1. HBV-STOP study: Large hepatitis B virus flares off nucleot(s)ide analog therapy cause large innate immune response.
- Author
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Bowden S., Jackson K., Locarnini S., Visvanathan K., Thompson A., Hall S., Burns G., Anagnostou D., Morris R., Mooney B., Levy M., Sievert W., Lubel J., Nicoll A., Strasser S., Desmond P., Ngu M., Angus P., Meredith C., Revill P., Bowden S., Jackson K., Locarnini S., Visvanathan K., Thompson A., Hall S., Burns G., Anagnostou D., Morris R., Mooney B., Levy M., Sievert W., Lubel J., Nicoll A., Strasser S., Desmond P., Ngu M., Angus P., Meredith C., and Revill P.
- Abstract
Background and Aim: Current guidelines recommend indefinite nucleot( s)ide analog (NA) therapy for patients with HBeAg-negative chronic hepatitis B virus (HBV). However, sustained virological response (SVR) has been described in patients after discontinuation of long-term NA therapy. The HBV-STOP study is a prospective multicenter study of NA discontinuation in patients who have achieved long-term virological suppression on treatment. In addition to previously describing clinical outcomes after treatment discontinuation, we also aim to detail the immunological response in this scenario, especially that of the innate immune system. Method(s): Stimulation study: To gauge the potential innate activation of the peripheral blood cells by the flare, we stimulated peripheral blood mononuclear cell (PBMC) samples of HBV-STOP study patients by toll-like receptor (TLR)-specific ligands (TLR-2, TLR-3, TLR-4, TLR-7/8, and TLR-9) ex vivo. These patients either had a large biochemical flare (alanine aminotransferase [ALT] level > 10 x ULN) or did not have a biochemical flare (ALT < ULN). PBMCs were tested at baseline and peak ALT level time points, and matched non-flare samples were used as controls. Cytokine levels (IL-6, IL-8, IL-10, TNF, CCL-2, and CXCL-10) were measured after PBMC stimulation. Flow cytometry study: Additionally, we performed flow cytometry on PBMC samples of HBV-STOP study patients who either had a large biochemical flare (ALT > 10 x ULN) or did not have a biochemical flare. We did these studies at baseline and peak ALT level time points. Non-flare samples were matched to the closest respective week. Flow cytometry was used to isolate specific natural killer (NK) cell and monocyte populations using CD 56, CD 3, CD 16, and CD 14 cell surface markers. Expression of various immune markers was assessed in each cell population, including NKP46, NKG2D, TLR2, TLR4, and TREM1. Result(s): The stimulation study cohort consisted of 13 patients with flares and 12 patient
- Published
- 2021