Obesity in acute alcoholic hepatitis increases morbidity and mortality

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Obesity in acute alcoholic hepatitis increases morbidity and mortality. / Parker, R; Kim, SJ; Im, GY; Nahas, J; Dhesi, B; Vergis, N; Sinha, A; Ghezzi, A; Rink, MR; McCune, A; Aithal, GP; Newsome, PN; Weston, CJ; Holt, A; Gao, B.

In: EBioMedicine, Vol. 45, 03.07.2019, p. 511-518.

Research output: Contribution to journalArticlepeer-review

Harvard

Parker, R, Kim, SJ, Im, GY, Nahas, J, Dhesi, B, Vergis, N, Sinha, A, Ghezzi, A, Rink, MR, McCune, A, Aithal, GP, Newsome, PN, Weston, CJ, Holt, A & Gao, B 2019, 'Obesity in acute alcoholic hepatitis increases morbidity and mortality', EBioMedicine, vol. 45, pp. 511-518. https://doi.org/10.1016/j.ebiom.2019.03.046

APA

Parker, R., Kim, SJ., Im, GY., Nahas, J., Dhesi, B., Vergis, N., Sinha, A., Ghezzi, A., Rink, MR., McCune, A., Aithal, GP., Newsome, PN., Weston, CJ., Holt, A., & Gao, B. (2019). Obesity in acute alcoholic hepatitis increases morbidity and mortality. EBioMedicine, 45, 511-518. https://doi.org/10.1016/j.ebiom.2019.03.046

Vancouver

Author

Parker, R ; Kim, SJ ; Im, GY ; Nahas, J ; Dhesi, B ; Vergis, N ; Sinha, A ; Ghezzi, A ; Rink, MR ; McCune, A ; Aithal, GP ; Newsome, PN ; Weston, CJ ; Holt, A ; Gao, B. / Obesity in acute alcoholic hepatitis increases morbidity and mortality. In: EBioMedicine. 2019 ; Vol. 45. pp. 511-518.

Bibtex

@article{9793b0ce5a5d4f77a7eb25af6c2cd8d5,
title = "Obesity in acute alcoholic hepatitis increases morbidity and mortality",
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.",
keywords = "Adipose, Alcoholic hepatitis, Obesity",
author = "R Parker and SJ Kim and GY Im and J Nahas and B Dhesi and N Vergis and A Sinha and A Ghezzi and MR Rink and A McCune and GP Aithal and PN Newsome and CJ Weston and A Holt and B Gao",
year = "2019",
month = jul,
day = "3",
doi = "10.1016/j.ebiom.2019.03.046",
language = "English",
volume = "45",
pages = "511--518",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Obesity in acute alcoholic hepatitis increases morbidity and mortality

AU - Parker, R

AU - Kim, SJ

AU - Im, GY

AU - Nahas, J

AU - Dhesi, B

AU - Vergis, N

AU - Sinha, A

AU - Ghezzi, A

AU - Rink, MR

AU - McCune, A

AU - Aithal, GP

AU - Newsome, PN

AU - Weston, CJ

AU - Holt, A

AU - Gao, B

PY - 2019/7/3

Y1 - 2019/7/3

N2 - 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.

AB - 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.

KW - Adipose

KW - Alcoholic hepatitis

KW - Obesity

UR - http://www.scopus.com/inward/record.url?scp=85068229869&partnerID=8YFLogxK

U2 - 10.1016/j.ebiom.2019.03.046

DO - 10.1016/j.ebiom.2019.03.046

M3 - Article

C2 - 31278069

VL - 45

SP - 511

EP - 518

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -