The following is a summary of “Hepatitis B Virus Flares After Nucleot(s)ide Analogue Cessation Are Associated With Activation of Toll-Like Receptor Signaling Pathways,” published in the January 2023 issue of Infectious Diseases by Hall, et al.
For a study, researchers examined the expression of Toll-like receptor (TLRs), natural killer (NK) cell activation, and patterns of peripheral TLR signaling activity in a group of patients who had severe hepatitis flare-ups after terminating nucleot(s)ide analogs (NAs) medication.
Patients with chronic hepatitis B recruited in a prospective trial of NA withdrawal provided longitudinal samples. Patients with hepatitis flares contrasted with those with normal alanine aminotransferase levels. TLR ligands were used to excite peripheral blood mononuclear cells (PBMCs), and the number of cytokines secreted in the cell culture supernatant was then assessed. On monocytes, NK, and NK-T cells, expression of TLR2/4, NKG2D, NKp46, and triggering receptor expressed on myeloid cells-1 (TREM-1) was assessed.
Twelve individuals without flares and seventeen patients with severe reactivation hepatitis flares were compared. Increased TLR2-8 and TLR9 signaling activity in PBMCs at the height of the flare relative to baseline was linked to hepatitis flares. Additionally, TLR2 overexpression and NK TREM-1 receptor expression were linked to hepatitis flares. Patients with flares and those without flares did not vary at baseline.
The innate inflammatory response in hepatitis flares caused by NA treatment was considerable and included increased TLR signaling on peripheral monocytes and TLR2 and TREM-1 expression on NK cells. In addition, it linked the immunopathogenesis of hepatitis B flares to the innate immune system.