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

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.

Energy balance, glucose and lipid metabolism, cardiovascular risk and liver disease burden in adult patients with type 1 Gaucher disease.

Gaucher disease (GD), the most prevalent lysosomal storage disease, is characterized by systemic accumulation of macrophages engorged with glycosphingolipid-laden lysosomes. Even though both lysosomes and sphingolipids play a pivotal role in metabolic homeostasis, little is known on metabolic abnormalities associated with GD. In this review, we discuss the peculiarity of energy balance and glucose and lipid metabolism in adult type 1 GD patients. Moreover, we evaluate the potential relationship between these metabolic derangements, cardiovascular risk and chronic liver disease. The limited data available show that adult type 1 GD is characterized by a hypermetabolic state, peripheral insulin resistance and hypolipidemia with markedly reduced HDL-cholesterol levels, partially reverted by enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Although this unfavorable metabolic profile has not been associated with increased incidence of type 2 diabetes and premature atherosclerosis, a natural history study has shown that cardio-cerebrovascular events and malignancy are the leading causes of death in treated type 1 GD patients. Hepatomegaly is frequently observed in GD and ERT/SRT are highly effective in reducing liver volume. Nevertheless, patients with GD may be at increased risk of long-term liver complications including cirrhosis and hepatocellular carcinoma. The role that ERT/SRT and/or lifestyle habits may have on such metabolic features of GD patients, and subsequently on long-term prognosis, deserves further investigations. To gain more insights into the peculiarity of GD metabolism may serve both surveillance and treatment purposes by helping to identify new markers of disease severity and define an updated natural history of GD.

Prevalence and predictors of liver fibrosis evaluated by vibration controlled transient elastography in type 1 Gaucher disease.

BACKGROUND & AIMS: Long-term liver-related complications of Gaucher disease (GD) include cirrhosis, portal hypertension and hepatocellular carcinoma. Although liver fibrosis is the main determinant of adverse liver-related clinical outcomes, it has rarely been evaluated in previously published cohorts of GD patients. We aimed at: assessing the prevalence of significant liver fibrosis in a cohort of patients with type 1 GD; identifying its predictors among GD-related variables, enzyme replacement therapy (ERT) and metabolic features. METHODS: 37 adult type 1 GD patients from two Italian academic referral centers were prospectively submitted to vibration controlled transient elastography (Fibroscan®); significant fibrosis was defined as liver stiffness ≥7 kPa. RESULTS: Median liver stiffness was 4.6 [3-15.1] kPa and 7 patients (19%) had significant fibrosis. Significant fibrosis was associated with splenectomy (p = .046) and with scores (DS3: p = .002; SSI: p = .026) and biomarkers (ACE: p = .016; HDL cholesterol: p = .004) of GD severity. Length of ERT was significantly lower in GD patients with significant fibrosis. In the subgroup of 29 patients who were on stable ERT for at least 24 months, further to splenectomy, GD severity and non-N370S GBA1 genotypes, also diastolic blood pressure, BMI and the number of metabolic syndrome (MetS) components emerged as factors significantly associated with significant fibrosis. CONCLUSIONS: Significant fibrosis is present in a remarkable proportion of adult type 1 GD patients. Splenectomy, GD severity and GBA1 genotypes are major GD-related predictors of liver fibrosis. Length of ERT is inversely correlated with liver disease in GD patients, suggesting a beneficial effect of ERT on liver fibrosis. However, GD patients on stable ERT should be monitored for metabolic complications, since MetS features may enhance liver disease progression despite optimal GD control.

Prothrombotic state induced by COVID-19 infection as trigger for stroke in young patients: A dangerous association.

•COVID-19 infection could led to a pro-inflammatory and pro-thrombotic state.•Cerebrovascular involvement may occur in COVID-19 infection even in young patients.•Physicians should be aware that stroke may be the first COVID-19 manifestation.