Stopping nucleot(s)ide analogues in non‐cirrhotic HBeAg‐negative chronic hepatitis B patients: HBsAg loss at 96 weeks is associated with low baseline HBsAg levels

Abstract

Background and Aims: Current guidelines recommend long-term nucleot(s)ide analogue (NA) therapy for patients with HBeAg-negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss. Methods:We performed a prospective multi-centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg-negative CHB, the absence of cirrhosis and HBVDNA<lower limit of quantification for ≥18 months. We assessed virological

Editorial: is functional cure the only holy grail for treatment discontinuation in patients with HBeAg‐negative chronic hepatitis B?

“…First, this study validated that sustained responders had a higher functional cure rate than those with relapse 6 . Despite the increased natural killer (NK) cell function is associated with off‐NUC hepatitis and HBsAg loss after NUC cessation, 7 none of these flare patients in this study had HBsAg loss 1 . One reason is that off‐NUC flare patients had a higher HBsAg level than those without flare, which longer follow‐up time is required to achieve HBsAg loss.…”

“…By 2‐year follow‐up, 28% off‐Nuc patients turned into inactive carrier, 6% with functional cure, 32% in grey zone and only 30% be retreated. None developed hepatic decompensation or liver cancer 1 . Inactive carriers had comparably favourable prognosis as general population 9 and those in grey zone have similar HBsAg loss rate as inactive carrier which only 2.2%–15% transitioned into hepatitis 10 .…”

“…6 Despite the increased natural killer (NK) cell function is associated with off-NUC hepatitis and HBsAg loss after NUC cessation, 7 none of these flare patients in this study had HBsAg loss. 1 One reason is that off-NUC flare patients had a higher HBsAg level than those without flare, which longer follow-up time is required to achieve HBsAg loss. The functional programmed cell death protein 1-positive (PD-1 + )HBV-specific T cells, exerting non-cytolytic immune control on viral clearance, of the sustained responders, may be another reason for increased HBsAg loss.…”

“…This prospective study about nucleos(t)ide analogue (NUC) cessation in non‐cirrhotic hepatitis B e antigen (HBeAg)negative chronic hepatitis B (CHB) patients by Hall et al 1 validated the known findings that hepatitis B surface antigen (HBsAg) loss rate, also called “functional cure”, is higher in off‐NUC than on‐NUC patients 2,3 and that relapse events occurred much earlier in off‐tenofovir disoproxil fumarate (TDF) than off‐entecavir(ETV) patients 4,5 . The spotlight of this study addressed the objective incidence of off‐NUC events by a well‐designed follow‐up protocol.…”

“…The functional programmed cell death protein 1‐positive (PD‐1 + )HBV‐specific T cells, exerting non‐cytolytic immune control on viral clearance, of the sustained responders, may be another reason for increased HBsAg loss 8 . Second, 22.8% off‐Nuc flare patients achieved HBsAg reduction >1log 10 IU/ml, especially those with higher ALT (36.5 vs 13.8 times of upper limit of normal) during flare 1 . Our recent study of 441 off‐NUC flare patients showed that 18.1% of the off‐Nuc flare is effective, defined as HBsAg decline along with ALT surge, while the 3‐year HBsAg loss rate was 21% in these effective‐flare patients if un‐retreated.…”