Re-treatment for severe hepatitis flare in HBeAg-negative chronic hepatitis B: An appraisal with combined HBsAg/ALT kinetics.

To test the concept that off-therapy hepatitis flares with increasing qHBsAg require immediate re-treatment whereas re-treatment can be held or not necessary for those with decreasing qHBsAg, pre-retreatment combined HBsAg/ALT kinetics were classified in 22 patients with severe hepatitis flare (ALT > 30X ULN) and checked against their clinical response and qHBsAg changes during entecavir re-treatment. Timely re-treatment in 16 patients with increasing qHBsAg during hepatitis flare (Pattern I HBV/ALT kinetics) not only improved hepatitis and rescued impending/ensuring hepatic decompensation but also led to 'rapid HBsAg decline' with 14 patients showing HBsAg decline >1-4 log10  IU/mL within 12 months. In contrast, re-treatment in 6 patients with decreasing qHBsAg (Pattern II) resulted in small HBsAg decline in one patient and initial further HBsAg decline but rebound to pre-retreatment level in 3 patients. Of note, stopping 8-day re-treatment in a patient with pre-retreatment HBsAg decline >1 log10  IU/mL allowed further HBsAg decline to a low level (4 IU/mL) towards HBsAg loss. These findings suggest that immediate re-treatment is appropriate in severe hepatitis flare with Pattern I HBsAg/ALT kinetics but can be held or even not necessary in those with Pattern II HBsAg/ALT kinetics. Serial qHBsAg assays, more frequently during hepatitis flare, are helpful for re-treatment decision and close monitoring is mandatory to start, to hold or to stop re-treatment in patients with hepatitis flare.