Abstract
BACKGROUND AND AIMS: In patients with lysosomal acid lipase deficiency (LAL-D), elevations in alanine and aspartate aminotransferases (ALT, AST) are associated with liver damage. The objective of this analysis was to evaluate aminotransferase levels in patients treated with sebelipase alfa enzyme replacement therapy and untreated patients. METHODS: Patients in this observational study were from the International LAL-D Registry and included untreated and treated patients who started sebelipase alfa at age ≥ 6 months. Patients in the longitudinal analysis must have had baseline and longitudinal measures of ALT or AST. A subanalysis was performed on data from patients with 3 consecutive annual follow-up measures. RESULTS: Of 186 patients included in this analysis, 125 were treated with sebelipase alfa. Median age at diagnosis was 9.1 y for treated patients and 20.6 y for untreated patients. Baseline ALT levels were above the upper limit of normal in 93% of children aged < 18 years and 68% of adults aged ≥ 18 years. Among 53 treated patients who had ALT results reported at 3 consecutive annual measurements, 22 (42%) had ALT levels within normal limits after 1 year of sebelipase alfa treatment. Results were similar for AST. A repeated measures regression model of data from treated patients showed significant reductions from baseline in both ALT and AST levels across 3 years of the study. Untreated patients had no appreciable changes in aminotransferase elevations over time. CONCLUSIONS: Aminotransferase levels were elevated in most patients with LAL-D at baseline. There were sustained improvements with sebelipase alfa treatment. TRIAL REGISTRATION: International LAL-D Registry: NCT01633489, EUPAS13276.