Hepatotoxicity in Adeno-Associated Viral Vector Gene Therapy

Purpose of Review Recombinant adeno-associated virus (rAAV) is the commonest viral vector used in gene therapies. With the increase in the number of such therapies being employed in human clinical trials and approved clinical use, the associated adverse events are increasingly observed. Hepatotoxicity is the most common adverse event. Recent Findings Although mild in most, hepatotoxicity may affect gene therapy efficacy, lead to acute liver failure, death and persisting hepatitis necessitating prolonged use of immunosuppressants. There has been an increase in the referrals of such cases to hepatologists. Summary There is a lack of good quality evidence on the use of reactive immunosuppressants. There is a need to devise empiric protocols to diagnose and treat hepatotoxicity based on the side-effect profile of individual gene therapy, the present understanding of immunological basis of hepatotoxicity, the experience with various immunosuppressants in other disorders and the unique challenges and requirements of gene therapy.