Serum CC-Chemokine Profiling in Alcohol-Associated Liver Disease: Focus on MIP-3α/CCL20 as a Biomarker of Disease Severity

Background/Objectives: The inflammatory response is central to the pathogenesis of alcohol-associated liver disease (ALD), yet currently used prognostic scores, including Maddrey’s modified discriminant function (mDF), Child–Turcotte–Pugh (CTP), MELD-Na and MELD 3.0, reflect hepatic synthetic and excretory function rather than the underlying immune alterations. Since CC-motif chemokines (CCLs) regulate immune cell trafficking and hepatic stellate cell activation, they warrant deeper investigation, as reports on their role in ALD remain limited. Therefore, the primary objective of this study was to evaluate the diagnostic and prognostic performance of selected serum CCLs, and to correlate their levels with disease severity and short-term survival in patients with ALD. Methods: Serum MIP-3α/CCL20, MCP-1/CCL2 and TARC/CCL17 were measured in 63 patients with ALD and 25 healthy controls using ELISAs. Chemokine concentrations were correlated with liver function tests, inflammatory indices and short-term (30-day) survival. The diagnostic and prognostic performances of individual CC chemokines were assessed by ROC analysis and by univariate and multivariable logistic regression. Results: MIP-3α/CCL20 was increased more than 11-fold in ALD versus healthy controls and reached an AUC of 0.978 for distinguishing the two groups in a case-control comparison (a proof-of-principle, case-control result which requires validation against other chronic liver diseases). It increased across Child–Turcotte–Pugh classes and correlated with all other prognostic scales. MCP-1/CCL2 was significantly elevated in the ALD group but did not discriminate ALD severity. TARC/CCL17 was significantly lower in ALD than in controls. On multivariable regression, MIP-3α/CCL20 was the dominant predictor of both ALD status and severe liver dysfunction. Conclusions: In patients with ALD, MIP-3α/CCL20 appears to bridge hepatic inflammation and hepatocellular failure and is a candidate exploratory biomarker of disease severity that requires further confirmation against other chronic liver diseases. The short-term mortality analysis was based on only seven events. This evaluation is exploratory and underpowered, and its findings should not be interpreted as definitive prognostic evidence. MCP-1/CCL2 does not stratify ALD severity. Decreased TARC/CCL17 concentrations point to a separate immunoregulatory failure and are presented as a hypothesis requiring mechanistic testing in pre-clinical models.