UNASSIGNED: : Since its declaration as a global pandemic on March11th 2020, COVID-19 has had a significant effect on solid-organ transplantation. The aim of this study was to analyze the impact of COVID-19 on Liver transplantation (LT) in United States.
UNASSIGNED: : We retrospectively analyzed the United Network for Organ Sharing database regarding characteristics of donors, adult-LT recipients, and transplant outcomes during early-COVID period (March 11- September 11, 2020) and compared them to pre-COVID period (March 11 - September 11, 2019).
UNASSIGNED: : Overall, 4% fewer LTs were performed during early-COVID period (4107 vs 4277). Compared to pre-COVID period, transplants performed in early-COVID period were associated with: increase in alcoholic liver disease as most common primary diagnosis (1315 vs 1187, P< 0.01), higher MELD score in the recipients (25 vs 23, P<0.01), lower time on wait-list (52 vs 84 days, P<0.01), higher need for hemodialysis at transplant (9.4 vs 11.1%, P=0.012), longer distance from recipient hospital (131 vs 64 miles, P<0.01) and higher donor risk index (1.65 vs 1.55, P<0.01). Early-COVID period saw increase in rejection episodes before discharge (4.6 vs 3.4%, P=0.023) and lower 90-day graft/patient survival (90.2 vs 95.1 %, P<0.01; 92.2 vs 96.5 %, P<0.01). In multivariable cox-regression analysis, early-COVID period was the independent risk factor for graft failure at 90-days post-transplant (Hazard Ratio 1.77, P<0.01).
UNASSIGNED: : During early-COVID period in United States, overall LT decreased, alcoholic liver disease was primary diagnosis for LT, rate of rejection episodes before discharge was higher and 90-days post-transplant graft survival was lower.

UNASSIGNED: When listing for liver transplantation, one can transplant as soon as possible or introduce a test-of-time to better select patients, as the tumor\'s biological behavior is observed. Knowing the degree of harm caused by time itself is essential to advise patients and decide on the maximum duration of the test-of-time. Therefore, we investigated the causal effect of waiting time on post-transplant survival for patients with hepatocellular carcinoma.
UNASSIGNED: We analyzed the UNOS-OPTN dataset and exploited a natural experiment created by blood groups. Relations between variables and assumptions were described in a causal graph. Selection bias was addressed by inverse probability weighting. Confounding was avoided using instrumental variable analysis, with an additive hazards model in the second stage. The causal effect was evaluated by estimating the difference in 5-year overall survival if all patients waited 2 months instead of 12 months. Upper bounds of the test-of-time were evaluated for probable scenarios by means of simulation.
UNASSIGNED: The F-statistic of the first stage was 86.3. The effect of waiting 12 months vs. 2 months corresponded with a drop in overall survival rate of 5.07% (95% CI 0.277-9.69) and 8.33% (95% CI 0.47-15.60) at 5- and 10-years post-transplant, respectively. The median survival dropped by 3.41 years from 16.21 years (95% CI 15.98-16.60) for those waiting 2 months to 12.80 years (95% CI 10.72-15.90) for those waiting 12 months.
UNASSIGNED: From a patient\'s perspective, the choice between ablate-and-wait vs. immediate transplantation is in favor of immediate transplantation. From a policy perspective, the extra waiting time can be used to increase the utility of scarce donor livers. However, the duration of the test-of-time is bounded, and it likely should not exceed 8 months.
UNASSIGNED: When listing patients with liver cancer for transplantation, it is unclear whether a test-of-time or immediate transplantation offer better outcomes at the population level. In this study, we found that increased liver transplant waiting times are detrimental in patients with liver cancer. Furthermore, our simulation showed that a pre-operative observational period can be useful to ensure good donor liver allocation, but that its duration should not exceed 8 months.

Alcohol-related liver disease (ARLD) remains one of the leading causes of chronic liver disease and the prevalence of alcohol-related cirrhosis is still increasing worldwide. Thus, ARLD is one of the leading indications for liver transplantation (LT) worldwide especially after the arrival of direct-acting antivirals for chronic hepatitis C infection. Despite the risk of alcohol relapse, the outcomes of LT for ARLD are as good as for other indications such as hepatocellular carcinoma (HCC), with 1-, 5-, and 10- year survival rates of 85%, 74%, and 59%, respectively. Despite these good results, certain questions concerning LT for ARLD remain unanswered, in particular because of persistent organ shortages. As a result, too many transplantation centers continue to require 6 months of abstinence from alcohol for patients with ARLD before LT to reduce the risk of alcohol relapse even though compelling data show the poor prognostic value of this criterion. A recent pilot study even observed a lower alcohol relapse rate in patients receiving LT after less than 6 months of abstinence as long as addictological follow-up is reinforced. Thus, the question should not be whether LT should be offered to patients with ARLD but how to select patients who will benefit from this treatment.

UNASSIGNED: We compared posttransplant outcomes between patients bridged from temporary mechanical circulatory support to durable left ventricular assist device before transplant (bridge-to-bridge [BTB] strategy) and patients bridged from temporary mechanical circulatory support directly to transplant (bridge-to-transplant [BTT] strategy).
UNASSIGNED: We identified adult heart transplant recipients in the Organ Procurement and Transplantation Network database between 2005 and 2020 who were supported with extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary ventricular assist device as a BTB or BTT strategy. Kaplan-Meier survival analysis and Cox regressions were used to assess 1-year, 5-year, and 10-year survival. Posttransplant length of stay and complications were compared as secondary outcomes.
UNASSIGNED: In total, 201 extracorporeal membrane oxygenation (61 BTB, 140 BTT), 1385 intra-aortic balloon pump (460 BTB, 925 BTT), and 234 temporary ventricular assist device (75 BTB, 159 BTT) patients were identified. For patients supported with extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary ventricular assist device, there were no differences in survival between BTB and BTT at 1 and 5 years posttransplant, as well as 10 years posttransplant even after adjusting for baseline characteristics. The extracorporeal membrane oxygenation BTB group had greater rates of acute rejection (32.8% vs 13.6%; P = .002) and lower rates of dialysis (1.6% vs 21.4%; P < .001). For intra-aortic balloon pump and temporary ventricular assist device patients, there were no differences in posttransplant length of stay, acute rejection, airway compromise, stroke, dialysis, or pacemaker insertion between BTB and BTT recipients.
UNASSIGNED: BTB patients have similar short- and midterm posttransplant survival as BTT patients. Future studies should continue to investigate the tradeoff between prolonged temporary mechanical circulatory support versus transitioning to durable mechanical circulatory support.

Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of liver disease, which adversely affects prognosis. The disease is characterised by intrapulmonary vascular dilatations and shunts, resulting in impaired gas exchange. A complex interaction between the liver, the gut and the lungs, predominately impacting pulmonary endothelial cells, immune cells and respiratory epithelial cells, is responsible for the development of typical pulmonary alterations seen in HPS. Liver transplantation is the only therapeutic option and generally reverses HPS. Since the implementation of the model for end-stage liver disease (MELD) standard exception policy, outcomes in patients with HPS have been significantly better than they were in the pre-MELD era. This review summarises current knowledge and highlights what\'s new regarding the diagnosis and management of HPS, and our understanding of pathogenesis based on experimental models and translational studies.

UNASSIGNED: Patients with a left ventricular assist device with right ventricular failure are prioritized on the heart transplant waitlist; however, their post-transplant survival is less well characterized. We aimed to determine whether pretransplant right ventricular failure affects postoperative survival in patients with a left ventricular assist device as a bridge to transplant.
UNASSIGNED: We performed a retrospective review of the 2005-2018 Organ Procurement and Transplantation Network/United Network for Organ Sharing registry for candidates aged 18 years or more waitlisted for first-time isolated heart transplantation after left ventricular assist device implantation. Candidates were stratified on the basis of having right ventricular failure, defined as the need for right ventricular assist device or intravenous inotropes. Baseline demographic and clinical characteristics were compared among the 3 groups, and post-transplant survival was assessed.
UNASSIGNED: Our cohort included 5605 candidates who met inclusion criteria, including 450 patients with right ventricular failure, 344 patients with a left ventricular assist device and intravenous inotropes as a bridge to transplant, 106 patients with a left ventricular assist device and right ventricular assist device, and 5155 patients with a left ventricular assist device as a bridge to transplant without the need for right side support. Compared with patients without right ventricular failure, patients with a left ventricular assist device as a bridge to transplant with right ventricular failure were younger (median age 51 years, 55 vs 56 years, P < .001) and waited less time for organs (median 51 days, 93.5 vs 125 days, P < .001). These patients also had longer post-transplant length of stay (median 18 days, 20 vs 16 days, P < .001). Right ventricular failure was not associated with decreased post-transplant long-term survival on unadjusted Kaplan-Meier analysis (P = .18). Neither preoperative right ventricular assist device nor intravenous inotropes independently predicted worse survival on multivariate Cox proportional hazards analysis. However, pretransplant liver dysfunction (total bilirubin >2) was an independent predictor of worse survival (hazard ratio, 1.74; 95% confidence interval, 1.39-2.17; P < .001), specifically in the left ventricular assist device group and not in the left ventricular assist device + right ventricular assist device/intravenous inotropes group.
UNASSIGNED: Patients with biventricular failure are prioritized on the waiting list, because their critical pretransplant condition has limited impact on their post-transplant survival (short-term effect only); thus, surgeons should be confident to perform transplantation in these severely ill patients. Because liver dysfunction (a surrogate marker of right ventricular failure) was found to affect long-term survival in patients with a left ventricular assist device, surgeons should be encouraged to perform transplantation in these severely ill patients after a recipient\'s optimization by inotropes or a right ventricular assist device because even when the bilirubin level is elevated in these patients (treated with right ventricular assist device/inotropes), their long-term survival is not affected. Future studies should assess recipients\' optimization before organ acceptance to improve long-term survival.

Patients with cirrhosis of the liver are at high risk of developing portal vein thrombosis (PVT), which has a complex, multifactorial cause. The condition may present with a myriad of symptoms and can occasionally cause severe complications. Contrast-enhanced computed tomography (CT) is the gold standard for the diagnosis of PVT. There are uncertainties regarding the effect on PVT and its treatment outcome in patients with cirrhosis. The main challenge for managing PVT in cirrhosis is analyzing the risk of hemorrhage compared to the risk of thrombus extension leading to complications. All current knowledge regarding non-tumor PVT in cirrhosis, including epidemiology, risk factors, classification, clinical presentation, diagnosis, impact on natural history, and treatment, is discussed in the present article.

UNASSIGNED: Uncertainties exist surrounding the timing of liver transplantation (LT) among patients with acute-on-chronic liver failure grade 3 (ACLF-3), regarding whether to accept a marginal quality donor organ to allow for earlier LT or wait for either an optimal organ offer or improvement in the number of organ failures, in order to increase post-LT survival.
UNASSIGNED: We created a Markov decision process model to determine the optimal timing of LT among patients with ACLF-3 within 7 days of listing, to maximize overall 1-year survival probability.
UNASSIGNED: We analyzed 6 groups of candidates with ACLF-3: patients age ≤60 or >60 years, patients with 3 organ failures alone or 4-6 organ failures, and hepatic or extrahepatic ACLF-3. Among all groups, LT yielded significantly greater overall survival probability vs. remaining on the waiting list for even 1 additional day (p <0.001), regardless of organ quality. Creation of 2-way sensitivity analyses, with variation in the probability of receiving an optimal organ and expected post-transplant mortality, indicated that overall survival is maximized by earlier LT, particularly among candidates >60 years old or with 4-6 organ failures. The probability of improvement from ACLF-3 to ACLF-2 does not influence these recommendations, as the likelihood of organ recovery was less than 10%.
UNASSIGNED: During the first week after listing for patients with ACLF-3, earlier LT in general is favored over waiting for an optimal quality donor organ or for recovery of organ failures, with the understanding that the analysis is limited to consideration of only these 3 variables.
UNASSIGNED: In the setting of grade 3 acute-on-chronic liver failure (ACLF-3), questions remain regarding the timing of transplantation in terms of whether to proceed with liver transplantation with a marginal donor organ or to wait for an optimal liver, and whether to transplant a patient with ACLF-3 or wait until improvement to ACLF-2. In this study, we used a Markov decision process model to demonstrate that earlier transplantation of patients listed with ACLF-3 maximizes overall survival, as opposed to waiting for an optimal donor organ or for improvement in the number of organ failures.

UNASSIGNED: Acute-on-chronic liver failure (ACLF) is usually associated with a precipitating event and results in the failure of other organ systems and high short-term mortality. Current prediction models fail to adequately estimate prognosis and need for liver transplantation (LT) in ACLF. This study develops and validates a dynamic prediction model for patients with ACLF that uses both longitudinal and survival data.
UNASSIGNED: Adult patients on the UNOS waitlist for LT between 11.01.2016-31.12.2019 were included. Repeated model for end-stage liver disease-sodium (MELD-Na) measurements were jointly modelled with Cox survival analysis to develop the ACLF joint model (ACLF-JM). Model validation was carried out using separate testing data with area under curve (AUC) and prediction errors. An online ACLF-JM tool was created for clinical application.
UNASSIGNED: In total, 30,533 patients were included. ACLF grade 1 to 3 was present in 16.4%, 10.4% and 6.2% of patients, respectively. The ACLF-JM predicted survival significantly (p <0.001) better than the MELD-Na score, both at baseline and during follow-up. For 28- and 90-day predictions, ACLF-JM AUCs ranged between 0.840-0.871 and 0.833-875, respectively. Compared to MELD-Na, AUCs and prediction errors were improved by 23.1%-62.0% and 5%-37.6% respectively. Also, the ACLF-JM could have prioritized patients with relatively low MELD-Na scores but with a 4-fold higher rate of waiting list mortality.
UNASSIGNED: The ACLF-JM dynamically predicts outcome based on current and past disease severity. Prediction performance is excellent over time, even in patients with ACLF-3. Therefore, the ACLF-JM could be used as a clinical tool in the evaluation of prognosis and treatment in patients with ACLF.
UNASSIGNED: Acute-on-chronic liver failure (ACLF) progresses rapidly and often leads to death. Liver transplantation is used as a treatment and the sickest patients are treated first. In this study, we develop a model that predicts survival in ACLF and we show that the newly developed model performs better than the currently used model for ranking patients on the liver transplant waiting list.

UNASSIGNED: Significantly worse survival has been reported in patients with hepatopulmonary syndrome (HPS) and partial pressure of arterial oxygen (PaO2) <45 mmHg undergoing liver transplantation. Long-term pre- and post-transplant outcomes based on degree of hypoxaemia were re-examined.
UNASSIGNED: A retrospective analysis of 1,152 HPS candidates listed with an approved HPS model for end-stage liver disease (MELD) exception was performed. A Fine and Gray competing risks model was utilised to evaluate pre-transplant outcomes for PaO2 thresholds of <45, 45 to <60, and ≥60 mmHg. Post-transplant survival was analysed using the Kaplan-Meier method.
UNASSIGNED: Patients with a PaO2 <45 mmHg were significantly more likely to undergo transplantation (hazard ratio [HR] 1.51; 95% CI 1.12-2.03), whereas patients with higher MELD scores had lower hazard of transplant (HR 0.80, 95% CI 0.67-0.95, p = 0.011) and higher hazard of pre-transplant death (HR 2.29, 95% CI 1.55-3.37, p <0.001). Post-transplantation, patients with a PaO2 <45 mmHg had lower survival (p = 0.04) compared with patients with a PaO2 ≥45 to <50 mmHg, with survival curves significantly different at 2.6 years (75% survival compared with 86%) and median survival of 11.5 and 14.1 years, respectively. Cardiac arrest was a more likely (p = 0.025) cause of death for these patients. Cardiac arrest incidence in patients who died with a PaO2 >50 mmHg was 6.2%.
UNASSIGNED: Patients with a PaO2 <45 mmHg had a significantly higher rate of transplantation, and higher calculated MELD scores were associated with significantly higher pre-transplant mortality. Although post-transplant survival was lower in patients with a PaO2 <45 mmHg, the median survival was 11.5 years, and survival curves only became significantly different at 2.6 years. This suggests that patients with HPS do benefit from transplantation up to 2-3 years post-transplant regardless of the severity of pre-transplant hypoxaemia.
UNASSIGNED: A total of 1,152 patients with hepatopulmonary syndrome listed for liver transplant were analysed. Patients with a low PaO2 <45 mmHg had a high likelihood of transplantation. If associated with advanced liver disease, the mortality risk was higher for patients with hepatopulmonary syndrome on the wait list. After liver transplantation, patients with a PaO2 <45 mmHg had a lower survival, but this only became significant after 2.6 years, and the median survival was 11.5 years. This suggests that patients with hepatopulmonary syndrome do benefit from transplantation.