ScRNA-seq Identifies High CXCL8 Linked to Liver Fibrosis in HBeAg-negative Chronic Hepatitis B Patients With Low HBsAg

Background and Aims: Chemokine ligand 8 (CXCL8) is suggested as a potential biomarker in assessing the progression and severity of hepatitis B e antigen-negative treatment-naive patients with "chronic hepatitis". Analysis of CXCL8 expression in the liver and blood of such patients with low and high hepatitis B surface antigen (HBsAg) levels could provide insights into the immunopathogenesis of hepatitis B virus-related liver disease. Methods: , n = 23); both groups had elevated alanine aminotransferase levels (>1.2 × upper limit of normal). Histopathological analysis and plasma cytokine profiling were conducted in all 35 patients, while single-cell RNA sequencing was performed on peripheral blood mononuclear cells and intrahepatic immune cells in 6 patients. Results: patients showed distinct peripheral CD8_C2 cluster expressing GNLY, GZMH, GZMB, GZMA, ITGB1, CX3CR1, ADGRG1, CCL4, and TGFBR3 contributing to activation, cytotoxicity, and fibrosis. Conclusion: Elevated CXCL8 expression in plasma, peripheral, and intrahepatic mono-mac populations, along with distinct CD8 T-cell clusters, is associated with greater fibrosis in patients with low HBsAg levels.