Novel Association of Cholesterol Ester Storage Disease Due to Lysosomal Acid Lipase Deficiency and Non-Alcoholic Fatty Liver Disease: A Prospective Clinical Study

Non-alcoholic fatty liver disease (NAFLD) is a world-wide problem with a global prevalence estimated at 1.5 billion people. It is characterised by significant diversity and phenotypic heterogeneity. Morbidity rates are estimated at 20% to 30% in Western adults, increasing to 90% in patients who are morbidly obese or diabetic. Risk factors in non-obese NAFLD patients are of especial practical and theoretical importance. Cholesterol Ester Storage Disease (CESD) is an autosomal recessive chronic disease of variable phenotype, caused by a deficiency in lysosomal acid lipase (LAL) and characterized by accumulation of fat in tissues and organs. Hepatic accumulation of fat in this disorder can cause hepatomegaly with varying degrees of damage varying from steatosis to fibrosis, elevated aminotransaminases, and isolated splenomegaly. Since the contribution of LAL deficiency to non-obese NAFLD is poorly understood, the investigators propose to evaluating the association between NAFLD and LAL deficiency in a prospective study in our population.

Study Overview

• Status: Unknown
• Conditions: Non-alcoholic Fatty Liver Disease; Cholesterol Ester Storage Disease

• Study Type: Observational

Contacts and Locations

Study Locations

• Israel
  • Safed, Israel, 13100
    • Assy Nimer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

400 subjects will be enrolled and informed consent obtained. After clinical evaluation, subjects will undergo liver ultrasound, non-invasive liver elastography (Fibroscan) and standard biochemical evaluation including glucose, insulin, TG, HDL, LDL, leptin, adiponectin and TNF-alpha. They will then be divided into 2 groups: NAFLD, and NAFLD with fibrosis (NASH). In addition a cohort of healthy volunteers will also be studied. LAL activity in dry blood spots (DBS) will be measured using the substrate 4-methylumbelliferyl palmitate. LAL activity will be measured by measuring total lipase activity and lipase activity in the presence of Lalistat2.

Description

Inclusion Criteria:

• Age between 18-80 years;
• BMI 25-40;
• Fatty liver disease (bright liver, hepatomegaly by ultrasound (Liver span > 15 cm mid clavicle line), splenomegaly (>13 cm) or both.

Exclusion Criteria:

• Alcohol abuse>30 gm/day, or > 70 gram per week;
• Soft drink abuse;
• Drugs known to cause fatty liver;
• Chronic hepatitis (B and C);
• Biliary liver disease;
• Autoimmune hepatitis;
• HIV;
• Genetic/Metabolic liver disease (Wilson, alpha-1 antitrypsin, CF);
• Failure to give informed consent

Study Plan

How is the study designed?

Design Details

• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
NAFLD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
liver ultrasound, ultrasound Doppler of the common carotid artery, hepatic Fibroscan evaluation (transient elastography) for assessment of steatosis and fibrosis	year

Collaborators and Investigators

• Sponsor: Assy Nimer

Study record dates

Study Major Dates

• Primary Completion (Anticipated): February 1, 2014

Study Registration Dates

• First Submitted: February 10, 2013
• First Submitted That Met QC Criteria: February 13, 2013
• First Posted (Estimate): February 15, 2013

Study Record Updates

• Last Update Posted (Estimate): February 15, 2013
• Last Update Submitted That Met QC Criteria: February 13, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Lipidoses; Lipid Metabolism, Inborn Errors; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Cholesterol Ester Storage Disease
• Other Study ID Numbers: 0042-12-ZIV