ABSTRACT FINAL ID: 1892
TITLE: Serum HBsAg kinetics in relation to hepatitis flare during first 6 months of direct antiviral therapy
SPONSORSHIP - THIS STUDY WAS SPONSORED BY: (IF THIS ABSTRACT WAS NOT SPONSORED PLEASE INDICATE):
The decline of hepatitis B surface antigen (HBsAg) level during nucleos(t)ide analog (Nuc) therapy in chronic hepatitis B is usually slow and small. However, earlier study showed “rapid HBsAg decline” ≥0.5 log10 IU/mL by month 6 of entecavir therapy in over 50% of the patients with pretherapy alanine aminotransferase (ALT) > 5X upper limit of normal (ULN). Of note, “rapid HBsAg decline” was also observed in 7% of the patients with pretherapy ALT < 5X ULN.
Aim: To investigate who and why patients with pretherapy ALT <5X ULN showed “rapid HBsAg decline” during Nuc treatment
Patients and methods:
Patients with pretherapy ALT <5X ULN and HBsAg quantification at baseline, month 6 and 12 of Nuc tehrapy were included. “Significant ALT elevation” was defined as >10% increase above baseline level and >2X ULN during first 6 months of Nuc therapy. “Hepatitis flare” was defined as an event with abrupt ALT elevation to >5X ULN. Serum HBV DNA was measured using Cobas Amplicor HBV Monitor(Roche Diagnostics, Pleasanton, California; detection range 20-1.7*108IU/ml). HBsAg was measured using Roche Elecsys® II kit. (detection range 0.05-52000 IU/mL)
Among 263 patients meeting the inclusion criteria, 55 experienced transient “significant ALT elevation” [Group A], including 33 (12.6%) with peak ALT of 2-5X ULN [group A-1] and 22 (8.4%) > 5X ULN (hepatitis flare) [group A-2]. The remaining 208 patients showed no ”significant ALT elevation” [group B]. HBsAg decline at month 6 was significantly greater in group A than in group B (-0.364 vs -0.047 log10 IU/mL; P=0.000), greatest in group A-2 and smallest in group B-1 (-0.523 vs -0.025 log10 IU/mL; P=0.000). “Rapid HBsAg decline” by month 6 was documented in 38.2% of group A and 9.6% of group B patients (P=0.000), highest in group A-2 and lowest in group B-1 patients (50% vs 2.2%). Of the group B patients, those with a baseline ALT of 2-5X ULN (group B-2) showed greater HBsAg decline (-0.104 vs -0.025 log10 IU/mL, P=0.000) and more frequent rapid HBsAg decline (15.3% vs 2.2%; P=0.001) at month 6 of therapy than those with a baseline ALT of <2X ULN (group B-1).
Hepatitis B flare (ALT>5X ULN) developed during Nuc therapy in 8.4% of the patients with prehterapy ALT<5XULN, and 50% of the patients developing hepatitis flare showed “rapid HBsAg decline” >-0.5 log10 IU/mL by moth 6 of Nuc therapy. Only 10% of the patients without ”significant ALT elevation” showed “rapid HBsAg decline” which occurred mainly in those with pretherapy ALT of 2-5X ULN. These findings suggest the importance of immune factor(s) for HBsAg decline during Nuc therapy.