this study. Of these, 72 (27%) received a graft from a first‐degree living‐related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first‐degree living‐related, living‐unrelated, or deceased‐donor LT. Similarly, time to recurrence, recurrence‐related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first‐degree living‐related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.     

Liver transplantation for primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that progresses to end-stage liver disease. This report is a retrospective analysis of a Canadian centre experience with liver transplantation (LT) for PSC. Of 1107 LTs performed between 1984 and 2002, 132 were performed on 111 patients with PSC. Patient survival at 1, 3, 5, and 10 years was 84.5%, 84.5%, 83.4%, and 68.9%, respectively. Graft survival at 1, 3, 5, and 10 years was 80.8%, 79.8%, 72.7%, and 55.3%. These were not significantly different from overall patient survival (P =.91) or graft survival (P =.28) in non-PSC patients transplanted over the same time period. Early mortality was predominantly related to primary nonfunction and multi-organ failure; late mortality was predominantly related to malignancy. No patient with known cholangiocarcinoma (CCA) underwent LT, but three patients had an incidental CCA noted on explant pathology. All three died of widespread metastatic disease (10.8, 38.0, and 39.8 months after LT). Nineteen patients lost their primary grafts requiring retransplantation, and two of these patients required a third transplant. Recurrent PSC was detected in six patients and suspected in another six. Four patients have been retransplanted for recurrent PSC. Chronic rejection was detected in nine patients. Eight have required retransplantation. The incidence of biliary complications was 16.2%. CONCLUSIONS: LT is effective therapy for PSC. Patient and graft survival is comparable to that seen in patients transplanted for indications other than PSC, but long-term graft survival may be lower. Recurrent PSC and chronic rejection are the major determinants of graft loss.     

Liver transplantation for primary biliary cirrhosis: A long-term pathologic study

Although recurrent primary biliary cirrhosis (PBC) after liver transplantation (LT) has been reported, the full spectrum of changes and progression to fibrosis and cirrhosis is not yet established. We performed a detailed retrospective clinicopathologic analysis of 43 patients who underwent LT for PBC. Eight patients (18.6%) had definite recurrent PBC with florid duct lesions, 5 patients (11.6%) had recurrence with features of autoimmune liver disease, not otherwise specified (AILD-NOS), 7 patients (16.3%) had plasmacytosis only, 4 patients (9.3%) had chronic rejection, 18 patients (41.9%) have no recurrence at present, and 1 patient (2.3%) had acquired hepatitis C. Although definite diagnoses of PBC and AILD-NOS recurrences (n = 13) were made 1 month to 14 years (median, 4 years) post-LT, all patients had plasmacytosis in their earlier biopsy specimens. Also, these patients showed similar pre-LT and post-LT clinical features, with progressive fibrosis in 4 of 8 and 2 of 5 patients, respectively. Four of 13 patients with definite recurrence and 14 of 18 patients with no recurrence were administered azathioprine (AZA) as part of their post-LT therapy (P = .01). Six of 13 and 16 of 18 patients currently are alive, with median follow-ups of 11 and 5 years, respectively. No significant differences were seen with donor-recipient group A, group B, group O blood type, sex, or HLA mismatches; native liver histological characteristics; or tacrolimus-based therapy. In conclusion, recurrent autoimmune liver disease was seen in 30% of patients after LT for PBC and had features of PBC and/or AILD-NOS. Progression seen in 46% of patients was associated with late graft failure. Patients with no recurrent disease had shorter follow-up periods and more frequent immunosuppression, including AZA; some may still develop recurrence with longer follow-up. (Liver Transpl 2003;9:87-96.)     

Causes of early acute graft failure after liver transplantation: analysis of a 17-year single-centre experience

Despite satisfactory overall results reported, early post-operative period after liver transplantation (LT) still represents a critical time with persistently high rate of graft loss. We retrospectively reviewed our experience of 17 yr in LT, analysing the impact on grafts and patient survivals of the acute complications affecting the graft in the early period following LT. To evaluate the changes that occurred over the years in case of early acute graft failure (EAGF), the study population was divided into three equal groups of 223 patients corresponding to three different periods. Ninety (13.5%) experienced an EAGF. Causes of EAGF were hepatic artery thrombosis (HAT) in 32 cases (4.8%), primary graft non-function in 29 cases (4.3%), caval stenosis in 19 (2.8%), early irreversible acute rejection in 6 (0.9%) and portal vein thrombosis in 4 (0.6%). The use of elderly donors and the introduction of the piggyback technique proved to be associated with a higher incidence of HAT and caval stenosis, respectively. Female recipients of male donors were independently associated with Primary graft non-function. Of 90 patients with EAGF, 20 (22.2%) died within the first month after LT, 34 (37.8%) underwent retransplantation (ReLT) and 36 (40%) received conservative treatment. Conservative treatments increased from 3.6% in the first group to 47.0 and 66.8% in the second and third one (p = 0.000). One-year graft and patient survival of patients with EAGF significantly improved over the three eras analysed. The incidence of EAGF remains consistent. Nevertheless, a better understanding of the clinical situations and changes in treatment strategies have led to significant improvements in terms of graft and patient survival rates, now close to the survival rate of EAGF-free patients.     

Should we perform heart retransplantation in early graft failure?

Cardiac retransplantation represents the gold standard treatment for a failing cardiac graft but the decision to offer the patient a second chance is often made difficult by both lack of donors and the ethical issues involved. The aim of this study was to evaluate whether retransplantation is a reasonable option in case of early graft failure. Between November 1985 and June 2008, 922 patients underwent cardiac transplantation at our Institution. Of these, 37 patients (4%) underwent cardiac retransplantation for cardiac failure resulting from early graft failure ( n  = 11) or late graft failure (acute rejection: n  = 2, transplant-related coronary artery disease: n  = 24). Survival at 1, 5 and 10 years of patients with retransplantation was 59%, 50% and 40% respectively. An interval between the first and the second transplantation of less than ( n  = 11, all in early graft failure) or more than ( n  = 26) 1 month was associated with a 1-year survival of 27% and 73%, and a 5-year survival of 27% and 65% respectively ( P  = 0.01). The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation only in patients with transplant-related coronary artery disease. Early graft failure is a significant risk factor for survival after cardiac retransplantation and should be considered as an exclusion criteria.     

Long-term Clinical Outcomes of First and Second Kidney Transplantation in Patients With Biopsy-Proven IgA Nephropathy

Introduction

The recurrence of IgA nephropathy (IgAN) after kidney transplantation (KT) has an effect on graft survival, but there are few reports about long-term clinical outcomes of KT with recurrent IgAN. This study shows the long-term clinical outcomes of KT in patients with IgAN.

Benefit of transplantation in primary biliary cirrhosis between 1985-1997

BACKGROUND: In the 1980s, primary biliary cirrhosis (PBC) patients were shown to benefit from transplantation when compared to a mathematical model. This study, using the same model, evaluates a cohort of patients who underwent transplantation in the late 1980s and early 1990s before and after the introduction of therapy with ursodeoxycholic acid (UDCA). METHODS: All 73 PBC patients transplanted at the University of Toronto between 1985 and 1997 were included in the study. Actual survival posttransplantation, calculated with the Kaplan-Meier product-limit estimator, was compared to predicted survival without transplantation, as determined by the Mayo model. The effect of UDCA therapy on outcome was studied by dividing the cohort into those transplanted before and after 1992, the year in which UDCA use for PBC was introduced. RESULTS: At 2 years posttransplant, predicted survival without transplant was 55% whereas actual survival was 79%. At 7 years posttransplant, these figures were 22% and 68%, respectively (P=3 x 10(-8)). There was a nonsignificant trend towards improved survival in those transplanted during the UDCA era compared to those transplanted in the pre-UDCA era. CONCLUSIONS: Liver transplantation remains extremely beneficial for patients with end-stage PBC. There was no difference in outcome after liver transplantation in those transplanted during the UDCA era when compared to their pre-UDCA counterparts.     

Nonanastomotic biliary strictures after liver transplantation, part 2: Management, outcome, and risk factors for disease progression.

Nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation (OLT) are associated with high retransplant rates. The aim of the present study was to describe the treatment of and identify risk factors for radiological progression of bile duct abnormalities, recurrent cholangitis, biliary cirrhosis, and retransplantation in patients with NAS. We retrospectively studied 81 cases of NAS. Strictures were classified according to severity and location. Management of strictures was recorded. Possible prognostic factors for bacterial cholangitis, radiological progression of strictures, development of severe fibrosis/cirrhosis, graft survival, and patient survival were evaluated. Median follow-up after OLT was 7.9 years. NAS were most prevalent in the extrahepatic bile duct. Twenty-eight patients (35%) underwent some kind of interventional treatment, leading to a marked improvement in biochemistry. Progression of disease was noted in 68% of cases with radiological follow-up. Radiological progression was more prevalent in patients with early NAS and one or more episodes of bacterial cholangitis. Recurrent bacterial cholangitis (>3 episodes) was more prevalent in patients with a hepaticojejunostomy. Severe fibrosis or cirrhosis developed in 23 cases, especially in cases with biliary abnormalities in the periphery of the liver. Graft survival, but not patient survival, was influenced by the presence of NAS. Thirteen patients (16%) were retransplanted for NAS. In conclusion, especially patients with a hepaticojejunostomy, those with an early diagnosis of NAS, and those with NAS presenting at the level of the peripheral branches of the biliary tree, are at risk for progressive disease with severe outcome.     

Liver retransplantation of patients with hepatitis C infection is associated with acceptable patient and graft survival.

Infection with hepatitis C virus (HCV) is the leading cause of liver transplantation (LT), while liver retransplantation (RT) for HCV is controversial as a result of concerns over poor outcomes. We sought to compare patient and graft survival after RT in patients with and without HCV. We performed a retrospective chart review of all patients undergoing RT at our center between February 1998 and April 2004. Indications for RT, HCV status, patient, and donor characteristics, laboratory values, and hospitalization status at RT were collected. A total of 108 patients (48 HCV and 60 non-HCV) underwent RT during the study period, with mean post-RT follow-up of 1,096 days (range, 0-2,888 days). Grafts from donors aged>60 years were used less frequently in HCV patients at RT (6%) compared with LT (47%), P<0.001. There was no difference between HCV vs. non-HCV patients in 1- and 3-year patient survival (respectively, 79% vs. 63%, and 71% vs. 63%) and graft survival (respectively, 67% vs. 66%, and 59% vs. 56%). Post-RT mortality and graft failure in HCV patients occurred within the first year in 89% of patients, and 83% were unrelated to HCV recurrence. We conclude that patients should not be excluded from consideration for retransplantation solely on the basis of a diagnosis of HCV.     

Causes of late mortality in pediatric liver transplant recipients.

OBJECTIVE: This study was undertaken to review the incidence and causes of death in children who have survived long-term (more than 1 year) after liver transplantation (LT). SUMMARY BACKGROUND DATA: No studies of the causes of late mortality in pediatric LT recipients are currently available in the literature. METHODS: The study group consists of 212 pediatric patients who survived more than 1 year after LT. Twenty-three of these patients subsequently died (mean follow-up = 5.3 yr). Hospital records, office charts, and autopsy records were reviewed retrospectively to identify the causes of death. The patients who died were further evaluated by age, gender, length of survival, primary diagnosis, immunosuppression, and retransplantation. RESULTS: The most common cause of death was graft failure, followed closely by infection. In patients dying from graft failure, eight of the nine patients underwent retransplantation and no child survived more than three liver transplants. Overwhelming infections occurred suddenly in eight children who had been previously healthy. Noncompliance was the third most common cause of death, primarily in older children. One child died from a posttransplant lymphoproliferative disorder (PTLD). Actuarial survival at 10 years is 83.7% (based on 100% survival at 1 year). There was no difference in survival based on primary disease. Retransplantation was far more prevalent in the nonsurvivors (47.8%) compared with survivors (13.7%) (p < 0.05). There were no significant differences in survival based on age, gender, or immunosuppression. CONCLUSIONS: Late mortality in children continues to be directly related to complications of LT and immunosuppression, even after the first year of transplantation. This is in contrast to adult liver transplant recipients, where approximately 50% of late deaths were related to LT and the remainder were because of unrelated illnesses.     

Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder: duration of posttransplant lymphoproliferative disorder-induced operational graft tolerance,interleukin-18 course,and results of retransplantation

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD, and in whom we were able to perform IL-18 analyses. RESULTS: Patients were followed for up to 7 years after PTLD diagnosis. Treatment consisted of immunosuppression cessation with radiation therapy in cases with overt monomorphic lymphomas. All patients' PTLDs were resolved, and all patients but one (whose graft was removed) demonstrated a period of operational graft tolerance of up to 5 years. Five patients underwent retransplantation without sign of recurrence of the PTLD up to 3 years after transplantation. In the eight patients analyzed, IL-18 increased significantly during PTLD regression and follow-up in those with long-term operational tolerance. CONCLUSION: We report on a series of patients with resolved PTLDs demonstrating long-term recurrence-free survival, of whom most experienced a long period of operational graft tolerance. IL-18 seems to play a role in the resolution of the PTLDs. Five patients underwent retransplantation with standard immunosuppression without recurrence. A previous diagnosis of PTLD should not be regarded as a contraindication for later retransplantation.     

MELD and prediction of post-liver transplantation survival.

The model for end-stage liver disease (MELD) was developed to predict short-term mortality in patients with cirrhosis. It has since become the standard tool to prioritize patients for liver transplantation. We assessed the value of pretransplant MELD in the prediction of posttransplant survival. We identified adult patients who underwent liver transplantation at our institution during 1991-2002. Among 2,009 recipients, 1,472 met the inclusion criteria. Based on pretransplant MELD scores, recipients were stratified as low risk (< or = 15), medium risk (16-25), and high risk (>25). The primary endpoints were patient and graft survival. Mean posttransplant follow-up was 5.5 years. One-, 5- and 10-year patient survival was 83%, 72%, and 58%, respectively, and graft survival was 76%, 65%, and 53%, respectively. In univariable analysis, patient and donor age, patient sex, MELD score, disease etiology, and retransplantation were associated with posttransplantation patient and graft survival. In multivariable analysis adjusted for year of transplantation, patient age >65 years, donor age >50 years, male sex, and retransplantation and pretransplant MELD scores >25 were associated with poor patient and graft survival. The impact of MELD score >25 was maximal during the first year posttransplant. In conclusion, older patient and donor age, male sex of recipient, retransplantation, and high pretransplant MELD score are associated with poor posttransplant outcome. Pretransplant MELD scores correlate inversely with posttransplant survival. However, better prognostic models are needed that would provide an overall assessment of transplant benefit relative to the severity of hepatic dysfunction.     

Pediatric cardiac retransplantation: intermediate-term results

BACKGROUND: Cardiac retransplantation (re-CTx) in children is a controversial therapy, yet it remains the best treatment option to recipients with failing grafts. Our objective was to determine the incidence of re-CTx in a large pediatric population of recipients and evaluate the outcome of such therapy. METHODS: Between November 1985 and November 1999, 347 children underwent cardiac transplantation at the Loma Linda University Medical Center. Of these, 32 children were listed for re-CTx. Ten patients died while waiting, and 22 recipients underwent re-CTx. Median age at re-CTx was 7.1 years (range, 52 days to 20.1 years). RESULTS: Indications for re-CTx were allograft vasculopathy (n = 16), primary graft failure (n = 5), and acute rejection (n = 1). Two patients with primary graft failure underwent retransplantation within 24 hours of the first transplantation procedure while on extracorporeal membrane oxygenation support. Median time interval to re-CTx for the others was 7.2 years (range, 32 days to 9.4 years). Operative mortality for all cardiac re-CTx procedures was 13.6%. Causes of hospital mortality were pulmonary hypertension with graft failure (n = 2) and multiorgan failure (n = 1). Median hospital stay after re-CTx was 14.1 days (range, 6 to 45 days). There was one late death from severe rejection. Actuarial survival at 3 years for re-CTx was 81.9% +/- 8.9% compared with 77.3% +/- 2.6% for primary cardiac transplantation recipients (p = 0.70). CONCLUSIONS: Elective re-CTx can be performed with acceptable mortality. Although the number of patients undergoing retransplantation in this report is small and their long-term outcome is unknown, the intermediate-term survival after re-CTx is similar to that of children undergoing primary cardiac transplantation.     

Liver Retransplantation in Children: A SPLIT Database Analysis of Outcome and Predictive Factors for Survival

To examine outcomes and identify prognostic factors affecting survival after pediatric liver transplantation, data from 246 children who underwent a second liver transplantation (rLT) between 1996 and 2004 were analyzed from the SPLIT registry, a multi-center database currently comprised of 45 North American pediatric liver transplant programs. The main causes for loss of primary graft necessitating rLT were primary nonfunction, vascular complications, chronic rejection and biliary complications. Three-month, 1- and 2-year patient survival rates were inferior after rLT (74%, 67% and 65%) compared with primary LT (92%, 88% and 85%, respectively). Multivariate analysis of pretransplant variables revealed donor age less than 1 year, use of a technical variant allograft and INR at time of rLT as independent predictive factors for survival after rLT. Survival of patients who underwent early rLT (ErLT, <30 days after LT) was poorer than those who received rLT >30 days after LT (late rLT, LrLT): 3-month, 1- and 2-year patient survival rates 66%, 59%, and 56% versus 80%, 74% and 61%, respectively, log-rank p = 0.0141. Liver retransplantation in children is associated with decreased survival compared with primary LT, particularly, in the clinical settings of those patients requiring ErLT.     

A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C

Hepatitis C is the most common indication for liver transplantation (LT) in the United States. Recurrence of hepatitis C virus (HCV) infection post-LT remains a problem for which there is no completely satisfactory treatment. The aim of the present study is to evaluate mycophenolate mofetil (MMF), which has both immunosuppressive and antiviral properties, to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival. Between August 1995 and May 1998, a total of 106 patients who were HCV positive before LT were randomized to tacrolimus (TAC) and prednisone versus TAC, prednisone, and MMF therapy. The rate of recurrence of HCV, patient and graft survival, incidences of rejection, and histological findings were examined. Fifty six patients were randomized to TAC and steroid therapy (double [D] drug; group D), and 50 patients were randomized to TAC, steroid, and MMF therapy (triple [T] drug; group T). Liver biopsies were performed when liver function was abnormal; protocol liver biopsies were not performed. Mean follow-up was 4.3 [plusmn] 0.8 years. Actuarial patient survivals at 4 years were 72.6% in group D and 73.8% in group T (P = not significant). Actuarial graft survivals at 4 years were 65.6% in group D and 65.4% in group T. One patient in group D and 2 patients in group T underwent a second LT for recurrent HCV. One patient in each group died of recurrent HCV without re-LT. Twenty-six patients in group D (46.4%) and 23 patients in group T (46.0%) showed signs of recurrent HCV. Mean hepatitis activity index (HAI) scores were 7.4 [plusmn] 2.7 in group D and 7.0 [plusmn] 3.4 in group T, and mean fibrosis scores were 2.9 [plusmn] 1.7 in group D and 2.6 [plusmn] 1.1 in group T. The rate of rejection was 0.57/patient in each group for the entire follow-up period. None of these values reached statistical significance. Rates of HCV recurrence, graft loss or death from recurrent HCV, and 4-year actuarial patient and graft survival were not different between the groups. In liver transplant recipients with HCV, MMF has no impact on patient survival, graft survival, rejection, or rate of HCV recurrence based on biochemical changes and histological findings. In addition, there was no difference in HAI or fibrosis score between the two groups. Either MMF has no anti-HCV effect or its immunosuppressive properties overwhelm its antiviral effect in the clinical setting. (Liver Transpl 2002;8:40-46.)     

The Effect of Early Retransplantation on Early and Late Survival After Liver Transplantation

BackgroundEarly liver retransplantation after liver transplantation (LT) is the ultimate salvage procedure for irreversible graft failure. The aim of this study was to assess the impact of early retransplantation on 90-day and 5-year patient survival.MethodsThis retrospective cohort study included 2185 patients after LT in the period between 1997 and 2019. First, the patients undergoing first retransplantation within 6 months after initial LT were compared with naïve LT patients for early mortality (within 90 days). Second, to assess late survival, the patients who had retransplantation and survived at least 90 days post LT were compared with naïve LT patients for 5-year overall survival. The patients undergoing late retransplantation (>6 months) were excluded from analyses. Fisher's exact test was used to compare groups for early survival and log-rank test for late survival.ResultsThe cumulative 1-, 3-, and 5-year overall survival was 87.0%, 79.9%, 75.0%, respectively, and did not differ significantly between the groups. The patients undergoing early retransplantation had lower 90-day survival rate of 89.2% as compared to 95.7% for naïve LT patients (P < .001).ConclusionsThe early liver retransplantation has profound impact on post-LT 90-day survival; however, patients who survive that period can achieve long overall survival comparable with naïve LT patients.     

Cyclosporine A Protects Against Primary Biliary Cirrhosis Recurrence After Liver Transplantation

Primary biliary cirrhosis (PBC) reoccurs in a proportion of patients following liver transplantation (LT). The aims of our study were to evaluate the risk factors associated with PBC recurrence and determine whether recurrent disease constitutes a negative predictor for survival. One hundred and eight patients receiving LT for end‐stage PBC were studied. Recurrent disease was diagnosed in 28 patients (26%). Probability of recurrent PBC at 5 years was 13% and 29% at 10 years with an overall incidence of 3.97 cases per 100 patient years. By univariate Cox analysis use of tacrolimus (HR 6.28, 95% CI, 2.44–16.11, p < 0.001) and mycophenolate mofetil (HR 5.21, 95% CI, 1.89–14.33, p = 0.001) were associated with higher risk of recurrence; whereas use of cyclosporine A (CsA) and azathioprine were associated with reduced risk of recurrence (HR 0.13, 95% CI 0.05–0.35, p < 0.001 and HR 0.27, 95% CI 0.11–0.64, p = 0.003, respectively). In the multivariate Cox analysis, only CsA was independently associated with protection against recurrence (HR 0.17, 95% CI 0.06–0.71, p = 0.02). Five‐year probability of survival was 83% and 96%, in patients without and with recurrence (log‐rank test, p = 0.3). Although PBC transplant recipients receiving CsA have a lower risk of disease recurrence, the development of recurrent PBC did not impact on long‐term patient survival.     

Decision for retransplantation of the liver: an experience- and cost-based analysis

OBJECTIVE: To determine the patient factors affecting patient outcome of first liver retransplantation at a single center to help in the decision process for retransplantation. SUMMARY BACKGROUND DATA: Given the critical organ shortage, one of the most controversial questions is whether hepatic retransplantation, the only chance of survival for patients with a failing first organ, should be offered liberally despite its greater cost, worse survival, and the inevitable denial of access to primary transplantation to other patients due to the depletion of an already-limited organ supply. The authors' experience of 139 consecutive retransplantations was reviewed to evaluate the results of retransplantation and to identify the factors that could improve the results. METHODS: From 1986 to 2000, 1,038 patients underwent only one liver transplant and 139 patients underwent a first retransplant at the authors' center (first retransplantation rate = 12%). Multivariate analysis was performed to identify variables, excluding intraoperative and donor variables, associated with graft and patient long-term survival following first retransplantation. Lengths of hospital and intensive care unit stay and hospital charges incurred during the transplantation admissions were compared for retransplanted patients and primary-transplant patients. RESULTS: One-year, 5-year, and 10-year graft and patient survival rates following retransplantation were 54.0%, 42.5%, 36.8% and 61.2%, 53.7%, and 50.1%, respectively. These percentages were significantly less than those following a single hepatic transplantation at the authors' center during the same period (82.3%, 72.1%, and 66.9%, respectively). On multivariate analysis, three patient variables were significantly associated with a poorer patient outcome: urgency of retransplantation (excluding primary nonfunction), age, and creatinine. Primary nonfunction as an indication for retransplantation, total bilirubin, and factor II level were associated with a better prognosis. The final model was highly predictive of survival: according to the combination of the factors affecting outcome, 5-year patient survival rates varied from 15% to 83%. Retransplant patients had significantly longer hospital and intensive care unit stays and accumulated significantly higher total hospital charges than those receiving only one transplant.CONCLUSIONS These data confirm the utility of retransplantation in the elective situation. In the emergency setting, retransplantation should be used with discretion, and it should be avoided in subgroups of patients with little chance of success.     

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.