The purpose of this study was to see how long-term (104 weeks) therapy with recombinant sebelipase alpha (rhSA) affected blood lipid and hepatic transaminase levels, as well as liver histology in four siblings with lysosomal acid lipase deficiency (LAL-D). In 2015, four male brothers from the same nonconsanguineous parents were diagnosed with the LAL-D late-onset phenotype. At baseline and after 104 weeks of enzyme replacement with rhSA, liver specimens were collected by biopsy. Hepatic transaminase, cholesterol, and lipoprotein levels were measured at the start and every 16 weeks for a total of 104 weeks. Hepatic steatosis was assessed using hematoxylin and eosin-stained tissues, while fibrosis was assessed using trichrome-stained specimens collected at baseline and after 104 weeks of rhSA therapy. Following rhSA therapy, all four siblings’ serum lipid and hepatic transaminase levels improved. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels fell by an average of 47 and 56 percent from baseline, respectively. Fasting triglyceride and low-density lipoprotein cholesterol (LDL-C) levels dropped by an average of 43% and 60% from baseline, respectively. Hepatic steatosis improved from grade 3 to grade 1 after therapy. After 104 weeks of rhSA therapy, hepatic fibrosis did not progress and in one sibling, it retreated.

Four siblings with LAL-D were treated with rhSA for 104 weeks, and their hepatic transaminase and serum lipid levels improved, as did hepatic steatosis and fibrosis development.