Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome

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Authors

Abstract

BACKGROUND AND AIMS: Alström syndrome (AS) is a recessive monogenic syndrome characterised by obesity, extreme insulin resistance and multi-organ fibrosis. Despite phenotypically being high risk of non-alcoholic fatty liver disease (NAFLD), there is a lack of data on the extent of fibrosis in the liver and its close links to adipose in patients with AS. Our aim is to characterise the hepatic and adipose phenotype in patients with AS.

METHODS: Observational cohort study with comprehensive assessment of metabolic liver phenotype including liver elastography (Fibroscan(®) ), serum Enhanced Liver Fibrosis (ELF) Panel and liver histology. In addition, abdominal adipose histology and gene expression was assessed. We recruited 30 patients from the UK national AS clinic. A subset of 6 patients underwent adipose biopsies which was compared with control tissue from 9 healthy participants.

RESULTS: Patients were overweight/obese (BMI 29.3 (25.95-34.05) kg/m2). 80% (24/30) were diabetic. 74% (20/27) had liver ultrasound scanning suggestive of NAFLD. As judged by the ELF panel, 96% (24/25) were categorized as having fibrosis and 10/21 (48%) had liver elastography consistent with advanced liver fibrosis/cirrhosis. In 7/8 selected cases, there was evidence of advanced NAFLD on liver histology. Adipose tissue histology showed marked fibrosis as well as disordered pro-inflammatory and fibrotic gene expression profiles.

CONCLUSIONS: NAFLD and adipose dysfunction are common in patients with AS. The severity of liver disease in our cohort supports the need for screening of liver fibrosis in AS. This article is protected by copyright. All rights reserved.

Details

Original languageEnglish
JournalLiver International
Early online date14 May 2016
Publication statusE-pub ahead of print - 14 May 2016

Keywords

  • NAFLD, Alström syndrome, Adipocyte biology, Insulin resistance