Predicting liver fibrosis in Gaucher disease: Investigation of contributors and development of a clinically applicable Gaucher liver fibrosis score

Mol Genet Metab. 2025 Jan 3:109010. doi: 10.1016/j.ymgme.2025.109010. Online ahead of print.

Abstract

Gaucher disease (GD) is a rare genetic disorder with multi-system involvement. Liver fibrosis is a long-term complication of GD, potentially leading to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. There are currently no validated clinical tools for the monitoring of liver fibrosis in patients with GD. In this study, we aim at assessing the validity of common fibrosis-predicting scores, developed for other diseases, for the use in GD, using transient elastography as a gold-standard, as well as developing the first GD-specific liver fibrosis predicting score. We enrolled 19 adult patients with GD who had been on treatment for a minimum of 1 year on enzyme replacement therapy or substrate reduction therapy and who had no evidence of any other liver disease except GD or metabolic-associated steatotic liver disease (MASLD), which is a common comorbidity of GD. We analyzed the correlation between liver stiffness and genotype, treatment modality (imiglucerase or other therapies), clinical severity, and clinical laboratory tests. We found that the common liver fibrosis scores APRI, FIB-4, and NFS did not accurately predict liver fibrosis in people with GD. We also found that male sex, the DS3 score, AST, and GGT levels significantly correlated with liver stiffness, and used these to create a simple but accurate fibrosis-predicting score specifically for GD (the "Gaucher liver fibrosis score", or GLFS), with high accuracy (AUC = 0.8571, p = 0.0206). We believe that our new GLFS may be used in clinical practice to help prioritize GD patients for closer monitoring of liver fibrosis.

Keywords: Cirrhosis; DS3; Gaucher disease; Gaucher liver fibrosis score; Liver fibrosis; Transient elastography.