Highly significant differences in HBsAg kinetics among patients with two types of hepatitis B flare, with and without retreatment

Background: Off-therapy hepatitis flare may be detrimental or, conversely, facilitate hepatitis B surface antigen (HBsAg) decline. Retreatment decisions are crucial. Methods: HBsAg was quantified before and during flares, at peak/retreatment start and at Months 6 and 12 in 336 entecavir/tenofovir-retreated and 105 non-retreated hepatitis B e antigen (HBeAg)-negative patients. Increasing HBsAg during ALT flare defined a ‘virus-dominating flare’ and decreasing HBsAg a ‘host-dominating flare’. Results: Two hundred and eighty-eight retreated patients with a virus-dominating flare showed greater 1 year HBsAg decline (#1.0 versus #0.01 log₁₀ IU/mL; P < 0.0001), more frequent rapid decline (69.8% versus 8.3%; P < 0001) and higher 3 year incidence of HBsAg < 100 IU/mL (32% versus 12%; P = 0.026) than 48 patients with a host-dominating flare, of whom 16 (33.3%) showed 3.8-fold (2 to 52-fold) HBsAg rebound on retreatment (versus 2/288; P < 0.0001). Compared with non-retreated controls, 1 year HBsAg decline was greater (#1.0 versus #0.47 log₁₀ IU/mL; P < 0.0001) and faster (69.8% versus 42.5%; P < 0.0001) in patients with a virus-dominating flare, whereas 1 year HBsAg decline (#0.01 versus #0.16 log₁₀ IU/mL) and 3 year HBsAg loss rate (0% versus 21%; P = 0.009) were lower in patients with a host-dominating flare. Conclusions: Entecavir/tenofovir retreatment effectively decreases HBsAg level in patients with a virus-dominating flare but is ineffective/worse in patients with a host-dominating flare. These results support the use of combined HBsAg/ALT kinetics for the decision to retreat patients with a virus-dominating flare and withhold retreatment for patients with a host-dominating flare.