Adeno-associated viral vector gene therapy: Challenges for the paediatric hepatologist

Hepatoxicity associated with recombinant adeno-associated virus gene therapy is being increasingly encountered by hepatologists in tertiary and quaternary referral units due to the recent increase of these therapies for neuromuscular and haematological disorders. The challenges in managing the condition stem from a lack of good-quality evidence on the appropriate protocols for immunosuppressants due to lack of representative animal models. There is a need for protocols for diagnosing and treating hepatotoxicity and this possible with further research to understand the problem and its management. The review also highlights the importance of a multidisciplinary team in managing hepatotoxicity and recommends further research to better identify at-risk individuals, define the extent of the problem and assess the long-term effects of liver injury and immunosuppressants. What is Known Paediatric hepatologists are increasingly encountering hepatotoxicity related to recombinant adeno-associated virus gene therapy. The hepatoxicity may result in life-threatening complications, loss of transgene activity and adverse events related to immunosuppression use.What is New There is a need for research to better understand the problem and its management to guide immunosuppression protocols for treating hepatotoxicity. Long-term outcomes of hepatotoxicity and immunosuppression also need to be studied. Early and reliable identification of individuals at risk for hepatotoxicity could decrease morbidity and mortality.