The Evolving Role of Liver Transplantation as Enzyme Replacement Therapy in the Era of RNA Nanotherapies

Abstract

Background/aims: 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- and post-FDA approval of patisiran and lumasiran respectively.

Results: We used the Scientific Registry of Transplant Recipients (SRTR)/United Network of Organ Sharing (UNOS) database, including all waitlisted patients for SOT between October 2013 to June 2023. We showed significant decrease in the proportion of patients newly waitlisted for LT with ATTR (0.14% vs 0.07%, p=0.0005) following FDA approval of patisiran. These patients had increased median MELD score and creatinine at time of waitlisting. Similarly, the proportion of patients newly waitlisted for LT with PH decreased post-FDA approval of lumasiran. We found an increased proportion of patients waitlisted for non-liver SOT due to ATTR.

Conclusion: 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.

Keywords: Solid organ transplantation; amyloidosis; liver transplantation; primary hyperoxaluria; small interfering RNA therapy.