Fabio Nascimbeni1, Elena Cassinerio2, Annalisa Dalla Salda1, Irene Motta3, Serena Bursi1, Salvatore Donatiello4, Vincenzo Spina4, Maria Domenica Cappellini3, Francesca Carubbi5. 1. Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU Modena, University of Modena and Reggio Emilia, Modena, Italy. 2. Rare Diseases Center, Department of Medicine, "Ca' Granda" Foundation IRCCS, Milan, Italy. 3. Rare Diseases Center, Department of Medicine, "Ca' Granda" Foundation IRCCS, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Italy. 4. Radiology Division, Civil Hospital, AOU, Modena, Modena, Italy. 5. Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU Modena, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: carubbi@unimore.it.
Abstract
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.
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 GDpatients. 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 GDpatients 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 GDpatients 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-N370SGBA1 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 GDpatients. Splenectomy, GD severity and GBA1 genotypes are major GD-related predictors of liver fibrosis. Length of ERT is inversely correlated with liver disease in GDpatients, suggesting a beneficial effect of ERT on liver fibrosis. However, GDpatients on stable ERT should be monitored for metabolic complications, since MetS features may enhance liver disease progression despite optimal GD control.