Obesity Increases Morbidity and Mortality in Alcoholic Hepatitis
30 Pages Posted: 19 Feb 2019More...
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
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