Liver Disease Exception Research Articles

Association of nonstandardized model for end-stage liver disease score exceptions with waitlist mortality in adult liver transplant candidates

In the US liver allocation system, nonstandardized model for end-stage liver disease (MELD) exceptions (NSEs) increase the waitlist priority of candidates whose MELD scores are felt to underestimate their true medical urgency. We determined whether NSEs accurately depict pretransplant mortality risk by performing mixed-effects Cox proportional hazards models and estimating concordance indices. We also studied the change in frequency of NSEs after the National Liver Review Board’s implementation in May 2019. Between June 2016 and April 2022, 60,322 adult candidates were listed, of whom 10,280 (17.0%) received an NSE at least once. The mean allocation MELD was 23.9, an increase of 12.0 points from the mean laboratory MELD of 11.9 (P < .001). A 1-point increase in allocation MELD score due to an NSE was associated with, on average, a 2% reduction in hazard of pretransplant death (cause-specific hazard ratio: 0.98; 95% CI: 0.96, 1.00; P = .02) compared with those with the same laboratory MELD. Laboratory MELD was more accurate than allocation MELD with NSEs in rank-ordering candidates (c-index: 0.889 vs 0.857). The proportion of candidates with NSEs decreased significantly after the National Liver Review Board from 21.5% to 12.8% (P < .001). NSEs substantially increase the waitlist priority of candidates with objectively low medical urgency.

The impact of MELD exception points for hydrothorax on posttransplant mortality: a propensity score-matched analysis.

Hepatic hydrothorax is a challenging complication of end-stage liver disease, and.patients with this complication can receive model for end-stage liver disease (MELD) exception points if they meet specific criteria as defined by United Network for Organ Sharing (UNOS). This research aimed to analyze the effect of receiving MELD exception points for hepatic hydrothorax on posttransplant mortality, using a national transplant database. Patients >18 years in the UNOS database awaiting liver transplant between 2012 and 2023 were identified based on their petition for MELD exception points. Using a 1: 1 propensity score-matched analysis, 302 patients who received MELD exception points for hepatic hydrothorax were compared with 302 patients who did not receive MELD exception points.Demographic, clinical and laboratory values were compared. The primary outcome was posttransplant mortality. Multivariate logistic regression controlled for potential confounders. No significant difference was observed in mean age (58.20 vs 57.62 years), mean initial MELD score (16.93 vs 16.54), or mean Child-Pugh score (9.77 vs 9.74) in patients with hepatic hydrothorax receiving MELD exception points versus their matched cohort who did not recieve exception points. The proportion of males was slightly higher among patients who received MELD exception points (57.6% males vs 53.6% males). A majority of patients in both groups had Child-Pugh grade C (>56%). Patients receiving MELD exception points for hepatic hydrothorax had a statistically significant 44% decrease in the odds of posttransplant death compared to those who did not (OR 0.56; 95% CI 0.37-0.88; P = 0.01). Among the combined cohort, each year increase in age resulted in a 3.9% increase in mortality (OR 1.04; 95% CI 1.01-1.07; P = 0.005), and every one-unit increase in serum creatinine resulted in a 40% increase in mortality (OR 1.40; 95% CI 1.03-1.92; P = 0.03). Receiving MELD exception points for hepatic hydrothorax is associated with a significant reduction in the odds of posttransplant mortality. These findings underscore the importance of MELD exception points for hepatic hydrothorax among patients with decompensated cirrhosis, potentially improving patient prioritization for liver transplantation and influencing clinical decision-making.

Clinical Characteristics Associated With Posttransplant Survival Among Adults 70 Years Old or Older Undergoing Liver Transplantation.

We sought to identify pre-liver transplantation (LT) characteristics among older adults associated with post-LT survival. The proportion of older patients undergoing deceased-donor liver transplantation (DDLT) has increased over time. We analyzed adult DDLT recipients in the United Network for Organ Sharing registry from 2016 through 2020, excluding patients listed as status 1 or with a model of end-stage liver disease exceptions for hepatocellular carcinoma. Kaplan-Meier methods were used to estimate post-LT survival probabilities among older recipients (age ≥70 y). Associations between clinical covariates and post-LT mortality were assessed using Cox regressions. Of 22,862 DDLT recipients, 897 (4%) were 70 years old or older. Compared with younger recipients, older recipients had worse overall survival ( P < 0.01) (1 y: 88% vs 92%, 3 y: 77% vs 86%, and 5 y: 67% vs 78%). Among older adults, in univariate Cox regressions, dialysis [hazards ratio (HR): 1.96, 95% CI: 1.38-2.77] and poor functional status [defined as Karnofsky Performance Score (KPS) <40] (HR: 1.82, 95% CI: 1.31-2.53) were each associated with mortality, remaining significant on multivariable Cox regressions. The effect of dialysis and KPS <40 at LT on post-LT survival (HR: 2.67, 95% CI: 1.77-4.01) was worse than the effects of either KPS <40 (HR: 1.52, 95% CI: 1.03-2.23) or dialysis alone (HR: 1.44, 95% CI: 0.62-3.36). Older recipients with KPS >40 without dialysis had comparable survival rates compared with younger recipients ( P = 0.30). While older DDLT recipients had worse overall post-LT survival compared with younger recipients, favorable survival rates were observed among older adults who did not require dialysis and had poor functional status. Poor functional status and dialysis at LT may be useful to stratify older adults at higher risk for poor post-LT outcomes.

From Patients to Providers: Assessing Impact of Normothermic Machine Perfusion on Liver Transplant Practices in the US.

Normothermic machine perfusion (NMP) of livers allows for the expansion of the donor pool and minimization of posttransplant complications. Results to date have focused on both donor and recipient outcomes, but there remains potential for NMP to also impact transplant providers. Using United Network for Organ Sharing Standard Transplant Analysis file data, adult deceased donors who underwent transplantation between January 1, 2016, and December 31, 2022, were identified. Transplanted livers were divided by preservation methods (static cold storage [SCS] and NMP) and case time (day-reperfusion 8 am to 6 pm ). Patient factors, transplant characteristics, and short-term outcomes were analyzed between Mahalanobis-metric-matched groups. NMP livers represented 742 (1.4%) of 52,132 transplants. NMP donors were more marginal with higher Donor Risk Index scores (1.78 ± 0.50 NMP vs 1.49 ± 0.38 SCS, p < 0.001) and donation after cardiac death frequency (36.9% vs 8.4%, p < 0.001). NMP recipients more often had model for end-stage liver disease (MELD) exception status (29.9% vs 23.4%, p < 0.001), lower laboratory MELD scores (20.7 ± 9.7 vs 24.3 ± 10.9, p < 0.001), and had been waitlisted longer (111.5 [21.0 to 307.0] vs 60.0 [9.0 to 245.0] days, p < 0.001). One-year graft survival (90.2% vs 91.6%, p = 0.505) was similar between groups, whereas length of stay was lower for NMP recipients (8.0 [6.0 to 14.0] vs 10.0 [6.0 to 16.0], p = 0.017) after adjusting for confounders. Notably, peak case volume occurred at 11 am with NMP livers (vs 9 pm with SCS). Overall, a higher proportion of transplants was performed during daytime hours with NMP (51.5% vs 43.0%, p < 0.001). NMP results in increased use of marginal allografts, which facilitated transplantation in lower laboratory MELD recipients who have been waitlisted longer and often have exception points. Importantly, NMP also appeared to shift peak caseloads from nighttime to daytime, which may have significant effects on the quality of life for the entire liver transplant team.

The Clinical Course of Portopulmonary Hypertension and Outcomes With Endothelin Receptor Antagonist Treatment: Observational Study of Data From the US Organ Procurement and Transplantation Network

Background. Portopulmonary hypertension (PoPH) occurs in patients with advanced liver disease and can be a contraindication to liver transplant (LT). Improvement of hemodynamic parameters with pulmonary arterial hypertension (PAH) therapies (including endothelin receptor antagonists [ERAs]) may help some patients to become eligible for LT. Methods. We conducted a retrospective secondary data analysis to describe the clinical course and management of PoPH in patients on a US registry LT waitlist and outcomes in patients receiving an ERA. Results. At the time of LT waitlist entry (1996–2019), patient characteristics and disease severity were similar in the 685 patients with PoPH enrolled overall (LT waitlist data set) and the 420 of them who underwent LT (LT data set). Most patients (92.0%) had a model for end-stage liver disease exception granted before entering the LT waitlist. Patients spent a median of 8.9 mo (interquartile range, 3.7–19.7) on the LT waitlist before undergoing LT. Overall, 77.1% of patients received PAH treatment at LT waitlist entry (ERAs, 30.1%). Hemodynamic parameters improved in ≥95% of patients between the first assessment versus the second (median interval, 9 mo) and last assessments (median interval, 14 mo). At the first assessment, 49.6% of patients had mean pulmonary arterial pressure ≥45 mm Hg versus 2.6% and 1.8% of patients at the second and last assessments, respectively; 47.5% of patients had pulmonary vascular resistance &gt;450 dynes·s/cm5 versus 0.9% and 0.2% of patients at the second and last assessments. One-year survival was 90.6% (95% confidence interval [CI], 87.6-92.9) following LT waitlist entry and was 86.4% (95% CI, 82.6-89.5) after LT; 5-y survival was 67.4% (95% CI, 60.0-73.8) while on the LT waitlist (before LT) and was 75.6% (95% CI, 70.4-80.0) following LT. Conclusions. This large US study of patients with PoPH on an LT waitlist confirms that effective PAH treatments can help patients achieve acceptable hemodynamics, providing the opportunity to undergo LT.

Significant Reduction in Posttransplant Hepatocellular Carcinoma Recurrence in the Post 6-Mo Waiting Policy Era.

In 2015, the United Network for Organ Sharing implemented a policy introducing a 6-mo waiting period before granting model for end-stage liver disease exception points to liver transplant (LT) candidates with hepatocellular carcinoma (HCC). This study analyzes the policy impact on post-LT HCC recurrence. This was a United Network for Organ Sharing retrospective cohort study of patients with HCC who underwent LT from January 1, 2010, to May 31, 2019. HCC-specific data included alpha-fetoprotein, tumor characteristics, locoregional therapy (LRT), and explant data used to calculate the Risk Estimation of Tumor Recurrence After Transplant score. The primary exposure was pre-/post-policy era, divided on October 8, 2015. Survival analysis techniques were used to evaluate the unadjusted and sequentially adjusted association between policy era and HCC recurrence, accounting for competing risks. A total of 7940 patients were included, 5879 (74.0%) pre-policy era and 2061 (26.0%) post-policy era. Post-policy patients were older, received more LRT, and had lower alpha-fetoprotein levels and smaller tumor sizes at transplant. Incidence rates of HCC recurrence were 19.8 and 13.7 events per 1000 person-years for pre- and post-policy eras, respectively. Post-policy era was associated with an unadjusted 35% reduction in the risk of HCC recurrence ( P < 0.001). After adjusting for recipient, donor, and tumor characteristics at listing this association remained (subhazard ratio 0.69; 95% confidence interval, 0.55-0.86; P = 0.001); however, after additionally adjusting for LRT episodes and Risk Estimation of Tumor Recurrence After Transplant score, there was no longer a statistically significant association (subhazard ratio 0.77; 95% confidence interval, 0.59-1.00; P = 0.054). We observed a significant reduction in post-LT HCC recurrence after policy implementation. This may be due to waitlist selection of healthier patients, increased LRT utilization, and potential selection of favorable tumor biology.

Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exception policy and outcomes in pediatric patients with hepatopulmonary syndrome requiring liver transplantation.

Hepatopulmonary syndrome (HPS) is associated with increased waitlist mortality in liver transplantation (LT) candidates. Children with HPS are granted Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) exception points for waitlist prioritization in the United States based on criterion developed for adults. In this study, the impact of this MELD/PELD exception policy on post-LT survival in children was examined. A retrospective cohort of patients aged younger than 18 years with a MELD/PELD exception request who underwent LT between 2007 and 2018 were identified in the Scientific Registry of Transplant Recipients. Patients were stratified by waitlist partial pressure of arterial oxygen (PaO 2 ) to assess risk factors for waitlist mortality and post-LT survival. Among 3082 pediatric LT recipients included in the study, 124 patients (4%) received MELD/PELD exception points for HPS. Patients with HPS were a median age of 9 years (interquartile range: 6, 12 years), 54.8% were girls, and 54% were White. Most patients (87.9%) were listed with laboratory MELD/PELD scores <15. Waitlist mortality for patients with HPS exception points was rare and not different from patients without HPS. When stratified by pre-LT PaO 2 , hypoxemia severity was not associated with differences in 1-, 3-, or 5-year survival rates after LT ( p = 0.13). However, patients with HPS showed a slightly lower survival rate at 5 years compared with patients without HPS (88.7% vs. 93.4%; p = 0.04). MELD/PELD exceptions for children with HPS mitigated waitlist mortality, and recipients with HPS experienced excellent 5-year survival after LT, although slightly lower than in patients without HPS. Unlike adults with HPS, the severity of pre-LT hypoxemia in children does not impact post-LT survival. These data suggest that adult criteria for granting MELD/PELD exception points may not appropriately capture HPS severity in pediatric patients. Further prospective multicenter studies to examine the risk factors predicting negative survival outcomes in children with HPS are warranted.

Temporal Trends in Portopulmonary Hypertension Model for End-stage Liver Disease Exceptions and Outcomes.

Using data from the Organ Procurement and Transplantation Network database, we describe the frequency of POPH MELD exceptions between 2006 and 2019, compare baseline patient characteristics, and characterize trends in liver disease and POPH severity' as well as POPH treatment and outcomes' over time. To facilitate comparison, we divided this 14-y period into 3 "eras" (2006-2010, 2011-2015, and 2016-2019). Between 2006 and 2019, 504 unique POPH MELD exceptions were granted. Both liver disease severity and patient age have increased over time (P = 0.04 and P = 0.006, respectively). Posttreatment hemodynamic values (mean pulmonary arterial pressure and pulmonary vascular resistance) have significantly improved (P < 0.001 and P = 0.008, respectively). Treatment with endothelin receptor antagonists has become more prevalent, whereas use of parenteral therapy and monotherapy regimens has decreased (P < 0.001). Neither waitlist nor liver transplant mortality outcomes have significantly changed over the eras analyzed. In conclusion, 504 patients have received POPH MELD exceptions between 2006 and 2019. Since 2010, nearly all patients granted POPH MELD exceptions have met hemodynamic criteria for POPH. Over time, there has been a trend toward older age and higher MELD scores with significant changes in pulmonary arterial hypertension treatment patterns and an improvement in posttreatment hemodynamics without major change in outcomes.

National Experience on Waitlist Outcomes for Down-Staging of Hepatocellular Carcinoma: High Dropout Rate in All-Comers

The United Network for Organ Sharing (UNOS) grants priority listing for liver transplant for patients with hepatocellular carcinoma after successful down-staging to Milan criteria. We evaluated the national experience on down-staging by comparing 2 down-staging groups: tumor burden meeting UNOS down-staging (UNOS-DS) inclusion criteria, and all-comers (AC)-DS with initial tumor burden beyond UNOS-DS criteria vs patients always within Milan criteria. We performed a retrospective analysis of the UNOS database of 23,398 patients listed for liver transplant who had submitted a hepatocellular carcinoma Model for End-Stage Liver Disease exception application from 2010 to 2019, classified as always within Milan (n= 20,579), UNOS-DS (n= 2151), and AC-DS (n= 668). The 2-year cumulative probabilities of dropout were 19% for Milan, 25% for UNOS-DS (P < .001), and 30% for AC-DS (P < .001). In multivariate analysis of the down-staging groups, factors predicting dropout included Model for End-Stage Liver Disease at listing (hazard ratio [HR], 1.06; P < .001) and initial total tumor diameter (HR, 1.04; P= .002). Compared with α-fetoprotein (AFP) level ≤20 ng/mL, AFP levels of 21 to 100, 101 to 1000, and greater than 1000 ng/mL were associated with a higher risk of dropout (HRs, 1.63, 2.06, and 4.58, respectively; P < .001). A subset of all-comers with AFP levels greater than 100 ng/mL had a 2-year probability of dropout of 52% vs 26% for all others beyond Milan criteria (P < .001). All-comers had a significantly higher risk for waitlist dropout compared with the UNOS-DS and Milan groups after initial successful down-staging to Milan criteria. In particular, the subgroup of AC-DS with an AFP level greater than 100 ng/mL had a greater than 50% probability of dropout in the next 2 years. These observations suggest a high likelihood of failure when expanding the indications for down-staging.

Is there value in volume? An assessment of liver transplant practices in the United States since the inception of MELD

BackgroundLiver transplantation has increased in volume and provides substantial survival benefit. However, there remains a need for value-based assessment of this costly procedure. MethodsModel for end stage liver disease era adult recipients were identified using United Network for Organ Sharing Standard Transplant Analysis file data (n = 75,988) and compared across time periods (period A: February 2002 to January 2007; B: February 2007 to January 2013; C: February 2013 to January 2019). Liver centers were divided into volume tertiles for each period (small, medium, large). Value for the index transplant episode was defined as percentage graft survival ≥1 year divided by mean posttransplant duration of stay. ResultsAll centers increased value over time due to ubiquitous improvement in 1-year graft survival. However, large centers demonstrated the most significant value change (large +17% vs small +7.0%, P < .001) due to a –8.5% reduction in large centers duration of stay from period A to C, while small centers duration of stay remained unchanged (–0.1%). Large centers delivered higher value despite more complex care: older recipients (54.8 ± 10.3 vs 53.0 ± 11.4 years P < .001), fewer model for end stage liver disease exceptions (34.0% vs 38.2%, P < .001), higher rates of candidate portal vein thrombosis (10.1% vs 8.5%, P < .001) and prior abdominal surgery (43.4% vs 37.4%, P < .001), and more marginal donor utilization (donor risk index 1.45 ± 0.38 vs 1.36 ± 0.33, P < .001). Mahalanobis metric matching demonstrated that compared with small centers, large centers progressively shortened recipient duration of stay per transplant in each period (A: –0.36 days, P = .437; B: –2.14 days, P < .001; C: –2.49 days, P < .001). ConclusionThere is value in liver transplant volume. Adoption of value-based practices from large centers may allow optimization of health care delivery for this costly procedure.

Liver Transplant for Nonhepatocellular Malignancies: A Review for Radiologists.

Although liver transplant is traditionally only performed for hepatocellular carcinoma (HCC), the last decade has seen a resurgence in its use for non-HCC malignancies, likely due to improvements in neoadjuvant treatment regimens and the establishment of well-defined eligibility criteria. Given promising survival results, patients with perihilar cholangiocarcinoma, neuroendocrine liver metastases, and hepatic hemangioendothelioma are eligible to receive Model for End-Stage Liver Disease (MELD) exception points for tumors that meet well-defined criteria. Patients with additional tumors such as colorectal cancer liver metastases, intrahepatic cholangiocarcinoma, and hepatocellular cholangiocarcinoma may undergo transplant at specialized centers with well-defined protocols, although these patients are not yet eligible for MELD exception. Transplant eligibility criteria commonly incorporate imaging findings; however, because of the relatively novel and evolving nature of liver transplant for non-HCC malignancies, radiologists may be unaware of relevant criteria or the implications of their imaging interpretations. Knowledge of the allocation process, previous studies, and liver transplant selection criteria facilitates radiologists' active participation in multidisciplinary discussion, leading to better and more equitable care for transplant candidates with non-HCC malignancy. This review provides an overview of transplant allocation and selection criteria in patients with non-HCC malignancy, with an emphasis on imaging features and the role of the radiologist.

Low Utilization of External Beam Radiation Therapy for Patients With Unresectable Hepatocellular Carcinoma: An Analysis of the United Network for Organ Sharing Database

External beam radiation therapy (EBRT) is a safe and emerging bridging liver-directed therapy (LDT) to liver transplant (LT) for patients with hepatocellular carcinoma (HCC). The prevalence and clinical characteristics of patients receiving EBRT as an LDT for LT have not been evaluated. Our aim was to describe the utilization of EBRT in patients with HCC evaluated for LT in the United States. We analyzed United Network for Organ Sharing data from October 2013 to June 2020 and identified patients with HCC who applied for model for end-stage liver disease (MELD) exceptions for LT wait list prioritization. The primary outcome was the period prevalence of EBRT. We examined associations between clinical variables and EBRT and fit survival models with EBRT as a time-varying predictor. We identified 18,543 patients with HCC with MELD exception applications. EBRT was used in 658 patients (3.5%) either alone (1.2%) or combined with other LDT (2.3%). Transarterial chemoembolization was the most used LDT (59.3%), followed by thermal ablation (27.9%) and radioembolization (15.2%). EBRT prevalence rose by an average of 12.2% per year (P=.001). Use of EBRT differed by geographic region, ranging from 2% to 8% (P < .001). EBRT and no EBRT groups had similar initial MELD score, portal vein thrombosis, tumor diameter, number of tumors, bilirubin, and α-fetoprotein (P > .05). Median time-to-transplant from wait list registration for EBRT versus no EBRT groups was 10 months (95% confidence interval, 9.4-10.9) versus 11.9 months (95% confidence interval, 11.7-12.2; P < .001). Evaluated as a time-varying predictor, EBRT increased the risk of LT by 30% (sub-hazard ratio, 1.30; P < .001), while the effect of EBRT on the risk of wait list removal due to clinical deterioration or death (sub-hazard ratio, 1.07; P=.489) was nonsignificant. In the United States, EBRT is rarely used compared with other LDTs and exhibits geographic variation. Low EBRT utilization highlights a gap in the treatment armamentarium for HCC.

Use of neural network models to predict liver transplantation waitlist mortality.

Current liver transplantation (LT) organ allocation relies on Model for End-Stage Liver Disease-sodium 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, 2002, and June 30, 2021, using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. We excluded patients listed with Model for End-Stage Liver Disease (MELD) exception scores and those listed for multiorgan transplant, except for liver-kidney transplant. A subset of data from the waiting list was used to create a mortality prediction model at 90days after listing with 105,140 patients. A total of 28 variables were selected for model creation. The data were split using random sampling into training, validation, and test data sets in a 60:20:20 ratio. The performance of the model was assessed using area under the receiver operating curve (AUC-ROC) and area under the precision-recall curve (AUC-PR). AUC-ROC for 90-day mortality was 0.936 (95% confidence interval [CI], 0.934-0.937), and AUC-PR was 0.758 (95% CI, 0.754-0.762). The NN 90-day mortality model outperformed MELD-based models for both AUC-ROC and AUC-PR. The 90-day mortality model specifically identified more waitlist deaths with a higher recall (sensitivity) of 0.807 (95% CI, 0.803-0.811) versus 0.413 (95% CI, 0.409-0.418; p<0.001). The performance metrics were compared by breaking the test data set 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.

Mending the Model for End-Stage Liver Disease: An in-depth review of the past, present, and future portopulmonary hypertension Model for End-Stage Liver Disease exception.

Patients with portopulmonary hypertension (POPH) have an increased cardiovascular and overall mortality risk when undergoing liver transplantation (LT). However, such risk is not captured in their Model for End-Stage Liver Disease (MELD) laboratory score. POPH MELD exception criteria were established in 2006 with the aim of prioritizing these patients for LT prior to pulmonary hypertension (PH) progression and eventual right heart failure. The original criteria emphasized a posttreatment, pre-LT mean pulmonary arterial pressure (mPAP) of <35mmHg and pulmonary vascular resistance (PVR) <400 dynes-s-cm-5 or <5Wood units (WU). Since 2006, there have been important advances in the treatment of POPH with pulmonary arterial hypertension (PAH)-targeted therapies and newer evidence regarding LT outcomes and risk factors for perioperative mortality. Specifically, PVR rather than mPAP has been shown to be more strongly associated with outcomes, including mortality. In addition, among treated patients with POPH, mPAP may be persistently elevated related to an elevated cardiac output or other factors that do not necessarily reflect POPH disease severity. Thus, in February 2021, the Organ Procurement and Transplantation Network approved proposed modifications to POPH MELD exception criteria, now allowing either of the following posttreatment, pre-LT hemodynamic profiles: mPAP less than 35mmHg and posttreatment PVR less than 400 dynes-s-cm-5 (or less than 5WU) or mPAP greater than or equal to 35mmHg and less than 45mmHg and posttreatment PVR less than 240 dynes-s-cm-5 (or less than 3WU). This article reviews the history of the POPH MELD exception criteria, describes the recent modifications to the exception criteria and the evidence supporting them, and highlights unanswered questions and areas for future research.

National experience with living donor liver transplantation for hepatocellular carcinoma.

Living donor liver transplantation (LDLT) is an attractive option to decrease waitlist dropout, particularly for patients with hepatocellular carcinoma (HCC) who face lengthening waiting times. Using the United Network for Organ Sharing (UNOS) national database, trends in LDLT utilization for patients with HCC were evaluated, and post-LT outcomes for LDLT versus deceased donor liver transplantation (DDLT) were compared. From 1998 to 2018, LT was performed in 20,161 patients with HCC including 726 (3.6%) who received LDLT. The highest LDLT utilization was prior to the 2002 HCC Model for End-Stage Liver Disease (MELD) exception policy (17.5%) and dropped thereafter (3.1%) with a slight increase following the 6-month wait policy in 2015 (3.8%). LDLT was more common in patients from long-wait UNOS regions with blood type O, in those with larger total tumor diameter (2.3 vs. 2.1cm, p=0.02), and higher alpha-fetoprotein at LT (11.5 vs. 9.0ng/ml, p=0.04). The 5-year post-LT survival (LDLT 77% vs. DDLT 75%), graft survival (72% vs. 72%), and HCC recurrence (11% vs. 13%) were similar between groups (all p>0.20). In conclusion, LDLT utilization for HCC has remained low since 2002 with only a slight increase after the 6-month wait policy introduction in 2015. Given the excellent post-LT survival, LDLT appears to be an underutilized but valuable option for patients with HCC, especially those at high risk for waitlist dropout.

Long-Term Outcomes of Living Donor Versus Deceased Donor Liver Transplant for Hepatocellular Carcinoma in the United States.

Although living donor liver transplant has become a vital treatment option in hepatocellular carcinoma, controversy remains on whether recurrence and survival rates are different versus deceased donor recipients. Here, we compared clinical characteristics and outcomes between recipients of living and deceased donor liver transplants for hepatocellular carcinoma in the United States. Our comparisons used data from the United Network of Organ Sharing/Organ Procurement and Transplantation Network. There were 385 living donor and 25 274 deceased donor liver transplant recipients with diagnosis of hepatocellular carcinoma. Transplant list wait times of ≥6 months were more common in deceased donor(55.9%) versus living donor recipients (45.2%; P < .001). Both recipient groups were comparable with regard to alpha-fetoprotein level <200 ng/mL (P = .18). Only a small percentage in both groups had ≥3 total tumors (P = .73); both groups had similar low transplants outside of Milan criteria (P = .45). Overall, 1-, 5-, and 10-year overall survival rates for deceased versus living donor recipients were similar (91.2% vs 92%, 74% vs 76.4%, 58.9% vs 56.5%; P = .69). On multivariate analysis, Black/African American race/ethnicity was associated with worse outcomes than White race/ethnicity as reference (P < .001), whereas Hispanic and Asian race/ethnicity were more protected. Hepatitis C virus as liver disease etiology was associated with worse outcomes than other etiologies. Tumor characteristics, ≥3 lesions, tumor size, and higher alpha-fetoprotein levels were associated with worse outcomes. Living donor transplant was not associated with higher hazard of death. Among living donor recipients only, largest tumor size was associated with higher risk of death (P = .005). Survival was similarin between the living donor versus deceased donor recipients with hepatocellular carcinoma. With changes in Model for End-Stage Liver Disease exception policies for hepatocellular carcinoma in the United States, living donor transplant for hepatocellular carcinoma could expand the donor pool.

Are Current National Review Board Downstaging Protocols for Hepatocellular Carcinoma Too Restrictive?

Liver transplantation (LT) is an effective strategy for patients with unresectable hepatocellular carcinoma (HCC). To qualify for standardized LT model for end-stage liver disease exception points, the United Network for Organ Sharing National Liver Review Board (NLRB) requires that the presenting and final HCC tumor burden be within the University of California San Francisco criteria, which were recently expanded (within expanded UCSF [W-eUCSF]). Current NLRB criteria may be too restrictive because it has been shown previously that the initial burden does not predict LT failure when tumors downstage to UCSF. This study aims to assess LT outcomes for HCC initially presenting beyond expanded UCSF (B-eUCSF) criteria in a large multicenter collaboration. Comparisons of B-eUCSF and W-eUCSF candidates undergoing LT at seven academic institutions between 2001 and 2017 were made from a multi-institutional database. Survival outcomes were compared by Kaplan-Meier and Cox regression analyses. Of 1,846 LT recipients with HCC, 86 (5%) met B-eUCSF criteria at initial presentation, with the remainder meeting W-eUCSF criteria. Despite differences in tumor burden, B-eUCSF candidates achieved comparable 1-, 5- and 10-year overall (89%, 70%, and 55% vs 91%, 74%, and 60%, respectively; p = 0.2) and disease-free (82%, 60%, and 53% vs 89%, 71%, and 59%, respectively; p = 0.07) survival to patients meeting W-eUCSF criteria after LT. Despite increased tumor recurrence in B-eUCSF vs W-eUCSF patients (24% vs 10%, p = 0.0002), post-recurrence survival was similar in both groups (p = 0.69). Transplantation for patients initially presenting with HCC B-eUSCF criteria offers a survival advantage similar to those with tumors meeting W-eUCSF criteria at presentation. The current NLRB policy is too stringent, and considerations to expand criteria should be discussed.

Lower Alpha-Fetoprotein Threshold of 500 ng/mL for Liver Transplantation May Improve Posttransplant Outcomes in Patients With Hepatocellular Carcinoma.

Under current United Network for Organ Sharing (UNOS) policy, patients with hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) levels ≥1000 ng/mL are required to show a reduction in AFP level to <500ng/mL before liver transplantation (LT). However, effects of AFP reduction on post-LT HCC outcomes among patients with HCC with moderately elevated AFP levels between 100 and <1000ng/mL are unclear. Adults in the UNOS registry who underwent LTs from January 2005 to September 2015 with initial AFP levels of 100 to 999ng/mL at listing for Model for End-Stage Liver Disease exceptions were included. Primary predictor was AFP level at LT, categorized as <100, 100 to 499, or ≥500ng/mL, and patients with only 1 recorded pre-LT AFP value (AFP 1-value). Survival was compared using the Kaplan-Meier curve method. Factors associated with post-LT survival and HCC recurrence were assessed in a multivariable Cox regression model. Among 1766 included patients, 50.2% had AFP 1-value, followed by 24.7%, 18.9%, and 6.2% with AFP levels <100, 100 to 499, and ≥500ng/mL, respectively. The 5-year post-LT survival rate was lowest in the AFP ≥500 category, at 56.1%, compared with 72.7%, 70.4%, and 65.6% in the AFP <100, 100 to 499ng/mL, and AFP 1-value categories, respectively. In multivariable analysis, AFP ≥500 ng/mL at LT was associated with a greater risk of post-LT death (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.1-2.1) and HCC recurrence (HR, 1.9; 95% CI, 1.1-3.1) when compared with the AFP <100ng/mL category; other significant variables included donor risk index, age, race/ethnicity, Child-Turcotte-Pugh class, and tumor diameter. Among AFP levels ≥500 ng/mL at LT, 40.4% had AFP levels ≥1000, but no difference in post-LT survival or recurrence was seen between those patients with AFP levels < or ≥1000ng/mL. Mandating AFP <500 ng/mL at LT for all patients, not only for those with initial AFP levels ≥1000ng/mL, may improve post-LT outcomes and can be considered in future UNOS policy.

Changing Map of Liver Transplantation for HCC Following Implementation of New Acuity Circle Allocation System – Efforts to Overcome Disparities by Creating a New One

Introduction: The introduction of acuity circles-based allocation and change in the model for end-stage liver disease (MELD) exception points for hepatocellular carcinoma (HCC) has created a difference in transplant opportunity for hepatocellular carcinoma (HCC) patients.

Predictors of outcomes following liver transplant in hepatopulmonary syndrome: An OPTN database analysis

Hepatopulmonary syndrome (HPS) is a type of pulmonary vascular disease occurring exclusively in those with underlying liver disease, associated with significant mortality in patients awaiting liver transplantation (LT). LT is curative in HPS, and these patients are granted Model for End Stage Liver Disease (MELD) exception points to expedite LT. The purpose of this study is to use multivariable competing risk Accelerated Failure Time models and propensity matching to examine the relationship between pre-LT hypoxemia and post-LT outcomes in HPS. We performed a retrospective cohort study of UNOS/OPTN database of all adult patients undergoing LT between January 1, 2006 and January 12, 2020. Pre-LT PaO2 was significantly associated with post-LT mortality in HPS, with each 1 mmHg increase in PaO2 significantly decreasing the risk of post-LT mortality (coefficient 0.039, HR = 0.95, p = 0.001). HPS patients with a pre-LT PaO2 < 54 mmHg demonstrated increased mortality following LT as compared to matched non-HPS cirrhotic patients. We conclude that HPS patients with a PaO2, 54 mmHg are at increased risk of post-LT mortality and may identify high-risk patients who would benefit from additional resources during LT, and that the effects of HPS MELD exception points to optimize post-LT outcomes should be continuously re-evaluated.