Liver steatosis is highly prevalent and is associated with metabolic risk factors and liver fibrosis in adult patients with type 1 Gaucher disease

Abstract

Background and Aims Gaucher disease (GD) is associated with peculiar metabolic abnormalities (ie hypermetabolic state, peripheral insulin resistance, dyslipidaemia), partially reverted by enzyme replacement therapy (ERT) at the expense of weight gain. Such metabolic alterations together with an unhealthy lifestyle acquired by an ageing GD population may favour the development of liver steatosis. We aimed at evaluating the prevalence of significant liver steatosis and at identifying the factors associated with liver steatosis in a cohort of patients with type 1 GD. Methods Twenty adult type 1 GD patients from an Italian academic referral centre were prospectively submitted to vibration‐controlled transient elastography (Fibroscan®) with controlled attenuation parameter (CAP); significant steatosis was defined as CAP values ≥250 dB/min. Results Median CAP values were 234 [165‐358] dB/min and 8 patients (40%) had significant steatosis. Significant steatosis was associated with indices of adiposity (weight, BMI and waist circumference), high blood pressure, insulin resistance and metabolic syndrome. GD‐related variables and dose and duration of ERT were not associated with significant steatosis. In the subgroup of 16 patients on stable ERT for at least 24 months, CAP resulted significantly and positively associated with liver stiffness (rho 0.559, P = .024). Conclusions Significant steatosis is highly prevalent in adult type 1 GD patients and is strongly associated with a worse metabolic profile, featuring metabolic dysfunction‐associated fatty liver disease (MAFLD). MAFLD may determine liver fibrosis progression in GD patients on stable ERT and may be a risk factor for long‐term liver‐related complications.

MAFLD: Now is the time to capitalize on the momentum

“…The utility of the MAFLD definition has also been shown in patients with other diseases such as hepatitis B, 18 hepatitis C, 19,20 HIV, 21 celiac disease, 22 myotonic dystrophy type 1 (DM1) 23 and Gaucher disease. 24 This all begs the question, why do we not put the debate aside, capitalize on maintaining momentum and progress the field with the only thing that can more evidence. The MAFLD proposal can be the steppingstone for new vigour among clinicians for patient management on the one hand and on the other, to enhance community and other stakeholder engagement for the benefit of patients.…”

MAFLD: A game changer redefining fatty liver disease for adults and children

“…The definition identifies patients with significant hepatic fibrosis, 6,7 cardiovascular disease, 8,9 chronic kidney disease, 7,10 and those who would benefit from an evaluation of genetic risks for fatty liver 11 better than the previous NAFLD criteria. Its utility has also been demonstrated in patients with other diseases such as hepatitis B, 12,13 hepatitis C, 14,15 HIV, 16 coeliac disease 17 and Gaucher disease, 18 in all of which NAFLD cannot be concomitantly diagnosed. Hegarty et al, express their enthusiastic support for the MAFLD definition and indicate that the rationale behind the redefinition of fatty liver disease in adults is equally applicable for children.…”

The role of glucosylceramide and glucosylceramide synthase in liver disease: from bench to bedside

“…Type 1 Gaucher disease generally presenting with visceromegaly, and liver involvement is almost universal and ranges from with or without liver enzymes alterations, to liver fibrosis (Cox et al, 2017). The latest study showed that significant liver steatosis was highly prevalent in type 1 Gaucher disease patients, reaching about 40% (Nascimbeni et al, 2020). Liver steatosis is characterized by the ectopic storage of triglycerides in hepatocytes and featuring metabolic dysfunction-associated fatty liver disease which is strongly associated with the risk of liver fibrosis/cirrhosis (Younossi et al, 2018).…”