Donor-recipient race-ethnicity concordance and patient survival after liver transplantation.

INTRODUCTION: We assessed the association between patient survival after liver transplantation (LT) and donor-recipient race-ethnicity (R/E) concordance. METHODS: The Scientific Registry of Transplant Recipients (SRTR) was retrospectively analyzed using data collected between 2002 and 2019. Only adults without history of prior organ transplant and recipients of LT alone were included. The primary outcome was patient survival. Donors and recipients were categorized into five R/E groups: White/Caucasian, African American/Black, Hispanic/Latino, Asian, and Others. Statistical analyses were performed using Kaplan-Meier survival curves and Cox Proportional Hazards models, adjusting for donor and recipient covariates. RESULTS: 85,427 patients were included. Among all the R/E groups, Asian patients had the highest 5-year survival (81.3%; 95% CI = 79.9-82.7), while African American/Black patients had the lowest (71.4%; 95% CI = 70.3-72.6) (P < 0.001). Lower survival rates were observed in recipients who received discordant R/E grafts irrespective of their R/E group. The fully adjusted hazard ratio for death was statistically significant in African American/Black (aHR 1.07-1.18-1.31; P < 0.01) and in White∕Caucasian patients (aHR 1.00-1.04-1.07; P = 0.03) in the presence of donor-recipient R/E discordance. CONCLUSION: Disparities in post-LT outcomes might be influenced by biological factors in addition to well-known social determinants of health.

Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.

An evaluation of the safety and preliminary efficacy of peri- and post-operative treprostinil in preventing ischemia and reperfusion injury in adult orthotopic liver transplant recipients.

BACKGROUND: Orthotopic liver transplantation (OLT) is the only treatment option for various end-stage liver diseases. Ischemia and reperfusion (I/R) injury is one of the unavoidable complications/conditions in OLT. In 2019, a total of 8896 livers were transplanted of which >94% organs were procured from deceased donors. An increase in the use of extended criteria donor (ECD) livers for transplantation further unraveled the role of hepatic I/R injury on short-term and long-term graft outcomes. Despite promising outcomes with the use of antioxidants, free radical scavengers, and vasodilators; I/R-mediated liver injury persists and significantly influences the overall clinical outcomes. Treprostinil, a synthetic prostacyclin I2  (PGI2 ) analog, due to its vasodilatory property, antiplatelet activity, and its ability to downregulate pro-inflammatory cytokines can potentially minimize I/R injury. AIM: We investigated the safety and preliminary efficacy of continuous intravenous infusion of treprostinil in liver transplant recipients in a prospective, single-center, non-randomized, interventional study. MATERIAL AND METHODS: This was a dose escalation (3 + 3 design) phase 1/2 study. Deceased donor liver transplant recipients received 5 ng/kg/min for two days, or 2.5, 5, and 7.5 ng/min/kg for 5 days as a continuous infusion. Multiple blood samples were collected for biochemical parameter assessment and for measuring treprostinil levels. Indocyanine green plasma disappearance rate was used as a measure of hepatic functional capacity. RESULTS: Subjects tolerated continuous infusion of treprostinil up to 5 ng/kg/min for 120 h with no occurrence of primary graft non-function (PNF), minimized need for ventilation support, reduced hospitalization time, 100% graft and patient survival, and improved hepatobiliary excretory function comparable to normal healthy adults. DISCUSSION: Treprostinil can be administered to liver transplant patients safely during the perioperative period. CONCLUSION: Based on this phase 1/2 study, further efficacy studies of treprostinil in preventing I/R injury of liver should be conducted to potentially increase the number of livers available for transplantation.

Portal vein thrombosis and renal dysfunction: a national comparative study of liver transplant recipients for NAFLD versus alcoholic cirrhosis.

The prevalence of portal vein thrombosis (PVT), renal dysfunction (RD), and simultaneous PVT/RD in liver transplantation (LT) is poorly understood. We analyzed the prevalence of PVT, RD, simultaneous PVT/RD, and the outcomes of adult recipients of LT for nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) between 2006 and 2016 in the United States. We found that the prevalence of PVT (7.2% â†’ 11.3%), RD (33.8% â†’ 39.2%), and simultaneous PVT/RD (2.4% â†’ 4.5%) has increased significantly over the study period (all P-values <0.05). NAFLD patients had a higher proportion of PVT (14.8% vs. 9.2%), RD (45.0% vs. 42.1%), and simultaneous PVT/RD (6.5% vs. 3.9%; all P-values <0.05). 90-day mortality was 3.8%, 6.3%, 6.8%, and 9.8% for PVT(-)/RD(-), PVT(-)/RD(+), PVT(+)/RD(-), and PVT(+)/RD(+) recipients, respectively (P < 0.01). 5-year survival was 82.1%, 75.5%, 74.8%, and 71.1% for PVT(-)/RD(-), PVT(-)/RD(+), PVT(+)/RD(-), and PVT(+)/RD(+) recipients, respectively (P < 0.05). In conclusion, the prevalence of PVT, RD, and simultaneous PVT/RD has increased among LT recipients, especially for those with NAFLD. The short- and long-term outcomes of recipients with PVT, RD, and simultaneous PVT/RD were inferior to patients without those risk factors irrespective of their indication for LT. No differences in patient outcomes were found between ALD and NAFLD recipients after stratification by risk factors.

Hepatic Resection for Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of 7226 Patients.

Objective: To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with nonalcoholic fatty liver disease (NAFLD) versus other risk factors. Background: Different clinical and tumor characteristics are associated with HCC in the setting of NAFLD in comparison to other risk factors. It is still unclear whether these differences impact patient survival after radical hepatectomies. Methods: Randomized controlled trials and observational studies published in the English literature between July 1980 and June 2020 were searched using multiple databases. Patients' baseline characteristics and the hazard ratios (HRs) of the OS and DFS were extracted and meta-analyses were performed. Results: Fifteen retrospective cohort studies with a total of 7226 patients were included. Among them, 1412 patients (19.5%) had NAFLD and 5814 (80.4%) had other risk factors (eg, viral hepatitis B or C, alcoholic cirrhosis, or cryptogenic cirrhosis). Summary statistics showed that patients with NAFLD had better DFS (HR = 0.81; 95% CI: 0.70-0.94; P = 0.006) and OS (HR = 0.78; 95% CI: 0.67-0.90; P = 0.001) than the control group. Subgroups analyses also indicated that the OS favored NAFLD patients versus patients with viral hepatitis B or C (HR = 0.80; 95% CI: 0.67-0.96; P = 0.017) or alcoholic and cryptogenic cirrhosis (HR = 0.68; 95% CI: 0.47-1.0; P = 0.05). Conclusion: After hepatic resections for HCC, NAFLD patients have better DFS and OS than patients with other risk factors. Subgroup analysis and meta-regression suggested that the survival advantage of NAFLD patients was more pronounced in studies published after 2015 and from Asian centers.

The liver transplant risk score prognosticates the outcomes of liver transplant recipients at listing.

BACKGROUND: We assessed if the risk of post-liver transplant mortality within 24 h could be stratified at the time of listing using the liver transplant risk score (LTRS). Secondary aims were to assess if the LTRS could stratify the risk of 30-day, 1-year mortality, and survival beyond the first year. METHODS: MELD, BMI, age, diabetes, and the need for dialysis were the five variables used to calculate the LTRS during patients' evaluation for liver transplantation. Mortality rates at 24 h, 30 days, and 1-year were compared among groups of patients with different LTRS. Patients with ABO-incompatibility, redo, multivisceral, partial graft and malignancies except for hepatocellular carcinoma were excluded. Data of 48,616 adult liver transplant recipients were extracted from the Scientific Registry of Transplant Recipients between 2002 and 2017. RESULTS: 24-h mortality was 0.9%, 1.0%, 1.1%, 1.7%, 2.3%, 2.0% and 3.5% for patients with LTRS of 0,1,2,3,4, 5 and ≥ 6, respectively (P < 0.001). 30-day mortality was 3.5%, 4.2%, 4.9%, 6.2%, 7.6%, 7.2% and 10.1% respectively (P < 0.001). 1-year mortality was 8.6%, 10.8%, 12.9%, 13.9%, 18.5%, 20.3% and 28.6% respectively (P < 0.001). 10-year survival was 61%, 56%, 57%, 54%, 47%, and 31% for patients with 0, 1, 2, 3, 4, 5 and ≥ 6 points respectively (P < 0.001). CONCLUSION: Perioperative mortality and long-term survival of patients undergoing LT can be accurately estimated at the time of listing by the LTRS.

Preoperative Stratification of Liver Transplant Recipients: Validation of the LTRS.

BACKGROUND: The liver transplant risk score (LTRS) was developed to stratify 90-day mortality of patients referred for liver transplantation (LT). We aimed to validate the LTRS using a new cohort of patients. METHODS: The LTRS stratifies the risk of 90-day mortality of LT recipients based on their age, body mass index, diabetes, model for end-stage liver disease (MELD) score, and need for dialysis. We assessed the performance of the LTRS using a new cohort of patients transplanted in the United States between July 2013 and June 2017. Exclusion criteria were age <18 years, ABO incompatibility, redo or multivisceral transplants, partial grafts, malignancies other than hepatocellular carcinoma and fulminant hepatitis. RESULTS: We found a linear correlation between the number of points of the LTRS and 90-day mortality. Among 18 635 recipients, 90-day mortality was 2.7%, 3.8%, 5.2%, 4.8%, 6.7%, and 9.3% for recipients with 0, 1, 2, 3, 4, and ≥5 points (P < 0.001). The LTRS also stratified 1-year mortality that was 5.5%, 7.7%, 9.9%, 9.3%, 10.8%, and 15.4% for 0, 1, 2, 3, 4, and ≥5 points (P < 0.001). An inverse correlation was found between the LTRS and 4-year survival that was 82%, 79%, 78%, 82%, 78%, and 66% for patients with 0, 1, 2, 3, 4, and ≥5 points (P < 0.001). The LTRS remained an independent predictor after accounting for recipient sex, ethnicity, cause of liver disease, donor age, cold ischemia time, and waiting time. CONCLUSIONS: The LTRS can stratify the short- and long-term outcomes of LT recipients at the time of their evaluations irrespective of their gender, ethnicity, and primary cause of liver disease.