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Hepatology. 2017 Aug;66(2):575-590. doi: 10.1002/hep.29242. Epub 2017 Jun 30.

Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study.

Author information

1
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN.
2
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
3
Roudebush Veterans Administration Medical Center, Indiana University School of Medicine, Indianapolis, IN.
4
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN.
5
Division of Gastroenterology and Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, VA.
6
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
7
Department of Biostatistics, Indiana University School of Medicine and Richard M. Fairbanks School of Public Health, Indianapolis, IN.
8
National Institute of Alcoholism and Alcohol Abuse, National Institutes of Health, Rockville, MD.
9
Internal Medicine, Eskenazi Health, Indianapolis, IN.

Abstract

Alcoholic hepatitis (AH) develops in only a small proportion of heavy drinkers. To better understand the mechanisms underlying this disparity, we conducted a study to define the relationship between AH development and dysregulated immune responses that might be ameliorated by alcohol abstinence. Sixty-eight AH patients, 65 heavy drinking controls without liver disease (HDC), and 20 healthy controls were enrolled and followed up to 12 months. At baseline, HDC and healthy controls had no significant differences in their plasma levels of 38 inflammatory cytokines/chemokines measured using multiplex immunoassays. However, compared to HDC, AH patients had higher baseline levels of 11 cytokines/chemokines (tumor necrosis factor alpha, interleukin 6 [IL-6], IL-8, interferon gamma-induced protein 10, IL-4, IL-9, IL-10, fibroblast growth factor 2, IL-7, IL-15, and transforming growth factor alpha) but lower levels of the anti-inflammatory macrophage-derived chemokine. AH patients also had more activated yet dysfunctional immune cells as monocytes, T cells, and B cells expressed higher levels of cluster of differentiation 38 (CD38) and CD69 but low levels of human leukocyte antigen DR, CD80, and CD86 at baseline. In addition, CD4 T cells produced less interferon-gamma in response to T-cell stimulation. Up-regulated IL-6, IL-8, CD38, and CD69 and down-regulated macrophage-derived chemokine, human leukocyte antigen DR, CD86, and CD80 correlated positively and negatively, respectively, with disease severity. Longitudinal analysis indicated that levels of IL-6, IL-8, CD38, and CD69 were reduced, whereas levels of macrophage-derived chemokine, human leukocyte antigen DR, CD80, and CD86 were increased in abstinent AH patients. All of the cellular immune abnormalities were reversed by day 360 in abstinent AH patients; however, plasma levels of tumor necrosis factor alpha, IL-8, IL-10, fibroblast growth factor 2, and IL-7 remained higher.

CONCLUSION:

AH patients were in a highly immune-dysregulated state, whereas HDC showed little evidence of immune activation; alcohol abstinence reversed most, but not all, of the immunological abnormalities. (Hepatology 2017;66:575-590).

PMID:
28466561
PMCID:
PMC5548491
DOI:
10.1002/hep.29242
[Indexed for MEDLINE]
Free PMC Article

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