A Prospective Clinical Trial in Chronic Hepatitis B Patients NAs (Nucleotides or Nucleosides) Experienced (Anchor Study)

Inclusion Criteria:

1. Male and female patients from 18 to 65 years of age;

2. HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year includingpatients with nucleotides or nucleoside resistance history if their HBV DNA obtainedcontrol;

3. Before nucleotides or nucleosides treatment, ALT > 2 ULN, HBV DNA >10000copies/ml,HBsAg positive;

4. Serum HBV DNA < 1000 copies/ml;

5. Serum HBsAg < 3000 IU/ml;

6. HBsAg positive;

7. Negative urine or serum pregnancy test (for women of childbearing potential)documented within the 24-hour period prior to the first dose of test drug;

8. Absence of cirrhosis confirmed by ultrasonic test;

9. Agree to participate in the study and sign the patient informed consent.

Exclusion Criteria:

1. Patients who had NAs resistance and HBV DNA > 1000 copies/ml, or treatment of drugswith IFN longer than 6 months;

2. Other antiviral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) 6 months prior to the first dose ofrandomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1month prior to first administration of randomized treatment). Patients who areexpected to need systemic antiviral therapy other than that provided by the study atany time during their participation are also excluded;

3. Women with ongoing pregnancy or breast-feeding;

4. Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals whichhave the ability to do the test will do) and/or human immunodeficiency virus (HIV);

5. ALT >10 ULN;

6. Evidence of decompensated liver disease (Child-Pugh score > 5 ). Child-Pugh > 5 means,if one of the following 5 conditions are met, the patient has to be excluded: one of the following 5 conditions are met, the patient has to be excluded:

7. Serum albumin < 3.5 g/L;

8. Prothrombin time > 3 seconds prolonged;

9. Serum bilirubin > 34 µ mol/L;

10. History of encephalopathy;

11. History of variceal bleeding;

12. Ascites;

13. History or other evidence of a medical condition associated with chronic liver diseaseother than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolicliver disease, alcoholic liver disease, toxin exposures, thalassemia);

14. Signs or symptoms of hepatocellular carcinoma, patients with a value ofalpha-fetoprotein > 100 ng/mL are excluded, unless stability (less than 10% increase)has been documented over at least the previous 3 months. Patients with values < 20ng/mL but > 100 ng/mL may be enrolled, if hepatic neoplasia has been excluded by liverimaging;

15. Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;

16. Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;

17. Serum creatinine level > 1.5 ULN in screening period.

18. Phosphorus < 0.65 mmol/L;

19. ANA > 1:100;

20. History of severe psychiatric disease, especially depression. Severe psychiatricdisease is defined as treatment with an antidepressant medication or a majortranquilizer at therapeutic doses for major depression or psychosis, respectively, forat least 3 months at any previous time or any history of the following: a suicidalattempt hospitalization for psychiatric disease, or a period of disability due to apsychiatric disease;

21. History of a severe seizure disorder or current anticonvulsant use;

22. History of immunologically mediated disease, (e.g., inflammatory bowel disease,idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia,scleroderma, rheumatoid arthritis etc.);

23. History of chronic pulmonary disease associated with functional limitation;

24. Diseases that IFN and Nucleotides or nucleosides are not suitable.