Comparison of the effects of normothermic machine perfusion and cold storage preservation on porcine intestinal allograft regenerative potential and viability.

Intestinal transplantation (IT) is the final treatment option for intestinal failure. Static cold storage (CS) is the standard preservation method used for intestinal allografts. However, CS and subsequent transplantation induce ischemia-reperfusion injury (IRI). Severe IRI impairs epithelial barrier function, including loss of intestinal stem cells (ISC), critical to epithelial regeneration. Normothermic machine perfusion (NMP) preservation of kidney and liver allografts minimizes CS-associated IRI; however, it has not been used clinically for IT. We hypothesized that intestine NMP would induce less epithelial injury and better protect the intestine's regenerative ability when compared with CS. Full-length porcine jejunum and ileum were procured, stored at 4 °C, or perfused at 34 °C for 6 hours (T6), and transplanted. Histology was assessed following procurement (T0), T6, and 1 hour after reperfusion. Real-time quantitative reverse transcription polymerase chain reaction, immunofluorescence, and crypt culture measured ISC viability and proliferative potential. A greater number of NMP-preserved intestine recipients survived posttransplant, which correlated with significantly decreased tissue injury following 1-hour reperfusion in NMP compared with CS samples. Additionally, ISC gene expression, spheroid area, and cellular proliferation were significantly increased in NMP-T6 compared with CS-T6 intestine. NMP appears to reduce IRI and improve graft regeneration with improved ISC viability and proliferation.

Hepatic Resection as the Primary Treatment Method for Hepatocellular Carcinoma After Orthotopic Liver Transplantation.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for end-stage liver disease and certain malignancies such as hepatocellular carcinoma (HCC). Data on the surgical management of de novo or recurrent tumors that develop in the transplanted allograft are limited. This study aimed to investigate the perioperative and long-term outcomes for patients undergoing hepatic resection for de novo or recurrent tumors after liver transplantation. METHODS: The study enrolled adult and pediatric patients from 12 centers across North America who underwent hepatic resection for the treatment of a solid tumor after LT. Perioperative outcomes were assessed as well as recurrence free survival (RFS) and overall survival (OS) for those undergoing resection for HCC. RESULTS: Between 2003 and 2023, 54 patients underwent hepatic resection of solid tumors after LT. For 50 patients (92.6 %), resection of malignant lesions was performed. The most common lesion was HCC (n = 35, 64.8 %), followed by cholangiocarcinoma (n = 6, 11.1 %) and colorectal liver metastases (n = 6, 11.1 %). The majority of the 35 patients underwent resection of HCC did not receive any preoperative therapy (82.9 %) or adjuvant therapy (71.4 %), with resection their only treatment method for HCC. During a median follow-up period of 50.7 months, the median RFS was 21.5 months, and the median OS was 49.6 months. CONCLUSION: Hepatic resection following OLT is safe and associated with morbidity and mortality rates that are comparable to those reported for patients undergoing resection in native livers. Hepatic resection as the primary and often only treatment modality for HCC following LT is associated with acceptable RFS and OS and should be considered in well selected patients.

Racial Disparities in Liver Transplant for Hepatitis C-Associated Hepatocellular Carcinoma.

BACKGROUND: In the United States, hepatitis C virus-associated hepatocellular carcinoma incidence and mortality are highest among minorities. Socioeconomic constraints play a major role in inequitable treatment. We evaluated the association between race/ethnicity and outcomes in a population that overcame treatment barriers. METHODS: We report a retrospective cohort study of 666 patients across 20 institutions in the United States Hepatocellular Carcinoma Liver Transplantation Consortium from 2015 to 2019 with hepatitis C virus-associated hepatocellular carcinoma who completed direct-acting antiviral therapy and underwent liver transplantation. Patients were excluded if they had a prior liver transplantation, hepatocellular carcinoma recurrence, no prior liver-directed therapy, or if race/ethnicity data were unavailable. Patients were stratified by race/ethnicity. Primary outcomes were recurrence-free survival and overall survival, and secondary outcome was major postoperative complication. RESULTS: Race/ethnicity was not associated with differences in 5-year recurrence-free survival (White 90%, Black 88%, Hispanic 92%, Other 87%; p = 0.85), overall survival (White 85%, Black 84%, Hispanic 84%, Other 93%; p = 0.70), or major postoperative complication. CONCLUSIONS: Race/ethnicity was not associated with worse oncologic or postoperative outcomes among those who completed direct-acting antiviral therapy and underwent liver transplantation, suggesting that overcoming socioeconomic constraints equalizes outcomes across racial/ethnic groups. Eliminating barriers that prohibit care access among minorities must be a priority.

Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium.

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.

Development and validation of a REcurrent Liver cAncer Prediction ScorE (RELAPSE) following liver transplantation in patients with hepatocellular carcinoma: Analysis of the US Multicenter HCC Transplant Consortium.

HCC recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need. Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (Random Survival Forest and Classification and Regression Tree models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant study group. Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria, 16.1% were initially beyond Milan criteria with 9.4% downstaged before LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1, 3, and 5 years was 89.7%, 78.6%, and 69.8% and 86.8%, 74.9%, and 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 months) and non-HCC mortality of 20.8%. A multivariable model identified maximum alpha-fetoprotein (HR = 1.35 per-log SD, 95% CI,1.22-1.50, p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95% CI,1.04-1.28, p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95% CI, 1.35-1.73, p < 0.001), microvascular (HR = 2.37, 95%-CI, 1.87-2.99, p < 0.001) and macrovascular (HR = 3.38, 95% CI, 2.41-4.75, p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95% CI, 1.29-2.37, p < 0.001; poor HR = 2.62, 95% CI, 1.54-3.32, p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). Machine learning algorithms incorporating additional covariates improved prediction of recurrence (Random Survival Forest C-statistic = 0.81). Despite significant differences in European Hepatocellular Cancer Liver Transplant recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2- and 5-year recurrence risk discrimination (AUCs 0.77 and 0.75, respectively). We developed and externally validated a RELAPSE score that accurately discriminates post-LT HCC recurrence risk and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.

An appraisal of technical variant grafts compared to whole liver grafts in pediatric liver transplant recipients: Multicenter analysis from the SPLIT registry.

BACKGROUND: Shortages of liver allografts for children awaiting transplantation have led to high LT waitlist mortality. Prior studies have shown that usage of TVG can reduce waiting time and waitlist mortality, but their use is not universal. We sought to compare patient and graft survival between WLG and TVG and to identify potential associated risk factors in a contemporary pediatric LT cohort. METHODS: We performed a retrospective analysis of patient survival, graft survival, and biliary and vascular complications for LT recipients <18 years old entered into the Society of Pediatric Liver Transplantation prospective multicenter database. RESULTS: Of 1839 LT recipients, 1029 received a WLG and 810 received a TVG from either a LD or a DD. There was no difference in patient survival or graft survival by graft type. Three-year patient survival and graft survival were 96%, 93%, and 96%, and 95%, 89%, and 92% for TVG-LD, TVG-DD, and WLG, respectively. Biliary complications were more frequent in TVG. Hepatic artery thrombosis was more frequent in WLG. Multivariate analysis revealed primary diagnosis was the only significant predictor of patient survival. Predictors for graft survival included time-dependent development of biliary and vascular complications. CONCLUSIONS: There were no significant differences in patient and graft survival based on graft types in this North American multi-center pediatric cohort. Widespread routine use of TVG should be strongly encouraged to decrease mortality on the waitlist for pediatric LT candidates.

Epidemiology of surgical site infections after solid organ transplants in the period 2015-2019: A single-center retrospective cohort study.

Surgical site infections (SSI) are severe complications of solid organ transplant (SOT). This retrospective study assessed the epidemiology of and outcomes associated with invasive primary SSI (IP-SSI) occurring within 3 months of transplantation in adult SOT recipients at Duke University over a 5-year period (2015-2019). Among 2073 consecutive SOT recipients, 198 IP-SSI were identified. The IP-SSI rate declined over the period (14.4% in 2015 vs. 8.3% in 2019) and was higher among multi-organ compared with single-organ transplants (33.9% vs. 8.1%, p < .01). SOT recipients with IP-SSI had longer hospital stays than patients without SSI (30.0 vs. 17.0 days, p < .01). Transplant hospitalization (9.6% vs. 2.2%, p < .01), 6-month (11.6% vs. 3.3%, p < .01), and 1-year mortality (15.7% vs. 5.8%, p < .01) were higher in SOT recipients with IP-SSI than in those without. While Gram-positive bacteria were the most common pathogens, urogenital Mollicute and atypical Mycobacteria were identified as an unexpected cause of IP-SSI, particularly among lung transplant recipients. The median time to IP-SSI was 24.0 (IQR 13.8-48.3) days, although the time to IP-SSI varied based on organ transplanted and the causative pathogen. IP-SSI is an important and potentially modifiable complication of SOT, associated with prolonged hospitalizations and reduced survival, particularly in the lung transplant population.

Surgical complications after living and deceased donor liver transplant: The NSQIP transplant experience.

This study used the prospective National Surgical Quality Improvement Program (NSQIP) Transplant pilot database to analyze surgical complications after liver transplantation (LT) in LT recipients from 2017to 2019. The primary outcome was surgical complication requiring intervention (Clavien-Dindo grade II or greater) within 90 days of transplant. Of the 1684 deceased donor and 109 living donor LT cases included from 29 centers, 38% of deceased donor liver recipients and 47% of living donor liver recipients experienced a complication. The most common complications included biliary complications (19% DDLT; 31% LDLT), hemorrhage requiring reoperation (14% DDLT; 9% LDLT), and vascular complications (6% DDLT; 9% LDLT). Management of biliary leaks (35.3% ERCP, 38.0% percutaneous drainage, 26.3% reoperation) and vascular complications (36.2% angioplasty/stenting, 31.2% medication, 29.8% reoperation) was variable. Biliary (aHR 5.14, 95% CI 2.69-9.8, P < .001), hemorrhage (aHR 2.54, 95% CI 1.13-5.7, P = .024) and vascular (aHR 2.88, 95% CI .85-9.7, P = .089) complication status at 30-days post-transplant were associated with lower 1-year patient survival. We conclude that biliary, hemorrhagic and vascular complications continue to be significant sources of morbidity and mortality for LT recipients. Understanding the different risk factors for complications between deceased and living donor liver recipients and standardizing complication management represent avenues for continued improvement.

Need for improvements in simultaneous heart-kidney allocation: The limitation of pretransplant glomerular filtration rate.

The incidence of simultaneous heart-kidney transplant (SHK) has increased markedly in the last 15 years. There are no universally agreed upon indications for SHK vs. heart alone (HA) transplant, and center evaluation processes vary widely. We utilized Scientific Registry of Transplant Recipients data from 2003 to 2017 to quantify changes in the practice of SHK, examine the survival of SHK vs. HA, and identify patients with marginal benefit from SHK. We used Kaplan-Meier curves and Cox proportional hazards to assess differences in survival. The incidence of SHK increased more than fourfold between 2003 and 2017 from 1.6% to 6.6% of total hearts transplanted, while the proportion of dialysis-dependent patients undergoing SHK has remained constant. SHK was associated with increased survival in dialysis-dependent patients (Median Survival SHK: 12.6 vs. HA: 7.1 years p < .0001) but not with nondialysis-dependent patients (Median Survival SHK: 12.5 vs. HA 12.3, p = .24). The marginal effect of SHK in decreasing the hazard of death diminished with increasing eGFR. Delayed graft function occurred in 26% of SHK recipients. Posttransplant chronic dialysis was similar for both operations (6.4% of HA and 6.0% of SHK). Further study is needed to define patients who benefit from SHK.

Transplant social worker and donor financial assistance to increase living donor kidney transplants among African Americans: The TALKS Study, a randomized comparative effectiveness trial.

Lack of donors hinders living donor kidney transplantation (LDKT) for African Americans. We studied the effectiveness of a transplant social worker intervention (TALK SWI) alone or paired with living donor financial assistance to activate African Americans' potential living kidney donors. African Americans (N = 300) on the transplant waiting list were randomly assigned to usual care; TALK SWI; or TALK SWI plus Living Donor Financial Assistance. We quantified differences in live kidney donor activation (composite rate of live donor inquiries, completed new live donor evaluations, or live kidney donation) after 12 months. Participants' mean age was 52 years, 56% were male, and 43% had annual household income less than $40,000. Most previously pursued LDKT. Participants were highly satisfied with TALK social workers, but they rarely utilized Financial Assistance. After 12 months, few (n = 39, 13%) participants had a new donor activation event (35 [12%] new donor inquiries; 17 [6%] new donor evaluations; 4 [1%] LDKT). There were no group differences in donor activation events (subdistribution hazard ratio [95% CI]: 1.09 [0.51-2.30] for TALK SWI and 0.92 [0.42-2.02] for TALK SWI plus Financial Assistance compared to Usual Care, p = 91). Alternative interventions to increase LDKT for African Americans on the waiting list may be needed. Trial registration: ClinicalTrials.gov (NCT02369354).

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

The Impact of the 2017 Kidney Allocation Policy Change on Simultaneous Liver-Kidney Utilization and Outcomes.

Historically in the United States, kidneys for simultaneous liver-kidney transplantation (SLKT) candidates were allocated with livers, prioritizing SLKT recipients over much of the kidney waiting list. A 2017 change in policy delineated renal function criteria for SLKT and implemented a safety net for kidney-after-liver transplantation. We compared the use and outcomes of SLKT and kidney-after-liver transplant with the 2017 policy. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to identify adults who received liver transplantations (LT) from August 10, 2007 to August 10, 2012; from August 11, 2012 to August 10, 2017; and from August 11, 2017 to June 12, 2019. LT recipients with end-stage renal disease (ESRD) were defined by dialysis requirement or estimated glomerular filtration rate <25. We evaluated outcomes and center-level, regional, and national practice before and after the policy change. Nonparametric cumulative incidence of kidney-after-liver listing and transplant were modeled by era. A total of 6332 patients received SLKTs during the study period; fewer patients with glomerular filtration rate (GFR) ≥50 mL/min underwent SLKT over time (5.8%, 4.8%, 3.0%; P = 0.01 ). There was also less variability in GFR at transplant after policy implementation on center and regional levels. We then evaluated LT-alone (LTA) recipients with ESRD (n = 5408 from 2012-2017; n = 2321 after the policy). Listing for a kidney within a year of LT increased from 2.9% before the policy change to 8.8% after the policy change, and the rate of kidney transplantation within 1 year increased from 0.7% to 4% (P < 0.001). After the policy change, there was no difference in patient survival rates between SLKT and LTA among patients with ESRD. Implementation of the 2017 SLKT policy change resulted in reduced variability in SLKT recipient kidney function and increased access to deceased donor kidney transplantation for LTA recipients with kidney disease without negatively affecting outcomes.

Posttransplant Outcomes in Older Patients With Hepatocellular Carcinoma Are Driven by Non-Hepatocellular Carcinoma Factors.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.

Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria.

BACKGROUND AND AIMS: The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013). APPROACH AND RESULTS: Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001). CONCLUSIONS: In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.

Efficacy and safety of mammalian target of rapamycin inhibitors following intestinal and multivisceral transplantation.

This is a descriptive study reviewing the outcomes of mammalian target of rapamycin inhibitors (mTORs) in intestinal (IT) and multivisceral transplantation (MVT). This study included 22 patients, 20 adults, and two children, and an overall mean age of 46 years old at the time of transplantation. Twelve patients (54.5%) received IT, and the remainder (45.5%) MVT. The mean time between transplantation and mTORs initiation was 24 months. The indication was worsening renal function in 13 patients (59%), with 9/13 (69.2%) noted to have an increase in glomerular filtration rate of at least 10 ml/min/1.73m2 . The indication for four patients (18.2%) was a history of neuroendocrine tumor. After mTOR initiation, 50% of patients were reduced or weaned off tacrolimus and 13.7% off prednisone. mTORs were discontinued in 11/22 patients. Six patients (54.5%) stopped due to side effects, two (18.1%) for surgery, and one (9%) for acute cellular rejection. Side effects were edema (33.3%), headaches (33.3%), diarrhea (16.7%), and oral ulcers (16.7%). The average duration of mTORs prior to discontinuation due to side effects was 7 months. mTORs may function in their own niche of patients due to the potential renal safety profile, but use is most limited by tolerance to side effects.

African Americans' discussions about living-donor kidney transplants with family or friends: Who, what, and why not?

BACKGROUND: Although discussions with family or friends can improve access to living-donor kidney transplantation (LDKT), they remain an understudied step in the LDKT process. METHODS: Among 300 African American transplant candidates, we examined how sociodemographic, clinical, LDKT-related, and psychosocial characteristics related to the occurrence of LDKT discussions with family or friends. We also analyzed the relation between discussion occurrence and donor activation on transplant candidates' behalves (at least one donor inquiry or completed donor evaluation in the medical record). We assessed associations of discussion characteristics (context, content, and perceptions) with donor activation among discussants, and we identified discussion barriers among non-discussants. RESULTS: Most candidates (90%) had discussed LDKT. Only family functioning was statistically significantly associated with discussion occurrence. Specifically, family dysfunction was associated with 62% lower odds of discussion than family function. Family functioning, discussion occurrence, and different discussion characteristics were statistically significantly related to donor activation. The most prevalent discussion barrier was never having thought about discussing LDKT. CONCLUSIONS: Family functioning affected the likelihood of discussing LDKT, and family functioning, discussion occurrence, and discussion characteristics were associated with donor activation. Advancing understanding of how family functioning and LDKT discussions affect progression to LDKT may benefit interventions to increase LDKT.

Definition and Analysis of Textbook Outcome: A Novel Quality Measure in Kidney Transplantation.

BACKGROUND: "Textbook outcome" (TO) is a novel composite quality measure that encompasses multiple postoperative endpoints, representing the ideal "textbook" hospitalization for complex surgical procedures. We defined TO for kidney transplantation using a cohort from a high-volume institution. METHODS: Adult patients who underwent isolated kidney transplantation at our institution between 2016 and 2019 were included. TO was defined by clinician consensus at our institution to include freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay > 75th percentile of kidney transplant patients, 90-day mortality, 30-day acute rejection, delayed graft function, and discharge with a Foley catheter. Recipient, operative, financial characteristics, and post-transplant patient, graft, and rejection-free survival were compared between patients who achieved and failed to achieve TO. RESULTS: A total of 557 kidney transplant patients were included. Of those, 245 (44%) achieved TO. The most common reasons for TO failure were delayed graft function (N = 157, 50%) and hospital readmission within 30 days (N = 155, 50%); the least common was mortality within 90 days (N = 6, 2%). Patient, graft, and rejection-free survival were significantly improved among patients who achieved TO. On average, patients who achieved TO incurred approximately $50,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in kidney transplantation was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer transplant centers a detailed performance breakdown to identify aspects of perioperative care in need of process improvement.