John F. Renz

Functional analysis of grafts from living donors. Implications for the treatment of older recipients.

OBJECTIVE Living-related liver transplantation (LRLT) has established efficacy in children. In a larger recipient, LRLT requires the use of a small graft because of limits on the donor hepatectomy. SUMMARY BACKGROUND DATA The minimum graft weight required for successful transplantation has not been well established, although a characteristic pattern of graft dysfunction has been observed in our patients who receive small grafts. The authors present a clinicopathologic study of small liver grafts obtained from living donors. METHODS Clinical and histologic data were reviewed for 25 patients receiving LRLT. In five older recipients (small group), the graft represented 50% or less of expected liver weight, whereas in 20 others (large group), the graft represented at least 60% of expected liver weight. A retrospective analysis of graft function was conducted by analyzing clinical parameters and histology. RESULTS In the small group, 2 of 5 grafts (40%) were lost due to poor function, leading to one patient death (20% mortality), whereas in the large group, 2 of 20 grafts (10%) were lost due to arterial thrombosis without patient mortality. Early ischemic damage related to transplant was comparable with aspartate aminotransferase 203 +/- 23 (small group) and 290 +/- 120 (large group) at 24 hours (p = not significant). Early function was significantly decreased in the small group, with prothrombin time 18.2 +/- 2.2 seconds versus 14.8 +/- 1.6 seconds (large group) on day 3 (p = 0.034). All small group patients developed cholestasis with significantly increased total bilirubin levels at day 7 (16 +/- 5.2 mg% vs. 3.7 +/- 2.7 mg%; p = 0.021) and day 14 (12.0 +/- 7.4 vs. 1.8 +/- 0.7; p = 0.021) compared with the large group. Protocol biopsies in the small group revealed a diffuse ischemic pattern with cellular ballooning on day 7, which progressed to cholestasis in subsequent biopsies. Large group biopsies showed minimal ischemic changes. Three small group patients recovered with normal liver function by 12 weeks. CONCLUSIONS Clinical recovery after a small-for-size transplant is characterized by significant functional impairment associated with paradoxical histologic changes typical of ischemia. These changes apparently are due to graft injury, which can only be the result of small graft size. These findings have significant implications for the extension of LRLT to adults.

Hypothermic Machine Preservation in Human Liver Transplantation: The First Clinical Series

Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP‐preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3–7 h using centrifugal perfusion with Vasosol® solution at 4–6°C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 ± 4.7 days vs. 15.3 ± 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case‐controlled series. Further multicenter HMP trials are now warranted.

Report of the Paris consensus meeting on expanded criteria donors in liver transplantation.

Because of organ shortage and a constant imbalance between available organs and candidates for liver transplantation, expanded criteria donors are needed. Experience shows that there are wide variations in the definitions, selection criteria, and use of expanded criteria donors according to different geographic areas and different centers. Overall, selection criteria for donors have tended to be relaxed in recent years. Consensus recommendations are needed. This article reports the conclusions of a consensus meeting held in Paris in March 2007 with the contribution of experts from Europe, the United States, and Asia. Definitions of expanded criteria donors with respect to donor variables (including age, liver function tests, steatosis, infections, malignancies, and heart‐beating versus non–heart‐beating, among others) are proposed. It is emphasized that donor quality represents a continuum of risk rather than “good or bad.” A distinction is made between donor factors that generate increased risk of graft failure and factors independent of graft function, such as transmissible infectious disease or donor‐derived malignancy, that may preclude a good outcome. Updated data concerning the risks associated with different donor variables in different recipient populations are given. Recommendations on how to safely expand donor selection criteria are proposed. Liver Transpl 14:1694–1707, 2008.

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.

Utilization of extended donor criteria liver allografts maximizes donor use and patient access to liver transplantation.

Objective:The objective of this study was to evaluate the effect of systematic utilization of extended donor criteria liver allografts (EDC), including living donor allografts (LDLT), on patient access to liver transplantation (LTX). Summary Background Data:Utilization of liver allografts that do not meet traditional donor criteria (EDC) offer immediate expansion of the donor pool. EDC are typically allocated by transplant center rather than regional wait-list priority (RA). This single-institution series compares outcomes of EDC and RA allocation to determine the impact of EDC utilization on donor use and patient access to LTX. Methods:The authors conducted a retrospective analysis of 99 EDC recipients (49 deceased donor, 50 LDLT) and 116 RA recipients from April 2001 through April 2004. Deceased-donor EDC included: age >65 years, donation after cardiac death, positive viral serology (hepatitis C, hepatitis B core antibody, human T-cell lymphotrophic), split-liver, hypernatremia, prior carcinoma, steatosis, and behavioral high-risk donors. Outcome variables included patient and graft survival, hospitalization, initial graft function, and complication categorized as: biliary, vascular, wound, and other. Results:EDC recipients were more frequently diagnosed with hepatitis C virus or hepatocellular carcinoma and had a lower model for end-stage liver disease (MELD) score at LTX (P < 0.01). Wait-time, technical complications, and hospitalization were comparable. Log-rank analysis of Kaplan-Meier survival estimates demonstrated no difference in patient or graft survival; however, deaths among deceased-donor EDC recipients were frequently the result of patient comorbidities, whereas LDLT and RA deaths resulted from graft failure (P < 0.01). EDC increased patient access to LTX by 77% and reduced pre-LTX mortality by over 50% compared with regional data (P < 0.01). Conclusion:Systematic EDC utilization maximizes donor use, increases access to LTX, and significantly reduces wait-list mortality by providing satisfactory outcomes to select recipients.

Split-liver transplantation in the United States: outcomes of a national survey.

Objective:Assess application and outcomes of split-liver transplantation within the United States. Summary Background Data:While a theoretically attractive mechanism to increase cadaver organ supply, split-liver transplantation has been infrequently applied. The American Society of Transplant Surgeons, in an attempt to gather preliminary data on split-liver transplantation, performed a data protected survey of transplant centers participating in the U.S. Scientific Registry for Transplant Recipients. Methods:Between April 2000 and May 2001, 89 surgical teams were surveyed. Elicited data included graft type, recipient status, procurement method, graft sharing, graft outcomes, recipient outcomes, and experience with cadaver, whole-organ transplantation. Results:Eighty-three surgical teams reported data on 207 left lateral segment, 152 right trisegment, 15 left lobe, and 13 right lobe grafts. The split procedure was performed ex vivo in 54% and in situ in 46% of grafts. Complications were frequent in all graft types with biliary and vascular complications equally distributed between grafts procured by either technique. Primary nonfunction, graft failure, and recipient death correlated with transplant status. Conclusions:Split-liver transplantation has been principally applied to adult-child pairs with at least one recipient critically ill. Biliary and vascular complications account for the majority of morbidity in grafts procured by either split technique with graft failure and recipient death observed more frequently in critically ill recipients. Enhanced utilization and improved results may be possible through improved information sharing and modification of allocation criteria.

Utilization, outcomes, and retransplantation of liver allografts from donation after cardiac death: implications for further expansion of the deceased-donor pool.

Objective:Utilization, outcomes, and retransplantation (ReTx) of liver allografts obtained by donation after cardiac death (DCD) are examined to identify mechanisms to optimize donation. Summary and Background Data:DCD for liver transplantation (LTX) has immediate potential to expand the donor pool but application is limited. Methods:Retrospective analysis of the Scientific Registry of Transplant Recipients (SRTR) from January 2002 to April 2007 identified 855 DCD and 21,089 donation after brain death (DBD) adult, initial, whole-organ, liver-only LTX. Donor, recipient, and transplant characteristics were compared. Outcome measures were listing for ReTx within 1 year and graft survival determined as death or ReTx. Results:DCD donors were younger (P < 0.001), with fewer African American and non-white race (P < 0.001), and fewer deaths secondary to stroke (P < 0.001). DCD recipients were older (P < 0.001), with lower Model for End-Stage Liver Disease (MELD) scores (P < 0.001), and less likely in intensive care (P = 0.02) or high-urgency status (P < 0.001). DCD allografts were more frequently imported from another allocation region (12% vs. 7%; P < 0.001). Cox regression analysis of time to DCD graft failure demonstrates higher DCD graft failure within the first 180 days (20.5% DCD vs. 11.5% DBD; P < 0.001) with convergence thereafter. DCD listing for ReTx and graft failure progressed continuously over180 days versus 20 days in DBD. At ReTx, DCD recipients waited longer and received higher risk allografts (P = 0.039) more often from another region. More DCD recipients remain waiting for ReTx with fewer removed for death, clinical deterioration, or improvement. Conclusions:DCD utilization is impeded by early outcomes and a temporally different failure pattern that limits access to ReTx. Allocation policy that recognizes these limitations and increases access to ReTx is necessary for expansion of this donor population.

Split-Liver Transplantation: A Review

Split‐liver transplantation (SLT), a procedure where one cadaver liver is divided to provide for two recipients, offers immediate expansion of the existing cadaver donor pool. To date, the principal beneficiaries of SLT have been adult/pediatric recipient pairs with excellent outcomes reported; however, the current scarcity of cadaver organs has renewed interest in expanding these techniques to include two adult recipients from one adult cadaver donor. Significant obstacles to the widespread application of SLT exist and must be resolved by the transplant community before greater utilization can be realized. This manuscript reviews the historic background, surgical techniques, current results, and obstacles impeding further application of SLT.

Failure patterns of cryopreserved vein grafts in liver transplantation

Reports of early success with cryopreserved saphenous veins (CSV) as arterial conduits led us to develop cryopreserved iliac veins (CIV) as interposition grafts for portal vein reconstruction in living-related liver transplantation (LRLT). Despite encouraging short-term results, retrospective analysis of long-term cryopreserved vein graft performance in LRLT at our institution has revealed a high rate of late graft failures. Between July 1992 and JUly 1994, interposition grafts (CIV for portal vein interposition n=4, CSV for portal vein interposition n=3, and CSV for hepatic artery interposition n=2) were utilized in 7 LRLT. (Two transplanted organs had both CIV and CSV grafts.) Recipients included 5 children and two small adults (median: 3.5 years, range: 0.5--59 years). Posttransplant follow-up in excess of 36 months revealed portal vein (PV) and hepatic artery (HA) complications of cryopreserved grafts in each patient. PV complications included aneurysm (n=4) diagnosed at 28, 24, 18, and 1.5 mo, stricture (n=1) diagnosed at 11 mo, and thrombosis (n=1) diagnosed at 18 mo posttransplantation. All portal vein complications have been managed without retransplantation, but one (PV thrombosis) necessitated surgical shunt therapy. Each CSV hepatic artery interposition graft has been complicated by thrombosis (diagnosed at 11 days and 24 mo posttransplant) necessitating retransplantation. Based on these observations, we have adopted alternative strategies for HA and PV reconstruction. At present, 11 LRLT have been performed without cryopreserved vein conduits over 17 mo with no vascular complications. While this study does not permit statistical analysis, these results discourage the use cryopreserved iliac veins for portal interposition and cryopreserved saphenous veins for arterial interposition in liver transplantation.

Racial disparities in utilization of liver transplantation for hepatocellular carcinoma in the United States, 1998-2002.

BACKGROUND AND AIMS:The extent of use of liver transplantation on a population scale to treat hepatocellular carcinoma (HCC) in the United States is unknown. We assessed recent predictors of use of liver transplantation and its effect on survival for those with nonmetastatic HCC.METHODS:The Surveillance, Epidemiology, and End Results (SEER) program is a collection of population-based cancer registries. We identified adults registered in SEER with HCC between 1998 and 2002. We examined determinants for receipt of a liver transplant in univariate and multivariable analyses. Kaplan–Meier survival curves were constructed for those who received and did not receive a transplant for HCC.RESULTS:We identified 1,156 adults with small (5 cm or less) nonmetastatic HCC. Approximately 45% were white, 29% Asian, 17% Hispanic, and 9% African American. Only 21% received a transplant. More recent year of diagnosis, younger age, being married, white race, and smaller tumor size each predicted receipt of transplant. African Americans and Asians were about half as likely to receive a transplant as compared with white patients (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.21–0.90 for African Americans, and 0.57, 95% CI 0.36–0.89 for Asians). Hispanics trended in the same direction, but this was not statistically significant (OR 0.66, 95% CI 0.39–1.12). Those who underwent liver transplantation for localized HCC had 3- and 5-yr survivals of 81% and 75%, respectively.CONCLUSIONS:Only one-fifth of those with small, nonmetastatic HCC received liver transplantation. Transplanted patients have long-term survival similar to that of the best single-institution studies. However, marked racial variations were seen, with African Americans and Asians significantly less likely to receive a transplant after controlling for other variables.