Serum CXCL-10 and CTLA-4 associated with inflammation in small treatment-naive chronic hepatitis B cohort

A small observational cohort study reported associations between serum CXCL-10 and CTLA-4 levels, HBV viral load, biochemical liver injury and histological inflammatory activity in people with treatment-naive chronic hepatitis B. The abstract indicates that both markers were highest among patients with elevated viral loads and correlated more strongly with the modified Ishak histological activity index than with fibrosis stage, but the findings remain exploratory because of the modest sample and absence of longitudinal data in the reported results.

The study enrolled 86 participants, including 21 healthy controls and 65 patients with treatment-naive chronic hepatitis B. Patients were divided by HBV DNA level into a group with levels at or below 10⁵ IU/mL, comprising 33 patients, and a group with levels above 10⁵ IU/mL, comprising 32 patients. Investigators also classified patients into European Association for the Study of the Liver clinical phenotypes using HBeAg status, HBV DNA and alanine aminotransferase levels. Serum CXCL-10 and CTLA-4 were measured by enzyme-linked immunosorbent assay, and investigators calculated laboratory-based inflammatory and fibrosis-related indices, including FIB-4 for all participants.

Serum concentrations of CXCL-10 and CTLA-4 differed significantly across the study groups and were highest in patients with elevated viral loads, with p-values below 0.001 for both comparisons. HBV DNA correlated with CXCL-10 at r = 0.786 and with CTLA-4 at r = 0.559. The two serum markers were also strongly correlated with one another, at r = 0.690; all three correlation coefficients had p-values below 0.001. These are measured associations in the enrolled cohort and do not establish that either marker causes changes in viral load or liver inflammation.

Histological data were available for 43 of the 65 patients, or 66.2% of the chronic hepatitis B group. Both serum markers correlated more strongly with the modified Ishak histological activity score than with fibrosis stage: r = 0.519 for CXCL-10 and r = 0.509 for CTLA-4, both with p-values below 0.001. CXCL-10 levels were elevated in EASL phase 2, identified in the abstract as HBeAg-positive chronic hepatitis, compared with phases 3 and 4, with p-values of below 0.001 and 0.005, respectively.

Descriptive receiver operating characteristic analyses showed moderate discrimination for CXCL-10 and CTLA-4, with areas under the curve of 0.78 and 0.76, respectively, and sensitivity of 47%. In a further exploratory analysis, CXCL-10 differentiated high histological activity, defined as a modified Ishak score of at least 7, from low activity, with an area under the curve of 0.77. The abstract does not report a validated diagnostic threshold or establish clinical use for either marker. Histological observations were limited to the 43 patients with biopsy data, and the reported analysis did not include longitudinal testing. The authors stated that the findings warrant confirmation in larger, longitudinal cohorts.

Subject of Research: Associations of serum CXCL-10 and CTLA-4 with viral load, liver injury and histological inflammation in treatment-naive chronic hepatitis B

Article Title: 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

Article References: Uğraklı, S., Ezer, B., Kasapoğlu, E., Esen, H. S., Kökbudak, N., & Özdemir, M. (2026). 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. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14501-1

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14501-1

Keywords: chronic hepatitis B, CXCL-10, CTLA-4, HBV DNA, liver inflammation, histological activity, fibrosis, immune markers, observational study, Serum, levels, treatment-naive