Liver Fibrosis Common in Gaucher Type 1, and ERT Is Seen to Be Beneficial, Study Reports

Liver Fibrosis Common in Gaucher Type 1, and ERT Is Seen to Be Beneficial, Study Reports
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Liver fibrosis is a common condition in patients with Gaucher disease type 1 (GD1) and can be predicted by factors such as disease severity and spleen removal, according to new research from Italy. The findings also indicate that stable enzyme replacement therapy (ERT) is associated with less fibrosis.

The study, “Prevalence and predictors of liver fibrosis evaluated by vibration controlled transient elastography in type 1 Gaucher disease,” was published in the journal Molecular Genetics and Metabolism.

An enlarged liver, called hepatomegaly, is common in GD1 patients, but usually has no clinical consequences. But other liver-related complications, such as cirrhosis — a late stage of fibrosis (or scarring), and hepatocellular carcinoma (HCC), the most common primary liver cancer — are associated with a worse prognosis.

Liver fibrosis is a common factor in the risk for different liver complications in Gaucher patients, indicating that its assessment may identify who could develop sequelae (a pathological condition resulting from a disease) from advanced liver disease.

Diagnosing and staging liver fibrosis has mainly been conducted using a liver biopsy. But the susceptiblity to bleeding makes this technique unsuitable in Gaucher disease patients.

Vibration controlled transient elastography (VCTE) is a noninvasive ultrasound-based method that assesses liver stiffness, an indicator of fibrosis. Current guidelines recommend VCTE and related techniques to assess severity of chronic liver disease, suggesting its potential for Gaucher patients with possible liver fibrosis.

Research reported that Gaucher patients with more severe, longstanding and multi-organ disease have a higher degree of liver involvement, but whether Gaucher patients are at greater risk for developing liver fibrosis is unknown.

The possible impact of Gaucher treatment, other liver diseases — such as chronic viral hepatitis or vascular liver diseases — and metabolic changes in liver fibrosis is also unclear.

In an effort to address these gaps, researchers from Italy used Fibroscan (by Echosens), a VCTE device to assess liver stiffness, in 37 adult GD1 patients (21 men, median age 46) monitored at two Italian referral centers from 2015 to 2017.

Results showed that most patients had mildly severe Gaucher disease, 10 had undergone spleen removal, and all but two were on ERT. Median ERT duration was 98 months, with 29 patients being treated for at least two years.

The median liver stiffness was within the normal range (3-6 kPa). However, seven patients (19%) had liver stiffness of at least 7 kPa, indicating significant fibrosis. Only four patients had potentially concurrent liver diseases.

Levels of ferritin — a protein that stores iron in tissues — were abnormally high in 11 patients. A significant proportion of patients (41%) were overweight or obese, had high blood pressure (38%), and had low HDL cholesterol (43%).

However, full-blown metabolic syndrome — defined by the simultaneous presence of at least three conditions among obesity, high blood pressure, altered glucose metabolism, low HDL cholesterol, and high blood levels of triglycerides — was found in only six patients.

Liver fibrosis was associated with spleen removal, with some Gaucher disease biomarkers, and with being on ERT for less than two years.

“This finding supports a positive effect of ERT on [Gaucher]-related liver disease,” the investigators wrote.

In the 29 patients on stable ERT for at least two years, spleen removal, moderate Gaucher disease severity, carrying two non-N370S variants in GBA1 — usually linked to a more severe phenotype — diastolic blood pressure, BMI, and the number of metabolic syndrome conditions were all associated with significant fibrosis.

“In conclusion, significant liver fibrosis as evaluated by VCTE is present in a remarkable proportion of adult [GD1] patients,” the researchers wrote.

“Since liver fibrosis is the main predictor of the risk of liver-related complications and HCC, all [Gaucher disease] patients should be investigated for the presence of liver fibrosis,” they added.

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