Nathan P. Goodrich

The Survival Benefit of Deceased Donor Liver Transplantation as a Function of Candidate Disease Severity and Donor Quality

The survival benefit of liver transplantation depends on candidate disease severity, as measured by MELD score. However, donor liver quality may also affect survival benefit. Using US data from the SRTR on 28 165 adult liver transplant candidates wait‐listed between 2001 and 2005, we estimated survival benefit according to cross‐classifications of candidate MELD score and deceased donor risk index (DRI) using sequential stratification. Covariate‐adjusted hazard ratios (HR) were calculated for each liver transplant recipient at a given MELD with an organ of a given DRI, comparing posttransplant mortality to continued wait‐listing with possible later transplantation using a lower‐DRI organ. High‐DRI organs were more often transplanted into lower‐MELD recipients and vice versa. Compared to waiting for a lower‐DRI organ, the lowest‐MELD category recipients (MELD 6–8) who received high‐DRI organs experienced significantly higher mortality (HR = 3.70; p < 0.0005). All recipients with MELD ≥20 had a significant survival benefit from transplantation, regardless of DRI. Transplantation of high‐DRI organs is effective for high but not low‐MELD candidates. Pairing of high‐DRI livers with lower‐MELD candidates fails to maximize survival benefit and may deny lifesaving organs to high‐MELD candidates who are at high risk of death without transplantation.

Donation after cardiac death as a strategy to increase deceased donor liver availability.

Objective:This study examines donation after cardiac death (DCD) practices and outcomes in liver transplantation. Summary Background Data: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. Methods: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. Results: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. Conclusions: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.

Predicted Lifetimes for Adult and Pediatric Split Liver Versus Adult Whole Liver Transplant Recipients

Split liver transplantation allows 2 recipients to receive transplants from one organ. Comparisons of predicted lifetimes for two alternatives (split liver for an adult and pediatric recipient vs. whole liver for an adult recipient) can help guide the use of donor livers. We analyzed mortality risk for 48 888 waitlisted candidates, 907 split and 21 913 whole deceased donor liver transplant recipients between January 1, 1995 and February 26, 2002. Cox regression models for pediatric and adult patients assessed average relative wait list and post‐transplant death risks, for split liver recipients. Life years gained compared with remaining on the waiting list over a 2‐year period were calculated. Seventy‐six splits (152 recipients) and 24 re‐transplants resulted from every 100 livers (13.1%[adult] and 18.0%[pediatric] 2‐year re‐transplant rates, respectively). Whole livers used for 93 adults also utilized 100 livers (re‐transplant rate 7.0%). Eleven extra life years and 59 incremental recipients accrued from each 100 livers used for split compared with whole organ transplants. Split liver transplantation could provide enough organs to satisfy the entire current demand for pediatric donor livers in the United States, provide more aggregate years of life than whole organ transplants and result in larger numbers of recipients.

Geographic Differences in Event Rates by Model for End-Stage Liver Disease Score

The ability of the model for end‐stage liver disease (MELD) score to accurately predict death among liver transplant candidates allows for evaluation of geographic differences in transplant access for patients with similar death risk.

Impact of MELD-Based Allocation on End-Stage Renal Disease after Liver Transplantation

The proportion of patients undergoing liver transplantation (LT), with concomitant renal dysfunction, markedly increased after allocation by the model for end‐stage liver disease (MELD) score was introduced. We examined the incidence of subsequent post‐LT end‐stage renal disease (ESRD) before and after the policy was implemented. Data on all adult deceased donor LT recipients between April 27, 1995 and December 31, 2008 (n = 59 242), from the Scientific Registry of Transplant Recipients, were linked with Centers for Medicare & Medicaid Services’ ESRD data. Cox regression was used to (i) compare pre‐MELD and MELD eras with respect to post‐LT ESRD incidence, (ii) determine the risk factors for post‐LT ESRD and (iii) quantify the association between ESRD incidence and mortality. Crude rates of post‐LT ESRD were 12.8 and 14.5 per 1000 patient‐years in the pre‐MELD and MELD eras, respectively. Covariate‐adjusted post‐LT ESRD risk was higher in the MELD era (hazard ratio [HR]= 1.15; p = 0.0049). African American race, hepatitis C, pre‐LT diabetes, higher creatinine, lower albumin, lower bilirubin and sodium >141 mmol/L at LT were also significant predictors of post‐LT ESRD. Post‐LT ESRD was associated with higher post‐LT mortality (HR = 3.32; p < 0.0001). The risk of post‐LT ESRD, a strong predictor of post‐LT mortality, is 15% higher in the MELD era. This study identified potentially modifiable risk factors of post‐LT ESRD. Early intervention and modification of these risk factors may reduce the burden of post‐LT ESRD.

Development, management, and resolution of biliary complications after living and deceased donor liver transplantation: a report from the adult-to-adult living donor liver transplantation cohort study consortium.

Adult recipients of living donor liver transplantation (LDLT) have a higher incidence of biliary complications than recipients of deceased donor liver transplantation (DDLT). Our objective was to define the intensity of the interventions and the time to resolution after the diagnosis of biliary complications after liver transplantation. We analyzed the management and resolution of posttransplant biliary complications and investigated the comparative effectiveness of interventions in LDLT and DDLT recipients. For the analysis of biliary complications (leaks or strictures), we used a retrospective cohort of patients who underwent liver transplantation at 8 centers between 1998 and 2006 (median follow‐up from onset=4.7 years). The numbers, procedure types, and times to resolution were compared for LDLT and DDLT recipients. Posttransplant biliary complications occurred in 47 of the 189 DDLT recipients (25%) and in 141 of the 356 LDLT recipients (40%). Biliary leaks constituted 38% of the post‐DDLT biliary complications (n=18) and 65% of the post‐LDLT biliary complications (n=91). The median times to first biliary complications were similar for DDLT and LDLT (11 versus 14 days for leaks, P=0.63; 69 versus 107 days for strictures, P=0.34). Overall, 1225 diagnostic and therapeutic procedures, including reoperation and retransplantation, were performed (6.5±5.4 per recipient; 5.5±3.6 for DDLT versus 6.8±5.8 for LDLT, P=0.52). The median number of months to the resolution of a biliary complication (i.e., a tube‐, stent‐, and drain‐free status) did not significantly differ between the DDLT and LDLT groups for leaks (2.3 versus 1.3 months, P=0.29) or strictures (4.9 versus 2.3 months, P=0.61). Although the incidence of biliary complications is higher after LDLT versus DDLT, the treatment requirements and the time to resolution after the development of a biliary complication are similar for LDLT and DDLT recipients. Liver Transpl 19:259–267, 2013.

Short-Term Pretransplant Renal Replacement Therapy and Renal Nonrecovery after Liver Transplantation Alone

BACKGROUND AND OBJECTIVES Candidates with AKI including hepatorenal syndrome often recover renal function after successful liver transplantation (LT). This study examined the incidence and risk factors associated with renal nonrecovery within 6 months of LT alone among those receiving acute renal replacement therapy (RRT) before LT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Scientific Registry of Transplant Recipients data were linked with Centers for Medicare and Medicaid Services ESRD data for 2112 adult deceased-donor LT-alone recipients who received acute RRT for ≤90 days before LT (February 28, 2002 to August 31, 2010). Primary outcome was renal nonrecovery (post-LT ESRD), defined as transition to chronic dialysis or waitlisting or receipt of kidney transplant within 6 months of LT. Cumulative incidence of renal nonrecovery was calculated using competing risk analysis. Cox regression identified recipient and donor predictors of renal nonrecovery. RESULTS The cumulative incidence of renal nonrecovery after LT alone among those receiving the pre-LT acute RRT was 8.9%. Adjusted renal nonrecovery risk increased by 3.6% per day of pre-LT RRT (P<0.001). Age at LT per 5 years (P=0.02), previous-LT (P=0.01), and pre-LT diabetes (P<0.001) were significant risk factors of renal nonrecovery. Twenty-one percent of recipients died within 6 months of LT. Duration of pretransplant RRT did not predict 6-month post-transplant mortality. CONCLUSIONS Among recipients on acute RRT before LT who survived after LT alone, the majority recovered their renal function within 6 months of LT. Longer pre-LT RRT duration, advanced age, diabetes, and re-LT were significantly associated with increased risk of renal nonrecovery.

Patient-Specific Prediction of ESRD after Liver Transplantation

Incident ESRD after liver transplantation (LT) is associated with high post-transplant mortality. We constructed and validated a continuous renal risk index (RRI) to predict post-LT ESRD. Data for 43,514 adult recipients of deceased donor LT alone (February 28, 2002 to December 31, 2010) were linked from the Scientific Registry of Transplant Recipients and the Centers for Medicare and Medicaid Services ESRD Program. An adjusted Cox regression model of time to post-LT ESRD was fitted, and the resulting equation was used to calculate an RRI for each LT recipient. The RRI included 14 recipient factors: age, African-American race, hepatitis C, cholestatic disease, body mass index ≥ 35, pre-LT diabetes, ln creatinine for recipients not on dialysis, ln albumin, ln bilirubin, serum sodium<134 mEq/L, status-1, previous LT, transjugular intrahepatic portosystemic shunt, and acute dialysis at LT. This RRI was validated and had a C statistic of 0.76 (95% confidence interval, 0.75 to 0.78). Higher RRI associated significantly with higher 5-year cumulative incidence of ESRD and post-transplant mortality. In conclusion, the RRI constructed in this study quantifies the risk of post-LT ESRD and is applicable to all LT alone recipients. This new validated measure may serve as an important prognostic tool in ameliorating post-LT ESRD risk and improve survival by informing post-LT patient management strategies.

Recent Trends and Results for Organ Donation and Transplantation in the United States, 2005: Donation and Transplantation Trends, 2005

This overview provides a summary of many aspects of solid organ transplantation in the United States, and is produced as part of the 2005 OPTN/SRTR Annual Report. The Annual Report is prepared by the Scientific Registry of Transplant Recipients (SRTR) in collaboration with the Organ Procurement and Transplantation Network (OPTN) under contract with the Health Resources and Services Administration (HRSA). The Annual Report is intended to provide valuable information to patients, the transplant community, the public, and the Federal Government by publishing a vast array of knowledge on activities related to solid organ transplantation.

Liver transplantation for status 1: The consequences of good intentions

Status 1 is the listing category reserved for patients awaiting liver transplantation who are at risk of imminent death. This high allocation priority was intended to benefit patients with acute liver failure and children with severe chronic liver failure. However, the status 1 criteria were not well defined. The aims of this study, which used the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients database for patients wait‐listed between February 27, 2002, and September 30, 2003, were to determine the indication and numbers of children and adults at status 1 (including regional variations); examine death rates on the waiting list for children at vs. not at status 1; and examine time to death, transplant, or removal from the waiting list for both pediatric and adult status 1 candidates. During the study period, 40.3% of children and 6.1% of adults were transplanted at status 1. The indication was acute liver failure in 52.1% of adults and 31% of children. Among status 1 transplants, Regional Review Board exceptions were granted for 16.7% of children and 10.1% of adults. Death rates for children listed at status 1 by exception per patient‐year at risk were substantially lower (0.51) than those of children with acute liver failure (4.06) or with chronic liver disease and Pediatric End‐Stage Liver Disease score ≥25 (4.63). The percentage of adults who died while on the waiting list within 90 days of listing was more than twice that of children, whereas the percentages transplanted were similar. Patients listed and transplanted at status 1 were a heterogeneous population with an overrepresentation of children with varying degrees of chronic liver disease and other exceptions, and an associated wide variation in waiting list mortality. Recent changes in status 1 criteria provide stricter definitions, particularly for children, including the removal of the “by exception” category, with the intent that all candidates listed at status 1 share a similar mortality risk. Liver Transpl 13:699–707, 2007.