Orphanet Journal of Rare Diseases | Assessment of Liver and Spleen Stiffness and Hepatic Steatosis in Gaucher Disease

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This study is the first systematic assessment of liver stiffness, spleen stiffness, and changes in hepatic steatosis before and after enzyme replacement therapy (ERT) in adult Gaucher disease patients, and explores clinical and metabolic factors associated with liver fibrosis, providing important evidence for long-term follow-up and risk assessment.

 

Literature Overview

This article titled "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", published in the journal Orphanet Journal of Rare Diseases, reviews and summarizes differences in liver and spleen stiffness and hepatic steatosis among 25 adult patients with type 1 Gaucher disease (GD) receiving enzyme replacement therapy (ERT) and healthy controls. It emphasizes the improvement of liver fibrosis-related parameters by ERT, as well as the potential impact of metabolic syndrome on hepatic steatosis.

Background Knowledge

Type 1 Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the GBA1 gene, characterized by hepatosplenomegaly, anemia, thrombocytopenia, and bone involvement. Patients with long-term untreated disease may develop liver fibrosis or even cirrhosis. Enzyme replacement therapy (ERT) is the main treatment currently, effectively improving organ enlargement and metabolic abnormalities, but some patients still experience persistent liver damage. Transient Elastography (TE, Fibroscan®) is a non-invasive technique widely used for evaluating liver fibrosis and steatosis, but its application in GD patients remains limited. This study fills the gap in assessing liver and spleen stiffness using TE in GD patients, providing clinically relevant data on liver fibrosis and steatosis, and exploring their associations with disease duration, inflammatory markers, and delay in ERT initiation.

 

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Research Methods and Experiment

The study included 25 adult patients diagnosed with type 1 Gaucher disease (GD) who received enzyme replacement therapy (ERT), along with 25 healthy controls. All participants underwent Transient Elastography (TE) assessment, including controlled attenuation parameter (CAP) for hepatic steatosis, liver stiffness (LS), and spleen stiffness (SS) measurements. The study compared clinical parameter changes before and after ERT and performed cross-sectional analysis to evaluate differences in weight, BMI, liver and spleen volume, and inflammatory markers between GD patients and controls. Additionally, the study analyzed factors associated with liver fibrosis, such as ALT, GGT, FIB4, and APRI scores.

Key Findings and Insights

• 44% of GD patients exhibited significant liver fibrosis (LS ≥ 7 kPa), while no such phenomenon was observed in the control group.
• After ERT, weight, BMI, and the incidence of metabolic syndrome (MetS) significantly increased (p < 0.001).
• Liver fibrosis was positively correlated with ALT, GGT, ferritin levels, disease duration, and delayed initiation of ERT.
• Hepatic steatosis was more prevalent after ERT (32% vs. 16%) and was significantly associated with MetS.
• Spleen stiffness was significantly higher in GD patients compared to controls (17.6 vs. 11.1 kPa; p = 0.032).
• Hepatic fibrosis was more likely to develop in patients receiving 60 IU/kg ERT (p = 0.042).
• Although some inflammatory markers decreased, ferritin remained significantly correlated with liver fibrosis (p = 0.002).

Research Implications and Future Directions

This study highlights the importance of monitoring liver fibrosis and steatosis even after ERT. It recommends regular non-invasive TE assessments in GD patients, especially those with MetS or longer disease duration. Future studies with larger sample sizes and prospective designs are needed to validate the long-term predictive value of TE in GD.

 

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Conclusion

By comparing 25 patients with type 1 Gaucher disease to healthy controls, this study revealed a significant increase in weight, BMI, and metabolic syndrome (MetS) after ERT, while liver fibrosis and steatosis remained common. The study identified associations between liver fibrosis and ALT, GGT, ferritin levels, and delayed ERT initiation, suggesting that early intervention may improve long-term liver outcomes. Although ERT effectively alleviates inflammation, the increase in MetS may contribute to the progression of hepatic steatosis. The study supports the inclusion of Transient Elastography (TE) as a non-invasive assessment tool in clinical follow-ups to monitor liver damage and fibrosis progression. Future research should include more baseline and post-treatment TE data and integrate multi-omics analysis to further explore the molecular mechanisms and intervention strategies of GD-related liver disease.

 

Ummu Mutlu, Bilger Cavus, Hulya Hacisahinogullari, Kadir Demir, and Refik Tanakol. 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. Orphanet Journal of Rare Diseases.