Transjugular Intrahepatic Portosystemic Shunt and Locoregional Therapies in Patients Undergoing Orthotopic Liver Transplantation: A Protocol for a Retrospective, Linked United Network for Organ Sharing Cohort

ABSTRACTIntroductionOrthotopic Liver Transplantation (OLT) is the potential curative treatment option for patients with end-stage liver disease (ESLD) or hepatocellular carcinoma (HCC) within organ procurement and transplantation network (OPTN) criteria. However, these groups of patients may require bridging interventions, including Transjugular Intrahepatic Portosystemic Shunt (TIPS) or Locoregional Therapies (LRTs), given the nationwide organ shortage and increasing waitlist time. The perioperative and long-term post-OLT survival and clinical outcomes require further investigation to evaluate the clinical utility and therapeutic advantages of these bridging interventions, if any. We propose a large retrospective database analysis that will evaluate both perioperative and long-term effects of these OLT-related interventions.Methods and analysisThree datasets from the United Network for Organ Sharing (UNOS) database will be included and linked to estimate the causal effect of 1) Transjugular Intrahepatic Portosystemic Shunts and 2) Locoregional therapies in patients undergoing OLT, the latter among patients with HCC. Only therapy naïve adult patients, without multivisceral transplants, and without living donor transplants will be included. The primary outcome will be overall survival. Secondary outcomes will include perioperative clinical outcomes, post-operative survival, and postoperative clinical outcomes. The inverse probability of treatment weighted models with Cox regression will be utilized to analyze survival outcomes, logistic regression for categorical outcomes, and ordinary least squares regression for continuous outcomes. A sensitivity analysis will be conducted to assess the appropriateness of a complete-case analysis for the primary outcome and ensure the robustness of the findings.Ethics and DisseminationThis study protocol was reviewed by the Emory University School of Medicine Institutional Review Board (IRB), and ethical approval was waived due to the retrospective analysis of the originally anonymized database. The results will be disseminated in peer-reviewed journals and presented at relevant conferences. It was not appropriate or possible to involve patients or the public in the design, or conduct, or reporting, or dissemination plans of our research.STRENGTHS AND LIMITATIONS OF THIS STUDYStrengthsThe proposed study:Will be the first study evaluating the causal effect of TIPS in OLT candidates and of locoregional therapies in OLT candidates with HCCWill be the first study to link UNOS datasets to investigate the estimands, thereby providing insight into the clinical impact of TIPS and LRTs at various stages in the clinical pathway.LimitationsThe proposed study:Will be a retrospective study and thus subject to poor or inadequate reporting in the registry, though propensity score matching will be doneMay be subject to unmeasured confounding and sensitive to model misspecificationMay lack the necessary sample size and subsequently be underpowered to estimate the target estimands