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

Laura L Gathercole; Jonathan M Hazlehurst; Matthew J Armstrong; Rachel Crowley; Sarah Boocock; Michael W O'Reilly; Maria Round; Rachel Brown; Shaun Bolton; Robert Cramb; Philip Newsome; Robert K Semple; Richard Paisey; Jeremy W Tomlinson; Tarekegn Geberhiwot

doi:10.1111/liv.13163

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

Laura L Gathercole, Jonathan M Hazlehurst, Matthew J Armstrong, Rachel Crowley, Sarah Boocock, Michael W O'Reilly, Maria Round, Rachel Brown, Shaun Bolton, Robert Cramb, Philip Newsome, Robert K Semple, Richard Paisey, Jeremy W Tomlinson, Tarekegn Geberhiwot

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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.

Original language	English
Journal	Liver International
Early online date	14 May 2016
DOIs	https://doi.org/10.1111/liv.13163
Publication status	E-pub ahead of print - 14 May 2016

Keywords

NAFLD
Alström syndrome
Adipocyte biology
Insulin resistance

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/liv.13163Licence: None: All rights reserved

Gathercole_et_al-2016-Liver_International
This is the peer reviewed version of the following article: Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome which has been published in final form at 10.1111/liv.13163. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Accepted author manuscript, 493 KBLicence: Other (please specify with Rights Statement)

Glucocorticoid Metabolism and the Control of Metabolic Phenotype
Tomlinson, J.
Medical Research Council
1/10/09 → 30/09/14
Project: Research Councils

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Gathercole, L. L., Hazlehurst, J. M., Armstrong, M. J., Crowley, R., Boocock, S., O'Reilly, M. W., Round, M., Brown, R., Bolton, S., Cramb, R., Newsome, P., Semple, R. K., Paisey, R., Tomlinson, J. W., & Geberhiwot, T. (2016). Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome. Liver International. Advance online publication. https://doi.org/10.1111/liv.13163

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title = "Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alstr{\"o}m syndrome",

abstract = "BACKGROUND AND AIMS: Alstr{\"o}m 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({\textregistered}) ), 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.",

keywords = "NAFLD, Alstr{\"o}m syndrome, Adipocyte biology, Insulin resistance",

author = "Gathercole, {Laura L} and Hazlehurst, {Jonathan M} and Armstrong, {Matthew J} and Rachel Crowley and Sarah Boocock and O'Reilly, {Michael W} and Maria Round and Rachel Brown and Shaun Bolton and Robert Cramb and Philip Newsome and Semple, {Robert K} and Richard Paisey and Tomlinson, {Jeremy W} and Tarekegn Geberhiwot",

year = "2016",

month = may,

day = "14",

doi = "10.1111/liv.13163",

language = "English",

journal = "Liver International",

issn = "1478-3223",

publisher = "Wiley",

}

TY - JOUR

T1 - Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome

AU - Gathercole, Laura L

AU - Hazlehurst, Jonathan M

AU - Armstrong, Matthew J

AU - Crowley, Rachel

AU - Boocock, Sarah

AU - O'Reilly, Michael W

AU - Round, Maria

AU - Brown, Rachel

AU - Bolton, Shaun

AU - Cramb, Robert

AU - Newsome, Philip

AU - Semple, Robert K

AU - Paisey, Richard

AU - Tomlinson, Jeremy W

AU - Geberhiwot, Tarekegn

PY - 2016/5/14

Y1 - 2016/5/14

N2 - 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.

AB - 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.

KW - NAFLD

KW - Alström syndrome

KW - Adipocyte biology

KW - Insulin resistance

U2 - 10.1111/liv.13163

DO - 10.1111/liv.13163

M3 - Article

C2 - 27178444

SN - 1478-3223

JO - Liver International

JF - Liver International

ER -

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

Abstract

Keywords

UN SDGs

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Glucocorticoid Metabolism and the Control of Metabolic Phenotype

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