Currently, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleons(t)ide analogues. The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a (peg-IFNα-2a). Interferon is administered for a finite duration while nucleotide analogues are usually administered for many years. But among hepatitis B e antigen （HBeAg） positive patients with high serum hepatitis B virus DNA levels, the rates of virological response are poor. And antiviral drug resistance is a major limiting factor to the success of nucleotide analogue treatment. Therefore, combination therapy using peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy. However, the addition of lamivudine to peg-IFNα-2a therapy led to a greater decrease in serum HBV DNA levels during treatment but did not increase the rate of HBeAg sero¬conversion. Entecavir is a nucleoside analogue superior to lamivudine and adefovir in achieving higher virological response, histological improvement and normalisation of ALT. Moreover, Entecavir has a high genetic barrier with a very low incidence of drug resistance. This study is aimed to investigate the efficacy of combination or sequential therapy using peg-IFNα-2a and entecavir in HBeAg-positive chronic hepatitis B(CHB) patients.

Inclusion Criteria:

1. Age≥16 years
2. HBsAg positive for more than 6 months, and HBeAg detection is positive for two times in 6 months before enrollment
3. Serum HBVDNA >2×10^4IU/ml
4. 80U/L < serum ALT < 400U/L, and TBIL < 34 umol/L
5. Serum ALT < 80U/L, but hepatic inflammation scores ≥ G2 or hepatic fibrosis stage ≥ S3

Exclusion Criteria:

1. Co-infected with HCV, HDV or HIV, or autoimmune liver diseases combined
2. Hepatic decompensation
3. received antiviral therapy or immunosuppressant drugs before 6 months prior to enrollment
4. Blood routine examination: WBC <3×10^9/L，neutrophile granulocyte < 1.5×10^9/L，PLT <80×10^9/L
5. Renal function: creatinine >1.5 times of upper normal limit
6. Alcoholism or a history of addiction and abuse
7. Combined with hepatocarcinoma