Great and rapid HBsAg decline in patients with on‐treatment hepatitis flare in early phase of potent antiviral therapy

Summary HBsAg decline during nucleos(t)ide analogue therapy in chronic hepatitis B with lower pretherapy ALT is usually small and slow. This study aimed to investigate why ~10% of such patients showed “rapid HBsAg decline” ≥0.5 log10 IU/mL by month 6 of therapy. Patients with persistent pretherapy ALT 10% increase above baseline to >2X ULN during first 6 months of therapy. Of the 256 patients treated, 51 experienced transient “on‐treatment ALT elevation” [group A], including 30 (11.7%) with ALT elevation to 2‐5X ULN [group A‐1] and 21 (8.2%) flared to >5X ULN [group A‐2]. The magnitude of qHBsAg decline and rate of “rapid HBsAg decline” by month 6 was significantly greater and more frequent in group A (−0.446 vs −0.042 log10 IU/mL; 45.1 vs 8.8%, respectively, P = 0.000) than in the remaining 205 patients without on‐treatment ALT elevation (group B), being greatest in patients with hepatitis flare (group A‐2: −0.559 log10 IU/mL and 57.1%, respectively). In patients with therapy ≥2 years, patients with “on‐treatment ALT elevation” also showed significantly greater annual HBsAg decline, more frequent to 5X ULN, during entecavir therapy or tenofovir therapy may enhance/accelerate HBsAg decline, suggesting the effect of immune restoration upon potent viral suppression.