To the Editor:
With great interest, I read the invited commentary “Lessons Learned From the Long-term Use of Enzyme Replacement Therapy in the Treatment of Lysosomal Acid Lipase Deficiency” (1), written by Drs. Strong and Ficicioglu in response to the article, “Long-term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency” (2). While I appreciate the authors’ assessments, additional considerations and insights might help readers confidently incorporate the study’s findings into practice.
Regarding the potential selection bias involving biopsy cohorts, the Week 96 biopsies were optional; patients who opted for biopsy were those with less response at Week 48. Therefore, results may reflect patients’ greater disease progression risk.
Attention to dietary fat intake, a substrate in this lysosomal storage disease, is required. Fat-restricted nutrition can affect treatment response (3,4). Unrecorded dietary regimens and nonadherence to regimens may obscure effects of enzyme replacement therapy with sebelipase alfa.
Furthermore, longer treatment durations may be required to observe tangible liver histologic and fibrotic improvement across the patient population, as evidenced by studies in other liver diseases (5,6). Alongside improvement, halting progression to end-stage liver disease, decompensation, hepatocellular carcinoma, or transplantation is beneficial (7,8). Reducing risk of hepatic fibrosis and progression to cirrhosis can result in fewer cardiovascular- and cerebrovascular-related events (9).
More research is needed on causes of interpatient variability in disease progression and enzyme replacement therapy response, and on the natural history of lysosomal acid lipase deficiency.
1. Strong A, Ficicioglu C. Lessons learned from the long-term use of enzyme replacement therapy in the treatment of lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr. 2022;74:726–7.
2. Burton BK, Sanchez AC, Kostyleva M, et al. Long-term sebelipase alfa treatment in children and adults with lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr. 2022;74:757–64.
3. Vijay S, Brassier A, Ghosh A, et al. Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies. Orphanet J Rare Dis. 2021;16:13.
4. Hoffman EP, Barr ML, Giovanni MA, et al. Lysosomal acid lipase deficiency. Adam MP, Mirzaa GM, Pagon RA, et al, eds. In: GeneReviews. Seattle, WA: University of Washington, Seattle; 2016.
5. Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52:886–93.
6. Shiffman ML, Sterling RK, Contos M, et al. Long term changes in liver histology following treatment of chronic hepatitis C virus. Ann Hepatol. 2014;13:340–9.
7. Strebinger G, Müller E, Feldman A, Aigner E. Lysosomal acid lipase deficiency – early diagnosis is the key. Hepat Med. 2019;11:79–88.
8. Burton BK, Silliman N, Marulkar S. Progression of liver disease in children and adults with lysosomal acid lipase deficiency. Curr Med Res Opin. 2017;33:1211–4.
9. Pastores GM, Hughes DA. Lysosomal acid lipase deficiency: therapeutic options. Drug Des Devel Ther. 2020;14:591–601.