Efficacy of NA Combined With PEG-IFN-α2b in the Continuous Versus Pulsed Treatment of Patients With Chronic Hepatitis B

Prior treatment

• methaemoglobin greater than 100ng/ml at screening; or methaemoglobin that has not remained stable for 3 months prior to the trial and/or liver imaging suggestive of liver tumours;
• History of severe epilepsy or current treatment with anti-epileptic drugs. Unstable control of diabetes mellitus, hypertension, thyroid disease, etc. Patients with a history of severe retinopathy or as indicated by other evidence of retinopathy;

Other illness

• Combined active hepatitis A, C, D, E and/or HIV infection;
• History of severe psychiatric illness, especially depression. Major psychosis defined as major depressive disorder or psychosis, suicide attempts, hospitalisation for psychosis or incapacity for a period of time due to psychosis;
• history of immune-mediated disease (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis, rheumatoid arthritis) or abnormally elevated levels of autoimmune antibodies
• Patients with severe combined diseases of the heart, lungs, kidneys, brain, blood and other vital organs, combined with other malignancies
• History of any organ transplantation and existing functional grafts (except corneal or hair transplants);
• Patients who are allergic to interferon and its drug components and who, in the judgment of the investigator, are unsuitable for interferon application

Lab values

• decompensated liver disease (Child-Pugh score ≥ 7), meaning that patients will be excluded if one of the following is met: prolonged prothrombin time ≥ 3 seconds, serum bilirubin \> 34umol/L, history of hepatic encephalopathy, history of oesophageal variceal bleeding, ascites;
• Neutrophil count \< 1.5 x 10\^9/L or platelet count \< 90 x 10\^9/L and creatinine \> 1.5 ULN

Other

• Patients who are on future and intend to continue to use tibivudine
• pregnant or lactating women or patients with planned pregnancy during the study period and unwilling to use contraception
• Patients who, in the opinion of the investigator, are not suitable for participation in this study.

• Age 18 to 60 years, both sexes (both 18 and 60 years)
• HBsAg positive for more than 6 months;
• NAs treated patients on continuous NA therapy for more than 6 months with HBsAg ≥ 1500 IU/ml and HBV-DNA \< 500 IU/ml at enrolment;
• Primary treated patients with surface antigen \>1500 IU, unlimited E antigen and unlimited HBV DNA at enrolment, meeting the treatment indications of the 2019 edition of the guidelines for the prevention and treatment of chronic hepatitis B.
• negative urine or serum pregnancy test within 24 hours prior to the first dose (for women of childbearing age)