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

Eunice Tan; Nilah Ahimsadasan; Naomi Khaing Than Hlaing; Janessa Low; Sara Naimimohasses; Shiyi Chen; Mamatha Bhat

doi:10.1016/j.ajt.2025.08.003

Back

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

Journal article

Peer reviewed

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

Eunice Tan, Nilah Ahimsadasan, Naomi Khaing Than Hlaing, Janessa Low, Sara Naimimohasses, Shiyi Chen and Mamatha Bhat

American journal of transplantation, Vol.25(12), pp.2611-2620

12/2025

DOI: 10.1016/j.ajt.2025.08.003

PMID: 40812616

View Online

Abstract

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. 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. 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.

small interfering RNA therapy

amyloidosis

Solid organ transplantation

primary hyperoxaluria

liver transplantation

Details

Title: Subtitle: The Evolving Role of Liver Transplantation as Enzyme Replacement Therapy in the Era of RNA Nanotherapies
Creators: Eunice Tan
Nilah Ahimsadasan - University Health Network
Naomi Khaing Than Hlaing - University Health Network
Janessa Low
Sara Naimimohasses - University of Iowa Hospitals and Clinics
Shiyi Chen - University Health Network
Mamatha Bhat - University Health Network
Resource Type: Journal article
Publication Details: American journal of transplantation, Vol.25(12), pp.2611-2620
DOI: 10.1016/j.ajt.2025.08.003
PMID: 40812616
NLM abbreviation: Am J Transplant
ISSN: 1600-6135
eISSN: 1600-6143
Publisher: Elsevier; NEW YORK
Grant note: Novo NordiskMerckPaladinTransplant GenomicsNateraOncousticsRoche
M.B. has received IIT grants from Novo Nordisk, Merck, Paladin, Transplant Genomics, Natera, Oncoustics, and Roche.
Language: English
Electronic publication date: 08/12/2025
Date published: 12/2025
Academic Unit: Gastroenterology and Hepatology; Internal Medicine
Record Identifier: 9984946839302771

Metrics

13 Record Views