Clinical and Histologic Liver Improvement in Siblings With Lysosomal Acid Lipase Deficiency After Enzyme Replacement


Lyons H, Vouyoukas E, Higgins M, Maciejko JJ.J Pediatr Gastroenterol Nutr. 2020 May;70(5):635-639. doi: 10.1097/MPG.0000000000002671.PMID: 32097366



Objectives: To assess the effect of long-term (104 weeks) treatment with recombinant sebelipase alpha (rhSA) on serum lipid and hepatic transaminase levels, and liver histopathology in 4 siblings diagnosed with lysosomal acid lipase deficiency (LAL-D).

Methods: Four male siblings from the same nonconsanguineous parents were diagnosed with the late-onset phenotype of LAL-D in 2015. Liver specimens were obtained by biopsy at baseline and after 104 weeks of enzyme replacement with rhSA (1 mg/kg, IV, every 2 weeks). Hepatic transaminase, lipid and lipoprotein levels were assessed at baseline and sequentially every 16 weeks for 104 weeks. Hepatic steatosis was evaluated from hematoxylin and eosin-stained specimens, and fibrosis was evaluated (Metavir-scoring system) from trichrome-stained specimens obtained at baseline and following 104 weeks of treatment with rhSA.

Results: All 4 siblings had improvement in their serum lipid and hepatic transaminase levels after treatment with rhSA. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from baseline by an average of 47% and 56%, respectively. The fasting triglyceride and low-density lipoprotein cholesterol (LDL-C) levels decreased from baseline by an average of 43% and 60%, respectively. Hepatic steatosis decreased from baseline grade 3 to posttreatment grade 1. Hepatic fibrosis did not advance following 104 weeks of treatment with rhSA and regressed in 1 sibling.

Conclusions: Treatment with rhSA for 104 weeks in 4 siblings with LAL-D demonstrated improvement in their hepatic transaminase and serum lipid levels, accompanied by reduction of hepatic steatosis and no progression of fibrosis.