Short recipient warm ischemia time improves outcomes in deceased donor liver transplantation

While adverse effects of prolonged recipient warm ischemia time (rWIT) in liver transplantation (LT) have been well investigated, few studies have focused on possible positive prognostic effects of short rWIT. We aim to investigate if shortening rWIT can further improve outcomes in donation after brain death liver transplant (DBD-LT). Primary DBD-LT between 2000 and 2019 were retrospectively reviewed. Patients were divided according to rWIT (≤30, 31-40, 41-50, and \u3e50 min). The requirement of intraoperative transfusion, early allograft dysfunction (EAD), and graft survival were compared between the rWIT groups. A total of 1,256 patients of DBD-LTs were eligible. rWIT was ≤30min in 203 patients (15.7%), 31-40min in 465 patients (37.3%), 41-50min in 353 patients (28.1%), and \u3e50min in 240 patients (19.1%). There were significant increasing trends of transfusion requirement (P \u3c 0.001) and increased estimated blood loss (EBL, P \u3c 0.001), and higher lactate level (P \u3c 0.001) with prolongation of rWIT. Multivariable logistic regression demonstrated the lowest risk of EAD in the WIT ≤30min group. After risk adjustment, patients with rWIT ≤30 min showed a significantly lower risk of graft loss at 1 and 5-years, compared to other groups. The positive prognostic impact of rWIT ≤30min was more prominent when cold ischemia time exceeded 6 h. In conclusion, shorter rWIT in DBD-LT provided significantly better post-transplant outcomes

Disease-specific waitlist outcomes in liver transplantation - a retrospective study

This study aimed to evaluate possible discrepancies in waitlist outcomes between liver diseases, including alcohol-related liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis C virus infection (HCV), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). Patients registered for liver transplantation from January 11, 2016, to June 30, 2018, were evaluated using OPTN/UNOS registry. Waitlist outcomes were compared between the five-disease groups. Patients were categorized by initial MELD-Na-score (6-20, 21-29, and ≥30) to identify outcome variations. Prognostic impact of transplantation was assessed according to final MELD-Na scores using Cox regression analysis modeling transplantation as a time-dependent covariate. 6053 with ALD, 3814 with NASH, 1558 with HCV, 602 with PBC, and 819 with PSC were eligible. Compared to ALD with comparable MELD-Na-scores, NASH with lower [adjusted hazard ratio (aHR) = 1.30, P = 0.042] and mid-scores (aHR = 1.35, P = 0.008) showed significantly higher risk of 1-year waitlist mortality, and PBC with higher scores showed significantly higher risk of 90-day (aHR = 1.69, P = 0.03) and 1-year waitlist mortality (aHR = 1.69, P = 0.02). Positive prognostic impact of transplantation was not seen until score of 24-27 in ALD, 18-20 in HCV, 15-17 in NASH, and 24-27 in PBC and PSC. There are significant differences in waitlist outcomes among etiologies, which may differ the optimal transplant timing

Effect of mandatory 6-month waiting period on waitlist and transplant outcomes in patients with hepatocellular carcinoma

OPTN/UNOS policy mandates a 6-month waiting period before exception scores are granted to liver transplant candidates with hepatocellular carcinoma (HCC). This study aims to evaluate waitlist and post-transplant outcomes, in HCC patients, before and after implementation of the 6-month waiting rule. We examined two groups from the UNOS registry; Group 1 (pre 6-month rule) comprised patients registered as transplant candidates with HCC from Jan. 1, 2013 to Oct. 7, 2015 (n=4,814). Group 2 (post 6-month rule) comprised patients registered from Oct. 8, 2015 to Jun. 30, 2018 (n=3,287). As expected, the transplant probability was higher in the first six months after listing in Group 1 than Group 2 at 42.0% vs 6.3% (

Liver transplant waitlist outcomes in alcoholic hepatitis compared with other liver diseases: An analysis of UNOS registry

There is growing interest in performing liver transplantation (LT) in patients with alcoholic hepatitis (AH) without a mandated abstinence period. The aim of this study is to investigate waitlist outcomes in AH patients compared to those with other liver diseases. Using data from the UNOS registry, adult patients listed for LT between 2009 and 2018 were evaluated. Waitlist outcomes were compared among liver diseases. A total of 64 646 patients were eligible, including 286 with AH, 16 871 with alcoholic cirrhosis (AC), 13 730 with hepatitis C (HCV), 10 315 with non-alcoholic steatohepatitis (NASH), and 5841 with cholestatic liver disease (CLD). In comparison with AH patients, patients with HCV, NASH, and CLD had a significantly higher risk of waitlist mortality and a lower likelihood of recovery on the waitlist. These trends were more prominent in the waiting-time period of 91-365 days than in shorter periods. In intention-to-treat analysis, positive prognostic effect of LT was significant in AH patients with MELD score ≥35 (HR 0.04, P \u3c .001). AH patients showed lower mortality risk and a higher chance of recovery while on waitlist than other liver diseases, especially when waiting time exceeded 90 days. These results indicate the importance of continuous evaluation of disease progression in AH patients awaiting LT

Hepatitis E Diagnosis and Management After Liver, Kidney, or Heart Transplant: A Single-Center Experience

BACKGROUND: Transplant-related hepatitis E virus (HEV) infection is a rarely recognized phenomenon with significant clinical importance given its potential to result in chronic hepatitis posttransplant. METHODS: We retrospectively evaluated HEV diagnosis and treatment after liver, kidney, and heart transplant in a single center. We identified patients diagnosed with HEV by serologic testing and evaluated their treatment regimens. RESULTS: Fifteen transplant recipients (12 liver, 2 kidney, and 1 heart) presented with elevated liver enzymes and were positive for HEV IgM antibody. Liver enzymes normalized in 4 patients after being treated with ribavirin. One of the 4 patients had 2 recurrences with positive HEV RNA results following ribavirin treatment but recovered after 12 months of ribavirin therapy. After treatment with reduction in immunosuppression without antiviral treatment, 6 of 8 patients\u27 liver enzymes normalized. One of these patients died of acute pancreatitis 2 months after testing positive for HEV IgM antibody. CONCLUSIONS: The potential for complications related to active HEV infections in transplant recipients necessitates prompt diagnosis and treatment to prevent irreversible damage. Diagnosis with HEV reverse transcriptase-polymerase chain reaction should follow a positive HEV IgM antibody test. This manuscript provides evidence that ribavirin antiviral therapy and reducing immunosuppression are effective treatments for HEV infections in liver, kidney, and heart transplant recipients, which has not been sufficiently investigated in the population of the United States. Larger multicenter studies are needed to confirm the risks and benefits of using ribavirin antiviral therapy as first-line therapy of HEV posttransplant

Outcomes in living donor compared to deceased donor primary liver transplant in lower acuity patients with MELD score \u3c 30

While recent studies have reported favorable outcomes in living donor liver transplantation (LDLT), it remains unclear which populations benefit most from LDLT. The aim of this study is to evaluate post-transplant outcomes in LDLT compared to deceased donor liver transplant (DDLT) according to Model for End-Stage Liver Disease (MELD) score categories. Using data from the OPTN/UNOS registry, outcomes were compared between 1,486 LDLT, 13,568 donation after brain death (DBD) DDLT, and 1,171 donation after circulatory death (DCD) DDLT transplanted between 2009 and 2018. Because LDLT for patients with MELD score \u3e30 was rare (1.8% of all LDLT), all patients with scores \u3e 30 were excluded to equalize LDLT and DDLT cohorts. Risk factors for one-year graft loss were determined in LDLT and DDLT, separately. Compared with LDLT, DBD-DDLT had significantly lower risk of 30-day (aHR 0.60, P\u3c0.001) and one-year graft loss (aHR 0.57, P\u3c0.001). The significantly lower risk of graft loss was more prominent in the mid-MELD score category (score 15-29). DCD-DDLT, compared to LDLT, had significantly lower risk of 30-day graft loss, but comparable risk of one-year graft loss regardless of MELD score category. In LDLT, significant ascites was an independent risk factor for graft loss in patients with mid-MELD scores (aHR 1.68, P=0.02), but not in the lower-MELD score group. Risk of one-year graft loss in LDLT patients with ascites who received left liver was significantly higher than either those who received right liver or those without ascites who received left liver CONCLUSION: In LDLT, combinations of MELD score of 15-29, moderate/severe ascites and use of left liver, are associated with worse outcomes. These findings help calibrate appropriate patient and graft selection in LDLT

Transfusion requirements and alloimmunization to red blood cell antigens in orthotopic liver transplantation

BACKGROUND AND OBJECTIVES: Orthotopic liver transplantation (OLT) has been associated with high blood transfusion requirements. We evaluated the transfusion needs and frequency of alloimmunization to RBC antigens among OLT recipients pre- and post-transplantation. MATERIALS AND METHODS: We reviewed the medical records of patients who underwent a first OLT between January 2007 and June 2017. Transfusions given only during the perioperative period, defined by 1 week before OLT until 2 weeks following OLT, were included in this study. Records were reviewed in June 2019 for updated antibody testing results. RESULTS: A total of 970 patients underwent OLT during the study period. The median age of patients was 57 years; 608(62.7%) were male. During the perioperative period, transfused patients received an average of 10.7 (±10.7) RBC units, 15.6 (±16.2) thawed plasma units and 4.1 (±4.3) platelet units. At the time of OLT, a total of 101 clinically significant RBC alloantibodies were documented in 58(5.98%) patients. Fifty-three of these antibodies were directed against Rh blood group antigens. Twenty-two (37.9%) patients had more than one alloantibody. Patients with alloimmunization before OLT (N = 58) received perioperatively comparable number of RBCs to non-alloimmunized patients (10.5 ± 10.6 vs. 9.6 ± 10.7; p = 0.52). There was no significant difference in perioperative or intraoperative RBC transfusion between patients with one alloantibody and those with multiple alloantibodies. Only 16 patients (16/737; 2.17%) developed new alloantibodies at a median of 61 days after OLT. The overall alloimmunization rate was 9.8% (72/737), and female patients were more likely to be alloimmunized. CONCLUSION: Blood transfusion requirements in OLT remain high. However, the rate of RBC alloimmunization was not higher than the general patient population

Use of Neural Network Models to Predict Liver Transplant Waitlist Mortality

Current liver transplant (LT) organ allocation relies on MELD-Na scores to predict mortality in patients awaiting LT. This study aims to develop Neural Network (NN) models that more accurately predict LT waitlist mortality. The study evaluates patients listed for LT between February 27(th), 2002 and June 30(th), 2021 using the OPTN/UNOS registry. We excluded patients listed with MELD exception scores and those listed for multi-organ transplant, except for liver-kidney transplant. Subset of data from the waitlist was used to create a mortality prediction model at 90 days after listing with 105,140 patients. A total of 28 variables were selected for model creation. The data was split using random sampling into training, validation, and test datasets in a 60:20:20 ratio. The performance of the model was assessed using Area Under Receiver Operating Curve (AUC-ROC) and Area Under Precision-Recall curve (PR-AUC). AUC-ROC for 90-Day mortality was 0.936 (0.934-0.937, 95% CI), and PR-AUC was 0.758 (0.754-0.762, 95% CI). The NN 90-Day Mortality model outperformed MELD-based models for both AUC-ROC and PR-AUC. The 90-Day Mortality model specifically identified more waitlist deaths with a higher Recall (Sensitivity) of 0.807 (0.803-0.811, 95% CI) vs 0.413 (0.409 - 0.418, 95% CI) (P\u3c0.001). The performance metrics were compared by breaking the test dataset into multiple patient subsets by Ethnicity, Gender, Region, Age, Diagnosis Group, and Year of listing. The NN 90-Day Mortality model outperformed MELD-based models across all subsets in predicting mortality. In conclusion, organ allocation based on NN modeling has the potential to decrease waitlist mortality and lead to more equitable allocation systems in LT

Incidence and Risk Factors for Fatal Graft-versus-host Disease After Liver Transplantation

BACKGROUND: Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but serious complication. The aim of this study is to identify risk factors, including immunosuppressive regimens, for mortality due to GVHD (fatal GVHD). METHODS: Using data from the OPTN/UNOS registry, 77,416 adult patients who underwent LT between 2003 and 2018 were assessed. Risk factors for fatal GVHD were analyzed by focusing on induction and maintenance immunosuppression regimens. RESULTS: The incidence of fatal GVHD was 0.2% (121/77,416), of whom 105 (87%) died within 180 days and 13 (11%) died between 181 days and 1 year. Median survival after LT was 68.0 (49.5-125.5) days. Recipient age minus donor age greater than 20 years (HR 2.57, P\u3c0.001) and basiliximab induction (HR 1.69, P=0.018) were independent risk factors for fatal GVHD. Maintenance therapy with mycophenolate mofetil (MMF) was associated with a decrease in fatal GVHD (HR 0.51, P=0.001). In an increased risk cohort of patients with recipient-donor age discrepancy greater than 20 years, MMF use was associated with a 50% decline in fatal GVHD (HR 0.50, P\u3c0.001) CONCLUSIONS: Recipient age minus donor age greater than 20 years remains a significant risk factor for fatal GVHD. The risk of fatal GVHD significantly increases in association with basiliximab induction and decreases with MMF maintenance. These associations were pronounced in patients with recipient minus donor age greater than 20 years. These results emphasize the importance of donor age and individualized immunosuppression regimens on the risk of fatal GVHD