Sirolimus for the treatment of steroid-refractory hepatotoxicity following AAV gene therapy in patients with Duchenne muscular dystrophy.
Carmen Leon-Astudillo, Stephanie M Salabarria, Christina B Chadwick et al.
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Case in brief
Four boys aged 5–16 years with Duchenne muscular dystrophy developed acute liver inflammation after delandistrogene moxeparvovec-rokl gene therapy. All were already receiving chronic corticosteroids. Hepatic enzyme elevations appeared five to seven weeks after treatment; high-dose corticosteroids produced transient improvement or worsening of laboratory abnormalities. After oral sirolimus was added, gamma-glutamyl transferase normalized and transaminases improved within two to four weeks. Sirolimus was given for four to twelve weeks while corticosteroids were weaned. None developed hepatic synthetic dysfunction or serious infection.
What made this case unusual
The liver inflammation emerged subacutely, five to seven weeks after gene therapy, and did not respond consistently to increased corticosteroids; laboratory improvement followed addition of sirolimus.
Diagnostic / clinical pearl
In this case series, liver enzyme elevations after AAV gene therapy arose several weeks after administration. Persistent or worsening abnormalities despite corticosteroids prompted adjunctive sirolimus, followed by improvement in liver tests.
Why it matters
The cases support the potential role of mTOR inhibition in managing AAV-related hepatotoxicity, while the small case series does not establish comparative efficacy.