The impact of HBsAg on general and HBV-specific immunity

Bert, Nina Le; Meng, Hong; Tan, De; Kunasegaran, Kamini; Yang, Cheng; Brecht, E.; Gill, Upkar S.; Frey, Christian; Newell, Evan W.; Kennedy, Peter T.; Bertoletti, Antonio

doi:10.1016/s0168-8278(18)31862-2

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…32 CHB is associated with impairment of host immune pathways including Toll-like receptor signaling, 55 immune checkpoint signalling, 56 and increased immunosuppressive T-regulatory cells activity. 57 These actions ultimately lead to reduction and dysfunction of HBV-specific Tcell clones, 58,59 resulting in numerical and functional T-cell deficits against HBV.…”

Section: Rna Interference As a Therapeutic Strategy For Viral Infectionsmentioning

confidence: 99%

RNA interference as a novel treatment strategy for chronic hepatitis B infection

2022

View full text Add to dashboard Cite

Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality. Functional cure of CHB, defined as sustainable hepatitis B surface antigen (HBsAg) seroclearance, is associated with improved clinical outcomes.However, functional cure is rarely attainable by current treatment modalities.RNA interference (RNAi) by small-interfering RNA (siRNA) and anti-sense oligonucleotide (ASO) has been studied as a novel treatment strategy for CHB.RNAi targets post-transcriptional messenger RNAs and pregenomic RNAs to reduce hepatitis B virus (HBV) antigen production and viral replication. By reducing viral antigens, host immune reconstitution against HBV may also be attained. Phase I/ II trials on siRNAs have demonstrated them to be safe and well-tolerated. siRNA is effective when given in monthly doses with different total number of doses according to different trial design, and can lead to sustainable dose-dependent mean HBsAg reduction by 2 -2.5 log. Incidences of HBsAg seroclearance after siRNA therapy have also been reported. ASOs have also been studied in early phase trials, and a phase Ib study using frequent dosing regimen within 4 weeks could achieve similar HBsAg reduction of 2 log from baseline. Given the established efficacy and safety of nucleos(t)ide analogues (NAs), future RNAi regimens will likely include NA backbone. While the current evidence on RNAi appears promising, it remains undetermined whether the potent HBsAg reduction by RNAi can result in a high rate of HBsAg seroclearance with durability. Data on RNAi from phase IIb/III trials are keenly anticipated.

show abstract