Choi HSJ, Sonneveld MJ, Farag MS, et al. - ALT flares during PEGylated interferon-alpha (PEG-IFN-α) treatment are linked to subsequent HBsAg and HBV RNA decline and anticipate subsequent HBsAg loss. Flares occurred infrequently following PEG-IFN-α add-on therapy and were linked with low HBsAg loss rates. Combination regimens aimed at the window of heightened response have the potential to be effective.

• It was a post hoc analysis of four international randomized trials.

• For this trial, 269/130/124/128 patients on PEG-IFN-α monotherapy, PEG-IFN-α plus nucleos(t)ide analogue (NA) de novo combination, PEG-IFN-α add-on to NA, or NA monotherapy were involved, respectively.

• In 83/651 (13%) patients (median timing/magnitude: week 8 [IQR 4-12], 7.6×ULN [IQR 6.2-10.5]), on-treatment flares occurred.

• Flare patients were more likely to be Caucasians with genotype A/D, and they had greater baseline ALT, HBV DNA, HBV RNA, and HBsAg levels than the control group.

• PEG-IFN-α monotherapy (18%) and PEG-IFN+NA de novo combination (24%) resulted in more flares than PEG-IFN-α add-on (2%) or NA monotherapy (1%).

• On-treatment flares were significantly and independently linked to HBsAg and HBV RNA decreases ≥ 1 log10 at the final visit; declines began shortly before the flare and progressed to 24 weeks later.

• On-treatment flares occurred in 16/22 (73%) of individuals who achieved HBsAg reduction.