US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery.

Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures: cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

Liver transplantation for post-COVID-19 cholangiopathy: A case series.

BACKGROUND: Post-COVID-19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID-19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post-COVID-19 cholangiopathy. METHODS: Seven patients who underwent liver transplantation for post-COVID-19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi-center case series. RESULTS: At the time of initial COVID-19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID-19 diagnosis to the diagnosis of post-COVID-19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10-38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow-up of 11 months. CONCLUSIONS: Liver transplantation is a viable option for patients with post-COVID-19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential.

Addressing the Burden and Management Strategies for Disparities and Inequities Among Liver Transplant Professionals: The ILTS Experience.

Medical professional environments are becoming increasingly multicultural, international, and diverse in terms of its specialists. Many transplant professionals face challenges related to gender, sexual orientation or racial background in their work environment or experience inequities involving access to leadership positions, professional promotion, and compensation. These circumstances not infrequently become a major source of work-related stress and burnout for these disadvantaged, under-represented transplant professionals. In this review, we aim to 1) discuss the current perceptions regarding disparities among liver transplant providers 2) outline the burden and impact of disparities and inequities in the liver transplant workforce 3) propose potential solutions and role of professional societies to mitigate inequities and maximize inclusion within the transplant community.

Systematic review and meta-analysis of open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy.

The value of minimally invasive approaches for living donor hepatectomy remains unclear. Our aim was to compare the donor outcomes after open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy (OLDH vs. LALDH vs. PLLDH vs. RLDH). A systematic literature review of the MEDLINE, Cochrane Library, Embase, and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (up to December 8, 2021). Random-effects meta-analyses were performed separately for minor and major living donor hepatectomy. The risk of bias in nonrandomized studies was assessed using the Newcastle-Ottawa Scale. A total of 31 studies were included. There was no difference in donor outcomes after OLDH versus LALDH for major hepatectomy. However, PLLDH was associated with decreased estimated blood loss, length of stay (LOS), and overall complications versus OLDH for minor and major hepatectomy, but also with increased operative time for major hepatectomy. PLLDH was associated with decreased LOS versus LALDH for major hepatectomy. RLDH was associated with decreased LOS but with increased operative time versus OLDH for major hepatectomy. The scarcity of studies comparing RLDH versus LALDH/PLLDH did not allow us to meta-analyze donor outcomes for that comparison. There seems to be a marginal benefit in estimated blood loss and/or LOS in favor of PLLDH and RLDH. The complexity of these procedures limits them to transplant centers with high volume and experience. Future studies should investigate self-reported donor experience and the associated economic costs of these approaches.

Liver transplantation during COVID-19: Adaptive measures with future significance.

Following the outbreak of coronavirus disease 2019 (COVID-19), a disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the field of liver transplantation, along with many other aspects of healthcare, underwent drastic changes. Despite an initial increase in waitlist mortality and a decrease in both living and deceased donor liver transplantation rates, through the implementation of a series of new measures, the transplant community was able to recover by the summer of 2020. Changes in waitlist prioritization, the gradual implementation of telehealth, and immunosuppressive regimen alterations amidst concerns regarding more severe disease in immunocompromised patients, were among the changes implemented in an attempt by the transplant community to adapt to the pandemic. More recently, with the advent of the Pfizer BNT162b2 vaccine, a powerful new preventative tool against infection, the pandemic is slowly beginning to subside. The pandemic has certainly brought transplant centers around the world to their limits. Despite the unspeakable tragedy, COVID-19 constitutes a valuable lesson for health systems to be more prepared for potential future health crises and for life-saving transplantation not to fall behind.

Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study.

Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.

Liver Transplantation for Hepatic Adenoma: A UNOS Database Analysis and Systematic Review of the Literature.

BACKGROUND: Liver transplantation (LT) has been employed for hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA. METHODS: All patients listed or transplanted for HA in the United States were identified in the United Network for Organ Sharing (UNOS) database (1987-2020). A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. RESULTS: A total of 199 HA patients were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 HA patients underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 mo, death was reported in 18.3%. The 1-, 3-, and 5-y patient survival rates were 94.2%, 89.7%, and 86.3% in the UNOS cohort. The systematic review yielded 61 articles reporting on 99 nonoverlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), whereas 53.1% had glycogen storage disease. Over a median follow-up of 36.5 mo, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-y patient survival rates were all 95.0% in the systematic review. CONCLUSIONS: LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.

Liver transplant after donation from controlled circulatory death versus brain death: A UNOS database analysis and publication bias adjusted meta-analysis.

BACKGROUND: Donation after circulatory death (DCD) is an increasingly utilized alternative to donation after brain death (DBD) to expand the liver donor pool. We compared the outcomes of liver transplant (LT) after DCD versus DBD. METHODS: A PRISMA-compliant systematic literature review was performed using the PubMed, Cochrane Library, and Embase databases (end-of-search-date: July 2, 2020). US outcomes were analyzed using the UNOS database (February, 2002-September, 2020). Pooled hazard ratios (HR) for patient and graft survival were obtained through random effect meta-analyses and adjusted for publication bias. RESULTS: Thirteen studies reporting on 1426 DCD and 5385 DBD LT recipients were included. 5620 DCD and 87561 DBD LT recipients were analyzed from the UNOS database. Meta-analysis showed increased risk of patient mortality for DCD (HR = 1.36; 95%CI, 1.09-1.70; P = .01; I2  = 53.6%). When adjusted for publication bias, meta-analysis showed no difference in patient survival between DCD and DBD (HR = 1.15; 95%CI, .91-1.45; P = .25; I2  = 61.5%). Meta-analysis showed increased risk of graft loss for DCD (HR = 1.50; 95%CI, 1.20-1.88; P < .001; I2  = 67.8%). When adjusted for publication bias, meta-analysis showed a reduction in effect size (HR = 1.36; 95%CI, 1.06-1.74; P = .02; I2  = 73.5%). CONCLUSION: When adjusted for publication bias, no difference was identified between DCD and DBD regarding patient survival, while DCD was associated with an increased risk of graft loss.

Laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma: An individual patient data survival meta-analysis.

BACKGROUND: We compared the outcomes of laparoscopic hepatectomy (LH) vs. open hepatectomy (OH) for intrahepatic cholangiocarcinoma (iCCA). METHODS: A systematic review of the MEDLINE, EMBASE, Scopus, and Cochrane Library databases was performed using PRISMA guidelines (end-of-search date: 08-June-2020). Individual patient data on overall survival (OS) and recurrence-free survival (RFS) were extracted. Random-effects meta-analyses, and one- and two-stage survival analyses were conducted. RESULTS: Eight retrospective cohort studies comparing LH (n = 544) vs. OH (n = 2256) were identified. LH demonstrated lower overall complication (Risk ratio [RR] = 0.64, 95% confidence interval [CI]: 0.46-0.90; p = 0.01), surgical lymphadenectomy (RR = 0.74, 95% CI: 0.58-0.93; p = 0.01) and margin-positive resection (RR = 0.78, 95% CI: 0.62-0.99; p = 0.04) rates, and higher recurrence-free rate (RR = 1.24, 95% CI: 1.01-1.51; p = 0.04) vs. OH. In Cox regression, no difference was observed regarding OS (Hazard Ratio [HR] = 1.11, 95% CI: 0.65-1.91; p = 0.70) and RFS (HR = 1.19, 95% CI: 0.74-1.90; p = 0.47). CONCLUSION: The use of LH should be considered when feasible in well-selected iCCA patients by hepatobiliary surgeons with experience in minimally-invasive surgery.

Effect of Donor Transaminase Levels on Graft Survival Following Liver Transplant: An Analysis of the Organ Procurement and Transplantation Network Database.

OBJECTIVES: Despite data showing equivalent outcomes between grafts from marginal versus standard criteria deceased liver donors, elevated donor transaminases constitute a frequent reason to decline potential livers. We assessed the effect of donor transaminase levels and other characteristics on graft survival. MATERIALS AND METHODS: We performed a retrospective cohort analysis of adult first deceased donor liver transplant recipients with available transaminase levels registered in the Organ Procurement and Transplantation Network database (2008-2018). We used Cox proportional hazards regression to determine the effects of donor characteristics on graft survival. RESULTS: Of 53 913 liver transplants, 52 158 were allografts from donors with low transaminases (≤ 500 U/L; group A) and 1755 were from donors with elevated transaminases (> 500 U/L; group B). Group A recipients were more likely to be hospitalized (P = .01) or in intensive care (P < .001) or to have mechanical assistance (P < .001), portal vein thrombosis (P = .01), diabetes mellitus (P = .003), or dialysis the week before liver transplant (P = .004). Multivariable analysis (controlling for recipient characteristics) showed donor risk factors of graft failure included diabetes mellitus (P < .001), donation after cardiac death (P < .001), total bilirubin > 3.5 mg/dL (P < .001), serum creatinine > 1.5 mg/dL (P = .01), and cold ischemia time > 6 hours (P < .001). Regional organ sharing showed lower risk of graft failure (P = .02). Donor transaminases > 500 U/L were not associated with graft failure (relative risk, 1.02; 95% CI, 0.91-1.14; P = .74). CONCLUSIONS: Donor transaminases > 500 U/L should not preclude the use of liver grafts. Instead, donor total bilirubin > 3.5 mg/dL and serum creatinine > 1.5 mg/dL appear to be associated with higher likelihood of graft failure after liver transplant.

Liver Transplantation for Langerhans Cell Histiocytosis: A US Population-Based Analysis and Systematic Review of the Literature.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. Liver involvement is seen in 10.1% to 19.8% of patients with LCH and can lead to secondary sclerosing cholangitis requiring liver transplantation (LT). We describe the characteristics and outcomes of patients undergoing LT for LCH. All patients undergoing a first LT for LCH in the United States were identified in the Scientific Registry of Transplant Recipients (SRTR) database (1987-2018). The Kaplan-Meier curve method and log-rank tests evaluated post-LT survival. A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A total of 60 LCH LT recipients were identified in the SRTR, and 55 patients (91.7%) were children with median total bilirubin levels at LT of 5.8 mg/dL (interquartile range [IQR], 2.7-12.9). A total of 49 patients (81.7%) underwent deceased donor LT (DDLT). The 1-year, 3-year, and 5-year patient survival rates were 86.6%, 82.4%, and 82.4%, respectively. The systematic review yielded 26 articles reporting on 50 patients. Of the patients, 41 were children (82.0%), 90.0% had multisystem LCH, and most patients underwent DDLT (91.9%; n = 34/37). Pre-LT chemotherapy was administered in 74.0% and steroids in 71.7% (n = 33/46) of the patients, and a recurrence of LCH to the liver was reported in 8.0% of the patients. Of the 50 patients, 11 (22.0%) died during a median follow-up of 25.2 months (IQR, 9.0-51.6), and the 1-year patient survival rate was 79.4%. LT can be considered as a feasible life-saving option for the management of liver failure secondary to LCH in well-selected patients.

Machine Perfusion Decreases Delayed Graft Function in Donor Grafts With High Kidney Donor Profile Index.

OBJECTIVES: Kidney transplant is the optimal treatment for patients with end-stage renal disease. The effects of using machine perfusion for donor kidneys with varying Kidney Donor Profile Index scores are unknown. We sought to assess the impact of machine perfusion on the incidence of delayed graft function in different score groups of kidney grafts classified with the Kidney Donor Profile Index. MATERIALS AND METHODS: We conducted a retrospective analysis from January 2008 through September 2017 of adult recipients (≥ 18 years old) undergoing kidney-only transplant from deceased donors. All transplant recipients were followed until December 2017. Recipients who received multiorgan transplants or kidneys from living donors were excluded from our analyses. Recipients were divided according to 5 donor categories of Kidney Donor Profile Index scores (0-20, 21-40, 41-60, 61-80, and 81-100). Logistic regression analysis was performed for each score group to determine the effects of machine perfusion on development of delayed graft function within each score group. RESULTS: Our study included 101222 recipients who met the inclusion criteria. Multivariate analysis revealed that machine perfusion was associated with significantly decreased development of delayed graft function only in donors with high-risk profiles: the 61 to 80 score group (odds ratio = 0.83; confidence interval, 0.78-0.89) and the 81 to 100 score group (odds ratio = 0.72; confidence interval, 0.67-0.78). CONCLUSIONS: Machine perfusion is beneficial in reducing delayed graft function only in donor kidneys with a higher risk profile.

Liver Transplantation for Intrahepatic Cholangiocarcinoma: A Meta-analysis and Meta-regression of Survival Rates.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a contraindication to liver transplantation in most centers worldwide. Therefore, only a few such cases have been performed in each individual center, and the need for a systematic review and meta-analysis to cumulatively pool these results is apparent. METHODS: A systematic literature review was conducted using the MEDLINE and Cochrane Library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (end-of-search date: May 29, 2020). Meta-analyses of proportions were conducted to pool the overall survival (OS), recurrence-free survival (RFS), and overall recurrence rates using the random-effects model. Meta-regression was used to examine cirrhosis and incidental diagnosis as confounders on OS and RFS. RESULTS: Eighteen studies comprising 355 patients and a registry study of 385 patients were included. The pooled 1-, 3-, and 5-y OS rates were 75% (95% CI, 64%-84%), 56% (95% CI, 46%-67%), and 42% (95% CI, 29%-55%), respectively. The pooled 1-, 3-, and 5-y RFS rates were 70% (95% CI, 63%-75%), 49% (95% CI, 41%-57%), and 38% (95% CI, 27%-50%), respectively. Cirrhosis was positively associated with RFS, while incidental diagnosis was not. Neither cirrhosis nor incidental diagnosis was associated with OS. The pooled overall recurrence rate was 43% (95% CI, 33%-53%) over a mean follow-up of 40.6 ± 37.7 mo. Patients with very early (single ≤2 cm) iCCA exhibited superior pooled 5-y RFS (67%; 95% CI, 47%-86%) versus advanced iCCA (34%; 95% CI, 23%-46%). CONCLUSIONS: Cirrhotics with very early iCCA or carefully selected patients with advanced iCCA after neoadjuvant therapy may benefit from liver transplantation under research protocols.

Comparison of Wait-List Mortality Between Cholangiocarcinoma and Hepatocellular Carcinoma Liver Transplant Candidates.

Despite the divergent disease biology of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC), wait-list prioritization is identical for both diagnoses. We compared wait-list and posttransplant outcomes between CCA and HCC liver transplantation patients with Model for End-Stage Liver Disease exceptions using Scientific Registry of Transplant Recipients data. The 408 CCA candidates listed between 2003 and mid-2017 were matched to 2 HCC cohorts by listing date (±2 months, n = 816) and by Organ Procurement and Transplantation Network (OPTN) region and date (±6 months, n = 408). Cumulative incidence competing risk regression examined the effects of diagnosis, OPTN region, and center-level CCA listing volume on wait-list removal due to death/being too ill (dropout). Cox models evaluated the effects of diagnosis, OPTN region, center-level CCA volume, and waiting time on graft failure among deceased donor liver transplantation (DDLT) recipients. After adjusting for OPTN region and CCA listing volume (all P ≥ 0.07), both HCC cohorts had a reduced likelihood of wait-list dropout compared with CCA candidates (HCC with period matching only: subdistribution hazard ratio [SHR] = 0.63; 95% CI, 0.43-0.93; P = 0.02 and HCC with OPTN region and period matching: SHR = 0.60; 95% CI, 0.41-0.87; P = 0.007). The cumulative incidence rates of wait-list dropout at 6 and 12 months were 13.2% (95% CI, 10.0%-17.0%) and 23.9% (95% CI, 20.0%-29.0%) for CCA candidates, 7.3% (95% CI, 5.0%-10.0%) and 12.7% (95% CI, 10.0%-17.0%) for HCC candidates with region and listing date matching, and 7.1% (95% CI, 5.0%-9.0%) and 12.6% (95% CI, 10.0%-15.0%) for HCC candidates with listing date matching only. Additionally, HCC DDLT recipients had a 57% reduced risk of graft failure compared with CCA recipients (P < 0.001). Waiting time was unrelated to graft failure (P = 0.57), and there was no waiting time by diagnosis cohort interaction effect (P = 0.47). When identically prioritized, LT candidates with CCA have increased wait-list dropout compared with those with HCC. More granular data are necessary to discern ways to mitigate this wait-list disadvantage and improve survival for patients with CCA.

Population-Based Analysis of Hepatocellular Carcinoma in Children: Identifying Optimal Surgical Treatment.

BACKGROUND: Hepatocellular carcinoma (HCC) constitutes 0.5% of childhood malignancies and exhibits poor prognosis. Complete tumor extirpation either by partial liver resection (LR) or liver transplantation (LT) is the only curative treatment. Due to the poor initial outcomes of LT, LR has remained the mainstay of treatment for all but select children fulfilling the Milan criteria (originally designed for adults). METHODS: We conducted a retrospective cohort study of pediatric HCC patients (younger than 18 years of age) registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Survival analysis was performed by means of Kaplan-Meier methods, 2-sided stratified log-rank tests, and Cox regression models. RESULTS: Of 127 children with HCC, 46 did not undergo operation (36.2%), 32 underwent LT (25.2%), and 49 underwent LR (38.6%). Using the Kaplan-Meier method, the 5-year cancer-specific survival (CSS) rates for LT and LR were 87% and 63%, respectively. LT exhibited superior CSS vs LR (log-rank, p = 0.007). For T1 stage, LT showed equivalent CSS compared with LR (log-rank, p = 0.23), and for T2 and T3 stage, LT exhibited superior CSS (log-rank, p = 0.047 and p = 0.01, respectively). On multivariable Cox regression analysis, T3/T4 stage (adjusted hazard ratio 13.63; 95% CI, 2.9 to 64.07; p = 0.001), and LR (adjusted hazard ratio 7.51; 95% CI, 2.07 to 27.29; p = 0.002) were found to be independently associated with cancer-specific mortality. Fibrolamellar histology and lymph node status were not found to be associated with mortality. CONCLUSIONS: Our findings suggest that children diagnosed with nonmetastatic advanced-stage HCC have a favorable prognosis after LT compared with LR. Early inclusion of an LT consultation after the initial diagnosis is warranted, especially in children with unresectable HCC or when complete tumor extirpation with LR is not feasible.

Living vs deceased donor liver transplantation in cholestatic liver disease: An analysis of the OPTN database.

BACKGROUND: Living donor liver transplantation (LDLT) and donation after circulatory death (DCD) can expand the donor pool for cholestatic liver disease (CLD) patients. We sought to compare the outcomes of deceased donor liver transplant (DDLT) vs LDLT in CLD patients. METHODS: Retrospective cohort analysis of adult CLD recipients registered in the OPTN database who received primary LT between 2002 and 2018. Cox proportional hazards regression models with mixed effects were used to determine the impact of graft type on patient and graft survival. RESULTS: Five thousand, nine hundred ninety-nine DDLT (5730 donation after brain death [DBD], 269 DCD) and 912 LDLT recipients were identified. Ten-year patient/graft survival rates were DBD: 73.8%/67.9%, DCD: 74.7%/60.7%, and LDLT: 82.5%/73.9%. Higher rates of biliary complications as a cause of graft failure were seen in DCD (56.8%) than LDLT (30.5%) or DBD (18.7%) recipients. On multivariable analysis, graft type was not associated with patient mortality, while DCD was independently associated with graft failure (P = .046). CONCLUSION: DBD, DCD, and LDLT were associated with comparable overall patient survival. No difference in the risk of graft failure could be observed between LDLT and DBD. DCD can be an acceptable alternative to DBD with equivalent patient survival, but inferior graft survival likely related to the high rate of biliary complications.

New Evidence Supporting Increased Use of Split Liver Transplantation.

BACKGROUND: Young children and small-statured candidates are dying on liver candidate waitlists. The Organ Procurement and Transplantation Network and United Network for Organ Sharing have proposed a split liver (SL) variance encouraging transplant programs to split more livers to aid these smaller statured candidates. METHODS: We evaluated the US experience of splitting donor livers during 2002-2016. The results of our analysis provide new evidence to support this variance. RESULTS: During 2002-2016, SL grafts from 935 donors were transplanted into 1870 recipients. Controlling for recipient factors and using time period and program identification as random variables, a multivariable mixed Cox proportional hazards model for graft failure revealed that donor aged 3-10 years had a relative risk (RR) of 3.94 (2.86-5.44), and donor aged >30 years had a RR of 1.94 (1.59-2.35) for graft failure. Donor-to-recipient body surface area ratio <0.90 had a RR of 1.40 (1.13-1.75). Programs with experience transplanting <23 SLs had a RR of 1.43 (1.21-1.75). The same program transplanting both split segments had a RR of 1.38 (1.20-1.59). CONCLUSIONS: Splitting protocols based on these findings could improve graft survival after SL transplantation, which would encourage programs to opt into splitting more livers. The new protocols may consider donor age restrictions, necessary program experience, donor with body surface area appropriate for recipient, and improved logistical factors to share segments between transplant programs. The result would likely be a drastic reduction in liver waitlist deaths for young children and small-statured candidates.

Living Donation Versus Donation After Circulatory Death Liver Transplantation for Low Model for End-Stage Liver Disease Recipients.

In this era of organ scarcity, living donor liver transplantation (LDLT) is an alternative to using deceased donors, and in Western countries, it is more often used for recipients with low Model for End-Stage Liver Disease (MELD) scores. We sought to compare the patient survival and graft survival between recipients of liver transplantation from living donors and donation after circulatory death (DCD) donors in patients with low MELD scores. This is a retrospective cohort analysis of adult liver transplant recipients with a laboratory MELD of ≤20 who underwent transplantation between January 1, 2003 and March 31, 2016. Recipients were categorized by donor graft type (DCD or LDLT), and recipient and donor characteristics were compared. Ten-year patient and graft survival curves were calculated using Kaplan-Meier analyses, and a mixed-effects model was performed to determine the contributions of recipient, donor, and center variables on patient and graft survival. There were 36,705 liver transplants performed: 32,255 (87.9%) from DBD donors, 2166 (5.9%) from DCD donors, and 2284 (6.2%) from living donors. In the mixed-effects model, DCD status was associated with a higher risk of graft failure (relative risk [RR], 1.27; 95% confidence interval [CI], 1.16-1.38) but not worse patient survival (RR, 1.27; 95% CI, 0.96-1.67). Lower DCD center experience was associated with a 1.21 higher risk of patient death (95% CI, 1.17-1.25) and a 1.13 higher risk of graft failure (95% CI, 1.12-1.15). LDLT center experience was also predictive of patient survival (RR, 1.03; 95% CI, 1.02-1.03) and graft failure (RR, 1.05; 95% CI, 1.05-1.06). In conclusion, for liver transplant recipients with low laboratory MELD, LDLT offers better graft survival and a tendency to better patient survival than DCD donors.

Living liver donation improves patient and graft survival in the pediatric population.

BACKGROUND: The utilization of living donor grafts resulted in an increased availability of liver for pediatric recipients, and accordingly, this was associated with a significantly decreased waiting time before liver transplantation as well as reduced pre-transplant mortality. We hypothesized that the use of living donors in pediatric LT may lead to improved graft and patient survival, when compared to LT using deceased donors. METHODS: Retrospective cohort analysis of pediatric recipients (aged <18 years) registered in the UNOS database who received a primary liver transplant between February 2002 and December 2016. Covariates predictive of survival by multivariable analyses were included in the Cox proportional hazards regression models to determine predictors of patient and graft survival. RESULTS: A total of 6312 children received a primary LT from a LD (n = 800) or a deceased donor (n = 5517; partial graft n = 1784 and whole graft n = 3733). Vascular and biliary complications were similar. Kaplan-Meier graft and patient survival rates were superior in LD recipients compared with recipients of deceased whole and reduced graft (Figures 1 and 2). In the multivariable analysis, LD were an independent predictor of improved patient and graft survival. CONCLUSION: The use of LD in children is associated with improved patient and graft survival. The option of LD should be introduced early on in the evaluation of every pediatric patient being evaluated for liver transplant.