Lysosomal acid lipase deficiency allograft recurrence and liver failure- clinical outcomes of 18 liver transplantation patients.

Abstract

Lysosomal acid lipase deficiency (LAL-D) results in progressive microvesicular hepatosteatosis, fibrosis, cirrhosis, dyslipidemia, and vascular disease. Interventions available prior to enzyme replacement therapy development, including lipid lowering medications, splenectomy, hematopoietic stem cell and liver transplantation were unsuccessful at preventing multi-systemic disease progression, and were associated with significant morbidity and mortality. We report two sisters, diagnosed in infancy, who succumbed to LAL-D with accelerated disease progression following splenectomy and liver transplantation. The index patient died one year after hematopoietic stem cell transplant and liver transplantation. Her younger sister survived five years post liver-transplantation, complicated by intermittent, acute rejection. Typical LAL-D hepatopathology, including progressive, microvesicular steatosis, foamy macrophage aggregates, vacuolated Kupffer cells, advanced fibrosis and micronodular cirrhosis recurred in the liver allograft. She died before a second liver transplant could occur for decompensated liver failure. Neither patient received sebelipase alfa enzyme replacement therapy, human, recombinant, lysosomal acid lipase enzyme, FDA approved in 2015. Here are reviewed 18 LAL-D post-liver transplantation cases described in the literature. Multi-systemic LAL-D progression occurred in 11 patients (61%) and death in six (33%). These reports demonstrate that liver transplantation may be necessary for LAL-D-associated liver failure, but is not sufficient to prevent disease progression, or liver disease recurrence, since the pathophysiology is predominantly mediated by deficient enzyme activity in bone marrow-derived monocyte-macrophages. Enzyme replacement therapy addresses systemic disease and hepatopathology, potentially improving liver-transplantation outcomes. This is the first systematic review of liver transplantation for LAL-D, and the first account of liver allograft LAL-D-associated hepatopathology recurrence.

• Authors: Donna Lee Bernstein, Steven Lobritto, Alina Iuga, Helen Remotti, Thomas Schiano, Maria Isabel Fiel, Manisha Balwani
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 124 Issue 1 Pg. 11-19 (05 2018) ISSN: 1096-7206 [Electronic] United States
• PMID: 29655841 (Publication Type: Case Reports, Journal Article, Review)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Sterol Esterase
• Sebelipase alfa

Topics

• Adolescent
• Disease Progression
• Enzyme Replacement Therapy
• Fatal Outcome
• Female
• Graft Rejection (physiopathology)
• Hematopoietic Stem Cell Transplantation
• Humans
• Liver (pathology)
• Liver Diseases (drug therapy)
• Liver Failure (etiology)
• Liver Transplantation
• Macrophages (pathology)
• Male
• Recurrence
• Splenectomy
• Sterol Esterase (therapeutic use)
• Transplantation, Homologous
• Wolman Disease (complications, drug therapy, physiopathology)
• Wolman Disease