Gaucher patients need constant liver health monitoring, study finds



Although standard therapies for Gaucher disease (MG) generally reduce liver damage, some forms of treatment – particularly enzyme replacement therapy (ERT) – appear to be linked to a higher incidence of fatty liver disease, a study revealed.

The results underscore the importance of continuously monitoring liver health in people with Gaucher, even after starting treatment, the researchers said.

Entitled “Liver injury in patients with Gaucher disease types I and III”, The study was published in the journal Molecular Genetics and Metabolism Reports.

MG is caused by a mutation in the ACS gene, which leads to the abnormal production of the enzyme beta-glucocerebrosidase. The absence of the functional enzyme leads to the accumulation of a fatty substance called glucocerebroside inside immune cells called macrophages, which then become Gaucher cells.

These cells can then enter the liver, spleen, bone marrow, and nervous system, causing symptoms such as an enlarged liver and spleen, called hepatosplenomegaly. More recently, liver damage in MG has been associated with other disorders such as fibrosis (scarring), fatty liver known as steatosis and hepatocellular carcinoma or liver cancer.

To assess the possible effects of treatment on the health of the liver in people with type 1 and type 3 Gaucher, investigators in Brazil reviewed the medical records of patients who had been followed at the Hospital de Cliniques de Porto Alegre. from 2003 to 2018.

Among the 42 patients (median age 35 years) included in the study, 39 had been diagnosed with type 1 MG and three with type 3.

Most patients (37) were receiving ERT, while only two were receiving substrate reduction therapy (SRT). Three patients were not receiving any form of treatment for their condition.

ERT, a lifelong treatment given to the bloodstream, can help replace defective or deficient beta-glucocerebrosidase. Meanwhile, SRT uses small molecules that inhibit the synthesis of the cell membrane component that is broken down by beta-glucocerebrosidase. By reducing the enzyme substrate, waste levels can be reduced.

The median duration of treatment by patients was 124 months (approximately 10 years).

Elevated levels of liver enzymes, indicating liver damage and inflammation, were found in 68% of patients before the start of treatment, known as baseline. After treatment, at follow-up, more than half (55%) of patients continued to have elevated levels of these enzymes.

Enlarged liver was also seen in 67% of participants at the start of treatment, but fell to 39% at follow-up.

In contrast, the percentage of patients with signs of hepatic steatosis, or hepatic steatosis, increased from 8% at baseline to 39% at follow-up. Three-quarters (75%) of patients with fatty liver disease were overweight or obese.

“ERT is a powerful inducer of weight gain,” the researchers wrote. “Thus, it can be difficult to establish whether the high prevalence of steatosis is a manifestation of MG itself, a complication of its treatment, or a comorbidity.”

The researchers also found that seven patients with type 1 MG who received ERT for a median of 55 months – four years, seven months – had excessive levels of iron in their liver. This condition is known as iron overload.

Of the eight people who had liver biopsies, three had signs of fibrosis, while two had steatohepatitis (a type of fatty liver), and one has developed liver cancer. With the exception of two patients whose biopsies showed evidence of hepatic fibrosis before the start of treatment, all other biopsy results were taken after the start of treatment.

“Although the treatment [lessens liver] damage, it is associated with an increased rate of steatosis, ”the researchers wrote. “This study highlights the importance of monitoring liver integrity in these patients.”

Joana holds a bachelor’s degree in biology, a master’s degree in evolutionary and developmental biology and a doctorate in biomedical sciences from the Universidade de Lisboa, Portugal. His work has focused on the impact of non-canonical Wnt signaling on the collective behavior of endothelial cells – cells that make up the lining of blood vessels – found in the umbilical cord of newborns.

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José is a science journalist with a doctorate in neuroscience from the University of Porto, Portugal. He also studied biochemistry at the Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, New York, and the University of Western Ontario in London, Ontario, Canada. His work ranges from the association of central cardiovascular control and pain with the neurobiological basis of hypertension and the molecular pathways that cause Alzheimer’s disease.

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