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Obesity Increases Morbidity and Mortality in Alcoholic Hepatitis

30 Pages Posted: 19 Feb 2019

See all articles by Richard Parker

Richard Parker

Government of the United States of America - National Institute on Alcohol Abuse and Alcoholism; Government of the United Kingdom - Liver and Hepatobiliary Unit; University of Birmingham - Centre for Liver Research

SJ Kim

Government of the United States of America - National Institute on Alcohol Abuse and Alcoholism

GY Im

Mount Sinai Medical Centre

J Nahas

Mount Sinai Medical Centre

B Dhesi

NHS Foundation Trust

N Vergis

NHS Foundation Trust

A Sinha

NHS Foundation Trust

A Ghezzi

NHS Foundation Trust; University of Nottingham

M Rink

University of Birmingham

A McCune

NHS Foundation Trust

GP Aithal

NHS Foundation Trust; University of Nottingham

PN Newsome

NHS Foundation Trust; University of Birmingham

CJ Weston

University of Birmingham

A Holt

NHS Foundation Trust

B Gao

Government of the United States of America - National Institute on Alcohol Abuse and Alcoholism

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Abstract

Background: Alcohol and obesity synergise to increase the risk of liver-related mortality. We examined the influence of adiposity on clinical outcomes in alcoholic hepatitis (AH) and the underlying inflammatory crosstalk between adipose tissue (AT) and the liver.  

Methods: A cohort of patients with AH from the UK and USA provided data to analyse the effects of obesity in AH. Body mass index was corrected for the severity of ascites, termed cBMI. Inflammatory and metabolic profiling was undertaken by proteome analysis of human serum samples. The effect of alcohol on adipose tissue and CXCL11 expression was studied in 3T3-derived adipocytes and in mice using the high-fat diet-plus-binge ethanol model.  

Findings: Obesity was common amongst patients with AH, seen in 19% of individuals. cBMI correlated with volume AT (r2= 0.623, p<0.001), but not with volume of muscle (r2=0.03, p=0.215). Obesity (HR 2.22, 95%CI 1.1-4.3, p=0.022) and underweight (HR 2.38, 1.00-5.6, p=0.049) were independently associated with mortality at 3 months. Proteome analysis demonstrated multiple metabolic and inflammatory factors differentially expressed in obese AH verse lean AH, with CXCL11 being the most elevated factor in obese AH. In vitro analysis of cultured adipocytes and in vivo analysis of mouse models confirmed that alcohol induces CXCL11 expression in AT but not in liver.  

Interpretation: Obesity is common in AH and associated with a greater than two-fold increase in short-term mortality. Obese AH is associated with a different inflammatory phenotype, with the greatest elevation in CXCL11. These data confirm that adiposity is clinically important in acute alcohol-related liver disease and illustrate the adipose-liver inflammatory axis in AH.  

Funding: This work was supported in part by an EASL Sheila Sherlock Physician Scientist Fellowship. The funder played no role in gathering or analysing data or writing the manuscript.

Declaration of Interest: No authors have any conflicts of interest to declare.

Ethical Approval: The collection of samples was approved by research ethics committee (reference 06/Q27108/11).

Keywords: Alcohol, Obesity, Alcoholic hepatitis

Suggested Citation

Parker, Richard and Kim, SJ and Im, GY and Nahas, J and Dhesi, B and Vergis, N and Sinha, A and Ghezzi, A and Rink, M and McCune, A and Aithal, GP and Newsome, PN and Weston, CJ and Holt, A and Gao, B, Obesity Increases Morbidity and Mortality in Alcoholic Hepatitis (February 15, 2019). Available at SSRN: https://ssrn.com/abstract=3335008

Richard Parker (Contact Author)

Government of the United States of America - National Institute on Alcohol Abuse and Alcoholism ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Government of the United Kingdom - Liver and Hepatobiliary Unit ( email )

United Kingdom

University of Birmingham - Centre for Liver Research ( email )

United Kingdom

SJ Kim

Government of the United States of America - National Institute on Alcohol Abuse and Alcoholism

9000 Rockville Pike
Bethesda, MD 20892
United States

GY Im

Mount Sinai Medical Centre

United States

J Nahas

Mount Sinai Medical Centre

United States

B Dhesi

NHS Foundation Trust

London, SE5 8AZ
United Kingdom

N Vergis

NHS Foundation Trust

London, SE5 8AZ
United Kingdom

A Sinha

NHS Foundation Trust

London, SE5 8AZ
United Kingdom

A Ghezzi

NHS Foundation Trust

London, SE5 8AZ
United Kingdom

University of Nottingham

University Park
Nottingham, NG8 1BB
United Kingdom

M Rink

University of Birmingham

Edgbaston, Birmingham B15 2TT
United Kingdom

A McCune

NHS Foundation Trust

London, SE5 8AZ
United Kingdom

GP Aithal

NHS Foundation Trust

London, SE5 8AZ
United Kingdom

University of Nottingham

University Park
Nottingham, NG8 1BB
United Kingdom

PN Newsome

NHS Foundation Trust

London, SE5 8AZ
United Kingdom

University of Birmingham

Edgbaston, Birmingham B15 2TT
United Kingdom

CJ Weston

University of Birmingham

Edgbaston, Birmingham B15 2TT
United Kingdom

A Holt

NHS Foundation Trust

London, SE5 8AZ
United Kingdom

B Gao

Government of the United States of America - National Institute on Alcohol Abuse and Alcoholism

9000 Rockville Pike
Bethesda, MD 20892
United States

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