Diagnostic and Prognostic Potential of CXCL9 and CXCL10 Chemokines in Alcohol-Associated Liver Disease

Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality. In ALD, excessive inflammatory response may induce a massive loss of hepatocytes and lead to irreversible liver damage with progressive fibrosis. Chemokines stimulate the migration of immune cells to the site of inflammation and contribute to the inflammatory cascade that may result in organ failure. We aimed to investigate blood concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 chemokines and their diagnostic and prognostic significance in patients with ALD. In a prospective observational study, 88 individuals were recruited, including 63 patients with ALD (44 men and 19 women, aged 48.49 ± 10.88) and 25 healthy control volunteers matched for age, sex, and ethnicity. In blood samples, concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 were measured using immunoenzymatic ELISAs. Correlations were examined between CXCL levels and (a) traditional inflammatory markers (C-reactive protein, white blood cell count, neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio-NLR) and (b) liver dysfunction severity scores: Child-Turcotte-Pugh (CTP), MELD-NA, MELD 3.0, and modified Maddrey's discriminant function (mDF). Patients' survival within 30 days of hospital admission was recorded for analysis. CXCL capabilities in predicting the severity of liver dysfunction and ALD outcome were validated. ALD patients showed significant systemic upregulation of all studied chemokines compared to the control group. Patients with advanced liver disease, classified as MELD-Na ≥ 20, MELD3.0 > 19, and CTP class C, as well as poor short-term outcomes, presented with significantly higher CXCL9 and CXCL10 levels compared to their counterparts. ALD non-survivors had significantly higher concentrations of all studied CXCLs in comparison to controls. Positive correlations between CXCL16 and CRP, leukocytosis, neutrophils, and NLR were confirmed (0.67; 0.46; 0.48; 0.54, respectively). Although none of the chemokines correlated with ALT activity, CXCL9, CXCL10, and CXCL16 showed positive correlations with bilirubin and alkaline phosphatase and inverse correlations with albumin levels. Our findings revealed the diagnostic and prognostic value of the studied CXCLs in ALD. In particular, CXCL9 and CXCL10 may have potential for discrimination of severe liver dysfunction and poor short-term prognosis. Further multicenter studies are required to confirm our results.