Robert M. Merion

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Liver transplantation has rapidly advanced from an experimental therapy to a mainstream treatment option for a wide range of acute and chronic liver diseases. Indications for liver transplant have evolved to include previously contraindicated conditions such as hepatocellular carcinoma and alcohol-related liver disease. Cirrhosis from chronic hepatitis C infection remains the most common indication today. Multidisciplinary evaluation for liver transplantation is intended to confirm the patient's suitability and identify the appropriate timing of transplant, although the latter is problematic as a result of the ongoing donor organ shortage. Deceased liver donors have been increasing in number, but increasing donor age has been associated with less satisfactory posttransplant results. Living donor liver transplant is a dramatic but very infrequent procedure; risk to the living donor is of paramount concern. The main focus of deceased donor allocation has transitioned from waiting time to estimation of the likelihood of death without transplant (medical urgency), and now relies upon a laboratory-based Model for End-Stage Liver Disease (MELD) score for candidates with chronic liver disease. Those with acute liver failure are prioritized ahead of those with chronic conditions. Although not used as a direct criterion for allocation, development of the concept of transplant survival benefit, i.e., the extra years of life attributable to transplant, has facilitated better ordering of those candidates likely to have the most benefit, while restricting access to those whose lives will be extended minimally or not at all. Overall posttransplant outcomes have steadily improved, with unadjusted 5-year patient survival rates of 77% among patients transplanted with MELD score between 15 and 20, and 72% for those with MELD scores between 21 and 30.

Objective: To compare rates of hospitalization before and after adult-to-adult living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT). Summary Background Data: LDLT recipients have been reported to have lower mortality but a higher complication rate than DDLT recipients. The higher complication rate may be associated with greater consumption of inpatient hospital resources and a higher burden of disease for LDLT recipients. Methods: Data from the 9-center Adult-to-Adult Living Donor Liver Transplantation retrospective cohort study were analyzed to determine pretransplant, transplant, and posttransplant hospitalizations among LDLT candidates (potential living donor was evaluated) who received LDLT or DDLT. Hospital days and admission rates for LDLT and DDLT patients were calculated per patient-year at risk, starting from the date of initial potential donor history and physical examination. Rates were compared using overdispersed Poisson regression models. Results: Among 806 candidates, 384 received LDLT and 215 received DDLT. In addition to the 599 transplants, there were 1913 recipient hospitalizations (485 pretransplant; 1428 posttransplant). Mean DDLT recipient pretransplant, transplant, and posttransplant lengths of stay were 5.8 ± 6.3, 27.0 ± 32.6, and 9.0 ± 14.1 days, respectively, and for LDLT were 4.1 ± 3.7, 21.4 ± 24.3, and 7.8 ± 11.4 days, respectively. Compared with DDLT, LDLT recipients had significantly lower adjusted pretransplant hospital day and admission rates, but significantly higher posttransplant rates. Significantly higher LDLT admission rates were observed for biliary tract morbidity throughout the second posttransplant year. Overall hospitalization rates starting from the point of potential donor evaluation were significantly higher for eventual recipients of LDLT. Conclusions: LDLT recipients, despite lower acuity of disease, have higher hospitalization requirements when compared with DDLT recipients. Continuing efforts are warranted to reduce the incidence of complications requiring post-LDLT inpatient admission, with particular emphasis on biliary tract issues.

This study examines donation after cardiac death (DCD) practices and outcomes in liver transplantation. Livers procured from DCD donors have recently been used to increase the number of deceased donors and bridge the gap between limited organ supply and the pool of waiting list candidates. Comprehensive evaluation of this practice and its outcomes has not been previously reported. A national cohort of all DCD and donation after brain-death (DBD) liver transplants between January 1, 2000 and December 31, 2004 was identified in the Scientific Registry of Transplant Recipients. Time to graft failure (including death) was modeled by Cox regression, adjusted for relevant donor and recipient characteristics. DCD livers were used for 472 (2%) of 24,070 transplants. Annual DCD liver activity increased from 39 in 2000 to 176 in 2004. The adjusted relative risk of DCD graft failure was 85% higher than for DBD grafts (relative risk, 1.85; 95% confidence interval, 1.51-2.26; P < 0.001), corresponding to 3-month, 1-year, and 3-year graft survival rates of 83.0%, 70.1%, and 60.5%, respectively (vs. 89.2%, 83.0%, and 75.0% for DBD recipients). There was no significant association between transplant program DCD liver transplant volume and graft outcome. The annual number of DCD livers used for transplant has increased rapidly. However, DCD livers are associated with a significantly increased risk of graft failure unrelated to modifiable donor or recipient factors. Appropriate recipients for DCD livers have not been fully characterized and recipient informed consent should be obtained before use of these organs.

Transplantation using kidneys from deceased donors who meet the expanded criteria donor (ECD) definition (age > or =60 years or 50 to 59 years with at least 2 of the following: history of hypertension, serum creatinine level >1.5 mg/dL [132.6 micromol/L], and cerebrovascular cause of death) is associated with 70% higher risk of graft failure compared with non-ECD transplants. However, if ECD transplants offer improved overall patient survival, inferior graft outcome may represent an acceptable trade-off. To compare mortality after ECD kidney transplantation vs that in a combined standard-therapy group of non-ECD recipients and those still receiving dialysis. Retrospective cohort study using data from a US national registry of mortality and graft outcomes among kidney transplant candidates and recipients. The cohort included 109,127 patients receiving dialysis and added to the kidney waiting list between January 1, 1995, and December 31, 2002, and followed up through July 31, 2004. Long-term (3-year) relative risk of mortality for ECD kidney recipients vs those receiving standard therapy, estimated using time-dependent Cox regression models. By end of follow-up, 7790 ECD kidney transplants were performed. Because of excess ECD recipient mortality in the perioperative period, cumulative survival did not equal that of standard-therapy patients until 3.5 years posttransplantation. Long-term relative mortality risk was 17% lower for ECD recipients (relative risk, 0.83; 95% confidence interval, 0.77-0.90; P<.001). Subgroups with significant ECD survival benefit included patients older than 40 years, both sexes, non-Hispanics, all races, unsensitized patients, and those with diabetes or hypertension. In organ procurement organizations (OPOs) with long median waiting times (>1350 days), ECD recipients had a 27% lower risk of death (relative risk, 0.73; 95% confidence interval, 0.64-0.83; P<.001). In areas with shorter waiting times, only recipients with diabetes demonstrated an ECD survival benefit. ECD kidney transplants should be offered principally to candidates older than 40 years in OPOs with long waiting times. In OPOs with shorter waiting times, in which non-ECD kidney transplant availability is higher, candidates should be counseled that ECD survival benefit is observed only for patients with diabetes.