Abstract: Objective To observe the efficacy of pegylated interferon α-2a(PEG-IFN α-2a) in HBe Ag-negative chronic hepatitis B(CHB) patients and to analyze its influencing factors.Methods One hundred and three HBe Ag-negative CHB patients,who visited Department of Infectious Diseases,Nanfang Hospital,Southern Medical University,from May 2009 to December 2012,were enrolled in this study.The patients were treated with 135 μg of PEG-IFN α-2a for a mean period of 13 months and then followed up for 48 weeks.During treatment and follow-up,alanine aminotransferase and hepatitis B virus(HBV) DNA levels were measured every three months for each patient.The χ2test or t test was used to compare the frequency or means between groups,and binary multivariate logistic regression analysis was performed to determine influencing factors.Results At the end of treatment,eighty-four(81.6%) of the 103 patients achieved a combined response.Among the patients who achieved a combined response,33 patients(39.3%) relapsed during follow-up and 49 patients(47.6%) had a sustained response during follow-up within one year after treatment.Both univariate and multivariate statistical analyses showed that only HBe Ab positivity was an independent factor associated with sustained response(OR = 3.69,P = 0.013).Other baseline characteristics,including HBV DNA load,HBV genotype,pre C / BCP mutation,and liver histopathology,are not associated with the sustained response.Conclusion PEG-IFN α-2a is an effective treatment for HBe Ag-negative CHB,but the relapse rate is high.CHB patients with positive HBe Ab have a higher rate of sustained response.