Sex and Size Disparities in Access to Liver Transplant for Patients With Hepatocellular Carcinoma.

Importance: Women on the liver transplant waiting list are less likely to undergo a transplant than men. Recent approaches to resolving this disparity have involved adjustments to Model for End-Stage Liver Disease (MELD) scoring, but this will not affect candidates who rely on exception scores rather than calculated MELD score, the majority of whom have hepatocellular carcinoma (HCC). Objective: To evaluate the association between female sex, candidate size, and access to liver transplant among wait-listed patients with HCC. Design, Setting, and Participants: This retrospective cohort study used US transplant registry data of all adult (aged ≥18 years) wait-listed liver transplant candidates receiving an HCC exception score between January 1, 2010, and March 2, 2023. Exposure: Wait-listed liver transplant candidate sex. Main Outcomes and Measures: The association of female sex with (1) deceased-donor liver transplant (DDLT) and (2) death or waiting list removal for health deterioration were estimated using multivariable competing-risks regression. Results with and without adjustment for candidate height and weight (mediators of the sex disparity) were compared. Results: The cohort included 31 725 candidates with HCC (mean [SD] age at receipt of exception, 61.2 [7.1] years; 76.3% men). Compared with men, women had a lower 1-year cumulative incidence of DDLT (50.8% vs 54.0%; P < .001) and a higher 1-year cumulative incidence of death or delisting for health deterioration (16.2% vs 15.0%; P = .002). After adjustment, without accounting for size, women had a lower incidence of DDLT (subdistribution hazard ratio [SHR], 0.92; 95% CI, 0.89-0.95) and higher incidence of death or delisting (SHR, 1.06; 95% CI, 1.00-1.13) compared with men. When adjusting for candidate height and weight, there was no association of female sex with incidence of DDLT or death or delisting. However, at a height cutoff of 166 cm, short women compared with short men were still less likely to undergo a transplant (SHR, 0.93; 95% CI, 0.88-0.99). Conclusions and Relevance: In this study, women with HCC were less likely to receive a DDLT and more likely to die while wait-listed than men with HCC; these differences were largely (but not entirely) explained by sex-based differences in candidate size. For candidates listed with exception scores, additional changes to allocation policy are needed to resolve the sex disparity, including solutions to improve access to size-matched donor livers for smaller candidates.

Racial-ethnic differences in liver transplant waitlist outcomes in patients with hepatocellular carcinoma before and after recent changes to allocation policy.

BACKGROUND: In May 2019, liver transplant (LT) allocation policy changed to limit MELD exception points for hepatocellular carcinoma (HCC) to median MELD at transplant minus three (MMaT-3). We evaluated this policy's impact on waitlist outcomes for HCC candidates, by race and ethnicity, hypothesizing that the introduction of the MMaT-3 reduced inequities in waitlist outcomes. METHODS: Retrospective cohort study of the Scientific Registry for Transplant Recipients, including all adult LT candidates (N = 10 751) who received HCC exception points from May 17, 2017 to May 18, 2019 (pre-policy; N = 6627) to May 19, 2019 to March 1, 2021 (post-policy; N = 4124). We compared incidence of LT and waitlist removal for death or becoming too sick pre- and post-policy for non-Hispanic White, non-Hispanic Black, Hispanic/Latinx, and Asian patients using competing risk regression adjusted for candidate characteristics. RESULTS: One-year cumulative incidence of LT decreased significantly pre-/post-policy among White (77.4% vs. 64.5%; p < .01) and Black (76.2% vs. 63.1%; p < .01) candidates only, while a 1-year incidence of death/non-LT waitlist removal decreased significantly only among Hispanics (13.4% vs. 7.5%; p < .01). After covariate adjustment, the effect of the policy change was a significantly decreased incidence of LT for White (SHR: .63 compared to pre-policy; p < .001), Black (SHR: .62; p < .001), and Asian (SHR: .68; p = .002), but no change for Hispanic patients. Only Hispanic patients had a significant decrease in death/waitlist removal after the policy change (SHR:  .69; p = .04). Compared to White patients in the pre-policy era, Hispanic (SHR:  .88, p < .007) and Asian candidates (SHR:  .72; p < .001) had lower unadjusted incidence of LT. This disparity was mitigated in the post-policy era where Hispanic patients had higher likelihood of LT than Whites (SHR: 1.22; p = .002). For the outcome of death/non-LT waitlist removal, the only significant difference was a 42% lower incidence of waitlist removal for Asian compared to White patients in the post-policy era (SHR:  .58; p = .03). CONCLUSION: Among LT recipients with HCC, racial/ethnic subpopulations were differentially affected by the MMAT-3 policy, resulting in a post-policy reduction of some of the previous disparities.

Impact of Median MELD at Transplant Minus 3 National Policy on Quality of Transplanted Livers for Patients With and Without Hepatocellular Carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) have been overprioritized in the deceased donor liver allocation system. The United Network for Organ Sharing adopted a policy in May 2019 that limited HCC exception points to the median Model for End-Stage Liver Disease at transplant in the listing region minus 3. We hypothesized this policy change would increase the likelihood to transplant marginal quality livers into HCC patients. METHODS: This was a retrospective cohort study of a national transplant registry, including adult deceased donor liver transplant recipients with and without HCC from May 18, 2017, to May 18, 2019 (prepolicy) to May 19, 2019, to March 1, 2021 (postpolicy). Transplanted livers were considered of marginal quality if they met ≥1 of the following: (1) donation after circulatory death, (2) donor age ≥70, (3) macrosteatosis ≥30% and (4) donor risk index ≥95th percentile. We compared characteristics across policy periods and by HCC status. RESULTS: A total of 23 164 patients were included (11 339 prepolicy and 11 825 postpolicy), 22.7% of whom received HCC exception points (prepolicy versus postpolicy: 26.1% versus 19.4%; P = 0.03). The percentage of transplanted donor livers meeting marginal quality criteria decreased for non-HCC (17.3% versus 16.0%; P < 0.001) but increased for HCC (17.7% versus 19.4%; P < 0.001) prepolicy versus postpolicy. After adjusting for recipient characteristics, HCC recipients had 28% higher odds of being transplanted with marginal quality liver independent of policy period (odds ratio: 1.28; confidence interval, 1.09-1.50; P < 0.01). CONCLUSIONS: The median Model for End-Stage Liver Disease at transplant in the listing region minus 3 policy limited exception points and decreased the quality of livers received by HCC patients.

Temporal Changes and Regional Variation in Acceptance of Hepatitis C Virus-Viremic Livers.

The high efficacy of current hepatitis C virus (HCV) therapy and increased numbers of HCV-infected deceased donors have changed the paradigm of HCV in liver transplantation (LT). Modeling studies have been performed to evaluate the optimal timing of HCV treatment (before versus after LT) in HCV-infected patients and to assess the cost-effectiveness of transplanting HCV-infected livers into HCV- patients. However, these models rely on historical data and have not quantified the temporal changes in the median Model for End-Stage Liver Disease (MELD) score at transplant of recipients of an HCV-infected liver across geographic areas. We performed a retrospective cohort study of Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) data of nonstatus 1 deceased donor LT recipients from January 1, 2016, to December 31, 2018, and we calculated the difference in allocation MELD score in recipients of HCV nucleic acid test (NAT)- versus NAT+ livers by year and UNOS region. We used Pearson correlation coefficients to assess the relationship between MELD score difference in recipients of HCV NAT+ versus HCV NAT- livers and the proportion of non-HCV recipients of HCV NAT+ livers. Nationally, the allocation MELD score difference at LT in recipients of HCV NAT+ versus NAT- livers did not change (4-point difference). This stability was seen in regions 3, 5, and 10. In regions 1, 7, 8, 9, and 11, the MELD score difference decreased, which is a diminishing advantage. However, in regions 2 and 4, it increased, which is a rising advantage. In 2018, recipients of HCV NAT+ livers had a lower MELD score in 9/11 regions, and the MELD score advantage of accepting HCV NAT+ livers had a moderate inverse correlation with the regional use in non-HCV patients (r = -0.53). These data should be used to inform clinicians of the pre- and post-LT trade-offs of HCV treatment.

Effectiveness of Levetiracetam Monotherapy in Pediatric Patients With Epilepsy.

The main objective of this study was to assess the efficacy, safety, and retention rates of levetiracetam monotherapy in children with epilepsy. A retrospective review of pediatric patients receiving levetiracetam monotherapy at 2 large tertiary epilepsy centers over an 11-year period was conducted. One hundred two patients using levetiracetam monotherapy with a mean age of 13.1 years were identified. For the entire cohort, a 6-month retention rate was 61.1% and a 12-month retention rate 53.1%. With regard to seizure freedom, 46.8% of those patients that remained on monotherapy for at least 6 months became seizure free. Twelve-month seizure freedom was reached by 41.2%. About one-third (32.4%) of patients reported adverse effects, with irritability, moodiness, and depression being the most common. Despite a number of patients that reported adverse events, levetiracetam monotherapy was found to be potentially effective in this cohort of children with epilepsy and warrants further, prospective studies.