Prevalence and predictors of liver fibrosis evaluated by vibration controlled transient elastography in type 1 Gaucher disease

Fabio Nascimbeni, Elena Cassinerio, Annalisa Dalla Salda, Irene Motta, Serena Bursi, Salvatore Donatiello, Vincenzo Spina, Maria Domenica Cappellini, Francesca Carubbi

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)64-72
JournalMolecular Genetics and Metabolism
Volume125
Issue number1-2
DOIs
Publication statusPublished - 2018

Fingerprint

Elasticity Imaging Techniques
Gaucher Disease
Vibration
Liver Cirrhosis
Liver
Enzyme Replacement Therapy
Fibrosis
Splenectomy
Enzymes
Liver Diseases
Genotype
Stiffness
Blood Pressure
Disease control
Portal Hypertension
Blood pressure
Biomarkers
HDL Cholesterol

Keywords

  • Enzyme replacement therapy
  • Glucocerebrosidase deficiency
  • Liver stiffness
  • Metabolic syndrome
  • Vibration controlled transient elastography

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Prevalence and predictors of liver fibrosis evaluated by vibration controlled transient elastography in type 1 Gaucher disease. / Nascimbeni, Fabio; Cassinerio, Elena; Dalla Salda, Annalisa; Motta, Irene; Bursi, Serena; Donatiello, Salvatore; Spina, Vincenzo; Cappellini, Maria Domenica; Carubbi, Francesca.

In: Molecular Genetics and Metabolism, Vol. 125, No. 1-2, 2018, p. 64-72.

Research output: Contribution to journalArticle

Nascimbeni, Fabio ; Cassinerio, Elena ; Dalla Salda, Annalisa ; Motta, Irene ; Bursi, Serena ; Donatiello, Salvatore ; Spina, Vincenzo ; Cappellini, Maria Domenica ; Carubbi, Francesca. / Prevalence and predictors of liver fibrosis evaluated by vibration controlled transient elastography in type 1 Gaucher disease. In: Molecular Genetics and Metabolism. 2018 ; Vol. 125, No. 1-2. pp. 64-72.
@article{b994519af7264a6ebe74784312f55dac,
title = "Prevalence and predictors of liver fibrosis evaluated by vibration controlled transient elastography in type 1 Gaucher disease",
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{\circledR}); 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.",
keywords = "Enzyme replacement therapy, Glucocerebrosidase deficiency, Liver stiffness, Metabolic syndrome, Vibration controlled transient elastography",
author = "Fabio Nascimbeni and Elena Cassinerio and {Dalla Salda}, Annalisa and Irene Motta and Serena Bursi and Salvatore Donatiello and Vincenzo Spina and Cappellini, {Maria Domenica} and Francesca Carubbi",
year = "2018",
doi = "10.1016/j.ymgme.2018.08.004",
language = "English",
volume = "125",
pages = "64--72",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "Academic Press Inc.",
number = "1-2",

}

TY - JOUR

T1 - Prevalence and predictors of liver fibrosis evaluated by vibration controlled transient elastography in type 1 Gaucher disease

AU - Nascimbeni, Fabio

AU - Cassinerio, Elena

AU - Dalla Salda, Annalisa

AU - Motta, Irene

AU - Bursi, Serena

AU - Donatiello, Salvatore

AU - Spina, Vincenzo

AU - Cappellini, Maria Domenica

AU - Carubbi, Francesca

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Enzyme replacement therapy

KW - Glucocerebrosidase deficiency

KW - Liver stiffness

KW - Metabolic syndrome

KW - Vibration controlled transient elastography

UR - http://www.scopus.com/inward/record.url?scp=85051369607&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051369607&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2018.08.004

DO - 10.1016/j.ymgme.2018.08.004

M3 - Article

AN - SCOPUS:85051369607

VL - 125

SP - 64

EP - 72

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 1-2

ER -