Liver Fibrosis in Type I Gaucher Disease: Magnetic Resonance Imaging, Transient Elastography and Parameters of Iron Storage

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.

Hepatic MR Elastography: Clinical Performance in a Series of 1377 Consecutive Examinations

“…Transient elastography, another clinically widespread elastographic technique, would be a reasonable alternative method to assess tissue stiffness (38-40). However, transient elastography has several technical challenges of its own, including being limited to imaging between narrow intercostal spaces, having a limited penetration depth, and only providing 1-D measurements of a wave field with potential wave diffraction or interference effects (41, 42), a 3-5% technical failure rate, and a 15% incidence of unreliable measurements (43, 44).…”

Magnetic resonance elastography of liver and spleen: Methods and applications

“…Of note, MRE can also be used successfully to stage fibrosis in other diffuse liver diseases such as autoimmune hepatitis or Gaucher disease . Finally, MRE has been used to assess the response to treatment in HIV and HCV patients treated with simtuzumab …”

Magnetic Resonance Elastography of Liver

“…23,24,35,36 Possible reasons for this variability are inclusion of patients with different etiologies and combining normal and F0 livers as one group. Preliminary studies with single etiologies like chronic hepatitis B, 19 chronic hepatitis C, 37 nonalcoholic steatohepatitis (NASH), 38 alcohol, 39 and Gaucher disease 40 are now available, and the reported cutoff values may be useful for application in those specific etiologies.…”