We report a case of delayed acute liver injury (ALI) after treatment with delandistrogene moxeparvovec-rokl (DM), an adeno-associated virus–based gene therapy, in a 10-year-old ambulatory boy with Duchenne muscular dystrophy (DMD). The patient had a duplication of exons 8–11 in the DMD gene and was on chronic prednisone. He received prophylactic oral prednisone (1 mg/kg/d) starting 1 day before DM infusion. Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK) levels were elevated, consistent with DMD. On day 34 after infusion, ALT and AST began to rise without gamma-glutamyl transpeptidase (GGT) elevation. By day 41, transaminases were more than 7× baseline with elevated GGT and bilirubin, prompting hospitalization. He was treated with intravenous methylprednisolone, increased oral prednisone, and sirolimus. Liver enzymes rapidly improved and returned to baseline by day 69. Immunologic studies revealed CD8+ T-cell activation and innate immune activation via mildly elevated IL-18 that normalized without additional immunosuppression. The patient remained clinically stable. Infectious workup, liver ultrasonogram, and coagulation studies were unremarkable. Notably, the ALT/CK ratio increased more than 10-fold 1 week before GGT elevation and before ALT exceeded the 95% CI predicted by a CK- and age-adjusted model, suggesting its potential as an early biomarker of liver injury in DMD. This case highlights the challenges of interpreting liver enzymes in DMD, the potential utility of the ALT/CK ratio for early detection of ALI, and the role of immunophenotyping in guiding immunosuppressive therapy. Early recognition and timely escalation, including use of sirolimus, may help mitigate serious liver toxicity after gene therapy.
Drakou et al. (Thu,) studied this question.