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.

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.

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.

Lymphopenia at the time of transplant is associated with short-term mortality after deceased donor liver transplantation.

Absolute lymphocyte count (ALC) is considered a surrogate marker for nutritional status and immunocompetence. We investigated the association between ALC and post-liver transplant outcomes in patients who received a deceased donor liver transplant (DDLT). Patients were categorized by ALC at liver transplant: low (<500/µL), mid (500-1000/µL), and high ALC (>1000/µL). Our main analysis used retrospective data (2013-2018) for DDLT recipients from Henry Ford Hospital (United States); the results were further validated using data from the Toronto General Hospital (Canada). Among 449 DDLT recipients, the low ALC group demonstrated higher 180-day mortality than mid and high ALC groups (83.1% vs 95.8% and 97.4%, respectively; low vs mid: P = .001; low vs high: P < .001). A larger proportion of patients with low ALC died of sepsis compared with the combined mid/high groups (9.1% vs 0.8%; P < .001). In multivariable analysis, pretransplant ALC was associated with 180-day mortality (hazard ratio, 0.20; P = .004). Patients with low ALC had higher rates of bacteremia (22.7% vs 8.1%; P < .001) and cytomegaloviremia (15.2% vs 6.8%; P = .03) than patients with mid/high ALC. Low ALC pretransplant through postoperative day 30 was associated with 180-day mortality among patients who received rabbit antithymocyte globulin induction (P = .001). Pretransplant lymphopenia is associated with short-term mortality and a higher incidence of posttransplant infections in DDLT patients.

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.

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.

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.

Small bowel obstruction due to Roux-en-Y enterolith 13 years following deceased donor liver transplantation: a case report.

Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease, and liver transplantation (LT) is considered the only therapeutic option for patients with end-stage liver disease secondary to PSC. Intestinal obstruction in adults after LT surgery is a rare complication with diverse clinical presentations. The most common etiology is intestinal adhesions, but this can also result from other rare causes such as enterolith. We describe the first case report of small bowel obstruction secondary to biliary stone formation in the common limb of Roux-en-Y hepaticojejunostomy 13 years after the deceased donor LT. The patient failed initial conservative management and developed peritonitis, requiring urgent surgical exploration to remove the enterolith and resect the involved small bowel. In conclusion, small bowel obstructions due to enteroliths are unusual clinical complications following LT, which require a high degree of suspicion in patients who develop a bowel obstruction in the setting of a previous hepaticojejunostomy.

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.

Impact on Waitlist Outcomes from Changes in the Medical Eligibility of Candidates for Simultaneous Liver-Kidney Transplantation Following Implementation of the 2017 Organ Procurement and Transplantation Network/United Network for Organ Sharing Policy in the United States.

BACKGROUND The new simultaneous liver-kidney transplantation (SLK) listing criteria in the United States was implemented in 2017. We aimed to investigate the impact on waitlist and post-transplantation outcomes from changes in the medical eligibility of candidates for SLK after policy implementation in the United States. MATERIAL AND METHODS We analyzed adult primary SLK candidates between January 2015 and March 2019 using the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) registry. We compared waitlist practice, post-transplantation outcomes, and final transplant graft type in SLK candidates before and after the policy. RESULTS A total of 4641 patients were eligible, with 2975 and 1666 registered before and after the 2017 policy, respectively. The daily number of SLK candidates was lower after the 2017 policy (3.25 vs 2.89, P=0.01); 1956 received SLK and 95 received liver transplant alone (LTA). The proportion of patients who eventually received LTA was higher after the 2017 policy (7.9% vs 3.0%; P<0.001). The 1-year graft survival rate was worse in patients with LTA than in those with SLK (80.5% vs 90.4%; P=0.003). The adjusted risk of 1-year graft failure in patients with LTA was 2.01 (95% confidence interval 1.13-3.58, P=0.01) compared with patients with SLK among the SLK candidates. CONCLUSIONS Although the number of registrations for SLK increased, the number of SLK transplants decreased, and the number of liver transplants increased. LTA in this patient cohort was associated with worse post-transplantation outcomes.

Improvements in liver transplant outcomes in patients with HCV/HIV coinfection after the introduction of direct-acting antiviral therapies.

BACKGROUND: In recipients with HCV/HIV coinfection, the impact that the wider use of direct-acting antivirals (DAAs) has had on post-liver transplant (LT) outcomes has not been evaluated. We investigated the impact of DAAs introduction on post-LT outcome in patients with HCV/HIV coinfection. METHODS: Using Organ Procurement and Transplant Network/United Network for Organ Sharing data, we compared post-LT outcomes in patients with HCV and/or HIV pre- and post-DAAs introduction. We categorized these patients into two eras: pre-DAA (2008-2012 [pre-DAA era]) and post-DAA (2014-2019 [post-DAA era]). To study the impact of DAAs introduction, inverse probability of treatment weighting was used to adjust patient characteristics. RESULTS: A total of 17 215 LT recipients were eligible for this study (HCV/HIV [n = 160]; HIV mono-infection [n = 188]; HCV mono-infection [n = 16 867]). HCV/HIV coinfection and HCV mono-infection had a significantly lower hazard of 1- and 3-year graft loss post-DAA, compared pre-DAA (1-year: adjusted hazard ratio [aHR] 0.29, 95% confidence interval (CI) 0.16-0.53 in HIV/HCV, aHR 0.58, 95% CI 0.54-0.63, respectively; 3-year: aHR 0.30, 95% CI 0.14-0.61, aHR 0.64, 95% CI 0.58-0.70, respectively). The hazards of 1- and 3-year graft loss post-DAA in HIV mono-infection were comparable to those in pre-DAA. HCV/HIV coinfection had significantly lower patient mortality post-DAA, compared to pre-DAA (1-year: aHR 0.30, 95% CI 0.17-0.55; 3-year: aHR 0.31, 95% CI 0.15-0.63). CONCLUSIONS: Post-LT outcomes in patients with coinfection significantly improved and became comparable to those with HCV mono-infection after introducing DAA therapy. The introduction of DAAs supports the use of LT in the setting of HCV/HIV coinfection.

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.

Timing of Flap Coverage With Respect to Definitive Fixation in Open Tibia Fractures.

OBJECTIVES: We conducted a large, U.S wide, observational study of type III tibial fractures, with the hypothesis that delays between definitive fixation and flap coverage might be a substantial modifiable risk factor associated with nosocomial wound infection. DESIGN: A retrospective analysis of a multicenter database of open tibial fractures requiring flap coverage. SETTING: Fourteen level-1 trauma centers across the United States. PATIENTS: Two hundred ninety-six (n = 296) consecutive patients with Gustilo III open tibial fractures requiring flap coverage at 14 trauma centers were retrospectively analyzed from a large orthopaedic trauma registry. We collected demographics and the details of surgical care. We investigated the patient, and treatment factors leading to infection, including the time from various points in care to the time of soft-tissue coverage. INTERVENTION: Delay definitive fixation and flap coverage in tibial type III fractures. MAIN OUTCOME MEASUREMENTS: (1) Results of multivariate regression with time from injury to coverage, debridement to coverage, and definitive fixation to coverage in the model, to determine which delay measurement was most associated with infection. (2) A second multivariate model, including other factors in addition to measures of flap delay, to provide the estimate between delay and infection after adjustment for confounding. RESULTS: Of 296 adults (227 M: 69 F) with open Gustilo type III tibial fractures requiring flap coverage, 96 (32.4%) became infected. In the multivariate regression, the time from definitive fixation to flap coverage was most predictive of subsequent wound infection (odds ratio 1.04, 95% confidence interval 1.01 to 1.08, n = 260, P = 0.02) among the time measurements. Temporary internal fixation was not associated with an increased risk of infection in both univariate (P = 0.59) or multivariate analyses (P = 0.60). Flap failure was associated with the highest odds of infection (odds ratio 6.83, 95% confidence interval 3.26 to 14.27, P < 0.001). CONCLUSION: Orthoplastic teams that are dedicated to severe musculoskeletal trauma, that facilitate coordination of definitive fixation and flap coverage, will reduce the infection rates in Gustilo type III tibial fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.