Clinical characteristics of new-onset diabetes after liver transplantation and outcomes.

Background: We aimed to identify the characteristics of new-onset diabetes after liver transplantation (LT) (NODAT) and investigate its impacts on post-transplant outcomes. Methods: Adult LT patients between 2014 and 2020 who used tacrolimus as initial immunosuppression and survived 3 months at least were evaluated. Patients who developed NODAT within 3 months after LT were classified as NODAT group. Also, patients were further classified as history of diabetes before LT (PHDBT) and non-diabetes (ND) groups. Patient characteristics, post-LT outcomes, and cardiovascular and/or pulmonary complications were compared. Results: A total of 83, 225, and 263 patients were classified into NODAT, PHDBT, and ND groups. The proportion of cholestatic liver disease and rejection within 90 days were higher in NODAT group. Mean serum tacrolimus concentration trough level in the first week after LT was 7.12, 6.12, and 6.12 ng/mL (p < 0.001). Duration of corticosteroids was significantly longer in NODAT compared to PHDBD or ND (416, 289, and 228 days, p < 0.001). Three-year graft and patient survival were significantly worse in NODAT than ND (80.5% vs. 95.0%, p < 0.001: 82.0% vs. 95.4%, p < 0.001) but similar to PHDBT. Adjusted risks of 3-year graft loss and patient death using Cox regression analysis were significantly higher in NODAT compared to ND (adjusted hazard ratio [aHR] 3.41, p = 0.004; aHR 3.61, p = 0.004). Incidence rates of cardiovascular or pulmonary complications after LT in NODAT were significantly higher than ND but similar to PHDBT. Conclusion: Higher initial tacrolimus concentration and early rejection might be risk factors for NODAT. NODAT was associated with worse post-transplant outcomes.

Exception Policy Change Increased the Simultaneous Kidney-liver Transplant Probability of Polycystic Disease in the Centers With High Median MELD at Transplantation.

BACKGROUND: In 2019, Organ Procurement and Transplantation Network/United Network for Organ Sharing changed the exception policy for liver allocation to the median model for end-stage liver disease at transplantation (MMaT). This study evaluated the effects of this change on-waitlist outcomes of simultaneous liver-kidney transplantation (SLKT) for patients with polycystic liver-kidney disease (PLKD). METHODS: Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry, 317 patients with PLKD listed for SLKT between January 2016 and December 2021 were evaluated. Waitlist outcomes were compared between prepolicy (Era 1) and postpolicy (Era 2) eras. RESULTS: One-year transplant probability was significantly higher in Era 2 than in Era 1 (55.7% versus 37.9%; P = 0.001), and the positive effect on transplant probability of Era 2 was significant after risk adjustment (adjusted hazard ratio, 1.76; 95% confidence interval, 1.22-2.54; P = 0.002 [ref. Era 1]), whereas waitlist mortality was comparable. Transplant centers were separated into the high and low MMaT groups with a score of 29 (median MMaT) and transplant probability in each group between eras was compared. In the high MMaT transplant centers, the 1-y transplant probability was significantly higher in Era 2 (27.5% versus 52.4%; P = 0.003). The positive effect remained significant in the high MMaT center group (adjusted hazard ratio, 2.79; 95% confidence interval, 1.43-5.46; P = 0.003 [ref. Era 1]) but not in the low MMaT center group. Although there was a difference between center groups in Era 1 (P = 0.006), it became comparable in Era 2 (P = 0.54). CONCLUSIONS: The new policy increased 1-y SLKT probability in patients with PKLD and successfully reduced the disparities based on center location.

Improved Waitlist Outcomes in Liver Transplant Patients With Mid-MELD-Na Scores Listed in Centers Receptive to Use of Organs Donated After Circulatory Death.

BACKGROUND: Liver transplant (LT) using organs donated after circulatory death (DCD) has been increasing in the United States. We investigated whether transplant centers' receptiveness to use of DCD organs impacted patient outcomes. METHODS: Transplant centers were classified as very receptive (group 1), receptive (2), or less receptive (3) based on the DCD acceptance rate and DCD transplant percentage. Using organ procurement and transplantation network/UNOS registry data for 20 435 patients listed for LT from January 2020 to June 2022, we compared rates of 1-y transplant probability and waitlist mortality between groups, broken down by model for end-stage liver disease-sodium (MELD-Na) categories. RESULTS: In adjusted analyses, patients in group 1 centers with MELD-Na scores 6 to 29 were significantly more likely to undergo transplant than those in group 3 (aHR range 1.51-2.11, P < 0.001). Results were similar in comparisons between groups 1 and 2 (aHR range 1.41-1.81, P < 0.001) and between groups 2 and 3 with MELD-Na 15-24 (aHR 1.19-1.20, P < 0.007). Likewise, patients with MELD-Na score 20 to 29 in group 1 centers had lower waitlist mortality than those in group 3 (scores, 20-24: aHR, 0.71, P = 0.03; score, 25-29: aHR, 0.51, P < 0.001); those in group 1 also had lower waitlist mortality compared with group 2 (scores 20-24: aHR0.69, P = 0.02; scores 25-29: aHR 0.63, P = 0.03). One-year posttransplant survival of DCD LT patients did not vary significantly compared with donation after brain dead. CONCLUSIONS: We conclude that transplant centers' use of DCD livers can improve waitlist outcomes, particularly among mid-MELD-Na patients.

Design of an optical linear-discriminant filter: optimization for enhancement of filter transmittance and discrimination accuracy.

To discriminate fine concave and convex defects on a dielectric substrate, an optical machine learning system is proposed. This system comprises an optical linear-discriminant filter (OLDF) that performs linear discriminant analysis (LDA) of the scattered-wave distribution from target samples. However, the filter output from the OLDF is considerably weak and cannot be measured experimentally. Therefore, an algorithm is also proposed to improve the discrimination accuracy and filter transmittance. The designed filter is validated using a rigorous optical simulator based on vector diffraction theory. We also analyze and discuss a mechanism that provides high transmittance with high discrimination accuracy.

Important Constituents of Heavy Water-containing Solution for Cold Storage and Subsequent Reperfusion on an Isolated Perfused Rat Liver.

The University of Wisconsin (UW) solution is the most effective preservation solution currently used; however, to safely use expanded-criteria donor grafts, a new cold storage solution that alleviates graft injury more effectively is required. We prepared a heavy water (D2O)-containing buffer, Dsol, and observed strong protective effects during extended cold storage of rat hearts and livers. In the current study, we modified Dsol (mDsol) and tested its efficacy. The aim of the present study was to determine whether mDsol could protect the rat liver more effectively than the UW solution and to clarify the roles of D2O and deferoxamine (DFX). Rat livers were subjected to cold storage for 48 hours in test solutions: UW, mDsol, mDsol without D2O or DFX (mDsol-D2O[-], mDsol-DFX[-]), and subsequently reperfused on an isolated perfused rat liver for 90 minutes at 37°C. In the UW group, the liver was dehydrated during cold storage and rapidly expanded during reperfusion. Accordingly, the cumulative weight change was the highest in the UW group, together with augmented portal veinous resistance and ALT leakage and decreased oxygen consumption rate and bile production. These changes were significantly suppressed in the mDsol-treated group. In the mDsol-D2O(-) and mDsol-DFX(-) groups offered partial protection. In conclusion, mDsol appeared to be superior to the UW solution for simple cold storage of the rat liver, presumably due to improved microcirculation in the early phase of reperfusion. Both heavy water and deferoxamine are essential for alleviating seamless organ swelling that occurs during cold storage and subsequent reperfusion.

Post-transplant outcomes and financial burden of donation after circulatory death donor liver transplant after the implementation of acuity circle policy.

BACKGROUND: After implementation of the Acuity Circles (AC) allocation policy, use of DCD liver grafts has increased in the United States. METHODS: We evaluated the impact of AC on rates of DCD-liver transplants (LT), their outcomes, and medical costs in a single practice. Adult LT patients were classified into three eras: Era 1 (pre-AC, 1/01/2015-12/31/2017); Era 2 (late pre-AC era, 1/01/2018-02/03/2020); and Era 3 (AC era, 05/10/2020-09/30/2021). RESULTS: A total of 520 eligible LTs were performed; 87 were DCD, and 433 were DBD. With each successive era, the proportion of DCD increased (Era 1: 11%; Era 2: 20%; Era 3: 24%; p < .001). DCD recipients had longer ICU stays, higher re-admission/re-operation rates, and higher incidence of ischemic cholangiopathy compared to those with DBD. Direct, surgical, and ICU costs during first admission were higher with DCD than DBD (+8.0%, p < .001; +4.2%, p < .001; and +33.3%, p = .001). DCD-related costs increased after Era 1 (Direct: +4.9% [Era 2 vs. 1] and +12.4% [Era 3 vs. 1], p = .04; Surgical: +17.7% and +21.7%, p < .001). In the AC era, there was a significantly higher proportion of donors ≥50 years, and more national organ sharing. Compared to DCD from donors <50 years, DCD from donors ≥50 years was associated with significantly higher total direct, surgical, and ICU costs (+12.6%, p = .01; +9.5%, p = .01; +84.6%, p = .03). CONCLUSIONS: The proportion of DCD-LT, especially from older donors, has increased after the implementation of AC policies. These changes are likely to be associated with higher costs in the AC era.

Combination of Cold Storage in a Heavy Water-Containing Solution and Post-Reperfusion Hydrogen Gas Treatment Reduces Ischemia-Reperfusion Injury in Rat Livers.

We previously reported the efficacy of cold storage (CS) using a heavy water-containing solution (Dsol) and post-reperfusion hydrogen gas treatment separately. This study aimed to clarify the combined effects of these treatments. Rat livers were subjected to 48-hour CS and a subsequent 90-minute reperfusion in an isolated perfused rat liver system. The experimental groups were the immediately reperfused control group (CT), the CS with University of Wisconsin solution (UW) group, the CS with Dsol group, the CS with UW and post-reperfusion H2 treatment group (UW-H2), and the CS with Dsol and post-reperfusion H2 group (Dsol-H2). We first compared the Dsol-H2, UW, and CT groups to evaluate this alternative method to conventional CS. The protective potential of the Dsol-H2 group was superior to that of the UW group, as evidenced by lower portal venous resistance and lactate dehydrogenase leakage, a higher oxygen consumption rate, and increased bile production. Multiple comparison tests among the UW, Dsol, UW-H2, and Dsol-H2 groups revealed that both treatments, during CS and after reperfusion, conferred a similar extent of protection and showed additive effects in combination therapy. Furthermore, the variance in all treatment groups appeared smaller than that in the no-treatment or no-stress groups, with excellent reproducibility. In conclusion, combination therapy with Dsol during CS and hydrogen gas after reperfusion additively protects against graft injury.

Variation of Liver Transplant Practice and Outcomes During Public Holidays in the United States: Analysis of United Network for Organ Sharing Registry.

It has been reported that patients hospitalized outside regular working hours have worse outcomes. This study aims to compare outcomes following liver transplantation (LT) performed during public holidays and nonholidays. Methods: We analyzed the United Network for Organ Sharing registry data for 55 200 adult patients who underwent an LT between 2010 and 2019. Patients were grouped according to LT receipt during public holidays ±3 d (n = 7350) and nonholiday periods (n = 47 850). The overall post-LT mortality hazard was analyzed using multivariable Cox regression models. Results: LT recipient characteristics were similar between public holidays and nonholidays. Compared with nonholidays, deceased donors during public holidays had a lower donor risk index (median [interquartile range]: holidays 1.52 [1.29-1.83] versus nonholidays 1.54 [1.31-1.85]; P = 0.001) and shorter cold ischemia time (median [interquartile range]: holidays 5.82 h [4.52-7.22] versus nonholidays 5.91 h [4.62-7.38]; P < 0.001). Propensity score matching 4-to-1 was done to adjust for donor and recipient confounders (n = 33 505); LT receipt during public holidays (n = 6701) was associated with a lower risk of overall mortality (hazard ratio 0.94 [95% confidence interval, 0.86-0.99]; P = 0.046). The number of livers that were not recovered for transplant was higher during public holidays compared with nonholidays (15.4% versus 14.5%, respectively; P = 0.03). Conclusions: Although LT performed during public holidays was associated with improved overall patient survival, liver discard rates were higher during public holidays compared with nonholidays.

Hypothermic Machine Perfusion with Hydrogen Gas Reduces Focal Injury in Rat Livers but Fails to Restore Organ Function.

BACKGROUND: We have previously reported the efficacy of post-reperfusion H2 gas treatment in cold storage (CS) and subsequent reperfusion of the rat liver. The present study aimed to evaluate the effect of H2 gas treatment during hypothermic machine perfusion (HMP) in rat livers retrieved from donation after circulatory death (DCD) and elucidate the mechanism of action of H2 gas. METHODS: Liver grafts were procured from rats after 30 min of cardiopulmonary arrest. The graft was subjected to HMP for 3 hours at 7°C using Belzer MPS with or without dissolved H2 gas. The graft was reperfused using an isolated perfused rat liver apparatus at 37°C for 90 minutes. Perfusion kinetics, liver damage, function, apoptosis, and ultrastructure were evaluated. RESULTS: Portal venous resistance, bile production, and oxygen consumption rates were identical in the CS, MP, and MP-H2 groups. Liver enzyme leakage was suppressed by MP (vs control), whereas H2 treatment did not show a combination effect. Histopathology revealed poorly stained areas with a structural deformity just below the liver surface in the CS and MP groups, whereas these findings disappeared in the MP-H2 group. The apoptotic index in the CS and MP groups was high but decreased in the MP-H2 group. Mitochondrial cristae were damaged in the CS group but preserved in the MP and MP-H2 groups. CONCLUSIONS: In conclusion, HMP and H2 gas treatment are partly effective in DCD rat livers but insufficient. Hypothermic machine perfusion can improve focal microcirculation and preserve mitochondrial ultrastructure.

Effects of the implementation of acuity circle policy on waitlist and post-transplant outcomes of liver re-transplantation.

BACKGROUND: Acuity circle (AC) policy implementation improved the waitlist outcomes for certain liver transplant (LT)-candidates. The impact of the policy implementation for liver retransplant (reLT) candidates is unknown. METHODS: Using Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from January, 2018 to September, 2021, we investigated the effect of the AC policy on waitlist and post-LT outcomes among patients who had previously received a LT. Patients were categorized by relisting date: Pre-AC (Era 1: January 1, 2018-February 3, 2020; n = 750); and Post-AC (Era 2: February 4, 2020-June 30, 2021; n = 556). Patient and donor characteristics, as well as on-waitlist and post-reLT outcomes were compared across eras. RESULTS: In Era 2, the probability of transplant within 90 days overall and among patients relisted > 14 days from initial transplant (late relisting) were significantly higher compared to Era 1 (subdistribution hazard ratio [sHR] 1.40, 95% CI 1.18-1.64, p < .001; sHR 1.52, 95% CI 1.23-1.88, p = .001, respectively). However, there was no difference by era among patients relisted ≤14 days from initial transplant (early relisting; sHR 1.21, 95% CI .93-1.57, p = .15). Likewise, among early relisting patients, risks for 180-day graft loss and mortality were significantly higher in Era 2 versus Era 1 (adjusted hazard ratio [aHR] 5.77, 95% CI 1.71-19.51, p = .004; and aHR 8.22, 95% CI 1.85-36.59, p = .005, respectively); for late relisting patients, risks for these outcomes were similar across eras. CONCLUSION: Our results show that the implementation of AC policy has improved transplant rates and reduced waiting time for reLT candidates listed > 14 days from initial transplant. However, the impact upon early relisting patients may be mixed.

Liver Resection for Hepatocellular Carcinoma With Tumor Thrombus in the Inferior Vena Cava or Right Atrium: A Large-scale Multicenter Survey Conducted in Japan.

OBJECTIVE: To clarify the short and long-term postoperative outcomes and surgical indications for patients accompanied by hepatocellular carcinoma with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA). BACKGROUND: These patients are known to have an extremely poor prognosis; however, the postoperative outcomes have not been fully verified because of the rarity of this disease. METHODS: We contacted 211 specialized centers in Japan and collected data on liver resection for hepatocellular carcinoma with TT in the IVC or RA from centers with experience performing surgery for such patients. The patient characteristics, operative procedures, and surgical outcomes were then analyzed. RESULTS: A total of 119 patients from 23 institutions were enrolled; 49 patients had TT in the IVC below the diaphragm (type I), 42 had TT in the IVC above the diaphragm (type II), and 28 had TT entering the RA (type III). The severity and frequency of postoperative complications did not differ among the 3 groups. There was one surgery-related death in the type III group. The median survival times were 2.47 years in the type I group, 1.77 years in the type II group, and 1.02 years in the type III group. Multivariate analysis identified an indocyanine green retention rate at 15 minutes >15% and ≥3 tumors as prognostic factors affecting survival, whereas the use of cardiopulmonary bypass and ≥3 tumors were risk factors for recurrence. CONCLUSIONS: As the postoperative prognosis of patients with type I or type II disease and of patients with no risk factors is relatively good, surgery should be considered for these patient populations.

Multiple Pretransplant Treatments for Patients Without Pathological Complete Response may Worsen Posttransplant Outcomes in Patients with Hepatocellular Carcinoma.

BACKGROUND: Liver transplant (LT) candidates with hepatocellular carcinoma (HCC) often receive cancer treatment before transplant. We investigated the impact of pre-transplant treatment for HCC on the risk of posttransplant recurrence. METHODS: Adult HCC patients with LT at our institution between 2013 and 2020 were included. The impact of pre-LT cancer treatments on the cumulative recurrence was evaluated, using the Gray and Fine-Gray methods adjusted for confounding factors. Outcomes were considered in two ways: 1) by pathologically complete response (pCR) status within patients received pre-LT treatment; and 2) within patients without pCR, grouped by pre-LT treatment as A) none; B) one treatment; C) multiple treatments. RESULTS: The sample included 179 patients, of whom 151 (84%) received pretreatment and 42 (28% of treated) demonstrated pCR. Overall, 22 (12%) patients experienced recurrence. The 5-year cumulative post-LT recurrence rate was significantly lower in patients with pCR than those without pCR (4.8% vs. 19.2%, P = 0.03). In bivariable analyses, pCR significantly decreased risk of recurrence. Among the 137 patients without pCR (viable HCC in the explant), 28 (20%) had no pretreatment (A), 70 (52%) had one treatment (B), and 39 (20%) had multiple treatments (C). Patients in Group C had higher 5-year recurrence rates than those in A or B (39.6% vs. 8.2%, 6.5%, P = 0.004 and P < 0.001, respectively). In bivariable analyses, multiple treatments was significantly associated with recurrence. CONCLUSIONS: pCR is a favorable prognostic factor after LT. When pCR was not achieved by pre-LT treatment, the number of treatments might be associated with post-LT oncological prognosis.

Can Weather Be a Factor in Liver Transplant Waitlist and Posttransplant Outcomes? Analysis of United Network for Organ Sharing Registry.

BACKGROUND: Cold climate is known to affect the frequency and attributable mortality of various illnesses. This study aims to evaluate the effect of climate among regions on liver transplant (LT) outcomes. METHODS: We analyzed data from the United Network for Organ Sharing registry for 98,517 adult patients (aged ≥ 18 years) who were listed for LT between 2010 and 2019. During this period, 51,571 patients underwent single-organ, deceased LT. States were categorized based on their mean winter temperature: warm states (45°F-70°F), intermediate states (30°F-45°F), and cold states (0°F-30°F). Post-LT outcomes at 1 month, 1 year, and 3 years were compared using Cox proportional hazard models. Ninety-day and 1-year waitlist outcomes were compared among climate regions using Fine-Gray hazard regression model. RESULTS: After adjusting risks for recipient and donor characteristics, LT candidates in cold states had a significantly higher waitlist (90-day: subdistribution hazard ratio (HR) 1.46; 1-year: subdistribution HR 1.41; P < .001) and posttransplant mortality (30-day: subdistribution HR 1.23; P = .009, 1-year: subdistribution HR 1.16; P = .001; 3-year: subdistribution HR 1.08; P = .007). LT recipients in cold states had a higher proportion of deaths due to infections than warm states (cold states: 2.3%; intermediate states: 2.1%; and warm states: 1.7%; P < .001). CONCLUSIONS: Potential reasons include weather-related changes in the behavioral and physiological parameters of patients.

Impact of comorbid renal dysfunction in patients with hepatocellular carcinoma on long-term outcomes after curative resection.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the number of patients with chronic kidney disease (CKD) is on the rise because of the increase in lifestyle-related diseases. AIM: To establish a tailored management strategy for HCC patients, we evaluated the impact of comorbid renal dysfunction (RD), as stratified by using the estimated glomerular filtration rate (EGFR), and assessed the oncologic validity of hepatectomy for HCC patients with RD. METHODS: We enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 at our university hospital. We categorized patients into two (RD, EGFR < 60 mL/min/1.73 m2; non-RD, EGFR ≥ 60 mL/min/1.73 m2) and three groups (severe CKD, EGFR < 30 mL/min/1.73 m2; mild CKD, 30 ≤ EGFR < 60 mL/min/1.73 m2; control, EGFR ≥ 60 mL/min/1.73 m2) according to renal function as defined by the EGFR. Overall survival (OS) and recurrence-free survival (RFS) were compared among these groups with the log-rank test, and we also analyzed survival by using a propensity score matching (PSM) model to exclude the influence of patient characteristics. The mean postoperative observation period was 64.7 ± 53.0 mo. RESULTS: The RD patients were significantly older and had lower serum total bilirubin, aspartate aminotransferase, and aspartate aminotransferase levels than the non-RD patients (P < 0.0001, P < 0.001, P < 0.05, and P < 0.01, respectively). No patient received maintenance hemodialysis after surgery. Although the overall postoperative complication rates were similar between the RD and non-RD patients, the proportions of postoperative bleeding and surgical site infection were significantly higher in the RD patients (5.5% vs 1.8%; P < 0.05, 3.9% vs 1.8%; P < 0.05, respectively), and postoperative bleeding was the highest in the severe CKD group (P < 0.05). Regardless of the degree of comorbid RD, OS and RFS were comparable, even after PSM between the RD and non-RD groups to exclude the influence of patient characteristics, liver function, and other causes of death. CONCLUSION: Comorbid mild RD had a negligible impact on the prognosis of HCC patients who underwent curative hepatectomy with appropriate perioperative management, and close attention to severe CKD is necessary to prevent postoperative bleeding and surgical site infection.

Liver Transplant Recipient Characteristics Associated With Worse Post-Transplant Outcomes in Using Elderly Donors.

Advanced age of liver donor is a risk factor for graft loss after transplant. We sought to identify recipient characteristics associated with negative post-liver transplant (LT) outcomes in the context of elderly donors. Using 2014-2019 OPTN/UNOS data, LT recipients were classified by donor age: ≥70, 40-69, and <40 years. Recipient risk factors for one-year graft loss were identified and created a risk stratification system and validated it using 2020 OPTN/UNOS data set. At transplant, significant recipient risk factors for one-year graft loss were: previous liver transplant (adjusted hazard ratio [aHR] 4.37, 95%CI 1.98-9.65); mechanical ventilation (aHR 4.28, 95%CI 1.95-9.43); portal thrombus (aHR 1.87, 95%CI 1.26-2.77); serum sodium <125 mEq/L (aHR 2.88, 95%CI 1.34-6.20); and Karnofsky score 10-30% (aHR 2.03, 95%CI 1.13-3.65), 40-60% (aHR 1.65, 95%CI 1.08-2.51). Using those risk factors and multiplying HRs, recipients were divided into low-risk (n = 931) and high-risk (n = 294). Adjusted risk of one-year graft loss in the low-risk recipient group was similar to that of patients with younger donors; results were consistent using validation dataset. Our results show that a system of careful recipient selection can reduce the risks of graft loss associated with older donor age.

Disparities in the Effects of Acuity Circle-based Liver Allocation on Waitlist and Transplant Practice Between Centers.

Liver allocation in the United States was updated on February 4, 2020, by introducing the acuity circle (AC)-based model. This study evaluated the early effects of the AC-based allocation on waitlist outcomes. Methods: Adult liver transplant (LT) candidates listed between January 1, 2019, and September 30, 2021, were assessed. Two periods were defined according to listing date (pre- and post-AC), and 90-d waitlist outcomes were compared. Median transplant Model for End-stage Liver Disease (MELD) score of each transplant center was calculated, with centers categorized as low- (<25 percentile), mid- (25-75 percentile), and high-MELD (>75 percentile) centers. Results: A total of 12 421 and 17 078 LT candidates in the pre- and post-AC eras were identified. Overall, the post-AC era was associated with higher cause-specific 90-d hazards of transplant (csHR, 1.32; 95% confidence interval [CI], 1.27-1.38; P < 0.001) and waitlist mortality (cause-specific hazard ratio [csHR], 1.20; 95% CI, 1.09-1.32; P < 0.001). The latter effect was primarily driven by high-MELD centers. Low-MELD centers had a higher proportion of donations after circulatory death (DCDs) used. Compared with low-MELD centers, mid-MELD and high-MELD centers had significantly lower cause-specific hazards of DCD-LT in both eras (mid-MELD: csHR, 0.47; 95% CI, 0.38-0.59 in pre-AC and csHR, 0.56; 95% CI, 0.46-0.67 in post-AC and high-MELD: csHR, 0.11; 95% CI, 0.07-0.17 in pre-AC and csHR, 0.14; 95% CI, 0.10-0.20 in post-AC; all P < 0.001). Using a structural Bayesian time-series model, the AC policy was associated with an increase in the actual monthly DCD-LTs in low-, mid-, and high-MELD centers (actual/predicted: low-MELD: 19/16; mid-MELD: 21/14; high-MELD: 4/3), whereas the increase in monthly donation after brain death-LTs were only present in mid- and high-MELD centers. Conclusions: Although AC-based allocation may improve waitlist outcomes, regional variation exists in the drivers of such outcomes between centers.

The use of normothermic liver preservation in combined liver and lung transplantation: A single-center experience.

Combined liver and lung transplantation (CLLT) is indicated in patients with both end-stage liver and lung disease. Ex-situ normothermic machine perfusion (NMP) has been previously used for extended normothermic lung preservation in CLLT. We aim to describe our single-center experience using ex-situ NMP for extended normothermic liver preservation in CLLT. Four CLLTs were performed from 2019 to 2020 with the lung transplanted first for all patients. Median ex-situ pump time for the liver was 413 min (IQR 400-424). Over a median follow-up of 15 months (IQR 14-19), all patients were alive and doing well. Normothermic extended liver preservation is a safe method to allow prolonged cold ischemia using normothermic perfusion of the liver during CLLT.

Improved Survival With Higher-risk Donor Grafts in Liver Transplant With Acute-on-chronic Liver Failure.

Use of higher-risk grafts in liver transplantation for patients with acute-on-chronic liver failure (ACLF) has been associated with poor outcomes. This study analyzes trends in liver transplantation outcomes for ACLF over time based on the donor risk index (DRI). METHODS: Using the Organ Procurement and Transplantation Network and the United Network for Organ Sharing registry, 17 300 ACLF patients who underwent liver transplantation between 2002 and 2019 were evaluated. Based on DRI, adjusted hazard ratios for 1-y patient death were analyzed in 3 eras: Era 1 (2002-2007, n = 4032), Era 2 (2008-2013, n = 6130), and Era 3 (2014-2019, n = 7138). DRI groups were defined by DRI <1.2, 1.2-1.6, 1.6-2.0, and >2.0. RESULTS: ACLF patients had significantly lower risks of patient death within 1 y in Era 2 (adjusted hazard ratio, 0.69; 95% confidence interval, 0.61-0.78; P < 0.001) and Era 3 (adjusted hazard ratio, 0.48; 95% confidence interval, 0.42-0.55; P < 0.001) than in Era 1. All DRI groups showed lower hazards in Era 3 than in Era 1. Improvement of posttransplant outcomes were found both in ACLF-1/2 and ACLF-3 patients. In ACLF-1/2, DRI 1.2 to 1.6 and >2.0 had lower adjusted risk in Era 3 than in Era 1. In ACLF-3, DRI 1.2 to 2.0 had lower risk in Era 3. In the overall ACLF cohort, the 2 categories with DRI >1.6 had significantly higher adjusted risks of 1-y patient death than DRI <1.2. When analyzing hazards in each era, DRI > 2.0 carried significantly higher adjusted risks in Eras 1 and 3' whereas DRI 1.2 to 2.0 had similar adjusted risks throughout eras. Similar tendency was found in ACLF-1/2. In the non-ACLF cohort, steady improvement of posttransplant outcomes was obtained in all DRI categories. Similar results were obtained when only hepatitis C virus-uninfected ACLF patients were evaluated. CONCLUSIONS: In ACLF patients, posttransplant outcomes have significantly improved, and outcomes with higher-risk organs have improved in all ACLF grades. These results might encourage the use of higher-risk donors in ACLF patients and provide improved access to transplant.