End-Stage Liver Disease Exception Points Research Articles

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.

Outcomes in Hepatocellular Carcinoma Liver Transplantation before and after the Mandated Six-Month Wait Time

The United Network for Organ Sharing (UNOS) implemented a policy that requires patients with hepatocellular carcinoma seeking liver transplantation to wait six months before being granted Model for End-Stage Liver Disease exception points. We investigated the difference in resource utilization between patients who underwent liver transplantation before and after the present policy. We conducted a retrospective cohort study of adult liver transplants from 2013 to 2018. Patients were classified into prepolicy or postpolicy groups based on 964 days before or after the wait-time policy. We also retrieved national survival outcome data from United Network for Organ Sharing. Differences across compared groups for continuous variables were assessed using the independent sample t test, and the chi-squared test was used for binary variables. We found statistical differences in recipient age (P = 0.005), days on wait-list (P = 0.001), sustained virological response (P < 0.001), and hepatocellular carcinoma recurrence one year posttransplant (P = 0.04). There were statistically significant differences in the number of treatment days pretransplant and length of transplant admission stay, indicating an increase in resource utilization in the postpolicy group. No statistically significant differences were found between groups in one-year graft or patient survival despite an observed increase in resource utilization by the hepatocellular carcinoma postpolicy group.

Risk Factors for Dropout From the Liver Transplant Waiting List of Hepatocellular Carcinoma Patients Under Locoregional Treatment

BackgroundIn new organ allocation policy, patients with hepatocellular carcinoma (HCC) experience a 6-month delay in being granted Model for End-Stage Liver Disease exception points. However, it may not be fair for patients at risk of early progression of HCC. MethodsAll patients who were diagnosed as United Network for Organ Sharing (UNOS) stage 1 or 2 of HCC between January 2004 and December 2012 were included. Patients who received surgical resection or liver transplant (LT) as a primary treatment and who did not receive any treatment for HCC were excluded. Patients with baseline Model for End-Stage Liver Disease score ≥22 were also excluded because they have a higher chance of receiving LT. Patients who developed extrahepatic progression within 1 year were considered as high-risk for early recurrence after LT. ResultsA total of 586 patients were included. Mean (SD) age was 59.9 (10.3) years and 409 patients (69.8%) were men. The cumulative incidence of estimated dropout was 8.9% at 6 months; size of the maximum nodule (≥3 cm) and nonachievement of complete response were independent factors. Extrahepatic progression developed in 16 patients (2.7%) within 1 year; size of the maximum nodule (4 cm) and alpha-fetoprotein level (>100 ng/mL) were independent predictors. ConclusionsThe estimated dropout rate from the waiting list within 6 months was 8.9%. Advantage points might be needed for patients with maximum nodule size ≥3 cm or those with noncomplete response. However, in patients with maximum nodule size ≥4 cm or alpha-fetoprotein level >100 ng/mL, caution is needed.

Liver Transplant Waitlist Outcomes and the Allocation of Hepatocellular Carcinoma Model for End-Stage Liver Disease Exception Points at a Low-Volume Center

BackgroundOrgan scarcity continues to be the main problem limiting the number of liver transplants performed. Outcomes of patients waitlisted for an organ in an Asian country with low organ donation rate have not been well evaluated. Our current policy of allocating 15 exception points to patients with hepatocellular carcinoma (HCC) to render them competitive for a transplant also requires review. MethodsThe waiting list registry and the organ transplant registry of a single institution in Asia were reviewed from December 2005 to June 2016 for all patients who underwent liver transplantation. Patient characteristics and outcomes of waitlist dropouts were evaluated. Statistical analyses were performed using SPSS version 20.0. ResultsOne hundred seventy-three patients were waitlisted for a deceased donor liver-only transplant. The most common etiology of liver disease was hepatitis B, followed by cholestatic diseases. Approximately half of the patients had HCC (45.6%). Priority listing for transplant comprised 15.6% of cases. Median Model for End-Stage Liver Disease (MELD) at listing was 15, and median waiting time to transplant was 17 weeks (interquartile range = 6.5–43.5). Overall, 89 (51.4%) patients underwent liver transplantation and 68 (39.3%) dropped out. For patients with HCC, the most common cause of dropout was progression beyond University of California San Francisco transplant criteria (62.5%). The cumulative incidence of dropout at 3 months among patients with HCC who received exception MELD scores was 11%. This was higher than those listed with physiologic MELD of 14–16 points (7%) but lower than those with 17–19 points (16%). ConclusionsHepatitis B-related liver disease and HCC comprise the majority of patients listed for liver transplant. Dropout rates are high and this is due to the lack of donor organs. The current policy of allocating 15 exception MELD points to patients with HCC within transplant criteria may underestimate the dropout risk of patients with HCC in our population.

Model for end-stage liver disease exception points for treatment-responsive hepatocellular carcinoma.

Model for end-stage liver disease exception points for treatment-responsive hepatocellular carcinoma.

Portopulmonary Hypertension and Hepatopulmonary Syndrome: Is Transplant Always the Answer?

Portopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are two well-described liver–lung diseases. POPH is present in 5–10 % of patients with cirrhosis and is defined by the development of pulmonary arterial hypertension in the setting of portal hypertension. All patients who undergo a liver transplant (LT) evaluation are screened for this with a transthoracic echocardiogram, and if POPH is diagnosed, this may serve as a relative contraindication for a LT. If a patient with mild to moderate POPH responds to medical therapy, a LT may still be an option. HPS is more common affecting up to 30 % of patients with cirrhosis. These patients will have abnormal arterial oxygenation related to dilated intrapulmonary microvasculature. The development of HPS is an indication for a LT. Both of these conditions are recognized to increase morbidity and mortality, and a transplant center can apply for Model for End-Stage Liver Disease exception points in order to decrease a patient’s waitlist time.

Variable Use of Model for End-Stage Liver Disease Exception Points in Patients With Neuroendocrine Tumors Metastatic to the Liver and Its Impact on Patient Outcomes.

The role of liver transplantation in management of patients with metastatic neuroendocrine tumors (NETs) is controversial. Because many such patients have low waitlist priority, centers may apply for model for end-stage liver disease (MELD) exception points to increase likelihood of receiving a liver transplant. No formal criteria exist for application or receipt of exception points for this indication. Few studies have assessed waitlist and posttransplantation outcomes in patients with metastatic NETs, and none examined the impact of exception points. We analyzed all adult patients waitlisted for liver transplantation for metastatic NETs between February 27, 2002, and June 4, 2014, and fit a multivariable model to evaluate the association between exception point status and posttransplantation outcomes. There was variable use of MELD exception points across the United Network for Organ Sharing regions. Patients with an approved MELD exception were nearly twice as likely to be transplanted as those without exceptions (70.8% vs 39.1%, P < 0.001), and half as likely to be removed for death or clinical deterioration (9.2% vs 18.2%, P = 0.046). In multivariable models, posttransplantation survival was not associated with receipt of exception points, whereas risk of posttransplant mortality increased significantly with elevated serum total bilirubin level at transplantation. The 3-year posttransplant patient survival was 78% in transplant recipients with metastatic NETs whose total bilirubin level at transplantation was 1.3 mg/dL or less, compared to 36% in those with total bilirubin greater than 1.3 mg/dL. Serum total bilirubin may serve as a predictor of poor posttransplant survival in patients with metastatic NETs and could help risk-stratify patients applying for MELD exception points.

Heterogeneity and Disparities in the Use of Exception Scores in Pediatric Liver Allocation

Physicians apply for Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exception points on a case-by-case basis to improve an individual patient's chances of receiving a liver transplant. This retrospective cohort study describes trends in the use of exceptions among the pediatric liver waitlist population with chronic liver disease. The cohort (n = 3728) included all children with a diagnosis of chronic liver disease listed in the United Network for Organ Sharing transplant database for first isolated liver transplant between February 27, 2002 and March 31, 2013. Exception score requests were common (34%); 90% of requests were approved. The rate of exception score requests in 2013 was five times that of 2002 (incident rate ratios [IRR] 5.25, 95% confidence interval [CI] 3.19-8.63, p < 0.01). Patients of non-White race had exception score request rates 13% lower than patients of White race (IRR 0.87, 95% CI 0.77-0.98, p = 0.02). Older patients had lower rates of exception score requests than younger patients (p = 0.03). Request rates varied by region. Time spent at an active exception status nearly tripled the hazard rate for transplantation (hazard ratio = 2.90, 95% CI 2.62-3.21, p < 0.01). There is disparity in use of exceptions by race that is not explained by clinical disease severity, diagnosis, geography or other demographic factors.

Evaluating the validity of model for end-stage liver disease exception points for hepatocellular carcinoma patients with multiple nodules

Liver transplant allocation policy does not give model for end-stage liver disease (MELD) exception points for patients with a single hepatocellular carcinoma (HCC) <2cm in size, but does give points to patients with multiple small nodules. Because standard-of-care imaging for HCC struggles to differentiate HCC from other nodules, it is possible that a subset of patients receiving liver transplant for multiple nodules <2cm in size does not have HCC. We evaluate risk of post-transplant HCC recurrence and wait-list dropout for patients with multiple small nodules using competing risks regression based on the Fine and Gray model. We identified 5002 adult HCC patients in the OPTN/UNOS dataset diagnosed and transplanted between January 2006 and September 2010. Compared to patients with >1 tumor <2cm, risk of developing recurrence was significantly higher in patients with one or more tumors with only one tumor ≥2cm (SHR 1.63, p=0.009), as well as in patients with 2-3 tumors ≥2cm (SHR 1.84, p=0.02). Dropout risk was not significantly different among size categories. HCC recurrence risk was significantly lower in patients with multiple nodules <2cm in size than in those with larger tumors, supporting the possibility that some patients received unnecessary transplants. The priority given to these patients must be re-examined.

The Migrated Liver Transplantation Candidate: Insight into Geographic Disparities in Liver Distribution

A minority of liver transplantation (LT) candidates pursue listing at multiple centers to achieve transplantation. The purpose of this study was to assess the characteristics and outcomes of the migrated LT candidates, that is, those who travel to secondary centers seeking LT. Single-center retrospective study from January 1, 2005 to January 1, 2013 at a tertiary care center within United Network for Organ Sharing Region 1. Adult recipients who were listed at the primary center of interest, but subsequently achieved transplantation at a secondary center (Massachusetts General Hospital [MGH]-migrated; n= 44) were compared with recipients who achieved LT at the primary center (MGH-transplanted; n= 279). The MGH-migrated recipients most frequently traveled to United Network for Organ Sharing Region 3 (70.5%), with a mean (±SD) distance traveled of 1,134 (±392) miles. The MGH-migrated patients, when compared with MGH-transplanted recipients, spent more time on the waitlist (907.6 ± 930.1 days vs 354.9 ± 533.2 days; p < 0.00001), were more likely to have cholestatic liver disease (22.7% vs 6.8%; p= 0.0006) and private insurance (80.0% vs 51.6%; p= 0.0005), but were less likely to have alcoholic liver disease (2.3% vs 18.6%; p= 0.006) and Model for End-Stage Liver Disease exception points (6.8% vs 50.9%; p < 0.00001). On multivariable analysis, candidates with private insurance who lacked both alcoholic liver disease and Model for End-Stage Liver Disease exception point listing were significantly associated with the odds of pursuing migration. Despite achieving LT, MGH-migrated patients had inferior 5-year patient survival rates (63% vs 80%; p= 0.03). A small and distinctive cohort of LT recipients pursue migration to achieve transplantation. Travel patterns of migrated LT recipients appear to reflect the ongoing geographic disparities in liver distribution and underscore the need for alterations in policy to allow for equitable distribution.

Wait and Transplant for Stage 2 Hepatocellular Carcinoma With Deceased-Donor Liver Grafts

The method which donor organs are allocated to individuals on the waiting list for transplant is an important topic for research and debate. In recent years, there has been growing interest in applying the concept of utilitarianism to the organ allocation system, seeking the maximum survival benefit of the patient population as a whole, rather than that of an individual patient (1). Ideally, exceptions points were created to allow hepatocellular carcinoma (HCC) patients a fair access to the donor pool. However, the current allocation Model for End-stage Liver Disease exception points seem to overestimate the risk disease progression and dropout in HCC patients, and the likelihood of undergoing a liver transplantation still remains higher for HCC candidates in the United States (2). Therefore, an intention-to-treat analysis, such as that published in Transplantation by Chan et al. (3), is a promising tool to optimize organ donation in a more fair way. Tumor size has been associated with the risk of metastasis and HCC progression (4). Whether or not the Milan criteria could be extended without increasing waiting list mortality for non-HCC candidates depends on the availability of organs in each specific region. Thus, an optimal selection of the HCC patients for liver transplantation has an upmost importance in regions with a low donation rate. The wait-and-transplant policy proposed by Chan et al. provided almost the same chances of being transplanted for HCC and non-HCC patients, and the survival rates of those who were transplanted were almost the same in both groups (40.4% vs. 37.9%, respectively). However, most of the HCC patients in the waiting list died (n=18) or had to be excluded because of disease progression (7), and at the end of study, only 5 patients remained in conditions of being transplanted. As a matter of a fact, liver transplantation could not be offered in 48.2% (25/52) of the HCC patients. On the other hand, only 26.2% (27/103) of the non-HCC patients died in the waiting list during the same period, so 34.9% (35/103) of the non-HCC patients still had chances of receiving a liver graft when the study was ended. According to the intention-to-treat analysis, all alive and active patients should be considered as having a potential for long-term survival, regardless if they were transplanted or not. Although the outcomes of the patients who were still alive in the waiting list are unpredictable, a significant fraction of them probably will be transplanted in the following months, increasing the transplant patient rate and, consequently, the overall survival in the non-HCC group. We agree that wait-and-transplant policy is an interesting idea to avoid unnecessary liver transplant for patients at great risk of early tumor progression and recurrence, like the HCC candidates beyond the Milan criteria. The scenario of organ shortage increases even more the need to improve patient selection, but it seems to us that a shorter waiting period policy (3 months) could also combine the selection benefits of the 6-month wait-and-transplant policy with a lower dropout and mortality rate on the waiting list. Another argument reinforcing this idea is the fact that HCC patients who underwent living donor liver transplantation in the same study also achieved excellent postoperative survival outcomes despite a medium waiting time to transplant of 8.5 days. Cleber Rosito Pinto Kruel Aljamir D. Chedid Tomaz J.M. Grezzana-Filho Serviço de Cirurgia Digestiva Hospital de Clínicas de Porto Alegre Ramiro Barcelos, Porto Alegre RS, Brazil

Impact of the Hepatopulmonary Syndrome MELD Exception Policy on Outcomes of Patients After Liver Transplantation: An Analysis of the UNOS Database

Patients with hepatopulmonary syndrome (HPS) are prioritized for liver transplantation (given exception points) due to their high pre- and post-transplantation mortality. However, few studies have evaluated the outcomes of these patients. We performed a retrospective cohort study using data submitted to the United Network for Organ Sharing in a study of the effects of room-air oxygenation on pre- and post-transplantation outcomes of patients with HPS. We identified thresholds associated with post-transplantation survival using cubic spline analysis and compared overall survival times of patients with and without HPS. From 2002 through 2012, nine hundred and seventy-three patients on the liver transplant waitlist received HPS exception points. There was no association between oxygenation and waitlist mortality among patients with HPS exception points. Transplant recipients with more severe hypoxemia had increased risk of death after liver transplantation. Rates of 3-year unadjusted post-transplantation survival were 84% for patients with PaO2 of 44.1-54.0 mm Hg vs 68% for those with PaO2 ≤ 44.0 mm Hg. In multivariable Cox models, transplant recipients with an initial room-air PaO2 ≤ 44.0 mm Hg had significant increases in post-transplantation mortality (hazard ratio = 1.58; 95% confidence interval [CI]: 1.15-2.18) compared with those with a PaO2 of 44.1-54.0 mm Hg. Overall mortality was significantly lower among waitlist candidates with HPS exception points than those without (hazard ratio = 0.82; 95% CI: 0.70-0.96), possibly because patients with HPS have a reduced risk of pre-transplantation mortality and similar rate of post-transplantation survival. Although there was no association between pre-transplantation oxygenation and waitlist survival in patients with HPS Model for End-Stage Liver Disease exception points, a pre-transplantation room-air PaO2 ≤ 44.0 mm Hg was associated with increased post-transplantation mortality. HPS Model for End-Stage Liver Disease exception patients had lower overall mortality compared with others awaiting liver transplantation, suggesting that the appropriateness of the HPS exception policy should be reassessed.

Center variation in the use of nonstandardized model for end-stage liver disease exception points

The Model for End-Stage Liver Disease (MELD) score is an imperfect prognosticator of waitlist dropout, so transplant centers may apply for exception points to increase a waitlist candidate's priority on the waitlist. Exception applications are categorized as recognized exceptional diagnoses (REDs; eg, hepatocellular carcinoma) and non-REDs (eg, cholangitis). Although prior work has demonstrated regional variation in the use of exceptions, no work has examined the between-center variability. We analyzed all new waitlist candidates from February 27, 2002 to June 3, 2011 to explore variations in the use of non-REDs, for which no strict exception criteria exist. There were 58,641 new waitlist candidates, and 4356 (7.4%) applied for a non-RED exception. The number of applications increased steadily over time, as did the approval rates for such applications: from <50% in 2002 to nearly 75% in 2010. When we adjusted for patient factors, there was significant variability (P < 0.001) in the use of non-RED exceptions in 8 of 11 United Network for Organ Sharing (UNOS) regions and in the approval of these exceptions in 6 of 11 UNOS regions. The variability in the use and approval of non-REDs was clinically significant: waitlist candidates with approved exceptions were significantly more likely to undergo transplantation (68.3% versus 53.4%, P < 0.001) and were less likely to be removed for death or clinical deterioration (10.4% versus 16.2%, P < 0.001). Increased median MELD score at transplantation within a donor service area was the only center factor associated with increased odds of applying for exceptions, while no center factors were associated with having non-RED exceptions approved. Further work is needed to identify other sources of variation to ensure the appropriate and equitable use of non-RED exceptions.

Liver transplantation in septuagenarians receiving model for end-stage liver disease exception points for hepatocellular carcinoma: The national experience

We thank Dr. Perkins1 for lending his perspective on the complicated issue of performing transplantation for elderly patients with hepatocellular carcinoma, and we submit that the frequency with which transplant selection committees face this issue is greater than what most readers appreciate. Because the publicly available Scientific Registry of Transplant Recipients database does not further stratify patients older than 65 years, we have returned to the Standard Transplant Analysis and Research files2 and have determined that the actual percentage of septuagenarians undergoing liver transplantation with respect to the entire liver transplant database is 1.52% (ie, 1602 of 105,405 patients). With the rough figure of 1.5%, septuagenarians account for approximately 90 transplants per year (if we assume that roughly 6000 transplants are performed annually). In fact, in the most recent year for which data are available, 143 septuagenarians underwent transplantation. This is double the figure quoted for the increase in liver transplants to be expected from proposed changes in organ allocation policy. For example, liver simulated allocation modeling predicts 77 fewer deaths per year across all regions if a wholesale regional distribution policy is enacted.3 With the controversy surrounding recent changes in organ allocation as a backdrop, certainly the fate of 90 to 140 transplants per year is worth discussing. Often, as Perkins points out,1 the decision to approve an elderly patient for liver transplantation is framed in terms of the justice-versus-utility equation. In these cases, we agree with Perkins that the availability of other treatment options and a particular recipient's expected survival (both with and without liver transplantation) must be taken into consideration. In our study,4 we revealed that on the national stage, elderly liver transplant recipients (≥70 years) have a 5-year survival rate of only 55.2%. However, in contrast to younger cohorts, a diagnosis of hepatocellular carcinoma in this age group does not appear to influence survival (the rates are equally poor). Because survival is no different for elderly cohorts with and without hepatocellular carcinoma, on the basis of current United Network for Organ Sharing policy (which does not limit transplantation at the extremes of age), we have concluded that as long as chronological age does not eliminate an individual's transplant candidacy, a tumor diagnosis should not prejudice the granting of Model for End-Stage Liver Disease exception points for elderly recipients otherwise falling within accepted criteria for transplantation. However, we believe that Perkins1 may have misinterpreted our intentions. Basing our conclusions on current policy does not in any way speak to the policy's wisdom or signal support for the aggressive pursuit of liver transplantation in patients at advanced age. In fact, we are in agreement with Perkins that if patients in the same elderly subgroup were to undergo radiofrequency ablation, there would be lower cost expenditures, less morbidity, and similar, or perhaps even greater survival. In our article,4 we were merely attempting to frame the issue in the context of the national data and as a logical extension of allocation policy as it is currently written. In doing so, we hope that the availability of these data will be of use to members of transplant selection committees, policy makers, and others tasked with determining the eligibility of transplant recipients. Jason Schwartz M.D.*, Heather Thiesset M.P.H. , Terry Box M.D. , William Hutson M.D.§, John Sorensen, M.D. , * Division of Surgical Transplantation Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, Departments of General Surgery (Section of Transplantation), Medicine, University of Utah Salt Lake City, UT, § Division of Gastroenterology and Hepatology University of Maryland School of Medicine College Park, MD.

Liver transplantation in septuagenarians receiving model for end-stage liver disease exception points for hepatocellular carcinoma: The national experience

Current liver allocation policy in the United States grants liver transplant candidates with stage T2 hepatocellular carcinoma (HCC) a priority Model for End-Stage Liver Disease (MELD) score of 22, regardless of age. Because advanced age may portend an increase in all-cause mortality after transplantation for any diagnosis, the aim of this study was to examine overall posttransplant survival in elderly patients with HCC versus younger cohorts. Based on Organ Procurement and Transplantation Network data, Kaplan-Meier 5-year survival rates were compared. Recipients undergoing primary liver transplantation were stratified into cohorts based on age (<70 or ≥ 70 years) and the receipt of MELD exception points for HCC. Log-rank and Wilcoxon tests were used for statistical comparisons. In 2009, 143 transplants were performed for patients who were 70 years old or older. Forty-two percent of these patients received a MELD exception for HCC. Regardless of the diagnosis, the overall survival rate was significantly attenuated for the septuagenarians versus the younger cohort. After 5 years of follow-up, this disparity exceeded 10% to 15% depending on the populations being compared. The 1-, 2-, 3-, 4-, and 5-year actuarial survival rates were 88.4%, 83.2%, 79.6%, 76.1%, and 72.7%, respectively, for the patients who were younger than 70 years and 81.1%, 73.8%, 67.1%, 61.9%, and 55.2%, respectively, for the patients who were 70 years old or older. Five-year survival was negatively affected for patients with HCC who were younger than 70 years; this disparity was not observed for patients with HCC who were 70 years old or older. In conclusion, although patients who are 70 years old or older compose a small fraction of transplant recipients in the United States, patients in this group undergoing transplantation for HCC form an even smaller subset. Overall, transplantation in this age group yields outcomes inferior to those for younger cohorts. However, unlike patients who are less than 70 years old and receive MELD exception points, overall liver transplant survival is not affected by HCC at an advanced age.

Liver Transplantation for Hepatopulmonary Syndrome Due to Noncirrhotic Portal Hypertension

Background Hepatopulmomary syndrome is defined by the triad of chronic liver disease, increased alveolar-arterial gradient, and evidence of intrapulmonary vasodilation. It is commonly seen in association with cirrhosis (90%). Four percent to 8% of the hepatopulmomary syndrome cases are reported in noncirrhotic portal hypertension. The management of patients with hepatopulmomary syndrome due to noncirrhotic portal hypertension is not well described. Methods We report a case of a 26-year-old woman who underwent liver transplantation for hepatopulmomary syndrome due to noncirrhotic portal hypertension. The patient presented with dyspnea and platypnea, requiring home oxygen therapy. She had orthodexia, severe hypoxemia, and positive bubble echocardiography consistent with hepatopulmomary syndrome. Her Model for End-stage Liver Disease score was 10. Liver biopsy revealed diffuse nodular regenerative hyperplasia. Results The patient underwent liver transplantation with Model for End-stage Liver Disease exception points. Her oxygen requirements gradually improved during the postoperative period. The patient's symptoms and hypoxemia resolved at 15-month follow-up posttransplantation. Conclusion We suggest hepatopulmonary syndrome in this setting is an indication for liver transplantation despite the absence of cirrhosis.

Use of model for end-stage liver disease exception points for early liver transplantation and successful reversal of hepatic myelopathy with a review of the literature

Hepatic myelopathy (HM) is a rarely reported disorder characterized by progressive spastic paraparesis due to impaired corticospinal tract function in the setting of cirrhosis or portosystemic shunting. HM has not to date been recognized as a Model for End-Stage Liver Disease (MELD) exception for transplantation. Outcomes for a small number of patients from Europe and Asia who have undergone liver transplantation (LT) for HM suggest a potential neurological benefit, especially with earlier transplantation. We report the first use of MELD exception points for the condition of HM to enable early LT resulting in the reversal of marked spastic paraparesis. Our patient, whose myelopathy had markedly progressed without further hepatic decompensation, underwent LT 14 months after the diagnosis of HM with an adjusted MELD score of 30, which was granted as a United Network for Organ Sharing exception. After LT, there was significant neurological improvement as the patient progressed from wheelchair dependency to full ambulation. We reviewed the literature of other HM patients who had undergone LT. With our patient, there were in all 15 reported cases of LT in individuals with HM. LT can lead to a marked improvement in HM, particularly in the earlier clinical stages of the disorder. Early LT can be accomplished, as in our case, by the submission of an appeal for a MELD upgrade.