The evolving role of liver transplantation as enzyme replacement therapy in the era of RNA nanotherapies.

Solid organ transplantation (SOT) is a treatment for monogenic diseases like transthyretin amyloidosis (ATTR) and primary hyperoxaluria (PH). The advent of RNA nanotherapy has introduced new disease-modifying options for ATTR and PH. We examined the prevalence, clinical characteristics, and outcomes of SOT waitlisted candidates (due to ATTR/PH) pre-US Food and Drug Administration (US FDA) and post-US FDA approval of patisiran and lumasiran, respectively. We used the Scientific Registry of Transplant Recipients/United Network of Organ Sharing database, including all waitlisted patients for SOT between October 2013 and June 2023. We showed a significant decrease in the proportion of patients newly waitlisted for liver transplantation (LT) with ATTR (0.14% vs 0.07%, P = .0005) following US FDA approval of patisiran. These patients had increased median model for end-stage liver disease score and creatinine at the time of waitlisting. Similarly, the proportion of patients newly waitlisted for LT with PH decreased post-US FDA approval of lumasiran. We found an increased proportion of patients waitlisted for non-liver SOT due to ATTR. A lower proportion of patients were waitlisted for LT due to ATTR/PH in the post-FDA approval era, and these patients were also sicker. Changes in patient selection criteria in context of availability of less invasive strategies may have resulted in sicker patients being listed later in their disease course.