ABSTRACT FINAL ID: 1908
TITLE: Evolution and Predictive Role of Basal Core Promoter and Precore Mutants in Genotype B or C Hepatitis B E Antigen-Positive Chronic Hepatitis B Patients Undergoing Peginterferon Therapy
SPONSORSHIP - THIS STUDY WAS SPONSORED BY: (IF THIS ABSTRACT WAS NOT SPONSORED PLEASE INDICATE):
Grant DMR-101-012 from China Medical University Hospital in Taichung, Taiwan.
Background: The evolution of the basal core promoter(BCP), precore(PC), and preS2 deletion mutants in genotype B or C HBeAg-positive chronic hepatitis B(CHB) patients undergoing peginterferon(Peg-IFN) therapy is unclear.
Methods: 175 consecutive HBeAg-positive CHB patients receiving 24(n=69) or 48(n=106) weeks of Peg-IFN α-2a therapy and 48 weeks of post-treatment(PW48) follow-up were prospectively enrolled. Serum HBsAg and HBV DNA levels were quantified using the Abbott Architect HBsAg QT assay and the Cobas Amplicor HBV Monitor Test, respectively. The percentages of the BCP, PC and preS2 mutants were measured using quantitative real-time PCR assays reported previously.
Results: At baseline: mean age 35.4 years, 61% men, 61%/39% genotype B/C, mean ALT 148 IU/L, HBV DNA 7.5 log10IU/mL, and HBsAg 3.8 log10IU/mL, mean BCP, PC, and preS2 mutants %: 24.6, 19.9, and 26.6, respectively. At PW48, 24(14%), 42(24%), and 109(62%) patients achieved HBeAg loss + HBV DNA<2000 IU/mL(Group A), HBeAg loss + HBV DNA≥2000 IU/mL(Group B), and no HBeAg loss(Group C), respectively. At baseline, Gr A and B had significantly lower HBV DNA levels than Gr C. Gr A and B combined had higher BCP (36.4% vs 17.7%, P=0.0048) and PC mutants %(26.3% vs 15.9%, P=0.0138) than Gr C. Gr A had significantly lower BCP mutants % than Gr B at treatment week 12(TW12), end-of-treatment(EOT) and PW48, and significantly lower PC and preS2 mutants % than Gr B at EOT and PW48. By multivariate analyses, HBV DNA<2x107 IU/mL(OR:4.279, 95%CI:2.114-8.662), BCP mutants %(OR:1.016, 95%CI:1.003-1.030), and PC mutants %(OR:1.010, 95%CI:1.001-1.018) were baseline independent predictors for achieving HBeAg loss at PW48. No baseline factor predicted HBeAg loss + HBV DNA<2000 IU/mL at PW48. At TW12, HBV DNA<2x104 IU/mL(OR:3.343, 95%CI:1.033-10.820), HBsAg<600 IU/mL(OR:4.120, 95%CI:1.105-15.336), and BCP mutants %(OR:0.980, 95%CI:0.962-0.998) predicted HBV DNA<2000 IU/mL among patients with HBeAg loss at PW48.
Conclusions: Baseline and early on-treatment HBV DNA levels and BCP mutant kinetics predict outcomes to Peg-IFN therapy in HBeAg-positive CHB patients.