Multiorgan fibrosis in Gaucher disease type I: an unmet goal of enzyme replacement therapy.

Gaucher disease (GD), the most common lysosomal storage disorders, is characterized by glucocerebroside accumulation within macrophages, leading to multisystem involvement including organomegaly, cytopenias, and bone disease. This study aimed to assess the presence and extent of hepatic, splenic, and bone marrow (BM) fibrosis in GD1 patients by using transient elastography (FibroScan®). Analysis a series of 26 adult GD1 patients, both treatment-naïve and enzyme replacement therapy (ERT) treated, was evaluated for liver and spleen stiffness. Eight patients with persistent cytopenia and hepatosplenomegaly underwent BM biopsy. Median liver and spleen stiffness were 4.8 kPa and 26 kPa, respectively. Mild liver fibrosis was identified in 77% of patients, moderate fibrosis in 15%, and cirrhosis in 7.7%, with comparable prevalence between naïve and treated groups. Splenic fibrosis was observed in 54% of patients, more frequently among those receiving ERT. A strong correlation was found between hepatic and splenic fibrosis, as well as between organ stiffness and fibrosis severity. Bone marrow fibrosis was detected in 75% of biopsied patients. These findings indicate that fibrotic progression may persist despite ERT and is not limited to the liver. Integrating non-invasive fibrosis assessment into routine GD1 monitoring may improve early detection and management of this disease complications.