Defining the Need for Causal Inference to Understand the Impact of Social Determinants of Health: A Primer on Behalf of the Consortium for the Holistic Assessment of Risk in Transplantation (CHART).

Objective: This study aims to introduce key concepts and methods that inform the design of studies that seek to quantify the causal effect of social determinants of health (SDOH) on access to and outcomes following organ transplant. Background: The causal pathways between SDOH and transplant outcomes are poorly understood. This is partially due to the unstandardized and incomplete capture of the complex interactions between patients, their neighborhood environments, the tertiary care system, and structural factors that impact access and outcomes. Designing studies to quantify the causal impact of these factors on transplant access and outcomes requires an understanding of the fundamental concepts of causal inference. Methods: We present an overview of fundamental concepts in causal inference, including the potential outcomes framework and direct acyclic graphs. We discuss how to conceptualize SDOH in a causal framework and provide applied examples to illustrate how bias is introduced. Results: There is a need for direct measures of SDOH, increased measurement of latent and mediating variables, and multi-level frameworks for research that examine health inequities across multiple health systems to generalize results. We illustrate that biases can arise due to socioeconomic status, race/ethnicity, and incongruencies in language between the patient and clinician. Conclusions: Progress towards an equitable transplant system requires establishing causal pathways between psychosocial risk factors, access, and outcomes. This is predicated on accurate and precise quantification of social risk, best facilitated by improved organization of health system data and multicenter efforts to collect and learn from it in ways relevant to specialties and service lines.

Yttrium-90 Radioembolization of Unresectable Intrahepatic Cholangiocarcinoma: Long-Term Follow-up for a 136-Patient Cohort.

PURPOSE: Unresectable intrahepatic cholangiocarcinoma (ICC) signifies a poor prognosis with limited treatment options beyond systemic chemotherapy. This study's purpose was to evaluate the safety, efficacy, and potential for downstaging to resection of yttrium-90 (Y90) radioembolization for treatment of unresectable ICC. MATERIALS AND METHODS: From 2004 to 2020, 136 patients with unresectable ICC were treated with radioembolization at a single institution. Retrospective review was performed of a prospectively collected database. Outcomes were (1) biochemical and clinical toxicities, (2) local tumor response, (3) time to progression, and (4) overall survival (OS) after Y90. Univariate/multivariate survival analyses were performed. A subgroup analysis was performed to calculate post-resection recurrence and OS in patients downstaged to resection after Y90. RESULTS: Grade 3+ clinical and biochemical toxicities were 7.6% (n = 10) and 4.9% (n = 6), respectively. Best index lesion response was complete response in 2 (1.5%), partial response in 42 (32.1%), stable disease in 82 (62.6%), and progressive disease in 5 (3.8%) patients. Median OS was 14.2 months. Solitary tumor (P < 0.001), absence of vascular involvement (P = 0.009), and higher serum albumin (P < 0.001) were independently associated with improved OS. Eleven patients (8.1%) were downstaged to resection and 2 patients (1.5%) were bridged to transplant. R0-resection was achieved in 8/11 (72.7%). Post-resection median recurrence and OS were 26.3 months and 39.9 months, respectively. CONCLUSION: Y90 has an acceptable safety profile and high local disease control rates for the treatment of unresectable ICC. Downstaging to resection with > 3 years survival supports the therapeutic role of Y90 for unresectable ICC. LEVEL OF EVIDENCE: Level 3, single-arm single-center cohort study.

Single Center Experience with Incidence, Impact and Predictors of Biliary Complications in Donation After Circulatory Death Liver Transplantation.

Introduction: Utilizing allografts from donors after cardiac death (DCD) has improved organ availability, and DCD livers comprise a growing proportion of transplantations. However, it has been suggested that DCD transplantations have worse outcomes. Research Questions: We aimed to characterize outcomes in a large cohort of DCD transplantations, identify trends in outcomes over time, and identify factors associated with the development of biliary complications. Design: We conducted an observational retrospective cohort study of patients receiving DCD liver allografts within a large academic teaching hospital with a high transplantation volume. Consecutive patients who underwent Type III DCD liver transplantation from 2006-2016 were included in our cohort. Re-transplantations and multi-organ transplant recipients were excluded. Results: Ninety-six type III DCD transplantations occurred between 2006-2016. We report a 1one-year patient survival of 90.6% (87) and a 5five-year patient survival of 69.8% (67). Twenty-nine (30.2%) patients experienced any biliary complication in the first year following discharge, with 17 (17.7%) experiencing ischemic cholangiopathy. Five-year patient (P = 0.04) and graft (P = 0.005) survival improved over time. Post-operative biliary complications experienced during index admission and prior to discharge were found to be associated with the development of biliary complications (P = 0.005) and ischemic cholangiopathy (P = 0.01) following discharge. Conclusion: Our data suggested that outcomes using DCD allografts have improved, however biliary complications remain a significant issue in DCD transplantation. Patients who experienced post-operative biliary complications during index admission may require more frequent screening to allow the initiation of earlier treatment for biliary complications.

Safety and Efficacy of Segmental Yttrium-90 Radioembolization for Hepatocellular Carcinoma after Transjugular Intrahepatic Portosystemic Shunt Creation.

PURPOSE: To evaluate safety and efficacy of segmental yttrium-90 (Y90) radioembolization for hepatocellular carcinoma (HCC) after transjugular intrahepatic portosystemic shunt (TIPS) placement. The hypothesis was liver sparing segmental Y90 for HCC after TIPS would provide high antitumor response with a tolerable safety profile. MATERIALS AND METHODS: This single-arm retrospective study included 39 patients (16 women, 23 men) with ages 49-81 years old who were treated with Y90. Child-Pugh A/B liver dysfunction was present in 72% (28/39) with a median Model for End-stage Liver Disease score of 18 (95% confidence interval, 16.4-19.4). Primary outcomes were clinical and biochemical toxicities and antitumor imaging response by World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. Secondary outcomes were orthotopic liver transplantation (OLT), time to progression (TTP), and overall survival (OS) estimates by the Kaplan-Meier method. RESULTS: The 30-day mortality was 0%. Grade 3+ clinical adverse events and grade 3+ hyperbilirubinemia occurred in 5% (2/39) and 0% (0/39), respectively. Imaging response was achieved in 58% (22/38, WHO criteria) and 74% (28/38, EASL criteria), respectively. Median TTP was 16.1 months for any cause and 27.5 months for primary index lesions. OLT was completed in 88% (21/24) of listed patients at a median time of 6.1 months (range, 0.9-11.7 months). Median OS was 31.6 months and 62.9 months censored and uncensored to OLT, respectively. CONCLUSIONS: Segmental Y90 for HCC appears safe and efficacious in patients after TIPS. Preserved transplant eligibility suggests that Y90 is a useful tool for bridging these patients to liver transplantation.