A 10-year experience of liver transplantation for hepatitis C: analysis of factors determining outcome in over 500 patients

OBJECTIVE: To determine the factors affecting the outcome of orthotopic liver transplantation (OLT) for end-stage liver disease caused by hepatitis C virus (HCV) and to identify models that predict patient and graft survival. SUMMARY BACKGROUND DATA: The national epidemic of HCV infection has become the leading cause of hepatic failure that requires OLT. Rapidly increasing demands for OLT and depleted donor organ pools mandate appropriate selection of patients and donors. Such selection should be guided by a better understanding of the factors that influence the outcome of OLT. METHODS: The authors conducted a retrospective review of 510 patients who underwent OLT for HCV during the past decade. Seven donor, 10 recipient, and 2 operative variables that may affect outcome were dichotomized at the median for univariate screening. Factors that achieved a probability value less than 0.2 or that were thought to be relevant were entered into a stepdown Cox proportional hazard regression model. RESULTS: Overall patient and graft survival rates at 1, 5, and 10 years were 84%, 68%, and 60% and 73%, 56%, and 49%, respectively. Overall median time to HCV recurrence was 34 months after transplantation. Neither HCV recurrence nor HCV-positive donor status significantly decreased patient and graft survival rates by Kaplan-Meier analysis. However, use of HCV-positive donors reduced the median time of recurrence to 22.9 months compared with 35.7 months after transplantation of HCV-negative livers. Stratification of patients into five subgroups, based on time of recurrence, revealed that early HCV recurrence was associated with significantly increased rates of patient death and graft loss. Donor, recipient, and operative variables that may affect OLT outcome were analyzed. On univariate analysis, recipient age, serum creatinine, donor length of hospital stay, donor female gender, United Network for Organ Sharing (UNOS) status of recipient, and presence of hepatocellular cancer affected the outcome of OLT. Elevation of pretransplant HCV RNA was associated with an increased risk of graft loss. Of 15 variables considered by multivariate Cox regression analysis, recipient age, UNOS status, donor gender, and log creatinine were simultaneous significant predictors for patient survival. Simultaneously significant factors for graft failure included log creatinine, log alanine transaminase, log aspartate transaminase, UNOS status, donor gender, and warm ischemia time. These variables were therefore entered into prognostic models for patient and graft survival. CONCLUSION: The earlier the recurrence of HCV, the greater the impact on patient and graft survival. The use of HCV-positive donors may accelerate HCV recurrence, and they should be used judiciously. Patient survival at the time of transplantation is predicted by donor gender, UNOS status, serum creatinine, and recipient age. Graft survival is affected by donor gender, warm ischemia time, and pretransplant patient condition. The authors' current survival prognostic models require further multicenter validation.     

Effect of nonviral factors on hepatitis C recurrence after liver transplantation

OBJECTIVE: Hepatitis C (HCV) is now the most common indication for orthotopic liver transplantation (OLT). While graft reinfection remains universal, progression to graft cirrhosis is highly variable. This study examined donor, recipient, and operative variables to identify factors that affect recurrence of HCV post-OLT to facilitate graft-recipient matching. METHODS: Retrospective review of 307 patients who underwent OLT for HCV over a 10-year period at our center. Recurrence of HCV was identified by the presence of biochemical graft dysfunction and concurrent liver biopsy showing diagnostic pathologic features. Time to recurrence was the endpoint for statistical analysis. Five donor, 6 recipient, and 2 operative variables that may affect recurrence were analyzed by univariate comparison and Cox proportional hazard regression models. RESULTS: Recurrence-free survival in the 307 study patients was 69% and 34% at 1 and 5 years, respectively. Four predictive variables related to either donor or recipient characteristics were identified. Advanced donor age, prolonged donor hospitalization, increasing recipient age, and elevated recipient MELD scores were found to increase the relative risk of HCV recurrence. Examination of HLA disparity between donors and recipients demonstrated no correlation between class I or class II mismatches and recurrence-free survival. CONCLUSIONS: We have identified donor and recipient characteristics that significantly predict hepatitis C recurrence following liver transplantation. These factors are identifiable before transplant and, if considered when matching donors to HCV recipients, may decrease the incidence of HCV recurrence after OLT. A change in the current national liver allocation system would be needed to realize the full value of this benefit.     

Pretransplant model to predict posttransplant survival in liver transplant patients

OBJECTIVE: To develop a prognostic model that determines patient survival outcomes after orthotopic liver transplantation (OLT) using readily available pretransplant variables. SUMMARY BACKGROUND DATA: The current liver organ allocation system strongly favors organ distribution to critically ill recipients who exhibit poor survival outcomes following OLT. A severely limited organ resource, increasing waiting list deaths, and rising numbers of critically ill recipients mandate an organ allocation system that balances disease severity with survival outcomes. Such goals can be realized only through the development of prognostic models that predict survival following OLT. METHODS: Variables that may affect patient survival following OLT were analyzed in hepatitis C (HCV) recipients at the authors' center, since HCV is the most common indication for OLT. The resulting patient survival model was examined and refined in HCV and non-HCV patients in the United Network for Organ Sharing (UNOS) database. Kaplan-Meier methods, univariate comparisons, and multivariate Cox proportional hazard regression were employed for analyses. RESULTS: Variables identified by multivariate analysis as independent predictors for patient survival following primary transplantation of adult HCV recipients in the last 10 years at the authors' center were entered into a prognostic survival model to predict patient survival. Accordingly, mortality was predicted by 0.0293 (recipient age) + 1.085 (log10 recipient creatinine) + 0.289 (donor female gender) + 0.675 urgent UNOS - 1.612 (log10 recipient creatinine times urgent UNOS). The above variables, in addition to donor age, total bilirubin, prothrombin time (PT), retransplantation, and warm and cold ischemia times, were applied to the UNOS database. Of the 46,942 patients transplanted over the last 10 years, 25,772 patients had complete data sets. An eight-factor model that accurately predicted survival was derived. Accordingly, the mortality index posttransplantation = 0.0084 donor age + 0.019 recipient age + 0.816 log creatinine + 0.0044 warm ischemia (in minutes) + 0.659 (if second transplant) + 0.10 log bilirubin + 0.0087 PT + 0.01 cold ischemia (in hours). Thus, this model is applicable to first or second liver transplants. Patient survival rates based on model-predicted risk scores for death and observed posttransplant survival rates were similar. Additionally, the model accurately predicted survival outcomes for HCV and non-HCV patients. CONCLUSIONS: Posttransplant patient survival can be accurately predicted based on eight straightforward factors. The balanced application of a model for liver transplant survival estimate, in addition to disease severity, as estimated by the model for end-stage liver disease, would markedly improve survival outcomes and maximize patients' benefits following OLT.     

A cause-specific hazard rate analysis of prognostic factors among 877 adults who received primary orthotopic liver transplantation

BACKGROUND: In orthotopic liver transplantation (OLT) distinct causes of graft failure (GF) and death with a functioning graft (DFG) exist. Prognostic factors for one failure type may be distinctly different from those predictive of other types, and an accurate portrayal of these relationships may more clearly explain each factor's importance. METHODS: A multivariable cause-specific hazard (CSH) rate analysis using Cox stepwise regression was performed among 877 adults who received primary OLT during 1996-2004 with tacrolimus+steroids as immunosuppression. RESULTS: Older donor age (P=0.004) implied greater primary dysfunction GF, while primary sclerosing cholangitis (PSC; P=0.0002) implied greater vascular thrombosis GF. Recurrent nonmalignant liver disease GF was higher among hepatitis C virus patients (P<0.00001), and younger recipient age (P=0.005) implied greater death from recurrent (metastatic) hepatocellular carcinoma. African-American race (P<0.00001), PSC (P=0.003), and younger recipient age (P=0.005) were independently associated with greater GF due to chronic rejection. Older donor age (P=0.003) implied greater infection DFG, while older recipient age (P=0.003) and pretransplant diabetes (P=0.03) were independently associated with greater cardiovascular/cerebrovascular DFG. Finally, most of these cause-specific predictors were not significant in an overall Cox model for graft survival. CONCLUSIONS: The CSH approach should be more widely used in investigations of prognostic factors. The result of older donor age implying greater primary dysfunction GF and infection DFG but having no association with other failure types demonstrates that its impact is specific to the graft's early posttransplant functional status. In addition, while recipient age was an important prognosticator, its direction of association reverses depending upon the outcome being analyzed.     

Liver transplantation using donors older than 80 years: a single-center experience

AIM: The shortage of organs for orthotopic liver transplantation (OLT) has forced transplantation centers to expand the donor pool by using donors traditionally labeled as "extended criteria donors." One such example is OLT using a donor with advanced age. MATERIALS AND METHODS: We retrospectively evaluated 10 patients who received a liver graft from cadaveric donors older than 80 years. We analyzed pretransplantation donor and recipient characteristics, as well as the evolution of the recipients. RESULTS: All 10 donors were older than 80 years (median age, 83.5; range, 80-93). No steatosis (>30%) was accepted in the older donor group. Medium follow-up was 19.5 months. The most frequent cause for OLT was hepatitis C virus (HCV) cirrhosis (8/10 patients). We had 1 case of primary nonfunction, 1 patient died immediately after surgery because of extrahepatic complications (cardiac arrest), and 2 other patients had a severe HCV recurrence and died after 1 and 2 years from OLT, respectively. Five patients had HCV recurrence and biliary complications were present in 60% of the patients. No cases of acute or chronic rejection were described. Overall survival rates after 1 and 3 years were 80% and 40%, respectively. CONCLUSIONS: Old donor age is not an absolute contraindication to OLT. Liver grafts from donors older than 80 years can be used knowing that there is a high risk of postoperative complications. Furthermore, the increased risk of developing severe HCV recurrence, related to older donor age, suggests that such livers should be used in HCV-negative recipients.     

Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up

BACKGROUND: Recurrence of hepatitis C (HCV) infection after orthotopic liver transplantation (OLT) in HCV-positive patients is almost universal. Severity of graft hepatitis increases during the long-term follow-up, and up to 30% of patients develop severe graft hepatitis and cirrhosis. However, there are still no clear predictors for severe recurrence. The aim of this study was to examine the 10-year outcome and risk factors for graft failure caused by HCV recurrence. METHODS: In a prospective analysis, 234 OLTs in 209 HCV-positive patients with a median age of 53 years were analyzed. Immunosuppression was based on cyclosporine A or tacrolimus in different protocols. Predictors for outcome were genotype, viremia, donor variables, recipient demographics, postoperative immunosuppression, and human leukocyte antigen (HLA) compatibilities. RESULTS: Actuarial 5-, and 10-year patient survival was 75.8% and 68.8%. Eighteen of 209 (8.7%) patients died because of HCV recurrence, which was responsible for 35.9% of the total 53 deaths. Significant risk factors for HCV-related graft failure in an univariate analysis were multiple steroid pulses, use of OKT3, and donor age greater than 40. However, in a multivariate analysis, multiple rejection treatments with steroids and OKT3 treatment proved to be significantly associated with HCV-related graft loss. CONCLUSIONS: The analysis of causes leading to graft failure in patients with HCV showed that HCV recurrence is responsible for one of three deaths in HCV-positive patients. Rejection treatment contributed significantly to an enhanced risk for HCV-related graft loss. New antiviral treatments, as well as adapted immunosuppressive protocols, will be necessary to further improve the outcome of HCV-positive patients after liver transplantation.     

Risk factors for primary graft failure after pediatric cardiac transplantation: importance of recipient and donor characteristics.

BACKGROUND: Primary graft failure, or circulatory insufficiency immediately after transplantation, frequently occurs after pediatric cardiac transplantation and is the most common cause of death after infant transplantation. Risk factors for pediatric primary graft failure are poorly defined. METHODS: We retrospectively reviewed donor, procedural and recipient characteristics for primary graft failure in 165 pediatric cardiac transplant recipients (median age at transplant 1.1 years) by multivariatle logistic regression. Primary graft failure was defined as the need for mechanical circulatory support or use of multiple intravenous inotrope/pressors, including epinephrine, for circulatory support within the first 24 hours after transplantation. RESULTS: Primary graft failure occurred in 54 patients (33%); 24 patients (15%) required mechanical support for their graft failure; and primary graft failure was the cause of death or graft loss in 10 patients. Recipient risk factors associated with an increased risk of primary graft failure included diagnosis of congenital heart disease and a need for mechanical support before transplantation. Ventilator support before transplantation and maximal pulmonary vascular resistance index were risk factors for the development of isolated right ventricular graft failure. Donor risk factors associated with an increased risk for primary graft failure included increasing donor recipient weight and body surface area ratios; increasing donor ischemic time; anoxia as a cause of death; and increasing cardiopulmonary resuscitation time. Donor blood type O+ and hyperdynamic donor systolic function were associated with a decreased risk of primary graft failure. CONCLUSIONS: Multiple donor, recipient and procedural risk factors, including the type and severity of heart disease in the recipient before transplantation, are associated with primary graft failure after pediatric cardiac transplantation. Avoidance of matching high-risk donors to high-risk recipients may improve morbidity and mortality after transplantation.     

Factors differentially correlated with the outcome of liver transplantation in hcv+ and HCV- recipients

BACKGROUND: Survival following liver transplantation for hepatitis C virus (HCV) is significantly poorer than for liver transplants performed for other causes of chronic liver disease. The factors responsible for the inferior outcome in HCV+ recipients, and whether they differ from factors associated with survival in HCV- recipients, are unknown. METHODS: The UNOS database was analyzed to identify factors associated with outcome in HCV+ and HCV- recipients. Kaplan-Meier graft and patient survival and Cox proportional hazards analysis were conducted on 13,026 liver transplants to identify the variables that were differentially associated with outcome survival in HCV- and HCV+ recipients. RESULTS: Of the 13,026 recipients, 7386 (56.7%) were HCV- and 5640 were HCV+. In HCV- and HCV+ recipient populations, five-year patient survival rates were 83.5% vs. 74.6% (P<0.00001) and five-year graft survival rates 80.6% vs. 69.9% (P<0.00001), respectively. In a multivariate regression model, donor age and recipient creatinine were observed to be significant covariates in both groups, while donor race, cold ischemia time (CIT), female to male transplants, and recipient albumin were independent predictors of survival of HCV- recipients. In the HCV+ cohort, recipient race, warm ischemia time (WIT), and diabetes also independently predicted graft survival. CONCLUSIONS: A number of parameters are differentially correlated with outcome in HCV- and HCV+ recipients of orthotopic liver transplantation. These findings may not only have practical implications in the selection and management of liver transplant patients, but also may shed new insight into the biology of HCV infection posttransplant.     

Impact of donor age and year of transplantation on graft and patient survival following liver transplantation for hepatitis C virus

BACKGROUND: Hepatitis C virus (HCV) infection has become the most common indication for liver transplantation (LT). Graft and patient survival are adversely affected by recurrent infection of the graft. Recent publications have described an inferior outcome for recently transplanted HCV patients and have highlighted the impact of advancing donor age on severity of recurrent HCV. The donor age at which a measurable impact on graft and patient outcome can be observed has not clearly been defined. In addition, the impact of donor age on graft and patient survival for non-HCV patients needs to be examined. METHODS: We have examined a large European liver transplant database to define the impact of transplantation date and donor age on graft and patient survival for HCV patients (n = 4,736) and the impact for a comparison group of transplanted alcoholic liver disease patients (ALD, n = 5,406). RESULTS: For the entire cohorts, graft and patient survival of HCV patients was inferior to ALD patients. Since 1987, there has been a steady and ongoing improvement in the outcome of transplanted ALD patients, an improvement not observed for HCV patients. Every year since 1989, there has been an increase in liver donor age. Graft and patient survival for both ALD and HCV cohorts was adversely affected by advancing donor age. Comparison of graft and patient survival for HCV and ALD cohorts was made according to donor age (donor age subgrouped <20, 20-30, 30-40, 40-50, 50-60 and >60 years of age). For donors younger than 40 years of age, HCV and ALD recipient graft and patient survival are not significantly different. For donors older than 40, HCV recipient graft survival is inferior to ALD graft survival, an inferiority that increases for each advancing decade of donor age. For donors older than 50 years, HCV recipient patient survival is inferior to ALD patient survival, an inferiority that increases when the donor age is greater than 60 years. CONCLUSION: The results of liver transplantation for European HCV patients is inferior to a comparison group of ALD patients, and have not improved during the past 15 years. Liver donor age has increased significantly during that period. Advancing donor age has an adverse influence on graft and patient survival for ALD and HCV patients, but a significantly greater impact is observed for HCV patients when the donor is older than 40 years.     

Elderly donor kidney transplant: factors involved in graft survival

PURPOSE: To evaluate whether control of risk factors associated with worse results has improved graft survival, with respect of renal function quality and other factors influencing graft survival: recipient age, immunosuppressive therapy, cold ischemia time, acute tubular necrosis (ATN), acute rejection episodes (ARE) and 1-month creatinine levels. MATERIALS AND METHODS: Retrospective review of 147 patients who underwent kidney transplant between 1995 and 2001. Inclusion criteria were donor and recipient age older than 60 years, first renal transplant, follow-up period longer than 12 months, donor creatinine clearance higher than 75 mL/min, and less than 20% glomerulosclerosis observed in donor renal biopsy. RESULTS: Graft survivals were 87%, 83%, 78%, and 70% at first, second, third, and fifth year after transplantation, respectively. Mean serum creatinine levels were 2.3 mg/dL and mean follow-up time, 46 months. Multivariate analysis using a Cox regression model identified donor age, ARE, and serum creatinine levels 1 month after surgery as independent variables affecting graft survival. Recipient age, immunosuppressive therapy, and serum creatinine levels at 1 month after surgery were predictive variables of recipient survival. DISCUSSION: Renal transplantation is an accepted therapeutic option in elderly patients with chronic renal insufficiency, if both donor and recipient are carefully selected.     

Cholesterol as an independent predictor of outcome after renal transplantation

BACKGROUND: The debate on the role of high serum cholesterol levels in cardiovascular disease or chronic vascular rejection in kidney-transplanted patients has not yet been settled. METHODS: We studied the influence of serum cholesterol at 1 year after transplantation on the failure risk in all 676 kidney graft recipients who survived with a functioning graft. Other variables included in this analysis were donor/recipient age and gender, original disease, race, number of HLA-A and -B mismatches, previous transplants, postmortal or living-related transplantation, and transplantation year. At 1 year after transplantation, we included: serum cholesterol, serum creatinine, proteinuria, and hypertension. RESULTS: In the Cox proportional hazards analysis, serum cholesterol at 1 year after transplantation turned out to be an important, independent variable influencing all end points (adjusted for all other variables in the model). The influence on graft failure censored for death was log-linear, and there was interaction with serum creatinine at 1 year. The adverse effect of elevated serum cholesterol levels on the graft failure rate decreased with increasing serum creatinine levels. The influence of serum cholesterol on the rate ratio (RR) for patient failure was linear too, and here there was interaction with recipient age. The negative influence of serum cholesterol on the RR for patient failure decreased with increasing recipient age. The risk for over-all graft failure was influenced by increasing serum cholesterol levels, and there was interaction with recipient age. Because recipient age had interaction with donor age and serum creatinine, the influence of all four variables together on the RR was estimated. It is shown that whereas the RR for over-all graft failure in young recipients of a renal transplant increases significantly with higher cholesterol levels, there is very little influence on the RR of elderly recipients. The risk increases proportionally with increasing serum creatinine levels. CONCLUSION: Serum cholesterol levels have an independent influence on graft, patient, and over-all graft failure.     

Older donor livers show early severe histological activity, fibrosis, and graft failure after liver transplantation for hepatitis C

BACKGROUND: In hepatitis C virus (HCV)-positive liver transplant recipients, infection of the allograft and recurrent liver disease are important problems. Increased donor age has emerged as an important variable affecting patient and graft survival; however, specific age cutoffs and risk ratios for poor histologic outcomes and graft survival are not clear. METHODS: A longitudinal database of all HCV-positive patients transplanted at our center during an 11-year period was used to identify 111 patients who received 124 liver transplants. Graft survival and histological endpoints (severe activity and fibrosis) of HCV infection in the allografts were compared as a function of donor age at transplantation. RESULTS: By Kaplan-Meier analyses, older allografts showed earlier failure and decreased time to severe histological activity and fibrosis as compared with allografts from younger donors. By Cox proportional hazards analysis, older allografts were at greater risk for all severe histologic features and decreased graft survival as compared with younger allografts (P< or =0.02 for all outcomes). Analysis of donor age as a dichotomous variable showed that donors greater than 60 yr were at high risk for deleterious histologic outcomes and graft failure. An age cutoff of 60 yr showed a sensitivity of 94% and specificity of 67% for worse graft survival by receiver operating characteristics curve. CONCLUSIONS: Advanced donor age is associated with more aggressive recurrent HCV and early allograft failure in HCV-positive liver transplant recipients. Consideration of donor age is important for decisions regarding patient selection, antiviral therapy, and organ allocation.     

Impact of Donor Age on the Results of Liver Transplantation in Hepatitis C Virus-Positive Recipients

Objective

Hepatitis C virus (HCV)-cirrhosis is the most frequent indication for orthotopic liver transplantation (OLT) among adults in most European and American transplant centers. The aim of this study was to analyze the impact of donor age on graft survival among HCV-positive cirrhotic transplant patients.

Materials and Methods

We performed an observational, retrospective study between March 1997 and December 2004, analyzing 340 liver transplantations. The patients were divided into 4 groups, considering whether the HCV infection was the indication for OLT and whether the age of the donor was older or younger than 48 years: group 1 (HCV, <48 years); group 2 (HCV, >48 years); group 3 (non-HCV, <48 years); and group 4 (non-HCV, >48 years).

Results

A univariate analysis showed that posttransplantation graft survival was clearly influenced by recipient HCV serologic status (P = .018). However, no graft survival differences were found when the analysis variable was age (>48 or <48 years). When both variables were studied, a positive HCV serology did not modify graft survival when the donor age was <48 years (P = .32), but had a statistically significant negative impact when the age was >48 years (P = .02).

Conclusions

The use of older donors for HCV recipients resulted in worse graft and patient survivals in our study. This difference in survival was not present in non-HCV recipients or when grafts for HCV recipients were procured from younger donors. Donor age <30 years was a protective factor for graft survival among HCV recipients.     

Ischemia times and donor serum creatinine in relation to renal graft failure

BACKGROUND: The results of renal transplantation are dependent on many variables. To simplify the decision process related to a kidney offer, the authors wondered which variables had the most important influence on the graft failure risk. METHODS: All transplant patients (n=1,124) between January 1981 and July 2000 were included in the analysis (2.6% had missing values). The variables included were donor and recipient age and gender, recipient original disease, race, donor origin, current smoking, cardiovascular disease, body weight, peak and current panel reactive antibody (PRA), number of preceding transplants, type and duration of renal replacement therapy, and time since failure of native kidneys. Also, human leukocyte antigen (HLA) identity or not, first and second warm and cold ischemia times, left or right kidney and fossa, donor kidney anatomy, donor serum creatinine and proteinuria, and transplantation year were included. RESULTS: In a multivariate model, cold ischemia time and its time-dependent variable significantly influenced the graft failure risk censored for death (P<0.0001) independent of any of the other risk factors. The influence primarily affected the risk in the first week after transplantation; thereafter, it gradually disappeared during the first year after transplantation. Donor serum creatinine also significantly influenced the graft failure risk in a time-dependent manner (P<0.0001). The risk of a high donor serum creatinine is already enlarged in the immediate postoperative phase and increases thereafter; the curve is closely related to the degree of the elevation. The other variables with a significant influence on the graft failure rate were, in order of decreasing significance, recipient age, donor gender, donor age, HLA identity, transplantation year, preceding transplantations, donor origin, and peak PRA. CONCLUSIONS: Donor serum creatinine and cold ischemia time are important time-dependent variables independently influencing the risk of graft failure censored for death. The best strategy for improving the results of cadaveric transplantations is to decrease the cold ischemia time and to allocate kidneys from donors with an elevated serum creatinine to low-risk recipients.     

Optimizing Risk Assessment In Simultaneous Liver and Kidney Transplant: Donor and Recipient Factors Associated With Improved Outcome

Standardization in allocation of kidneys for transplant simultaneous with livers and the creation of a “safety net” for kidney transplant after liver transplant alone (LTA) was designed to encourage clinicians to list patients for LTA when the likelihood of renal recovery and the necessity of simultaneous liver and kidney (SLK) transplant were unclear. We analyzed the United Network for Organ Sharing database of SLK recipients starting January 1, 2015. Organs from one deceased donor were used in each individual case. Univariate analysis was used to analyze recipient and donor characteristics against patient and graft survival of at least 1 year. Cox regression was employed for multivariable analysis controlling for donor risk index variables. SLK recipients who failed to achieve 1 year of post-transplant survival were more likely to be older, have higher model for end-stage liver disease scores, have diabetes, have received dialysis within one week of transplant, and required intensive care unit admission at transplantation. Patients who failed to survive for at least 1 year after SLK were more likely to have received organs from donors who were older with a higher kidney donor profile index. Using national data we identified SLK donor and recipient characteristics associated with poor post-transplant outcome. Clinicians involved in the decision to list patients with liver failure for LTA or SLK may use these associations to help guide decision making.     

Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis

BACKGROUND: Renal dysfunction measured by serum creatinine (>1.5 mg/dL) at 1 year post-transplant correlates with long-term kidney graft survival. The purpose of this study was to compare the risk factors for elevated serum creatinine (SCr) >1.5 mg/dL at 1 year post-transplantation, and for long-term graft failure. METHODS: Between 1988 and 1999, 117,501 adult kidney transplants were reported to Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS). Of these, 96,091 were functioning at 1 year and SCr was available on 85,135 transplants. Donor and recipient demographics (age, sex, and race), transplant [living vs. cadaveric, previous transplantation, panel reactive antibody (PRA), human leukoocyte antigen (HLA) mismatch, cold ischemic time (CIT) and post-transplant delayed graft function (DGF), use of azathioprone vs. mycophenolate mofetil (MMF), cyclosporine A (CsA) vs. tacrolimus (Tac)], induction antibody, acute rejection within 1 year variables were used in the logistic regression model to estimate odds ratio (OR) for elevated 1 year serum creatinine (SCr). A Cox proportional hazard model was used to estimate the relative risk (RR) for long-term kidney graft failure with and without censoring for death with a functioning graft. RESULTS: Five-year actuarial graft survival for living donor transplant with SCr >1.5 and 1.5 mg/dL) declined from 54.5% in 1988 to 42.3% in 1999. There was a strong concordance between the key variables, such as cadaveric transplant, increasing CIT, HLA mismatch, DGF, and acute rejection, recipient race (black), younger age, and nondiabetics status; and donor race (black) and older age for elevated SCr and long-term graft failure. CONCLUSION: Donor (age), race (black), recipient race (black), immunologic variables (HLA mismatch, DGF, acute rejection) were identified as important risk factors for elevated SCr at 1 year post-transplantation and long-term graft failure. Elevated SCr should be used as a short-term marker for predicting long-term transplant survival.     

One hundred in situ split-liver transplantations: a single-center experience

OBJECTIVE: To identify predictors of graft and recipient survival from a single-institution series of in situ split-liver transplantations and compare outcomes to living donor and whole organs for adults and children. SUMMARY BACKGROUND DATA: Split-liver transplantation is a surgical technique that creates 2 allografts from a single cadaver donor. We have applied split-liver transplantation to all indications and categories of medical urgency for initial as well as retransplantation to expand the current donor pool and decrease reliance upon living donation. METHODS: A retrospective analysis was conducted of 100 consecutive in situ split-liver transplantations yielding a left lateral segment and right trisegment graft that were performed at the University of California Los Angeles between 9/91 and 02/03. These 100 transplantations generated 190 allografts for transplantation into 105 children and 60 adults, with the sharing of 25 allografts among transplant centers across the United States. Outcomes and incidence of complications were compared with living donor and whole organ recipients receiving liver transplantation during the same time period with independent predictors of split-liver graft and recipient survival identified by multivariate analysis. RESULTS: The incidence of biliary and vascular complications observed in recipients of left lateral segment grafts created by split-liver transplantation was not statistically different from recipients of left lateral segment grafts created from living donation or children receiving whole-organ grafts from pediatric donors. Kaplan-Meier survival estimations of left lateral segment graft and recipient survival also demonstrated no statistical difference among split-liver, living donor, and whole-organ recipients. Right trisegment grafts from split-liver transplantation demonstrated a 10% incidence of biliary and 7% incidence of vascular complications. Long-term graft function was excellent with patient and graft survival equal to 1086 recipients of cadaver whole-organ grafts from donors ages 10-40 years who underwent transplant operations during the same time period. Predictors of split-liver transplantation graft and recipient survival included United Network for Organ Sharing status at transplantation, indication, occurrence of a complication, donor creatinine, and donor length of hospitalization. CONCLUSIONS: Split-liver transplantation is an effective mechanism for immediate expansion of the cadaver donor pool that can reduce dependence upon living donation in adults and children.     

Renal transplantation in the elderly: a long-term, single-centre experience.

BACKGROUND: End-stage renal failure increases with advancing age and renal transplantation should be considered in end-stage renal failure patients older than 60 years. However, there is a paucity of data on long-term patient and graft survival in this population. METHODS: From October 1983 to March 1999, 310 renal transplantations were performed at Geneva University Hospital in 283 patients, of which 49 were done in 48 patients older than 60 years (mean age 65.6+/-4.1 years). The following data were analysed at 1, 5, and 10 years, and compared between the patients >60 years and <60 years old: actuarial patient and graft survival, serum creatinine, causes of graft loss, and patient death. RESULTS: Patient survival at 10 years was 81% for patients <60 years and 44% for patients >60 years. Graft survival at 10 years was 59% for patients <60 years and 32% for patients >60 years. Graft survival at 10 years censored for death with functioning graft was 65% for patients <60 years and 81% for patients >60 years. Main causes of mortality in the older patients were related to cardiovascular events (47%), neoplasia (41%), and sepsis (18%). Overall, recipient and donor age were not predictive factors for graft survival, as shown by multiple logistic regression. CONCLUSIONS: Renal transplantation should be considered in patients older than 60 years, since graft survival is excellent in this population. Although these patients have a shorter life expectancy, they benefit from renal transplantation similarly to younger kidney transplant recipients.     

The impact of donor variables on the outcome of orthotopic liver transplantation for hepatitis C

Morphologic characteristics of the graft have been proposed as a major contributor to the long-term outcomes in orthotopic liver transplantation (OLT). Our objective was to determine the impact of donor variables, including donor age, donor-recipient HLA match, and type of donation (DCD vs donation after brain death [DBD]), on the outcome of OLT in 192 patients with hepatitis C virus (HCV). Fourteen patients underwent OLT from donation after cardiac death (DCD) donors and 188 from DBD donors. Mean donor age, warm ischemia time at recovery, and cold ischemia time were similar between the groups. Overall graft survival rate at 1 year (55% DCD vs 85% DBD) and 5 years (46% DCD vs 78% DBD) was significantly lower in the DCD group (P = .0003). Similarly, patient survival rate at 1 year (62% DCD vs 93% DBD) and 5 years (62% DCD vs 82% DBD) was significantly lower in the DCD group (P = .0295). Incidences of hepatic artery thrombosis, portal vein thrombosis, and primary nonfunction were similar between the DCD and DBD groups. The incidence of liver abscess with ischemic-type biliary stricture was higher in recipients from DCD as compared with DBD (42% vs 2%). A trend toward lower graft survival was noted in recipients from donors older than 60 years of age in the HCV population (P = .07), with statistically lower patient survival (P = .02). Donor- recipient HLA matching did not appear to correlate with OLT outcome in patients with HCV. DCD donors and donors older than 60 years of age significantly impact patient and graft survival. Lower graft and patient survival in recipients from DCD donors does not appear to be related to early disease recurrence.     

Recipient survival and graft survival are not diminished by simultaneous liver-kidney transplantation: an analysis of the united network for organ sharing database

Recipients of solitary liver and kidney transplants are living longer, and this increases their risk of long-term complications such as recurrent hepatitis C virus (HCV) and drug-induced nephrotoxicity. These complications may require retransplantation. Since the adoption of the Model for End-Stage Liver Disease, the number of simultaneous liver-kidney transplantation (SLK) procedures has increased. However, there are no standardized criteria for organ allocation to SLK candidates. The aims of this study were to retrospectively compare recipient and graft survival with liver transplantation alone (LTA), SLK, kidney after liver transplantation (KALT), and liver after kidney transplantation (LAKT) and to identify independent risk factors affecting recipient and graft survival. The United Network for Organ Sharing/Organ Procurement and Transplantation Network database (1988-2007) was queried for adult LTA (66,026), SLK (2327), KALT (1738), and LAKT procedures (242). After adjustments for potential confounding demographic and clinical variables, there was no difference in recipient mortality rates with LTA and SLK (P = 0.02). However, there was a 15% decreased risk of graft loss with SLK versus LTA (hazard ratio = 0.85, P < 0.001). The recipient and graft survival rates with SLK were higher than the rates with both KALT (P <0.001 and P <0.001) and LAKT (P = 0.003 and P < 0.001). The following were all identified as independent negative predictors of recipient mortality and graft loss: recipient age ≥ 65 years, male sex, black race, HCV/diabetes mellitus status, donor age ≥ 60 years, serum creatinine level ≥2.0 mg/dL, cold ischemia time > 12 hours, and warm ischemia time > 60 minutes. Although the recent increase in the number of SLK procedures performed each year has effectively decreased the number of potential donor kidneys available to patients with end-stage renal disease (ESRD) awaiting kidney transplantation, SLK in patients with end-stage liver disease and ESRD is justified because of the lower risk of graft loss with SLK versus LTA as well as the superior recipient and graft survival with SLK versus serial liver-kidney transplantation.