title: Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome.
abstract: Alström syndrome (AS) is a recessive monogenic syndrome characterized 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 was to characterize the hepatic and adipose phenotype in patients with AS.
  
  
  
  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 six patients underwent adipose biopsies which was compared with control tissue from nine healthy participants.
  
  
  
  Patients were overweight/obese (BMI 29.3 (25.95-34.05) kg/m2). A total of 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.
  
  
  
  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.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Gathercole
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hazlehurst
authors.affiliation: Centre for Liver Research and NIHR Liver Biomedical Research Unit, University of Birmingham, Birmingham, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Armstrong
authors.affiliation: St Vincent's Hospital, Ireland and University College, Dublin, Ireland.
authors.forename: Rachel
authors.initials: R
authors.lastname: Crowley
authors.affiliation: Department of Endocrinology and Metabolism, University Hospitals Birmingham, Birmingham, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Boocock
authors.affiliation: Centre for Diabetes, Endocrinology and Metabolism, University of Birmingham, Birmingham, UK.
authors.forename: Michael W
authors.initials: MW
authors.lastname: O'Reilly
authors.affiliation: Department of Gastroenterology, University Hospitals Birmingham, Birmingham, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Round
authors.affiliation: Department of Pathology, University Hospital of Birmingham, Birmingham, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Brown
authors.affiliation: Department of Endocrinology and Metabolism, University Hospitals Birmingham, Birmingham, UK.
authors.forename: Shaun
authors.identifier: 0000-0003-0160-1505
authors.initials: S
authors.lastname: Bolton
authors.affiliation: Department of Endocrinology and Metabolism, University Hospitals Birmingham, Birmingham, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Cramb
authors.affiliation: Centre for Liver Research and NIHR Liver Biomedical Research Unit, University of Birmingham, Birmingham, UK.
authors.forename: Phillip N
authors.initials: PN
authors.lastname: Newsome
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Semple
authors.affiliation: Diabetes Research Unit, Horizon Centre, Torbay Hospital NHS Foundation Trust, Torquay, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Paisey
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Tomlinson
authors.affiliation: Department of Endocrinology and Metabolism, University Hospitals Birmingham, Birmingham, UK. tarekegn.geberhiwot@uhb.nhs.uk.|Centre for Diabetes, Endocrinology and Metabolism, University of Birmingham, Birmingham, UK. tarekegn.geberhiwot@uhb.nhs.uk.
authors.forename: Tarekegn
authors.initials: T
authors.lastname: Geberhiwot
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000328:Adult; D056769:Alstrom Syndrome / Q000150:complications*; D015331:Cohort Studies; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology* / Q000473:pathology; D009765:Obesity / Q000150:complications; D006113:United Kingdom; D055815:Young Adult
keywords: Alström syndrome; adipocyte biology; insulin resistance; non-alcoholic fatty liver disease