Serum CXCL-10 and CTLA-4 levels in treatment-naive chronic hepatitis B: associations with EASL-based clinical phenotypes, histological inflammatory activity, and non-invasive fibrosis indices

Chronic hepatitis B (CHB) is a major global health issue, as ongoing viral replication can drive hepatic inflammation and immune dysregulation, increasing the risk of cirrhosis and hepatocellular carcinoma. CXCL-10, a proinflammatory chemokine, and CTLA-4, an inhibitory immune checkpoint, may each capture a different facet of the immune response in CHB. This study evaluated serum CXCL-10 and CTLA-4 in CHB patients and their associations with HBV DNA, laboratory findings, and non-invasive fibrosis markers. In total, 86 individuals were enrolled: 21 healthy controls and 65 treatment-naive CHB patients. CHB patients were categorized by HBV DNA level into ≤ 10⁵ IU/mL ( n = 33) and > 10⁵ IU/mL ( n = 32). Patients were also classified into EASL (European Association for the Study of the Liver)-based clinical phenotypes using HBeAg status, HBV DNA, and ALT. Liver biopsy data (Ishak fibrosis stage and modified Ishak HAI score) were available for 43 patients (66.2%). FIB-4 was calculated for all participants. Serum CXCL-10 and CTLA-4 were measured by ELISA, and laboratory-based inflammatory and fibrosis-related indices were calculated. Group comparisons and correlation analyses were used to assess associations; ROC analyses were descriptive and exploratory. Serum levels of CXCL-10 and CTLA-4 differed significantly among study groups and were highest in patients with elevated viral loads (both p < 0.001). Viral load correlated strongly with CXCL-10 ( r = 0.786) and CTLA-4 ( r = 0.559), and CXCL-10 correlated strongly with CTLA-4 ( r = 0.690; all p < 0.001). Both CXCL-10 and CTLA-4 correlated more strongly with the modified Ishak HAI score ( r = 0.519 and r = 0.509, respectively; p < 0.001) than with fibrosis stage. CXCL-10 levels were elevated in Phase 2 (HBeAg-positive chronic hepatitis) compared to Phase 3 ( p < 0.001) and Phase 4 ( p = 0.005). The descriptive ROC performance was moderate (AUC 0.78 for CXCL-10; 0.76 for CTLA-4, sensitivity 47%); in an exploratory analysis, CXCL-10 differentiated high (HAI ≥ 7) from low histological activity (AUC 0.77). Serum CXCL-10 and CTLA-4 were associated with HBV DNA, biochemical liver injury, and histological inflammatory activity in treatment-naive CHB, correlating more strongly with the modified Ishak HAI score than with fibrosis stage. These findings suggest a role for CXCL-10 and CTLA-4 as markers of inflammatory and immunoregulatory activity in CHB, warranting confirmation in larger, longitudinal cohorts.