Hepatic Manifestations Following Gene Therapy

Area of Science:

• Biomedical Science
• Molecular Biology
• Immunology

Background:

• Gene therapy utilizes genetic material, often via viral vectors, to treat diseases.
• Increasing interest in gene therapy is paralleled by concerns regarding potential hepatotoxicity.
• Hepatotoxicity mechanisms include viral vector integration and immune responses, with immune activation being primary.

Purpose of the Study:

• To review the mechanisms and management of gene therapy-induced hepatotoxicity.
• To highlight the importance of pretreatment screening and ongoing monitoring for liver health.
• To discuss current and potential therapeutic strategies for managing liver injury.

Main Methods:

• Literature review of gene therapy, hepatotoxicity mechanisms, and clinical management strategies.
• Analysis of reported cases of liver injury following gene therapy administration.
• Synthesis of data on diagnostic approaches, monitoring protocols, and treatment modalities.

Main Results:

• Hepatotoxicity presents variably, from elevated aminotransferases (20-80%) to rare acute liver failure.
• Occurrence is unpredictable, influenced by patient factors, vector type/dose, and immune response.
• Corticosteroids are first-line immunosuppression; second-line agents are used for refractory cases.

Conclusions:

• Pretreatment screening for liver disease and noninvasive tests are essential.
• Multidisciplinary collaboration involving hepatologists is crucial for optimizing liver health.
• Standardized prophylactic and reactive strategies for managing hepatotoxicity are lacking, necessitating further research.