Obesity in acute alcoholic hepatitis increases morbidity and mortality

Research output: Contribution to journalArticle

Authors

  • S J Kim
  • G Y Im
  • J Nahas
  • B Dhesi
  • N Vergis
  • A Sinha
  • A Ghezzi
  • M R Rink
  • A McCune
  • G P Aithal
  • A Holt
  • B Gao

Colleges, School and Institutes

External organisations

  • Liver and Hepatobiliary Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Centre for Liver Research, University of Birmingham, Birmingham, UK; National Institute for Alcoholism and Alcohol Abuse, National Institutes of Health, Rockville, MD, USA. Electronic address: richardparker@nhs.net.
  • National Institute for Alcoholism and Alcohol Abuse, National Institutes of Health, Rockville, MD, USA.
  • Mount Sinai Medical Centre, New York, NY, USA.
  • Liver and Hepatobiliary Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Imperial College Healthcare NHS Foundation Trust, UK.
  • Department of Liver Medicine, University Hospitals Bristol NHS Foundation Trust, UK.
  • Centre for Liver Research, NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, Birmingham B15 2TT, UK.
  • Liver and Hepatobiliary Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Centre for Liver Research, University of Birmingham, Birmingham, UK.
  • NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University Of Nottingham, Nottingham, UK

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 233 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 3 T3-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. Obesity (HR 2.22, 95%CI 1.1-4.3, p = .022) and underweight (HR 2.38, 1.00-5.6, p = .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 showed that alcohol induced 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. FUND: 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. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Bibliographic note

Copyright © 2019. Published by Elsevier B.V.

Details

Original languageEnglish
Pages (from-to)511-518
Number of pages8
JournalEBioMedicine
Volume45
Publication statusPublished - 3 Jul 2019

Keywords

  • Adipose, Alcoholic hepatitis, Obesity