Immunohistochemical Signatures of Zone-Specificity in Alcohol-Induced Liver Damage

Alcohol-induced liver damage is linked to immune response activation and inflammation triggered by hepatocyte injury, exhibiting zone-specificity within liver lobules. Macrophages play a central role in regulating these responses, contributing to tissue repair and inflammation. The dual role of CD163-positive macrophages in tissue regeneration and fibrosis depends on the inflammatory environment, while the NF κB signalling pathway mediates ongoing inflammation in alcohol-related liver disease. Together, macrophage alternative activation and NF-κB signalling lead to a vicious cycle resulting in the progression of alcohol-induced liver tissue damage.
The aim of this research was to investigate the immunoexpression of CD163 and NF-κB in liver tissue from young healthy adults, age-matched alcohol users, and chronic alcohol users to evaluate macrophage activation and inflammation in the progression of alcohol induced liver damage.
Fifty-four liver tissue specimens were obtained and organised into three groups – controls (n=11), age-matched alcohol users (n=15), and chronic alcohol users (n=28). Tissue specimens were immunolabelled using anti-NF-κB and anti-CD163 antibodies. NF-κB expression was evaluated semi-quantitatively by grading intensity and distribution on a scale from 0 to 3, whereas CD163 expression was determined quantitatively by counting CD163 positive cells in fifteen visual fields. Statistical analysis was performed using SPSS 28.0.
Analysis of NF-κB expression revealed that the intensity of expression in the lobular area was significantly increased in the age-matched group (p=0.05), while both intensity and distribution in the chronic alcohol user group (p<0.001, p=0.02) were higher compared to the controls. Strong correlations between intensity and distribution in the lobular area (r=0.816, p<0.001) and portal area (r=0.984, p<0.001) were also observed. CD163-positive cell counts were higher in the lobular area of age-matched alcohol users (mean 135 ± SEM 43) and chronic alcohol users (mean 226 ± SEM 38) compared to controls (mean 59 ± SEM 14), following a similar trend in the portal and central vein areas. The cumulative CD163-positive cell count was significantly increased in the chronic alcohol user group, compared to the controls (p=0.012).
Chronic alcohol consumption leads to a significant increase in NF-κB expression, indicating persistent inflammation, while the elevation of CD163-positive macrophages suggests a shift towards M2-like polarisation, which likely contributes to fibrosis rather than regeneration. These findings highlight that alcohol abuse induces an early and sustained immune response with macrophage activation and inflammation driving the progression of liver damage, particularly in the lobular areas.