Tissue-resident memory CD8+T cells might enhance HBV DNA clearance in CHB patients with MASLD complication and normal ALT via the CCL-CCR pathways

Abstract

Background: HBV infection continues to pose a significant global health challenge, particularly in patients with normal alanine aminotransferase (ALT) level. The increasing prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) among individuals with chronic hepatitis B (CHB) also presents new complications in management. The study aimed to investigate the relationship between MASLD and HBV DNA clearance in CHB patients with normal ALT.

Methods: 403 patients with ALT levels below the normal threshold who underwent liver biopsy at our institution and subsequently received antiviral therapy with NAs were retrospectively examined. Among these, 177 patients were diagnosed with MASLD. Further single cell data analysis was conducted on GSE192740 and GSE182159.

Results: CHB patients concurrent with MASLD had a higher probability of achieving HBV DNA clearance. The proportion of CD8+Teff-GZMH cells was increased in the MASLD group. The interactions among CD8+ Trm-CD69 cells and other T cell subtypes were enhanced, especially within the active CCL-CCR pathways. An elevated proportion of Monocyte-THBS1 was also observed.

Conclusions: CD8+ Trm-CD69 T cells may be activated by Monocyte-THBS1 cells, thereby stimulating the immune system via the CCL-CCR signaling axis. This activation facilitates the recruitment of immune cells and enhances the clearance of hepatitis B virus (HBV).

Keywords: antiviral therapy; chronic hepatits B; liver biopsy; metabolic dysfunction-associated steatotic liver disease; single-cell RNA sequencing.