Affordable Care Act Medicaid expansion associated with increased liver transplant waitlist access without worsening mortality.

It is unclear what impact Affordable Care Act (ACA) Medicaid expansion has had on the liver transplantation (LT) waitlist. We aimed to assess associations between ACA Medicaid expansion and LT waitlist outcomes. The United Network for Organ Sharing Standard Transplant Analysis and Research (UNOS STAR) database was queried for patients listed for LT between January 1, 2009, and December 31, 2018. Our primary outcome was waitlist mortality and our secondary outcomes included Medicaid use on the LT waitlist and transplant rate. States were divided into groups based on their expansion status and the study period was divided into 2 time intervals-pre-expansion and post-expansion. Difference-in-difference (DiD) models were created to assess the impacts of expansion on each of the outcomes and for racial/ethnic and sex groups. In total, 56,414 patients from expansion states and 32,447 patients from nonexpansion states were included. Three-year waitlist mortality decreased at a similar rate in both cohorts [DiD estimate: 0.1, (95% CI, -1.1, -1.4), p = 0.838], but Medicaid use increased [DiD estimate: +7.7, (95% CI, 6.7, 8.7), p < 0.001] to a greater degree in expansion states after expansion than nonexpansion states. Between the 2 time intervals, Medicaid use on the LT waitlist increased from 19.4% to 26.1% in expansion states but decreased from 13.4% to 12.1% in nonexpansion states. In patients on Medicaid, there was a slight increase in the 3-year transplant rate associated with Medicaid expansion [DiD estimate +5.0, (95% CI, 1.8, 8.3), p = 0.002], which may in part be explained by differences in patient characteristics. Medicaid expansion was associated with increased Medicaid use on the LT waitlist without worsening overall waitlist mortality or transplant rate, suggesting that lenient and widespread public health insurance may increase access to the LT waitlist without adversely affecting outcomes.

Predictors for Early Liver Cancer Survival After Ablation and Surgical Resection: A Surveillance, Epidemiology, and End Results Program-Medicare Study.

OBJECTIVE: To identify independent predictors of all-cause and cancer-specific mortality after ablation or surgical resection (SR) for small hepatocellular carcinomas (HCCs), after adjusting for key confounders. METHODS: Using Surveillance, Epidemiology, and End Results Program-Medicare, HCCs less than 5 cm treated with ablation or SR in 2009 to 2016 (n = 956) were identified. Univariate and multivariable Cox regression models for all-cause and cancer-specific mortality were performed including demographics, clinical factors (tumor size, medical comorbidities, and liver disease factors), social determinants of health, and treatment characteristics. We also determined the most influential predictors of survival using a random forest analysis. RESULTS: Larger tumor size (3-5 cm) is predictive of all-cause (hazard ratio [HR] 1.31, P = .002) and cancer-specific mortality (HR 1.59, P < .001). Furthermore, chronic kidney disease is predictive of all-cause mortality (HR 1.43, P = .013), though it is not predictive of cancer-specific death. Multiple liver disease factors are predictive of all-cause and cancer-specific mortality including portal hypertension and esophageal varices (HRs > 1, P < .05). Though Asian race is protective in univariate models, in fully adjusted, multivariable models, Asian race is not a significant protective factor. Likewise, other social determinants of health are not significantly predictive of all-cause or cancer-specific mortality. Finally, treatment with SR, in later procedure years or at high-volume centers, is protective for all-cause and cancer-specific mortality. In machine learning models, year procedure was performed, ascites, portal hypertension, and treatment choice were the most influential factors. DISCUSSION: Treatment characteristics, liver disease factors, and tumor size are more important predictors of all-cause and cancer-specific death than social determinants of health for small HCCs.

Beyond Survival: Adverse Events and Care Delivery Outcomes after Early Liver Cancer Treatment in a Nationally Representative Cohort.

PURPOSE: To compare secondary outcomes after ablation (AB), surgical resection (SR), and liver transplant (LT) for small hepatocellular carcinomas (HCCs), including resource utilization and adverse event (AE) rates. MATERIALS AND METHODS: Using Surveillance, Epidemiology, and End Results Program (SEER)-Medicare, HCCs <5 cm that were treated with AB, SR, or LT in 2009-2016 (n = 1,067) were identified using Healthcare Common Procedure Coding System codes through Medicare claims. Index procedure length of stay, need for intensive care unit (ICU) level care, readmission rates, and AE rates at 30 and 90 days were compared using chi-square tests or Fisher exact tests. Examined AEs included hemorrhage, abscess formation, biliary injury, pneumonia, sepsis, liver disease-related AEs, liver failure, and anesthesia-related AEs, identified by International Classification of Diseases, Ninth/10th Revision, codes. RESULTS: The median length of stay for initial treatment was 1 day, 6 days, and 7 days for AB, SR, and LT, respectively (P < .001). During initial hospital stay, 5.0%, 40.8%, and 63.4% of AB, SR, and LT cohorts, respectively, received ICU-level care (P < .001). By 30 and 90 days, there were significant differences among the AB, SR, and LT cohorts in the rate of postprocedural hemorrhage, abscess formation, biliary injury, pneumonia, sepsis, liver disease-related AEs, and anesthesia-related AEs (P < .05). By 90 days, the readmission rates after AB, SR, and LT were 18.6%, 28.2%, and 40.6% (P < .001), respectively. CONCLUSIONS: AB results in significantly less healthcare utilization during the initial 90 days after procedure compared with that after SR and LT due to shorter length of stay, lower intensity care, fewer readmissions, and fewer AEs.

Long-Term Survival After Surgery Versus Ablation for Early Liver Cancer in a Large, Nationally Representative Cohort.

OBJECTIVE: To compare survival outcomes (all-cause, cancer-specific, and disease-free) for small hepatocellular carcinomas (HCCs), less than or equal to 5 cm, after ablation (AB) and surgical resection (SR) after adjusting for key confounders. Secondarily, to understand differential survival outcomes of liver transplant (TR) compared with SR and AB. METHODS: Using Surveillance, Epidemiology, and End Results Program-Medicare, HCCs less than 5 cm that were treated with AB, SR, or TR in 2009 to 2016 (n = 1,215) were identified using Healthcare Common Procedure Coding System codes through Medicare claims. The TR group was subdivided into two groups: TR with prior treatment and TR without prior treatment. All-cause survival, cancer-specific survival, and disease-free survival were analyzed using Kaplan-Meier curves and compared between groups using log-rank tests and Cox regression analyses. Propensity score-matched comparison of AB and SR groups was performed, with groups matched on demographics, social determinants of health, medical comorbidities, and liver disease severity prognostic indicators. RESULTS: Median study follow-up time was 2.71 years (interquartile range 1.25-3.83). Unadjusted 1-, 3-, and 5-year cancer-specific survivals were 85.9%, 67.6%, and 56.3% for the AB group; 91.7%, 82.6%, and 81.7% for the SR group; 93.5%, 88.7%, and 79.4% for TR without prior treatment group; and 96.4%, 93.2%, and 93.2% for TR with prior treatment group (P < .0001). With SR as the reference group, the propensity-matched hazard ratios for AB were 2.04 (95% confidence interval: 1.51-2.77) for all-cause mortality, 2.44 (95% confidence interval: 1.56-3.80) for cancer-specific mortality, and 2.12 (95% confidence interval: 1.61-2.78) for disease recurrence. DISCUSSION: SR is superior to AB for small HCCs in a large, nationally representative, modern cohort, and in secondary analysis TR was superior to both.

Medicaid Expansion Association With End-Stage Liver Disease Mortality Depends on Leniency of Medicaid Hepatitis C Virus Coverage.

The Affordable Care Act expanded Medicaid around the same time that direct-acting antivirals became widely available for the treatment of hepatitis C virus (HCV). However, there is significant variation in Medicaid HCV treatment eligibility criteria between states. We explored the combined effects of Medicaid expansion and leniency of HCV coverage under Medicaid on liver outcomes. We assessed state-level end-stage liver disease (ESLD) mortality rates, listings for liver transplantation (LT), and listing-to-death ratios (LDRs) for adults aged 25 to 64 years using data from United Network for Organ Sharing and Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. States were divided into 4 nonoverlapping groups based on expansion status on January 1, 2014 (expansion versus nonexpansion) and leniency of Medicaid HCV coverage (lenient versus restrictive coverage). Joinpoint regression analysis evaluated the significant changes in slope over time (joinpoints) during the pre-expansion (2009-2013) and postexpansion (2014-2018) time periods. We found significant changes in the annual percent change for population-adjusted ESLD deaths between 2014 and 2015 in all cohorts except for the nonexpansion/restrictive cohort, in which deaths increased at the same annual percent change from 2009 to 2018 (annual percent change of +2.5%; 95% confidence interval [CI], 1.8-3.3]). In the expansion/lenient coverage cohort, deaths increased at an annual percent change of +2.6% (95% CI, 1.8-3.5) until 2014 and then tended to decrease at an annual percent change of -0.4% (95% CI, -1.5 to 0.8). LT listings tended to decrease over time for all cohorts. For LDRs, only the expansion/lenient and expansion/restrictive cohorts had statistically significant joinpoints. Improvements in ESLD mortality and LDRs were associated with both Medicaid expansion and leniency of HCV coverage under Medicaid. These findings suggest the importance of implementing more lenient and widespread public health insurance to improve liver disease outcomes, including mortality.

Black Patients Have Unequal Access to Listing for Liver Transplantation in the United States.

BACKGROUND AND AIMS: The Model for End-Stage Liver Disease score may have eliminated racial disparities on the waitlist for liver transplantation (LT), but disparities prior to waitlist placement have not been adequately quantified. We aimed to analyze differences in patients who are listed for LT, undergo transplantation, and die from end-stage liver disease (ESLD), stratified by state and race/ethnicity. APPROACH AND RESULTS: We analyzed two databases retrospectively, the Center for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) and the United Network for Organ Sharing (UNOS) databases, from 2014 to 2018. We included patients aged 25-64 years who had a primary cause of death of ESLD and were listed for transplant in the CDC WONDER or UNOS database. Our primary outcome was the ratio of listing for LT to death from ESLD-listing to death ratio (LDR). Our secondary outcome was the transplant to listing and transplant to death ratios. Chi-squared and multivariable linear regression evaluated for differences between races/ethnicities. There were 135,367 patients who died of ESLD, 54,734 patients who were listed for transplant, and 26,571 who underwent transplant. Patients were mostly male and White. The national LDR was 0.40, significantly lowest in Black patients (0.30), P < 0.001. The national transplant to listing ratio was 0.48, highest in Black patients (0.53), P < 0.01. The national transplant to death ratio was 0.20, lowest in Black patients (0.16), P < 0.001. States that had an above-mean LDR had a lower transplant to listing ratio but a higher transplant to death ratio. Multivariable analysis confirmed that Black race is significantly associated with a lower LDR and transplant to death ratio. CONCLUSIONS: Black patients face a disparity in access to LT due to low listing rates for transplant relative to deaths from ESLD.

A Review of the Current State of Liver Transplantation Disparities.

Equity in access is one of the core goals of the Organ Procurement and Transplant Network (OPTN). However, disparities in liver transplantation have been described since the passage of the National Organ Transplant Act, which established OPTN in the 1980s. During the past few decades, several efforts have been made by the United Network for Organ Sharing (UNOS) to address disparities in liver transplantation with notable improvements in many areas. Nonetheless, disparities have persisted across insurance type, sex, race/ethnicity, geographic area, and age. African Americans have lower rates of referral to transplant centers, females have lower rates of transplantation from the liver waiting list than males, and public insurance is associated with worse posttransplant outcomes than private insurance. In addition, pediatric candidates and older adults have a disadvantage on the liver transplant waiting list, and there are widespread regional disparities in transplantation. Given the large degree of inequity in liver transplantation, there is a tremendous need for studies to propose and model policy changes that may make the liver transplant system more just and equitable.

Evaluation of Alcohol Taxes as a Public Health Opportunity to Reduce Liver Transplant Listings for Alcohol-Related Liver Disease.

BACKGROUND: Alcohol-related liver disease (ALD) is a leading indication for liver transplantation. METHODS: State consumption of spirits, wine, and beer was determined from published sources. Excise and ad valorem alcohol taxes of spirits, wine, and beer were calculated following standard practices and correlated using multiple logistic regression models to 2002 to 2015 ALD transplant listing data from the United Network for Organ Sharing database. RESULTS: 21.22% (29,161/137,440) of transplant listings were for ALD. Increased consumption of spirits was associated with increased ALD transplant listings (odds ratio [OR]: 1.67; 95% CI: 1.12 to 2.49, p = 0.01), but wine and beer consumption did not have a statistically significant association with ALD transplant listings. Spirits excise taxes on- and off-premise were inversely associated with ALD transplant listing (OR: 0.79 and 0.82, respectively, both p < 0.02). Beer and wine taxes were not significantly associated with ALD transplant listings. CONCLUSIONS: Transplant listings for ALD are directly associated with spirit consumption and inversely associated with spirits excise taxes. These findings suggest a possible public health benefit of increasing excise taxes for spirits.

Developing and testing models to predict mortality in the general population.

We have previously proposed an approach using information collected from published reports to generate prediction models. The goal of this project was to validate this technique to develop and test various prediction models. A risk indicator (R) is calculated as a linear combination of the hazard ratios for the following predictors: age, male gender, diabetes, albuminuria, and either CKD, CVD or both. We developed a linear and two exponential expressions to predict the probability of the outcome of 2-year mortality and compared to actual outcome in the target dataset from NHANES. The risk indicator demonstrated good performance with area under ROC curve of 0.84. The linear and two exponential expressions generated similar predictions in the lower categories of risk indicator (R ≤ 6). However, in the groups with higher R value, the linear expression tends to predict lower, and the exponential expressions higher, probabilities than the observed outcome. A Combined model which averaged the linear and logistic expressions was shown to approximate the actual outcome data the best. A simple technique (named Woodpecker™) allows derivation functional prediction models and risk stratification tools from reports of clinical outcome studies and their application to new populations by using only summary statistics of the new population.

A Call to Standardize Definitions, Data Collection, and Outcome Assessment to Improve Care in Alcohol-Related Liver Disease.

Alcohol-related liver disease (ALD) is highly prevalent and appears to be increasingly reported with worsening mortality; thus, optimizing care in this patient population is imperative. This will require a multidisciplinary, multifaceted approach that includes recognizing alcohol use disorder (AUD) and existing treatments for AUD. We must also acknowledge the full spectrum of ALD clinically and histologically. For example, our current clinical definitions of alcohol-related hepatitis (AH) do not address that >95% of severe AH occurs in the setting of cirrhosis with <60% of liver explants having hepatitis. Given that the majority of ALD studies rely on clinical diagnosis and lack pathologic confirmation, prior data on the efficacy of medical treatment or use of transplantation are likely limited by intertrial and intratrial heterogeneity. Added limitations of the current field include the inconsistent reporting of relapse with the use of varying definitions and unreliable assessments. Moreover, studies fail to consistently capture the data variables that likely influence the main outcomes of interest in this population-mortality and relapse-and a global effort to create a standardized data collection tool moving forward could help effectively and efficiently aid in the advancement of this field. Conclusion: To optimize patient care and make best use of a limited resource, a systematic change in the approach to research in this population must be undertaken that creates consistent definitions for use in future research to generate reliable and reproducible results. With this in mind, we concisely reviewed the literature to summarize the current state of treating and managing ALD, the heterogeneity in definitions, and the significant opportunities for clinical and research improvement.

Cost Effectiveness of Early Insertion of Transjugular Intrahepatic Portosystemic Shunts for Recurrent Ascites.

BACKGROUND & AIMS: Treatment options for recurrent ascites resulting from decompensated cirrhosis include serial large-volume paracentesis and albumin infusion (LVP+A) or insertion of a transjugular intrahepatic portosystemic shunt (TIPS). Insertion of TIPSs with covered stents during early stages of ascites (early TIPS, defined as 2 LVPs within the past 3 weeks and <6 LVPs in the prior 3 months) significantly improves chances of survival and reduces complications of cirrhosis compared with LVP+A. However, it is not clear if TIPS insertion is cost effective in these patients. METHODS: We developed a Markov model using the payer perspective for a hypothetical cohort of patients with cirrhosis with recurrent ascites receiving early TIPSs or LVP+A using data from publications and national databases collected from 2012 to 2018. Projected outcomes included quality-adjusted life-year (QALY), costs (2017 US dollars), and incremental cost-effectiveness ratios (ICERs; $/QALY). Sensitivity analyses (1-way, 2-way, and probabilistic) were conducted. ICERs less than $100,000 per QALY were considered cost effective. RESULTS: In base-case analysis, early insertion of TIPS had a higher cost ($22,770) than LVP+A ($19,180), but also increased QALY (0.73 for early TIPSs and 0.65 for LVP+A), resulting in an ICER of $46,310/QALY. Results were sensitive to cost of uncomplicated TIPS insertion and transplant, need for LVP+A, probability of transplant, and decompensated QALY. In probabilistic sensitivity analysis, TIPS insertion was the optimal strategy in 59.1% of simulations. CONCLUSIONS: Based on Markov model analysis, early placement of TIPSs appears to be a cost-effective strategy for management of specific patients with cirrhosis and recurrent ascites. TIPS placement should be considered early and as a first-line treatment option for select patients.

Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients: 24-Month Results for the North American Subpopulation.

BACKGROUND: A recent randomized phase III study of 719 de novo liver transplant recipients showed that early everolimus plus reduced-dose tacrolimus (EVR + rTAC) led to significantly better kidney function than standard TAC (TAC-C), without compromising efficacy. In that study, patients from North America (n = 211) had increased risk factors for posttransplant renal insufficiency at study start, relative to patients from Europe and rest of world (eg, worse renal function, more diabetes, older age). METHODS: A post hoc analysis was performed to assess whether these regional disparities affected study outcomes in North American patients. RESULTS: In this subpopulation, estimated glomerular filtration rates at randomization were higher in TAC-C over EVR + rTAC (76.4 vs 69.3 mL/min per 1.73 m). Mean changes in estimated glomerular filtration rate values (mL/min per 1.73 m) favored EVR + rTAC over TAC-C at months 12 (+3.7 vs -4.5; P = 0.032), 24 (+2.7 vs -6.6; P = 0.042), and 36 (+4.3 vs -8.1; P = 0.059). The composite efficacy endpoint of treated biopsy-proven acute rejection, graft loss, or death was 10.9%, 14.1%, and 14.1% for EVR + rTAC and 13.1%, 17.2%, and 19.3% for TAC-C at months 12, 24, and 36, respectively. CONCLUSIONS: Although the North American cohort had more comorbidities, results were consistent with the overall population for efficacy and renal function.

Fasting Blood Ammonia Predicts Risk and Frequency of Hepatic Encephalopathy Episodes in Patients With Cirrhosis.

BACKGROUND & AIMS: There is controversy over the use of measuring blood levels of ammonia (NH3) in the management of patients with overt hepatic encephalopathy (HE). METHODS: We performed a retrospective analysis of data from a randomized, double-blind study of 178 patients with cirrhosis given glycerol phenylbutyrate (an NH3-lowering agent) or placebo for 16 weeks. Blood samples were collected at baseline and on study days 7 and 14 and NH3 levels were measured. The probabilities of having an HE episode, based on ammonia values, were modeled using binary logistic regression. A Cox proportional model was used to determine the risk of HE episodes in patients with baseline fasting NH3 levels ≤1.5-fold the upper limit of normal (ULN) versus patients with fasting NH3 levels >1.5-fold the ULN. RESULTS: The risk and frequency of HE episodes and HE-related hospitalizations correlated with baseline (mean, 51 ± 6 µmol/L; ULN, 35 µmol/L) and on-study fasting levels of NH3, and increased sharply at levels >1.5-fold the ULN. Regardless of baseline level, NH3 exposure and the relative risk of HE episodes were decreased by glycerol phenylbutyrate. CONCLUSIONS: In analysis of data from a phase 2 study of the effects of glycerol phenylbutyrate in patients with cirrhosis, we found that fasting levels of NH3 in blood can identify patients at risk for HE-related morbidity. Patients with HE might benefit from NH3-lowering therapy. ClinicalTrials.gov no: NCT 00999167.

The intersectionality of postsecondary pathways: the case of high school students with special education needs.

Using data from the Toronto District School Board, we examine the postsecondary pathways of students with special education needs (SEN). We consider both university and college pathways, employing multilevel multinomial logistic regressions, conceptualizing our findings within a life course and intersectionality framework. Our findings reveal that having SEN reduces the likelihood of confirming university, but increases the likelihood of college confirmation. We examine a set of known determinants of postsecondary education (PSE) pathways that were derived from the literature and employ exploratory statistical interactions to examine if the intersection of various traits differentially impacts upon the PSE trajectories of students with SEN. Our findings reveal that parental education, neighborhood wealth, race, and streaming impact on the postsecondary pathways of students with SEN in Toronto.

Disparities in arteriovenous fistula placement in older hemodialysis patients.

The benefits of an arteriovenous fistula (AVF) as the preferred vascular access for hemodialysis have been clearly demonstrated. However, only about 20% of patients in the United States initiate hemodialysis with an AVF. In this study, we assessed whether disparities exist in the type of first hemodialysis access placed prior to dialysis start (rather than that used at dialysis initiation), to detect whether certain disadvantaged groups might have lower likelihood of AVF placement. Study cohort of 118,767 incident hemodialysis patients ≥67 years of age (1/2005-12/2008) derived from the United States Renal Data System was linked with Medicare claims data to identify the type of initial access placed predialysis. We used logistic regression model with outcome being the initial predialysis placement of an AVF as opposed to an arteriovenous graft or a central venous catheter. Increasing age, female sex, black race, lower body mass index, urban location, certain comorbidities, and shorter pre-end-stage renal disease nephrology care are all associated with a significantly lower likelihood of AVF placement as initial access predialysis. Our study suggests the presence of significant disparities in the placement of an AVF as initial hemodialysis vascular access. We suggest that additional attention should be paid to these patient groups to improve disparities by patient education, earlier referral, and close follow-up.