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Subacute liver failure: 2 case reports In a series of 2 cases, a 6-month-old boy and a 20-month-old girl developed subacute liver failure during treatment with nusinersen and onasemnogene abeparvovec for type 1 spinal muscular atrophy (SMA1) [not all routes, dosages and durations of treatment to reaction onsets stated]. Case 1: A 6-month-old ex-term boy, who was prenatally diagnosed with SMA1, received 4 doses of nusinersen between 12 days and 3 months of age. At the age of 4 months after receiving onasemnogene abeparvovec [AVXS-101] infusion (33mL of 1.1 x 1014 vector genomes/kg; 6.25 x 1014 Vg), he developed an adverse event characterised by vomiting and fever, requiring hospitalisation overnight. Seven weeks following the onasemnogene abeparvovec treatment, he presented with irritability, jaundice and scleral icterus. He had been off steroids for about 1 week at this presentation, having received 1 mg/kg/day of oral prednisolone one day before dosing and for 30 days following onasemnogene abeparvovec treatment, followed by a 10-day gradual taper off steroids. Notably, his serum aminotransferase levels were found to be increased before receiving onasemnogene abeparvovec. On examination, he was awake, but irritable and showed hypotonia, scleral icterus, head lag and jaundice. He was found to have acute liver failure with an INR of 5.3 (despite administration of vitamin K), mild encephalopathy and elevated levels of ALT, AST, total bilirubin, direct bilirubin, alkaline phosphatase, lactate dehydrogenase and GGT. Plasma factor levels were congruous with acute liver failure, with a high factor VIII level and low factor V and VII levels. Alpha fetoprotein was remarkably elevated. The creatinine kinase was only mildly increased. Evaluation for infection showed norovirus in the stool, but other testing for infectious diseases was negative. A thorough metabolic workup showed an increased lactate level. Serum ferritin was also elevated. The day after presentation, he underwent laparoscopic liver biopsy. Pathologic analysis showed massive ballooning degeneration with drop-out of hepatocytes in zone 3, a significant bile ductular reaction with neutrophilic periductular inflammation, extensive inflammation in the periportal areas and moderate periportal and significant central vein fibrosis. Respiratory chain enzyme analysis of the liver tissue revealed a low activity of complex II; however, it could not be determined whether this was a primary deficiency or secondary to poor liver function. Whole genome sequencing was remarkable for an incidental finding in the sodium voltage-gated channel alpha subunit 5 (SCN5A) gene; however, no pathogenic genetic variants associated with the patient phenotype were observed. Given the acute liver failure presentation and the active inflammation on liver biopsy, he was initiated on methylprednisolone for 3 days followed by a taper on hospital days 4–9. The aminotransferases and INR ameliorated, and on hospital day 13, he was discharged home on 1 mg/kg/day of oral prednisolone. Over th