Disparities in Access to Liver Transplant Referral and Evaluation among Patients with Hepatocellular Carcinoma in Georgia.

Liver transplantation offers the best survival for patients with early-stage hepatocellular carcinoma (HCC). Prior studies have demonstrated disparities in transplant access; none have examined the early steps of the transplant process. We identified determinants of access to transplant referral and evaluation among patients with HCC with a single tumor either within Milan or meeting downstaging criteria in Georgia.Population-based cancer registry data from 2010 to 2019 were linked to liver transplant centers in Georgia. Primary cohort: adult patients with HCC with a single tumor ≤8 cm in diameter, no extrahepatic involvement, and no vascular involvement. Secondary cohort: primary cohort plus patients with multiple tumors confined to one lobe. We estimated time to transplant referral, evaluation initiation, and evaluation completion, accounting for the competing risk of death. In sensitivity analyses, we also accounted for non-transplant cancer treatment.Among 1,379 patients with early-stage HCC in Georgia, 26% were referred to liver transplant. Private insurance and younger age were associated with increased likelihood of referral, while requiring downstaging was associated with lower likelihood of referral. Patients living in census tracts with ≥20% of residents in poverty were less likely to initiate evaluation among those referred [cause-specific hazard ratio (csHR): 0.62, 95% confidence interval (CI): 0.42-0.94]. Medicaid patients were less likely to complete the evaluation once initiated (csHR: 0.53, 95% CI: 0.32-0.89).Different sociodemographic factors were associated with each stage of the transplant process among patients with early-stage HCC in Georgia, emphasizing unique barriers to access and the need for targeted interventions at each step. SIGNIFICANCE: Among patients with early-stage HCC in Georgia, age and insurance type were associated with referral to liver transplant, race, and poverty with evaluation initiation, and insurance type with evaluation completion. Opportunities to improve transplant access include informing referring providers about insurance requirements, addressing barriers to evaluation initiation, and streamlining the evaluation process.

Geography, inequities, and the social determinants of health in transplantation.

Among the causes of inequity in organ transplantation, geography is oft-cited but rarely defined with precision. Traditionally, geographic inequity has been characterized by variation in distance to transplant centers, availability of deceased organ donors, or the consequences of allocation systems that are inherently geographically based. Recent research has begun to explore the use of measures at various geographic levels to better understand how characteristics of a patient's geographic surroundings contribute to a broad range of transplant inequities. Within, we first explore the relationship between geography, inequities, and the social determinants of health. Next, we review methodologic considerations essential to geographic health research, and critically appraise how these techniques have been applied. Finally, we propose how to use geography to improve access to and outcomes of transplantation.

Racial and ethnic disparities in psychosocial evaluation and liver transplant waitlisting.

Health disparities have been well-described in all stages of the liver transplantation (LT) process. Using data from psychosocial evaluations and the Stanford Integrated Psychosocial Assessment, our objective was to investigate potential racial and ethnic inequities in overall LT waitlisting and not waitlisting for medical or psychosocial reasons. In a cohort of 2271 candidates evaluated for LT from 2014 to 2021 and with 1-8 years of follow-up, no significant associations were noted between race/ethnicity and overall waitlisting and not waitlisting for medical reasons. However, compared with White race, Black race (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.07-2.56) and Hispanic/Latinx ethnicity (OR, 2.10; 95% CI, 1.16-3.78) were associated with not waitlisting for psychosocial reasons. After adjusting for sociodemographic variables, the relationship persisted in both populations: Black (OR, 1.95; 95% CI, 1.12-3.38) and Hispanic/Latinx (OR, 2.29; 95% CI, 1.08-4.86) (reference group, White). High-risk Stanford Integrated Psychosocial Assessment scores were more prevalent in Black and Hispanic/Latinx patients, likely reflecting upstream factors and structural racism. Health systems and LT centers should design programs to combat these disparities and improve equity in access to LT.

Epidemiology beyond its limits.

In 1995, journalist Gary Taubes published an article in Science titled "Epidemiology faces its limits," which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.

Factors Associated With Geographic Disparities in Gastrointestinal Cancer Mortality in the United States.

BACKGROUND & AIMS: Significant geographic variability in gastrointestinal (GI) cancer-related death has been reported in the United States. We aimed to evaluate both modifiable and nonmodifiable factors associated with intercounty differences in mortality due to GI cancer. METHODS: Data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research platform were used to calculate county-level mortality from esophageal, gastric, pancreatic, and colorectal cancers. Multivariable linear regression models were fit to adjust for county-level covariables, considering both patient (eg, sex, race, obesity, diabetes, alcohol, and smoking) and structural factors (eg, specialist density, poverty, insurance prevalence, and colon cancer screening prevalence). Intercounty variability in GI cancer-related mortality explained by these covariables was expressed as the multivariable model R2. RESULTS: There were significant geographic disparities in GI cancer-related county-level mortality across the US from 2010-2019 with the ratio of mortality between 90th and 10th percentile counties ranging from 1.5 (pancreatic) to 2.1 (gastric cancer). Counties with the highest 5% mortality rates for gastric, pancreatic, and colorectal cancer were primarily in the Southeastern United States. Multivariable models explained 43%, 61%, 14%, and 39% of the intercounty variability in mortality rates for esophageal, gastric, pancreatic, and colorectal cancer, respectively. Cigarette smoking and rural residence (independent of specialist density) were most strongly associated with GI cancer-related mortality. CONCLUSIONS: Both patient and structural factors contribute to significant geographic differences in mortality from GI cancers. Our findings support continued public health efforts to reduce smoking use and improve care for rural patients, which may contribute to a reduction in disparities in GI cancer-related death.

Listing at non-local transplant centers is associated with increased access to deceased donor kidney transplantation.

The ability of kidney transplant candidates to travel outside of their usual place of care varies by sociodemographic factors, potentially exacerbating disparities in access. We used Transplant Referral Regions (TRRs) to overcome previous methodological barriers of using geographic distance to assess the characteristics and outcomes of patients listed for kidney transplant at centers in neighboring TRR or beyond neighboring TRRs. Among listed kidney transplant candidates, 20.9% traveled to a neighbor and 5.6% beyond a neighbor. A higher proportion of travelers were White, had some college education, and lived in ZIP codes with lower poverty. Travel to a neighbor was associated with a 7% increase in likelihood of deceased donor transplant (cHR: 1.07, 95% CI: 1.05, 1.09) and traveling beyond a neighbor with a 19% increase (cHR: 1.19, 95% CI: 1.15, 1.24). Travelers had similar rates of living donor transplant and waitlist mortality as patients who did not travel; those who traveled beyond a neighbor had slightly lower posttransplant mortality (HR: 0.91, 95% CI: 0.83, 0.99). In conclusion, the ability to travel outside of the recipient's assigned TRR increases access to transplantation and improves long-term survival.

Understanding gastrointestinal cancer mortality disparities in a racially and geographically diverse population.

BACKGROUND: Gastrointestinal (GI) cancers represent a diverse group of diseases. We assessed differences in geographic and racial disparities in cancer-specific mortality across subtypes, overall and by patient characteristics, in a geographically and racially diverse US population. METHODS: Clinical, sociodemographic, and treatment characteristics for patients diagnosed during 2009-2014 with colorectal cancer (CRC), pancreatic cancer, hepatocellular carcinoma (HCC), or gastric cancer in Georgia were obtained from the Surveillance, Epidemiology, and End Results Program database. Patients were classified by geography (rural or urban county) and race and followed for cancer-specific death. Multivariable Cox proportional hazards models were used to calculate stratified hazard ratios (HR) and 95% confidence intervals (CIs) for associations between geography or race and cancer-specific mortality. RESULTS: Overall, 77% of the study population resided in urban counties and 33% were non-Hispanic Black (NHB). For all subtypes, NHB patients were more likely to reside in urban counties than non-Hispanic White patients. Residing in a rural county was associated with an overall increased hazard of cancer-specific mortality for HCC (HR = 1.15, 95% CI = 1.02-1.31), pancreatic (HR = 1.11, 95% CI = 1.03-1.19), and gastric cancer (HR = 1.17, 95% CI = 1.03-1.32) but near-null for CRC. Overall racial disparities were observed for CRC (HR = 1.18, 95% CI = 1.11-1.25) and HCC (HR = 1.12, 95% CI = 1.01-1.24). Geographic disparities were most pronounced among HCC patients receiving surgery. Racial disparities were pronounced among CRC patients receiving any treatment. CONCLUSION: Geographic disparities were observed for the rarer GI cancer subtypes, and racial disparities were pronounced for CRC. Treatment factors appear to largely drive both disparities.

Association of balanced abdominal organ transplant center volumes with patient outcomes.

BACKGROUND: The volume-outcome relationship for organ-specific transplantation is well-described; it is unknown if the relative balance of kidney compared with liver volumes within an institution relates to organ-specific outcomes. We assessed the association between relative balance within a transplant center and outcomes. METHODS: National retrospective analysis of isolated kidney and liver transplants in United States 2005-2014 followed through 2019. Latent class analysis defined transplant center phenotypes. Multivariate Cox models estimated death-censored graft loss and mortality. RESULTS: Latent class analysis identified four phenotypes: kidney only (n = 117), kidney dominant (n = 36), mixed/balanced (n = 90), and liver dominant (n = 13). Compared to mixed centers, the risk of kidney graft loss was higher at kidney-dominant (HR 1.07, p < .001) and liver-dominant (HR 1.10, p < .001) centers, while kidney-only (HR 1.06, p = .01) centers had higher mortality. Liver graft loss was not associated with phenotype, but risk of patient death was lower (HR 0.93, p = .02) at liver dominant and higher (HR 1.06, p = .02) at kidney-dominant centers. CONCLUSIONS: A mixed phenotype was associated with improved kidney transplant outcomes, whereas liver transplant outcomes were best at liver-dominant centers. While these findings need to be verified with center-level resources, optimization of shared resources could improve patient and organ outcomes.

Variation in Racial Disparities in Liver Transplant Outcomes Across Transplant Centers in the United States.

Little is known about the role that transplant centers may play in perpetuating racial disparities after liver transplantation, which are unexplained by patient-level factors. We examined variation in between-center and within-center disparities among 34,114 Black and White liver transplant recipients in the United States from 2010 to 2017 using Scientific Registry of Transplant Recipient (SRTR) data. We used Cox proportional hazards models to calculate transplant center-specific Black-White hazard ratios and hierarchical survival analysis to examine potential effect modification of the race-survival association by transplant center characteristics, including transplant volume, proportion of Black patients, SRTR quality rating, and region. Models were sequentially adjusted for clinical, socioeconomic, and center characteristics. After adjustment, Black patients experienced 1.11 excess deaths after liver transplant per 100 person-years compared with White patients (95% confidence interval [CI], 0.65-1.56), corresponding to a 21% increased mortality risk (95% CI, 1.12-1.31). Although there was substantial variation in this disparity across transplant centers, there was no evidence of effect modification by transplant center volume, proportion of minority patients seen, quality rating, or region. We found significant racial disparities in survival after transplant, with substantial variation in this disparity across transplant centers that was not explained by selected center characteristics. This is the first study to directly evaluate the role transplant centers play in racial disparities in transplant outcomes. Further assessment of the qualitative factors that may drive disparities, such as selection processes and follow-up care, is needed to create effective center-level interventions to address health inequity.

Kidney transplant program waitlisting rate as a metric to assess transplant access.

Kidney transplant program performance in the United States is commonly measured by posttransplant outcomes. Inclusion of pretransplant measures could provide a more comprehensive assessment of transplant program performance and necessary information for patient decision-making. In this study, we propose a new metric, the waitlisting rate, defined as the ratio of patients who are waitlisted in a center relative to the person-years referred for evaluation to a program. Furthermore, we standardize the waitlisting rate relative to the state average in Georgia, North Carolina, and South Carolina. The new metric was used as a proof-of-concept to assess transplant-program access compared to the existing transplant rate metric. The study cohorts were defined by linking 2017 United States Renal Data System (USRDS) data with transplant-program referral data from the Southeastern United States between January 1, 2012 and December 31, 2016. Waitlisting rate varied across the 9 Southeastern transplant programs, ranging from 10 to 22 events per 100 patient-years, whereas the program-specific waitlisting rate ratio ranged between 0.76 and 1.33. Program-specific waitlisting rate ratio was uncorrelated with the transplant rate ratio (r = -.15, 95% CI, -0.83 to 0.57). Findings warrant collection of national data on early transplant steps, such as referral, for a more comprehensive assessment of transplant program performance and pretransplant access.

County Differences in Liver Mortality in the United States: Impact of Sociodemographics, Disease Risk Factors, and Access to Care.

BACKGROUND AND AIMS: Data have demonstrated state-wide variability in mortality rates from liver disease (cirrhosis + hepatocellular carcinoma), but data are lacking at the local level (eg, county) to identify factors associated with variability in liver disease-related mortality and hotspots of liver disease mortality. METHODS: We used Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research data from 2009 to 2018 to calculate county-level, age-adjusted liver disease-related death rates. We fit multivariable linear regression models to adjust for county-level covariates related to demographics (ie, race and ethnicity), medical comorbidities (eg, obesity), access to care (eg, uninsured rate), and geographic (eg, distance to closest liver transplant center) variables. We used optimized hotspot analysis to identify clusters of liver disease mortality hotspots based on the final multivariable models. RESULTS: In multivariable models, 61% of the variability in among-county mortality was explained by county-level race/ethnicity, poverty, uninsured rates, distance to the closest transplant center, and local rates of obesity, diabetes, and alcohol use. Despite adjustment, significant within-state variability in county-level mortality rates was found. Of counties in the top fifth percentile (ie, highest mortality) of fully adjusted mortality, 60% were located in 3 states: Oklahoma, Texas, and New Mexico. Adjusted mortality rates were highly spatially correlated, representing 5 clusters: South Florida; Appalachia and the eastern part of the Midwest; Texas and Oklahoma; New Mexico, Arizona, California, and southern Oregon; and parts of Washington and Montana. CONCLUSIONS: Our data demonstrate significant intrastate differences in liver disease-related mortality, with more than 60% of the variability explained by patient demographics, clinical risk factors for liver disease, and access to specialty liver care.

Using Geographic Catchment Areas to Measure Population-based Access to Kidney Transplant in the United States.

BACKGROUND: Monitoring efforts to improve access to transplantation requires a definition of the population attributable to a transplant center. Previously, assessment of variation in transplant care has focused on differences between administrative units-such as states-rather than units derived from observed care patterns. We defined catchment areas (transplant referral regions [TRRs]) from transplant center care patterns for population-based assessment of transplant access. METHODS: We used US adult transplant listings (2006-2016) and Dartmouth Atlas catchment areas to assess the optimal method of defining TRRs. We used US Renal Data System and Scientific Registry of Transplant Recipient data to compare waitlist- and population-based kidney transplant rates. RESULTS: We identified 110 kidney, 67 liver, 85 pancreas, 68 heart, and 43 lung TRRs. Most patients were listed in their assigned TRR (kidney: 76%; liver: 75%; pancreas: 75%; heart: 74%; lung: 72%), although the proportion varied by organ (interquartile range for kidney, 65.7%-82.5%; liver, 58.2%-78.8%; pancreas, 58.4%-81.1%; heart, 63.1%-80.9%; lung, 61.6%-76.3%). Patterns of population- and waitlist-based kidney transplant rates differed, most notably in the Northeast and Midwest. CONCLUSIONS: Patterns of TRR-based kidney transplant rates differ from waitlist-based rates, indicating that current metrics may not reflect transplant access in the broader population. TRRs define populations served by transplant centers and could enable future studies of how transplant centers can improve access for patients in their communities.