Neighborhood-level social determinants of health measures independently predict receipt of living donor liver transplantation in the United States.

Disparities exist in the access to living donor liver transplantation (LDLT) in the United States. However, the association of neighborhood-level social determinants of health (SDoH) on the receipt of LDLT is not well-established. This was a retrospective cohort study of adult liver transplant recipients between January 1, 2005 and December 31, 2021 at centers performing LDLT using the United Network for Organ Sharing database, which was linked through patients' ZIP code to a set of 24 neighborhood-level SDoH measures from different data sources. Temporal trends and center differences in neighborhood Social Deprivation Index (SDI), a validated scale of socioeconomic deprivation ranging from 0 to 100 (0=least disadvantaged), were assessed by transplant type. Multivariable logistic regression evaluated the association of increasing SDI on receipt of LDLT [vs. deceased donor liver transplantation (DDLT)]. There were 51,721 DDLT and 4026 LDLT recipients at 59 LDLT-performing centers during the study period. Of the 24 neighborhood-level SDoH measures studied, the SDI was most different between the 2 transplant types, with LDLT recipients having lower SDI (ie, less socioeconomic disadvantage) than DDLT recipients (median SDI 37 vs. 47; p < 0.001). The median difference in SDI between the LDLT and DDLT groups significantly decreased from 13 in 2005 to 3 in 2021 ( p = 0.003). In the final model, the SDI quintile was independently associated with transplant type ( p < 0.001) with a threshold SDI of ~40, above which increasing SDI was significantly associated with reduced odds of LDLT (vs. reference SDI 1-20). As a neighborhood-level SDoH measure, SDI is useful for evaluating disparities in the context of LDLT. Center outreach efforts that aim to reduce disparities in LDLT could preferentially target US ZIP codes with SDI > 40.

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.

Recipient and Center Factors Associated With Immunosuppression Practice Beyond the First Year After Liver Transplantation and Impact on Outcomes.

BACKGROUND: Immunosuppression is a critical aspect of post-transplant management, yet practices at intermediate and late time points after liver transplantation (LT) are poorly characterized. METHODS: A retrospective cohort of 11 326 adult first LT alone recipients between 2007 and 2016 was identified by linking United Network for Organ Sharing transplant data to Medicare administrative claims. The immunosuppression regimen was obtained from Medicare billing claims. Factors associated with calcineurin inhibitor (CNI) monotherapy at 1-, 3-, and 5-y post-LT were investigated using mixed-effects logistic regression. Center practice heterogeneity was evaluated. The association of immunosuppression regimen (time-updating) with patient and graft survival was studied. RESULTS: CNI monotherapy was used in 51.9% at 1-y post-LT and 68.6% at 5-y post-LT. Center-specific rates ranged from 20.0%-79.9% to 15.4%-95.2%, respectively. CNI monotherapy at 1- and 3-y post-LT was less likely among Black recipients ( P = 0.027 and P = 0.015 versus White, respectively). CNI plus antimetabolite was associated with improved adjusted patient (hazard ratio, 0.59; P < 0.001) and graft (hazard ratio, 0.62; P < 0.001) survival versus CNI monotherapy. The benefit of CNI plus antimetabolite on patient and graft survival increased with older age. CONCLUSIONS: In this first longitudinal analysis of LT immunosuppression practices among Medicare beneficiaries, a CNI plus antimetabolite approach led to improved outcomes. Significant center heterogeneity in practice was observed.

The Stanford Integrated Psychosocial Assessment for Transplant Is Associated With Outcomes Before and After Liver Transplantation.

The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a standardized psychosocial evaluation tool used in liver transplantation (LT) evaluation. We assessed the impact of the SIPAT score and subdomains on transplant waitlisting decisions and post-LT outcomes including immunosuppression (IS) nonadherence, biopsy-proven rejection, andmortality/graft failure. We conducted a single-center observational cohort study of 1430 patients evaluated for LT. Patients were divided in 2 groups based on a SIPAT cutoff score of <21 or ≥21 (higher SIPAT scores indicate higher psychosocial risk). Regression models assessed relationships between total SIPAT score and domain scores and waitlisting decisions, IS nonadherence, allograft rejection, and death/graft failure. Elevated total SIPAT and SIPAT domain scores were associated not being added to the waitlist (total SIPAT core ≥21 adjusted odds ratio [aOR], 1.78 [95% confidence interval, CI, 1.36-2.33]; readiness score ≥5 aOR, 2.01 [95% CI, 1.36-2.76]; social support score ≥4aOR, 1.50 [95% CI, 1.15-1.94]; psychopathology score ≥7 aOR, 1.45 [95% CI, 1.07-1.94]; lifestyle/substance abuse score ≥12 aOR, 1.72 [95%CI, 1.23-2.39]) and were more likely to experience IS nonadherence as measured by the tacrolimus coefficient of variation (CoV) (total SIPAT score ≥21 aOR, 2.92 [95% CI, 1.69-5.03]; readiness score ≥5 aOR, 3.26 [95% CI, 1.63-6.52]; psychopathology score ≥7 aOR, 1.88 [95% CI, 1.00-3.50]; lifestyle substance abuse score ≥12 aOR, 3.03 [95% CI, 1.56-5.86]). SIPAT readinessscore ≥5 was associated with biopsy-proven allograft rejection (aOR, 2.66; 95% CI, 1.20-5.91). The SIPAT score was independently associated with LT listing decisions and IS nonadherence, and the readiness domain was associated with the risk of allograft rejection. These findings offer insights into higher risk recipients who require additional support before and aftertransplantation.

Functional status, healthcare utilization, and the costs of liver transplantation.

The Model for End-Stage Liver Disease (MELD) score predicts higher transplant healthcare utilization and costs; however, the independent contribution of functional status towards costs is understudied. The study objective was to evaluate the association between functional status, as measured by Karnofsky Performance Status (KPS), and liver transplant (LT) costs in the first posttransplant year. In a cohort of 598 LT recipients from July 1, 2009 to November 30, 2014, multivariable models assessed associations between KPS and outcomes. LT recipients needing full assistance (KPS 10%-40%) vs being independent (KPS 80%-100%) were more likely to be discharged to a rehabilitation facility after LT (22% vs 3%) and be rehospitalized within the first posttransplant year (78% vs 57%), all P < .001. In adjusted generalized linear models, in addition to MELD (P < .001), factors independently associated with higher 1-year post-LT transplant costs were older age, poor functional status (KPS 10%-40%), living donor LT, pre-LT hemodialysis, and the donor risk index (all P < .001). One-year survival for patients in the top cost decile was 83% vs 93% for the rest of the cohort (log rank P < .001). Functional status is an important determinant of posttransplant resource utilization; therefore, standardized measurements of functional status should be considered to optimize candidate selection and outcomes.

Characterizing the Risk of False-Positive Hepatocellular Carcinoma in Recipients Transplanted With T2 MELD Exceptions.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) can receive Model for End-Stage Liver Disease (MELD) exception points to increase waitlist priority for liver transplantation. This process does not require a biopsy and is based on radiologic criteria. However, imaging modalities are imperfect, and some will ultimately have no HCC on explant. METHODS: This was a retrospective cohort study using national explant pathology data from 2012 to 2015. False-positive HCC was defined as answering "no" to the question: "was evidence of HCC (viable or nonviable) found in the explant?" in patients with T2 MELD exceptions. RESULTS: Four thousand one hundred seventeen patients received T2 MELD exceptions, of which 245 (6%) had false-positive HCC. Maximal tumor diameter of 3 to 5 cm and serum α fetoprotein (AFP) greater than 100 ng/mL at transplant yielded a 50% lower risk of false-positive HCC (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.27-0.73 and OR, 0.57; 95% CI, 0.37-0.88, respectively). Recipients with immune-mediated liver disease were twice as likely to have no HCC on explant (OR, 2.12; 95% CI, 1.18-3.83) and had a predicted probability of false positive HCC greater than 10% regardless of largest tumor size or AFP. Significant among-center variability in the rate of false-positive HCC was seen. CONCLUSIONS: The risk of false-positive HCC is markedly higher in certain groups, such that biopsy may be warranted before T2 MELD exception point approval. Transplant centers with high false-positive HCC rates may benefit from greater oversight.

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.

Exception point applications for 15 points: an unintended consequence of the share 15 policy.

In 2005, the United Network for Organ Sharing (UNOS) adopted the Share 15 policy to improve organ allocation by facilitating transplantation for local and regional patients with Model for End-Stage Liver Disease (MELD) scores of 15 or higher. There has been concern that the lack of standardization in the use of exception points is potentially diminishing the benefits of this policy. We reviewed all applications for 15 exception points submitted through UNOS from January 1, 2005 through March 14, 2011 (notably, there were only 5 applications for 15 MELD exception points submitted before the initiation of the Share 15 policy). Four hundred fifty-two applications were submitted for 301 patients. There was significant regional variability, with regions 3 and 10 submitting 72.1% of all applications. More than one-quarter of the applications (32.7%) specifically requested exception points to make a patient eligible for a local, regional, or higher risk organ. All applications were accepted for 74.1% of the patients, and 72.2% of these patients ultimately underwent transplantation; however, when all applications were denied, only 54.0% underwent transplantation (P = 0.006). Overall, 197 applicants (65.4%) underwent transplantation with a deceased donor organ, and 80.2% of these patients had a native MELD score at transplantation less than 15. In conclusion, these analyses demonstrate several important changes in practice that have occurred as a result of the implementation of the Share 15 policy. Since 2005, there has been a marked increase in the number of applications for 15 exception points, with significant regional variability in their use and a lack of standardization in their approval.