150: The Gut-immune-liver Axis in Patients With Alcohol Use Disorder & Clinically Low Serum Zinc Levels

Statement of Purpose, Innovation or Hypothesis: Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol-associated liver disease (ALD). Early-stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut-barrier dysfunction, pro-inflammatory response, hepatocyte injury and death; and potential sex-differences in AUD patients.

Description of Methods & Materials: Thirty-nine male and female AUD patients were grouped by normal [≥71 μg/dL (Group 1, number (n)=26)] and low [ < 71 μg/dL (Group 2, n=13)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), Heavy Drinking Days in the past 90-days (HDD90), Total Drinks in the past 90-days (TD90), Number of Drinking Days in the past 90-days (NDD90), Average Drinks Per Day in the past 90-days (AvgDPD90) were collected (Table 1). Blood samples were tested for Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), coagulation markers, gut-barrier dysfunction markers, cytokines, and hepatocyte death markers.

Data & Results: Gr.2 females exhibited lower LTDH than Gr.2 males (p=0.028), but higher recent drinking. Aspartate transaminase: alanine transaminase (AST: ALT) ratio was higher (p=0.049) in Gr.2 males compared to Gr.1 males. Overall, Gr.2 showed three-fold higher interleukin 8 (IL-8) levels than Gr.1; these were seven-fold higher in Gr. 2 females than Gr.1 females. Gr.2 females also had higher K18M65, but lower K18M30 than Gr.2 females. Necrotic type of cell death (K18M65) was well-described only in Gr.2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF-α) (R²=0.633, p=0.037) (Figure 1).

Interpretation, Conclusion or Significance: Our findings demonstrated the role of the gut-immune-liver axis in describing hepatocyte injury and death in zinc-deficient AUD patients. These patients represented an arrangement of gut-barrier dysfunction and an exacerbated immune response. Shift in the cell-death mechanism from apoptosis in zinc-replete females to necrosis in zinc-deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.

Disclosures: Nothing to disclose.

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