Background: Acute liver injury (ALI) is a known adverse effect following delandistrogene moxeparvovec (DM) treatment, leading to hospitalization in 5.8% of ambulatory boys. Elevated transaminase levels are often a first marker of liver injury following viral gene transfer, but the reliability of transaminases alone in assessing liver injury in Duchenne muscular dystrophy is challenging given the baseline transaminase elevations due to release from degenerating muscle. Current recommendations include weekly post-DM liver enzyme tests and corticosteroid escalation when gamma-glutamyl transpeptidase (GGT) reaches ≥3x baseline.
Objectives: To describe the real-world experience of ALI after DM in a single center and evaluate the utility of ALT/CK ratio for earlier identification of ALI.
Methods: We reviewed clinical and laboratory data for all patients treated with DM commercially at Nationwide Children’s Hospital.
Results: Twenty-two ambulatory patients ages 4.3 to 11.7 years old received DM. Five (23%), ages 4.3 to 10.8 y, developed liver injury at 33 to 55 days post DM. Oral corticosteroid dose was increased in all five cases; 3/5 (60%) additionally received IV methylprednisolone and 1/5 (20%) received sirolimus. Two (9% of the total cohort) were hospitalized, each for four days. All five ultimately met the recommended threshold of GGT >3x baseline. However, 2/5 patients had an ALT/CK increase of >10x baseline one week prior to meeting the GGT criterion. All returned to baseline steroids after a median of 19 weeks (IQR 18-19). None experienced liver failure and all fully recovered.
Conclusion: In this cohort, ALI occurred at similar hospitalization rates to previously reported. We propose that a 10-fold increase from baseline in the ALT/CK ratio may enable earlier identification of ALI than the recommended GGT criterion alone. Incorporation of ALT/CK ratio may enhance post-DM monitoring and guide timely immunosuppression escalation.