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Objective To investigate the efficiency of pegylated interferon α therapy for patients with HBeAg-positive chronic hepatitis B (CHB) and explore whether liver histopathological features and other factors might inlfuence HBeAg seroconversion. Methods Total of 80 HBeAg-positive CHB patients who received liver puncture were treated with pegylated interferonαonce a week for 48 weeks. The rate of HBeAg seroconversion was determined after therapy, and the factors inlfuencing HBeAg seroconversion were analyzed. Results The rate of HBeAg seroconversion was 30.00% at the end of treatment. The rate of HBeAg seroconversion gradually increased with the elevation of liver inlfammatory activity (χ2=9.170, P=0.027). But liver ifbrosis has little correlation with the rate of HBeAg seroconversion (χ2=5.917, P=0.116). Except HBeAg, other baseline indexes including gender, age, serum ALT and serum HBV DNA 1evels had no statistical difference between the patients with HBeAg seroconversion and the patients without HBeAg seroconversion. By binary logistic regression analysis, liver inlfammation and HBeAg were inlfuencing factors for HBeAg seroconversion. Conclusions Pegylated interferonαtherapy induces a higher rate of HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients with severe liver inlfammation, so the liver biopsies should be performed in time.