Off‐tenofovir hepatitis flares in HBeAg‐negative patients occur earlier, more frequent and severe than those off‐entecavir therapies

Abstract

The strategy of finite nucleos(t)ide analogue (Nuc) therapy in hepatitis B virus (HBV) suppressed hepatitis B e antigen (HBeAg)-negative patients has been considered as feasible and reasonably safe. 1,2 The strategy is increasingly accepted 3 and included, at least as an option, in recent American and European guidelines. 4,5 Of note is that clinical relapse (CR), defined as HBV relapse with alanine aminotransferase (ALT) elevation over two times upper limit of normal (ULN), may occur more frequently and earlier in those who stopped

Finite nucleos(t)ide analogue therapy in hepatitis B e antigen‐negative chronic hepatitis B: From an “option” to an “active recommendation”

“…14 More importantly, hepatitis flare (CR + ALT >5X ULN) may occur in 41.8% within 2 years, being numerically higher off-TDF than off-ETV and may deteriorate to hepatic decompensation (4.4% and 3.4%, respectively), of which liver cirrhosis and off-TDF are the two independent risk factors. 38 Of note, these rates were documented in studies with proper off-Nuc monitoring plan of APASL stopping rule. If off-Nuc patients were not properly monitored, the incidence of hepatitis flare might be underestimated but the incidence of severe flare and hepatic decompensation or even fatality was much higher in 3322 patients who stopped Nuc therapy not by particular stopping rules 39 as compared with studies by APASL stopping rule.…”

“…If off-Nuc patients were not properly monitored, the incidence of hepatitis flare might be underestimated but the incidence of severe flare and hepatic decompensation or even fatality was much higher in 3322 patients who stopped Nuc therapy not by particular stopping rules 39 as compared with studies by APASL stopping rule. 14,38 Clearly, to detect hepatitis flare and initiate retreatment timely is of paramount importance to prevent and/or rescue the detrimental outcomes. Hence, proper monitoring is an integral part of a successful strategy of finite Nuc therapy.…”

“…Earlier studies have clearly shown that the cessation of Nuc may be followed by virologic relapse (VR: HBV DNA >2000 IU/ml) and subsequent clinical (biochemical) relapse (CR: VR + ALT >2X ULN) up to 70% in 2 years after cessation of TDF and ~60% after stopping ETV ( p < 0.001) 14 . More importantly, hepatitis flare (CR + ALT >5X ULN) may occur in 41.8% within 2 years, being numerically higher off‐TDF than off‐ETV and may deteriorate to hepatic decompensation (4.4% and 3.4%, respectively), of which liver cirrhosis and off‐TDF are the two independent risk factors 38 . Of note, these rates were documented in studies with proper off‐Nuc monitoring plan of APASL stopping rule.…”

“…Of note, these rates were documented in studies with proper off‐Nuc monitoring plan of APASL stopping rule. If off‐Nuc patients were not properly monitored, the incidence of hepatitis flare might be underestimated but the incidence of severe flare and hepatic decompensation or even fatality was much higher in 3322 patients who stopped Nuc therapy not by particular stopping rules 39 as compared with studies by APASL stopping rule 14,38 …”

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

“…Last, the mechanism for different relapse pattern between NUCs await more in vitro or immunological evidence. It shall be cautious that severe relapse may still occur in off‐TDF patients with low HBsAg level 4 . Stringent follow‐up for off‐TDF patients is important to secure safety.…”