Noninvasive test may help monitor liver health in type 1 Gaucher disease
Study: Transient elastography can assess scarring, excess fat in the organ
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Transient elastography, a noninvasive test that uses ultrasound to detect liver stiffness and fat, may be used to assess tissue scarring and excess fat in the liver of adults with type 1 Gaucher disease, a study showed.
More severe liver scarring, or fibrosis, was significantly associated with higher blood levels of liver enzymes, which are indicative of liver damage, a greater delay in treatment initiation, and longer disease duration.
Significant excess liver fat, or steatosis, was significantly associated with a higher body mass index (BMI; a ratio of weight and height commonly used as a proxy of body fat) and metabolic syndrome — a cluster of conditions including a large waistline, high blood pressure, high blood sugar, and high levels of certain fatty molecules.
Transient elastography “is a valuable noninvasive method for assessing liver fibrosis and … steatosis in patients with type 1 GD [Gaucher disease] and may serve as a useful adjunct to routine monitoring in this population,” researchers wrote.
The study, “Assessment of liver and spleen stiffness and hepatic steatosis by transient elastography (Fibroscan®) in type 1 Gaucher disease: a single center case–control cohort study,” was published in the Orphanet Journal of Rare Diseases.
Type 1 Gaucher only form that doesn’t affect brain, spinal cord
Gaucher disease is caused by mutations in the GBA1 gene that result in missing or defective glucocerebrosidase (GCase), an enzyme required for the breakdown of fatty molecules, such as glucocerebroside (Gb1). As a result, Gb1 and other fatty molecules accumulate within cells, driving tissue damage and disease symptoms such as an enlarged spleen and liver, low levels of immune cells, and bone problems.
Type 1 Gaucher, the most common form, is the only type that doesn’t affect the brain or spinal cord. Liver enlargement is due to the accumulation of fatty molecules, and liver involvement may progress to fibrosis and cirrhosis, or irreversible fibrosis, which may lead to liver failure.
“Consequently, noninvasive assessment of [liver] fibrosis represents an important step in the risk stratification and longitudinal follow-up of patients with GD,” the researchers wrote. “To date, only a limited number of studies have evaluated liver stiffness, spleen stiffness, and [steatosis] measurements specifically in patients with type 1 GD.”
Assessments of liver fibrosis, cirrhosis showed reductions with ERT
In this study, a team of researchers at Istanbul University in Turkey conducted a retrospective study to assess liver and spleen stiffness and liver fat accumulation in people with type 1 Gaucher disease using transient elastography. This ultrasound-based noninvasive method is used to assess liver and spleen stiffness (a proxy of liver fibrosis), as well as liver steatosis.
The study involved 25 adults with type 1 Gaucher who received enzyme replacement therapy (ERT) and 25 healthy controls matched for sex, weight, and BMI. ERT, which delivers a working version of GCase, is the standard treatment for type 1 Gaucher.
Most patients were women (56%), with a mean age of 41.5 years and a median disease duration of 13 years. ERT was given for a median of six years. Almost all were on Cerezyme (imiglucerase), while two were on Elelyso (taliglucerase alfa).
After starting ERT, there was a significant increase in patients’ weight (63.6 vs. 57.3 kg), BMI (23.8 vs. 22 kg/m2), and frequency of metabolic syndrome (40% vs. 12%). Liver and spleen volumes were significantly reduced, as were blood levels of certain markers of inflammation, including ferritin.
The Aspartate Aminotransferase to Platelet Ratio Index and the Fibrosis-4 (FIB-4) index, two blood-based formulas commonly used to assess liver fibrosis and cirrhosis, also showed significant reductions with ERT, although levels remained higher than in healthy controls.
Transient elastography data showed that significant liver fibrosis, defined as a liver stiffness of 7 kilopascal (kPa) or higher, was present in 44% of treated patients, but in none of the healthy controls. Treated patients had significantly higher liver stiffness (6.6 kPa vs. 3.7 kPa) and spleen stiffness (17.6 kPa vs. 11.1 kPa).
There were no significant differences in steatosis measures between the patient and control groups.
[These results suggest that] “increased metabolic syndrome prevalence post-ERT may contribute to the development of [liver] steatosis in this patient population.
Further statistical analyses in patients showed that higher blood levels of liver enzymes and ferritin, a higher FIB-4 score, greater liver volume, a longer time from diagnosis to ERT initiation, and longer disease duration were each significantly associated with higher liver stiffness.
“The detection of fibrosis is particularly relevant in individuals with a prolonged disease course and elevated inflammatory markers,” the team wrote.
Moreover, eight patients (32%) had significant steatosis, defined as a controlled attenuation parameter (CAP) of 250 decibels/min or higher on transient elastography. Notably, all of them had metabolic syndrome, while this condition was found in only 17% of patients without steatosis.
A higher BMI, higher hemoglobin A1c (an indicator of diabetes), and older age at ERT initiation were each significantly associated with higher CAP, reflecting greater steatosis.
These results suggest that “increased metabolic syndrome prevalence post-ERT may contribute to the development of [liver] steatosis in this patient population,” the researchers wrote.
“Future [larger-scale] studies incorporating both pre- and post-ERT [transient elastography] measurements, along with broader demographic diversity, are warranted to better elucidate the long-term effects of ERT on liver and spleen stiffness,” they concluded.
