TITLE: Predictive Value of Baseline and On-Treatment Quantitative Serum HBsAg Levels in Therapeutic Outcome to Entecavir in Patients with Chronic Hepatitis B
AUTHORS (FIRST NAME, LAST NAME): Cheng-Yuan Peng1, Hsueh-Chou Lai1, Wen- Pang Su1, Chia-Hsin Lin1, Po-Heng Chuang1, Sheng-Hung Chen1
Institutional Author(s):
INSTITUTIONS (ALL): 1. Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
ABSTRACT BODY: Background: The predictive value of baseline and on-treatment quantitative serum hepatitis B surface antigen (qHBsAg) levels in the therapeutic outcome to entecavir (ETV) in chronic hepatitis B (CHB) patients remains unclear. Patients and Methods: Between June 2006 and May 2013, 321 treatment-naïve compensated CHB patients had been treated with ETV for at least 1 year. Serum HBsAg and HBV DNA levels were quantified using the Abbott Architect HBsAg QT assay and the Cobas Amplicor HBV Monitor Test during therapy, respectively. Results: The baseline features were: median age: 49 years, 75.1% men, 37.4% HBeAg-positive (N=120), 59.1% genotype B infection, median ALT: 79 IU/L, HBV DNA: 6.56 log10copies/mL, and qHBsAg: 3.29 log10IU/mL. Among them, 218, 163 and 81 patients have received ETV therapy for ≧3, 4 and 5 years, respectively, with the mean treatment duration of 45.8 ± 18.3 months. The cumulative rates for virological response (VR, HBV DNA <312 copies/mL) were 90.3%, 97.8% and 99.4% at 1, 2 and 3 years, respectively. The cumulative HBeAg loss rates were 12.5%, 32.9%, 50%, 59% and 77.4% at 1, 2, 3, 4 and 5 years, respectively. Multivariate logistic regression analyses identified baseline HBV DNA <8 log10 copies/mL(OR=5.746, P=0.0044) and qHBsAg decline from baseline ≧50% at 3 months of therapy (OR=4.202, P=0.0207) as predictors of VR at one year for the HBeAg-positive subgroup. Multivariate Cox regression analyses identified ALT ≧120 IU/L (HR=1.881, P=0.0369) and baseline qHBsAg level between 5000 to 16000 IU/mL (HR=4.421, P=0.0008) as predictors of HBeAg loss during treatment. The cumulative HBeAg loss rates after 5 years of therapy in patients with baseline qHBsAg ≧16000, 5000-16000, and <5000 IU/mL were 50%, 100%, and 77.8%, respectively (P=0.005). Multivariate Cox regression analyses showed that baseline qHBsAg level <3.5 log10 IU/mL (HR=4.784, P=0.021) and qHBsAg decline from baseline ≧50% at 3 months of therapy (HR=4.115, P=0.0368) were predictors of achieving qHBsAg level ≦2 log10IU/mL during treatment in HBeAg-positive patients, and that baseline qHBsAg level <2.5 log10 IU/mL (HR=3.965, P=0.0059) and qHBsAg decline from baseline ≧50% at 12 months of therapy (HR=22.355, P<0.0001) were predictors of achieving qHBsAg level ≦2 log10IU/mL during treatment in HBeAg-negative patients. Conclusion: Baseline qHBsAg and ALT levels are predictors of HBeAg loss during ETV therapy in HBeAg-positive patients. Baseline qHBsAg levels and on-treatment qHBsAg decline from baseline are predictors of achieving qHBsAg level ≦2 log10IU/mL during ETV therapy in both HBeAg-positive and -negative patients.