Abstract
Long term liver-related complications of type-1 Gaucher disease (GD), a lysosomal storage disorder, include fibrosis and an increased incidence of hepatocellular carcinoma. Splenectomy has been implicated as a risk factor for the development of liver pathology in GD. High ferritin concentrations are a feature of GD and iron storage in Gaucher cells has been described, but iron storage in the liver in relation to liver fibrosis has not been studied. Alternatively, iron storage in GD may be the result of iron supplementation therapy or regular blood transfusions in patients with severe cytopenia. In this pilot study, comprising 14 type-1 GD patients (7 splenectomized, 7 non-splenectomized) and 7 healthy controls, we demonstrate that liver stiffness values, measured by Transient Elastography and MR-Elastography, are significantly higher in splenectomized GD patients when compared with non-splenectomized GD patients (p = 0.03 and p = 0.01, respectively). Liver iron concentration was elevated (>60±30 µmol/g) in 4 GD patients of whom 3 were splenectomized. No relationship was found between liver stiffness and liver iron concentration. HFE gene mutations were more frequent in splenectomized (6/7) than in non-splenectomized (2/7) participants (p = 0.10). Liver disease appeared more advanced in splenectomized than in non-splenectomized patients. We hypothesize a relationship with excessive hepatic iron accumulation in splenectomized patients. We recommend that all splenectomized patients, especially those with evidence of substantial liver fibrosis undergo regular screening for HCC, according to current guidelines.
Highlights
Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders, currently treatable with enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) [1,2,3,4,5]
Several studies have reported on the occurrence of hepatocellular carcinoma (HCC) among GD patients [7,8,9,10,11,12,13] and one cohort study reported that the risk of developing HCC was increased in GD patients, suggesting that splenectomy – formerly the only treatment option – could be a risk factor for the development of HCC in GD patients as a result of advanced hepatic involvement after splenectomy [8]
This study is the first to demonstrate that liver stiffness values are significantly higher in splenectomized GD patients when compared with GD patients with an intact spleen, as measured by Transient Elastography (TE) and magnetic resonance elastography (MRE)
Summary
Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders, currently treatable with enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) [1,2,3,4,5]. Raised serum ferritin concentrations are a well-known laboratory feature of GD, and can be used to monitor response to treatment [16,17,18,19,20,21] These high ferritin concentrations have been suggested to reflect an altered iron metabolism in GD [22]. These patients may suffer from residual disease, which may cause partial unresponsiveness to treatment [26,27,28] As this cohort ages, particular care should be taken to ensure proper monitoring with respect to the occurrence of long term complications, including HCC. Since liver fibrosis and hepatic iron storage are known risk factor for the development of HCC, screening for both entities could be of additional value in the management of GD patients [29,30]. Our objective was to investigate whether GD patients with and without splenectomy (Sx) differed with respect to liver stiffness and iron content
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