Effect of glucocerebrosidase (GC) deficiency in osteoblasts on mineralization and osteoclastogenesis: Implications for bone pathology in Gaucher disease

Gaucher disease (GD) is one of the most common lysosomal diseases. It results from deficiency of the lysosomal enzyme glucocerebrosidase, which leads to accumulation of glucocerebroside and other glycolipids within the lysosomes of macrophages. Regarding liver involvement, hepatomegaly is universal and hepatic fibrosis typically occurs. Later in the disease, sinusoidal portal hypertension can be seen, but cirrhosis and hepatic failure are rare. Metabolic disorders are also common, and during enzymatic replacement therapy are characterized by hypometabolism and reduced levels of adiponectin which can be a risk factor for steatohepatitis. Transitory elastography (TE) is a novel non-invasive method for the assessment of hepatic fibrosis, by measuring liver stiffness. Controlled attenuation parameter (CAP), evaluated with transient elastography, is an efficient method to detect steatosis and define its grades. The AST-to-platelet ratio (APRI) can also be used to estimate fibrosis grade. For predicting significant fibrosis, an APRI cut-off of 0.7 had a sensitivity of 77% and a specificity of 72%. It was most studied in patients with hepatitis C. The aim of this study was to evaluate the hepatic involvement in a group of patients with GD, measuring fibrosis and steatosis by TE with CAP. We also compared the TE results with APRI index. Ten patients in treatment with taliglucerase were included. In 7 patients, TE values were compatible with fibrosis F0/F2 (lower than 9.5 kPA) and the APRI was lower than 0.7. In 2 patients, values were compatible with advanced fibrosis F4 (upper than 12.5 kPA) and APRI was higher than 0.7. In one patient, in whom the TE was difficult to perform because of obesity, there was a discordance between TE that was compatible with fibrosis (F0/F1) and the APRI (which was higher than 0.7). Concerning CAP values, 7 patients had values compatible with low, less than 11%, of steatosis. Two had values compatible with steatosis between 33–66% and 1 had a value compatiblewith steatosis greater than 67%. Therewas no correlation between fibrosis grade and values of CAP. None of the patients had values of transaminases higher than 2 times the upper limit value. TE with CAP can be a valuable tool to evaluate hepatic involvement in GD patients, and in this small sample had a good correlation with APRI index. Studies with larger numbers of subjects should be done to confirm this inference.