Search

Background/Aims: Novel agents acting against hepatitis B virus (HBV) are needed to improve HBsAg seroclearance or termed as 'functional cure'. Inarigivir (retinoic acid‐inducible gene I agonist) has immunomodulatory and direct antiviral actions against HBV. We aimed to determine the safety and efficacy of Inarigivir for the treatment of HBV infection. Patients/Methods: 80 treatment‐naïve patients were randomized in 4 ascending dose cohorts to receive 12 weeks of Inarigivir 25, 50, 100, 200 mg or placebo in a ratio of 4:1. All patients were then given tenofovir for another 12 weeks. Results: Least squares (LS) mean reductions in HBV DNA from baseline increased with higher doses of Inarigivir (0.6116 in 25 mg and 1.5774 in 200 mg groups vs. 0.0352 in placebo group) (95% CI 0.9518–0.2011 and 1.921–1.1634 respectively). LS mean changes in HBV RNA and HBsAg from baseline ranged from −0.3856 to −0.5794 versus −0.1474 and −0.0956 to −0.1818 versus +0.0026 in Inarigivir‐treated versus placebo groups respectively. During the tenofovir‐treated period, LS mean reductions in HBsAg in the Inarigivir‐treated groups ranged from 0.1709 to 0.3529 versus 0.1984 in the placebo group. Inarigivir‐treated groups showed mean reductions in ALT from baseline between 23.3 and 33.8 versus 0.7 U/L in the placebo group. Treatment‐emergent adverse events related to Inarigivir and placebo occurred in 4.7% and 6.3% patients respectively. Conclusions: Twelve‐week Inarigivir up to 200 mg dose was associated with a reduction of HBV DNA, HBV RNA and antigen levels. A trend for greater HBsAg reduction was observed in Inarigivir pre‐treated patients after switching to tenofovir. [ABSTRACT FROM AUTHOR]

Background and Aim: In HBeAg negative chronic hepatitis B (CHB) patients, clinical relapse (CR) occurs more frequently, much earlier and often more severely after stopping tenofovir (TDF) and other nucleos(t)ide analogues (Nucs) than after stopping entecavir (ETV). It is unknown whether off‐Nuc hepatitis flare can be alleviated by switching from one Nuc to another. Methods: HBeAg‐negative CHB patients who had stopped Nuc according to the APASL stopping rule and had been followed‐up for > 48 weeks after Nuc cessation were recruited. Patients were classified as four groups: ETV monotherapy (mono‐ETV), TDF monotherapy (mono‐TDF), switched to ETV (switch‐ETV), and switched to TDF (switch‐TDF). Both switch groups had switched to the replacement Nuc > 12 weeks prior to end of therapy. Propensity score matching (PSM) was performed to minimize confounders among groups. Cox regression analysis was used to identify risks factors for off‐Nuc CR and flares. Results: A total of 1309 patients (1022 mono‐ETV, 219 mono‐TDF, 40 switch‐ETV and 28 switch‐TDF) were enrolled. The median time to CR was 39, 13, 38 and 14 weeks in mono‐ETV, mono‐TDF, switch‐ETV and switch‐TDF respectively (P < 0.001). After PSM, the mono‐ETV (adjusted HR: 0.39, P < 0.001) and switch‐ETV patients (adjusted HR: 0.41, P = 0.003) had both significantly later occurrence and lower rates of CR and flare. Conclusion: In summary, the incidence and timing of CR was determined by ETV or TDF in the last 3 months prior to end of treatment. Patients treated with non‐ETV‐Nuc switched to ETV > 12 weeks before end of the original Nuc therapy may reduce/defer CR. [ABSTRACT FROM AUTHOR]