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Hepatic zinc deficiency dampens the acute phase response in patients with alcohol-associated hepatitis
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Hepatic zinc deficiency dampens the acute phase response in patients with alcohol-associated hepatitis
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Journal Article
Hepatic zinc deficiency dampens the acute phase response in patients with alcohol-associated hepatitis
2026
Overview
Zinc deficiency affects ~17% of the population globally, contributing to deficits in growth, metabolism and immunity. Serum zinc is greatly reduced in alcohol-associated hepatitis, driven by hepatic dysfunction and poor zinc retention. While zinc is an essential micronutrient with many beneficial anti-inflammatory and anti-oxidant properties, its role in the progression of alcohol-related liver disease (ALD) remains uncertain.
To identify broad transcriptomic responses to zinc, 11 publicly available datasets were examined to generate a transcriptomic zinc signature. Zinc signature genes were validated in vitro using primary immune cell and hepatocyte models supplemented with zinc or depleted of zinc using a S100A12 conjugated resin. The role of zinc deficiency in alcohol-associated hepatitis was examined bioinformatically, using large publicly available datasets, and confirmed
.
A nine gene zinc signature consisting primarily of metallothonein genes identified hepatic zinc deficiency among ALD patients that was associated with a down-regulation of the acute phase response pathway (e.g.,
and
genes).
studies using hepatocyte and immune cell cultures depleted of zinc demonstrated that macrophage induction of the acute phase response by LPS was dampened by zinc depletion.
Together, these data suggest that hepatic zinc stores among patients with alcohol-associated hepatitis are reduced, resulting in deficient acute-phase responses. Increasing hepatic zinc stores via supplementation and dietary modulation may improve acute responses to infection, and thus, long term outcomes in this patient group.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Acute-Phase Reaction - etiology
/ Acute-Phase Reaction - genetics
/ Acute-Phase Reaction - immunology
/ Acute-Phase Reaction - metabolism
/ alcohol-associated hepatitis
/ alcohol-related liver disease
/ Datasets
/ Female
/ Hepatitis, Alcoholic - genetics
/ Hepatitis, Alcoholic - immunology
/ Hepatitis, Alcoholic - metabolism
/ Humans
/ Male
/ Oxidants
/ Zinc
