Serum Progranulin Levels in Pediatric Patients with Gaucher Disease; Relation to Disease Severity and Liver Stiffness by Transient Elastography

Abstract

Background: Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is recognized for its role in a variety of physiologic and disease processes, including immunomodulation, cell growth, wound healing, host defense and inflammation. PGRN is a novel disease modifier in GD. The role of PGRN in liver disease and fibrosis has been shown in some studies but not in GD. Objectives: We determined PGRN levels in pediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE. Methods: Fifty-one GD patients (20 had type 1 and 31 had type 3), on enzyme replacement therapy for various durations, were studied focusing on visceral manifestations, neurological disease, hematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients with viral hepatitis infection were excluded. Results: By TE, 14 GD patients (27.5%) had significant fibrosis (F2 stage or higher). Liver stiffness was significantly higher in type 1 GD patients than type 3 (p=0.002), in splenectomized patients (p=0.012) and those with dysphagia (p<0.001). Liver stiffness was positively correlated to age of onset of ERT (p<0.001). PGRN levels were significantly lower in GD patients compared with controls (p<0.001). PGRN was significantly lower in GD patients with squint (p=0.025), dysphagia (p=0.036) and significant fibrosis by TE (p=0.015). PGRN was positively correlated to white blood cell count (r=0.455, p=0.002) and hemoglobin (r=0.546, p<0.001) while negatively correlated to severity score index (r=-0.529, p<0.001), liver volume (r=-0.298, p=0.034) and liver stiffness (r=-0.652, p<0.001). Severity score index, hemoglobin and liver stiffness were the significant independent variables related to increased PGRN levels by multivariable regression analysis. Conclusions: PGRN could be used as a biomarker for risk assessment of GD severity and identification of hepatic fibrosis in pediatric GD patients.