α-Fetoprotein level-dependent early hepatitis B surface antigen decline during entecavir therapy in chronic hepatitis B with hepatitis flare

Hepatitis B surface antigen (HBsAg) reduction during nucleos(t)ide analogue therapy is related to ALT level. ALT reflects hepatocytolysis while α-fetoprotein (AFP) ≥100 ng/mL during hepatitis flare reflects more extensive hepatocytolysis (bridging hepatic necrosis). The impact of AFP levels on early HBsAg kinetics during entecavir therapy was investigated.HBsAg level was measured at baseline and months 6 and 12 of entecavir therapy in 149 chronic hepatitis B patients with hepatitis flare, defined as ALT ≥5× upper limit of normal (ULN), and 58 patients with ALT <5× ULN.There was a significantly greater HBsAg reduction in an ALT (<5, 5-10, 10-20 and ≥20× ULN, P = 0.001) and AFP (<20, 20-99 and ≥100 ng/mL, P = 0.000) level-dependent manner. In hepatitis flares with a peak AFP level ≥20 ng/mL, the differences in HBsAg reduction across all ALT levels became non-significant. HBsAg reduction was greater in genotype B- than genotype C-infected patients with baseline ALT ≥20× ULN, but the difference became non-significant in those with peak AFP ≥100 ng/mL. Multivariate linear regression analysis showed that AFP level ≥100 ng/mL, baseline HBsAg level and genotype B were independent significant factors for greater HBsAg decline at month 6 of entecavir therapy.During entecavir therapy, early HBsAg reduction increased in an AFP and ALT level-dependent manner, suggesting the impact of hepatocytolysis rather than nucleos(t)ide analogue per se. Notably, a higher AFP level during hepatitis flare, reflecting more extensive hepatic necrosis, was a more powerful factor than ALT and genotype for greater HBsAg decline.