Report a case where treatment with onasemnogene abeparvovec-xioi in a patient with SMA led to diagnosis of occult Hepatitis-C infection.

Report a case where treatment with onasemnogene abeparvovec-xioi in a patient with SMA led to diagnosis of occult Hepatitis-C infection.

Patient diagnosed with SMA Type 1 in neonatal period via positive newborn screen and confirmatory genetic testing with two copies of SMN2 gene. Clinical examination significant for hypotonia, the patient qualified for treatment with onasemnogene abeparvovec-xioi. Screening labs revealed a normal transaminase level (AST <46U/L and ALT <35U/L). Treated with prednisolone 1 mg/kg post infusion, labs were followed weekly. Transaminase elevation occurred as steroids were weaned off at three months of age, but was less than two times the upper limit of normal. Continued follow-up showed consistent elevation with an AST peak at 354U/L and ALT peak at 667U/L. Further investigation with abdominal ultrasound revealed non-palpable hepatomegaly. Serum studies revealed hepatitis-C infection.

In clinical trials for treatment of SMA with onasemnogene abeparvovec-xioi, the most recognized adverse effect was transaminase elevation.  A course of steroids is recommended with gene therapy to diminish immune response and therefore prevent hepatotoxicity. Workup for hepatic transaminase elevation led to diagnosis of hepatitis C infection. Given the hepatotoxic nature of both gene therapy treatment and hepatitis C infection, we suspect that there was additive effect leading to hepatotoxicity.  Universal hepatitis-C screening is recommended in all adults and pregnant women except where prevalence of hepatitis C is less than 0.1%, however, this sentinel event encourages physicians to consider testing all potential SMA patients for occult infection prior to treatment with onasemnogene abeparvovec-xioi.