Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis

A prospective observational study

Wei Li, Tohti Amet, Yanyan Xing, Dennis Yang, Suthat Liangpunsakul, Puneet Puri, Patrick S. Kamath, Arun J. Sanyal, Vijay H. Shah, Barry Katz, Svetlana Radaeva, David Crabb, Naga Chalasani, Andy Yu

Research output: Contribution to journalArticle

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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).

Original languageEnglish (US)
Pages (from-to)575-590
Number of pages16
JournalHepatology
Volume66
Issue number2
DOIs
StatePublished - Aug 1 2017

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Alcohol Abstinence
Alcoholic Hepatitis
Observational Studies
Prospective Studies
Chemokine CCL22
Interleukin-8
HLA Antigens
Interleukin-7
Interleukin-6
Fibroblast Growth Factor 2
T-Lymphocytes
Chemokines
Interleukin-10
Tumor Necrosis Factor-alpha
Interleukin-9
Cytokines
Interleukin-15
Transforming Growth Factor alpha
Gastroenterology
Immunoassay

ASJC Scopus subject areas

  • Hepatology

Cite this

Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis : A prospective observational study. / Li, Wei; Amet, Tohti; Xing, Yanyan; Yang, Dennis; Liangpunsakul, Suthat; Puri, Puneet; Kamath, Patrick S.; Sanyal, Arun J.; Shah, Vijay H.; Katz, Barry; Radaeva, Svetlana; Crabb, David; Chalasani, Naga; Yu, Andy.

In: Hepatology, Vol. 66, No. 2, 01.08.2017, p. 575-590.

Research output: Contribution to journalArticle

Li, Wei ; Amet, Tohti ; Xing, Yanyan ; Yang, Dennis ; Liangpunsakul, Suthat ; Puri, Puneet ; Kamath, Patrick S. ; Sanyal, Arun J. ; Shah, Vijay H. ; Katz, Barry ; Radaeva, Svetlana ; Crabb, David ; Chalasani, Naga ; Yu, Andy. / Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis : A prospective observational study. In: Hepatology. 2017 ; Vol. 66, No. 2. pp. 575-590.
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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).",
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AU - Kamath, Patrick S.

AU - Sanyal, Arun J.

AU - Shah, Vijay H.

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