Document Type
Article
Publication Date
4-24-2025
Abstract
Gene therapy involves the introduction of genetic materials, most commonly using viral vectors, to alter gene expression to ameliorate or cure disease symptoms with minimal adverse events. While interest in gene therapy has been on the increase, concerns have arisen about the potential for hepatotoxicity, which arises from diverse mechanisms. While viral vectors can produce dose-dependent hepatotoxicity secondary to integration, immune responses appear to be the primary driving mechanism. A mild increase in aminotransferases is the most common hepatic manifestation, occurring variably in 20%-80%, while there has been rare progress to acute liver failure. The occurrence of hepatotoxicity is unpredictable and can vary depending on patient comorbidities, vector dose, vector type, and degree of immune activation. Pretreatment screening for underlying chronic liver disease and exclusion of advanced fibrosis or cirrhosis using noninvasive tests is essential. Literature on liver biopsy pre- and post-therapy is limited, but small studies show safety in the long term. Immunosuppression, most commonly using corticosteroids, is the first-line modality in management. Approaches vary between prophylactic and reactive strategies, and there remains an absence of consensus on the most appropriate strategies. First-line therapy for a variable duration and dose settles most cases of hepatotoxicity. In selected difficult-to-treat cases, second-line agents (sirolimus, mycophenolate mofetil, and calcineurin inhibitors) are required, while there is no current consensus on the ideal second-line strategy. Intense short-term and extended long-term hepatic monitoring is recommended. Variabilities in presentation and challenges in management strategies mandate a multidisciplinary collaboration with the active involvement of hepatologists/gastroenterologists to optimize liver health.
Recommended Citation
Roy, Akash; Bansal, Shalini; Kulkarni, Anand; and Reddy, K. Rajender, "Hepatic Manifestations Following Gene Therapy" (2025). SKMC Student Presentations and Publications. Paper 76.
https://jdc.jefferson.edu/skmcstudentworks/76
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Language
English
Included in
Hepatology Commons, Medical Genetics Commons, Therapeutics Commons
Comments
This article is the author's final published version in Gastro Hep Advances, Volume 4, Issue 8, 2025, Article number 100681.
The published version is available at https://doi.org/10.1016/j.gastha.2025.100681. Copyright © 2025 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute.