Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation?

The Banff schema incorporates a semiquantitative scoring system for grading of acute cellular rejection (ACR) of the liver allograft. The Banff rejection activity index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation (E); bile duct damage (B); and portal inflammation (P); the scores are combined to an overall score (the RAI). The purpose of this research was to determine the prognostic value of the Banff RAI score in predicting the response to increased immunosuppression and the long-term outcome of the graft. A retrospective study was done of patients undergoing primary liver transplantation between January 2000 and October 2004 with tacrolimus-based immunosuppression; 495 patients were included, 231 had histologically-confirmed ACR, 193 responded to 1 cycle of high-dose steroids. There was no correlation between the total RAI score and response to steroids, resistant rejection, development of chronic rejection, or graft survival. The E score was related to patient survival, a lower score being associated with a worse outcome (P = 0.048). In multivariable analysis, serum bilirubin, serum aspartate aminotransferase, and E score were significant predictors of death (P = 0.012). In univariable analysis, B score and bilirubin were significantly related to "resistant rejection" (P = 0.018 and 0.002, respectively), but only bilirubin was significant in multivariable analysis (logistic regression). In conclusion, although the Banff RAI score is a useful marker of the severity of rejection, neither the total RAI score nor any of the individual components correlated with response to steroids or graft survival.     

Does kidney transplantation with multiple arteries affect graft survival?

Introduction

We compared short- and long-term outcomes of renal transplants with single versus multiple arteries.

Patients and methods

We retrospectively analyzed data from kidney transplants from 208 living donors performed between 1994 and 2010. Renal grafts were divided into two groups: single renal artery (n = 164) versus multiple renal arteries (n = 44). The groups were compared regarding early and late vascular and urological complications. Patient and graft survivals were compared using Kaplan-Meier survivorship curves with comparisons using the log-rank test.

Results

Both groups were comparable regarding acute rejection episodes, posttransplant hypertension, postsurgery renal artery stenosis, and urologic complications. Only hemorrhagic complications and renal artery thrombosis were significantly higher in the multiple renal arteries group (P = .027 and .03, respectively). Warm ischemia time was significantly longer in the multiple renal arteries group without any influence on the incidence of acute tubular necrosis (P = .2). Mean creatinine clearance at 1 year was 65 versus 50 mL/min/1.73 m² (P = .5) and at 5 years, 60 versus 55 mL/min/1.73 m² (P = .1) for the single versus multiple renal arteries groups, respectively. Return to hemodialysis was necessary for 18.8% of the single and 16.1% of the multiple renal arteries group.

Conclusion

The use of an allograft with multiple renal arteries is a safe, successful surgical procedure, that does not influence patient or graft survivals or increase surgical complication rates provided the surgical team is evolved with technical skill.     

Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans?

Clinical acute lung rejection (AR) occurs in lung allografts usually within 50 days after transplantation. While perivascular infiltrates characterize AR, with moderate-to-severe acute rejection small airway injury occurs. We investigated the significance of small airway injury in AR and its relationship to the development of bronchiolitis obliterans (OB) in 11 recipients of combined heart-lung or double-lung allografts. In general, the intensity and persistence of early acute rejection episodes associated with injury to bronchioles correlated with the development of histologic bronchiolitis obliterans. Early AR may "prime" lymphocytes for subsequent respiratory epithelial injury and airway fibrosis late in the postoperative period.     

Does cytomegalovirus status influence acute and chronic rejection in heart transplantation during the ganciclovir prophylaxis era?

BACKGROUND: The effect of cytomegalovirus (CMV) status on acute rejection in heart transplantation is not well understood. Furthermore, there is some evidence to suggest that CMV antibody positivity is associated with cardiac allograft vasculopathy (CAV). METHODS: This study compared the effect of CMV antibody status in heart transplant donors (D) and recipients (R) on acute and chronic rejection episodes during the ganciclovir prophylaxis era. RESULTS: All heart transplant recipients at Papworth Hospital during the ganciclovir prophylaxis era were included (n = 374). They were grouped according to recipients and their respective donor CMV serology: R(-)/D(-) (n = 82); R(+)/D(-) (n = 114); R(-)/D(+) (n = 73); and R(+)/D(+) (n = 105). Ganciclovir prophylaxis was administered to the R(-)/D(+) group. The mean (SD) recipient and donor ages were 46 (11), 51 (9), 47 (11) and 52 (8) years (p < 0.001), and 32 (11), 33 (14), 36 (12) and 38 (14) years (p = 0.01), respectively, for the CMV groups. The mean number of acute rejection episodes (as confirmed by cardiac biopsy) per 100 patient-days was 0.13 (0.36), 0.11 (0.34), 0.12 (0.34) and 0.12 (0.34), respectively (p > 0.05) There was no statistical difference in the development of CAV as assessed by angiography (p = 0.92). At 2 years, the "freedom from CAV" rates were 96%, 97%, 97% and 98%, respectively. The 5-year post-operative survival rates were 83%, 79%, 67% and 73% (p = 0.08 overall). CONCLUSIONS: CMV status of heart transplant recipients and their respective donors does not influence acute or chronic rejection in terms of cardiac allograft vasculopathy.     

Antibody-mediated rejection: hyperacute rejection reality in liver transplantation? A case report

Hyperacute rejection is rare among ABO-compatible liver transplantations. The mechanism is donor preformed antibodies causing graft loss within a few days. Herein, we have described a case of an ABO-compatible liver transplantation that underwent hyperacute rejection, needing retransplantation for treatment. A 27-year-old man of blood group A positive who displayed fulminant hepatic failure due to hepatitis B (in agreement with the O'Grady criteria), received an ABO-compatible graft. He developed significant asthenia, fever, hypotension, oliguria, and coagulopathy. Ultrasonography revealed total thrombosis of the portal vein and absence of dilatation of bile ducts. The patient was priorized for retransplantation and underwent a good subsequent evolution. On anatomopathologic exam the explant revealed thrombosis of the intrahepatic branches of the portal vein with venous and ischemic infarcts compatible with a diagnosis of hyperacute rejection. The clinical findings of hyperacute rejection were characterized by progressive elevation of bilirubin and thrombocytopenia associated with signs of hepatic failure during the first days after transplantation. In this case, the histological exam was compatible with hyperacute rejection, excluding the diagnoses of hepatic artery thrombosis or biliary obstruction, despite the negative test for anti-HLA antibodies. The diagnosis of hyperacute rejection could be made associated with a short ischemic time and a good response after retransplantation.     

Can the preprocurement pancreas suitability score predict ischemia-reperfusion injury and graft survival after pancreas transplantation?

Background

Ischemia-reperfusion injury (IRI) is common after pancreas transplantation, leading to pancreatitis or thrombosis with the need for relaparotomy or even graft loss. Optimal donor selection may reduce the postoperative morbidity of IRI. The Eurotransplant preprocurement pancreas suitability score (P-PASS) seeks to identify ideal donors with a value <17. Owing to the organ shortage the waiting time for pancreas transplantation is increasing, a problem that may be addressed with the use of extended-criteria donors. We analyzed our pancreas transplantations regarding postoperative complications according to the P-PASS. To reflect IRI we used the peak C-reactive protein (CRP) levels during the first 3 postoperative days.

Methods

From January 2009 to July 2010, we transplanted 52 pancreas grafts, including, 50 simultaneous pancreas-kidney transplantations (SPK), 1 after a kidney graft, and 1 alone. For 3 SPK donors the P-PASS was not available. All transplantations were performed using systemic venous and enteric drainage. The immunosuppression protocol included antibody induction with antithymocyte globulin and maintenance therapy with steroids, tacrolimus, and mycophenolate mofetil. The peak CRP in the first 3 postoperative days was used as a marker for IRI.

Results

The mean P-PASS of our donors was 16.4 ± 2.6 (range, 12–22). We compared 24 patients receiving organs from “ideal” donors (P-PASS <17; ID) with 25 receiving grafts from extended-criteria donors (P-PASS ≥17; ED). There was no significant difference in the incidence of graft loss among ID versus ED grafts (20.8% vs 20.0%; P = 1.0). Comparing the rates of postoperative complications of patients, we did not observe a significant difference in graft thrombosis (4.2% vs 16.0%; P = .349), relaparotomy (29.2% vs 40.0%; P = .551), a pancreatic fistula (37.5% vs 28.0%; P = .543), or the length of hospital stay (36.5 ± 19.2 vs 37.4 ± 20.8 days; P = .875), respectively. Regarding IRI, there was no significant difference in peak CRP values (14.1 ± 5.5 vs 16.2 ± 6.0 mg/dL; P = .211).

Conclusion

This single center analysis failed to show that P-PASS significantly predicted pancreas graft survival, postoperative morbidity, or IRI severity. These findings suggested a chance to increase the donor pool using extended-criteria donors.     

Does multiorgan donation influence survival in heart transplantation?

Current heart transplant survival in Spain at 1, 5, and 10 years is 80%, 70%, and 60%, respectively. Our objective was to establish how donor type affects survival in heart transplantation. MATERIALS AND METHODS: This was a retrospective study of heart transplant recipients from 102 donors, divided into three types: (a) heart-liver-kidney donors (group I); (b) heart-liver-kidney-lung donors (group II); and (c) heart-liver-kidney-lung-pancreas donors (group III). We excluded retransplantations, pediatric transplantations, and cardiopulmonary transplantations. The outcome variable was the actuarial survival by type of donation. Statistical analysis was performed for event-free survival based on the Kaplan-Meier method (log-rank test). RESULTS: Groups I, II, and III included 63, 26, and 13 donors, respectively. The survival curves showed similar values for all three groups (P > .05). CONCLUSIONS: The different combinations of multiorgan donation do not entail a poorer prognosis in terms of cardiac transplant patient survival.     

Serum bile acids in liver transplantation – early indicator for acute rejection and monitor for antirejection therapy

We studied the course of serum bile acids to investigate its reliability in the diagnosis of acute rejection after liver transplantation in relation to pathohistological findings. Serum bile acid concentration, bilirubin and transaminases were measured in 41 patients who underwent liver transplantation. Their course was correlated to liver biopsy. Group I (n = 19) patients were without acute rejection, whereas group II (n = 22) patients showed acute rejection. Bile acid concentrations in group II showed a statistically highly significant (P≤ 0.001) threefold increase 3 days prior to biopsy. Successful antirejection treatment was correlated with a statistically significant (P = 0.008) decrease of serum bile acid 1 day after initiation of therapy. Patients without acute rejection showed a baseline bile acid concentration at the time of biopsy. Bilirubin and transaminases did not show any statistically significant correlation to acute rejection. Infection did not lead to a significant bile acid increase. Our study shows that serum bile acids monitored after liver transplantation can easily be used to detect acute rejection and at the same time they reflect the success of antirejection therapy. Received: 17 July 2000 Revised: 6 February 2001 Accepted: 13 September 2001     

Does the difference in donor and recipient weight influence renal graft survival?

Introduction

Grafts from older donors or those in recipients with a greater body mass index (BMI) as compared with the donor may develop hyperfiltration syndrome that shortens renal graft survival.

Objectives

To assess whether the differences in weight and BMI between donor and recipient correlated with renal function, proteinuria, or graft survival among recipients of grafts from expanded criteria donors.

Materials and methods

We undertook a prospective, observational study in 180 recipients of grafts from expanded criteria donors performed between 1999 and 2006. All grafts had been biopsied previously for viability. The recipients underwent immunosuppression with basiliximab, late introduction of tacrolimus, mycophenolate mofetil and steroids. The study population was divided into three groups, depending on the tertile of the donor-to-recipient weight ratio (<1, n = 64; 1-1.2, n = 56; >1.2, n = 60), and the donor-to-recipient BMI ratio (<0.97, n = 59; 0.97-1.13, n = 60; >1.13, n = 60). The glomerular filtration rate was estimated from the modified diet in renal disease (MDRD) equation.

Results

The mean age of the donors was 63.54 years and of the recipients, 58.38 years. The proportion of male-to-female donors was 52:48 and recipients 57.8:42.2 (P = NS). No significant differences in overall graft survival were observed between the tertiles. There was a negative correlation between the donor-to-recipient weight ratio and serum creatinine value at 1 (P < .001), 3 (P = .013), and 12 months (P = .005) after transplantation, and a positive correlation with the MDRD at 1 month (P < .001). No relation was noted between weight and proteinuria at 1 (P = .25), 3 (P = .51), or 12 months (P = .90). The results were similar after analyzing the ratio of the BMI to creatinine, MDRD or proteinuria, as well as in cases of a female donor to a male recipient.

Conclusions

Differences in weights between the donor and the recipient did not appear to affect graft survival or proteinuria among patients receiving grafts from expanded criteria donors, though it may be related to renal function during the early posttransplant stages.     

Does graft hemodynamics affect the risk of hepatocellular carcinoma recurrence after liver transplantation?

Although experimental studies have reported that hepatic ischemia-reperfusion injury promotes tumor growth and metastases, the impact of graft hemodynamics on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is unclear. To investigate the association between graft hemodynamics and HCC recurrence after LT, we conducted a retrospective analysis of 279 patients who underwent LT for HCC. Graft hemodynamics including portal vein flow (PVF), hepatic artery flow (HAF), and total hepatic flow (THF) was analyzed as a predictor of HCC recurrence, using competing risk regression analyses. The cutoff values of PVF, HAF, and THF were set at the lower quartile of distribution. A cumulative recurrence curve demonstrated that low THF (<1511 mL/min, P = .005) was significantly associated with increased recurrence, whereas neither low PVF (<1230 mL/min, P = .150) nor low HAF (<164 mL/min, P = .110) was significant. On multivariate analysis, outside Milan criteria (sub-hazard ratio [SHR] = 3.742; P < .001), microvascular invasion (SHR = 3.698; P < .001), and low THF (SHR = 2.359; P = .010) were independently associated with increased HCC recurrence. In conclusion, our findings suggest that graft hemodynamics may play an important role in HCC recurrence after LT.     

Does caval reconstruction technique affect early graft function after liver transplantation? A preliminary analysis

Background

In the past decades, the inferior vena cava (IVC) reconstruction technique has undergone several evolutions, such as biopump, piggyback technique (PB), and laterolateral approach (LLPB). Several advantages are reported comparing the PB technique to biopump use. However, comparison between PB and LLPB has not been as well investigated. The aim of this study was to compare the results in terms of immediate graft function and intermediate graft survival among 3 subgroups characterized by distinct caval reconstruction techniques.

Methods

We retrospectively analyzed a cohort of 200 consecutive adult patients who underwent liver transplantation from January 2001 to December 2009. The patients were stratified according to 3 caval reconstructive techniques: biopump (n = 135), PB (n = 32) and LLPB (n = 33).

Results

The LLPB group showed the shortest cold and warm ischemia times and the best immediate postoperative graft function. Survival analysis revealed LLPB patients to present the best 1-year graft survival rates: namely, 90.9% versus 75.0% and 74.1% among the PB and biopump groups, respectively (log-rank tests: LLPB vs biopump: P = .03; LLPB vs PB: P = .05). In our experience, LLPB showed the best graft survivals with an evident reduction in both cold and warm ischemia times. However, it is hard to obtain an irrefutable conclusion owing to the retrospective nature of this study, the small sample, and the different periods in which the groups were transplanted.

Conclusions

LLPB technique was a safe procedure that minimized the sequelal of ischemia-reperfusion damage. This technique yielded results superior to venovenous bypass. No definitive conclusions can to be obtained in this study comparing classic PB or LLPB.     

Does model for end-stage liver disease score predict the short-term outcome of living donor liver transplantation?

Objective

The objective of this study was to evaluate the predictive ability of the Model for End-Stage Liver Disease (MELD) score for short-term outcomes after living donor liver transplantation (LDLT).

Patients and Methods

The 135 consecutive patients who underwent LDLT did not include prisoners or their organs. Patients were divided into a low (group A; MELD score <15), a moderate (group B; MELD score ≥15 but <25), and a high MELD score (group C; MELD score ≥25) group according to their preoperative score. We retrospectively analyzed the data concerning complications, biochemical parameters, and survival over 90 postoperative days.

Results

Complications were similar among patients with a low, moderate, or high MELD score. The 90-day survival rates of group A, B, and C were 88%, 90%, and 90%, respectively (P = .960). Compared with groups A and B, group C showed a longer mean intensive care unit (ICU) stay.

Conclusion

Preoperative MELD score may not help to predict short-term outcomes of LDLT. However, a high MELD score may be related to a prolonged ICU stay.