There are about 400 million chronic hepatitis B virus (HBV) infection patients worldwide, posing a serious threat to global public health security. In China, HBV infection occured mainly in the perinatal period or infants, and about 10% of patients in the immune tolerance stage spontaneously transit to the immune clearance stage every year and become HBeAg-negative chronic HBV infection, resulting in a significant increase in the number of inactive chronic hepatitis B (CHB) patients.

In recent years, different guidelines have not reached consensus on the need to initiate antiviral therapy for inactive CHB patients: In the guidelines of Asian Pacific Association for The Study of Liver(APASL)-2015 and American Association for the Study of Liver Diseases(AASLD)-2018, antiviral therapy is generally not recommended for this group of patients, and regular outpatient follow-up is recommended. Guideline of European Association for the Study of the Liver(EASL)-2017 suggests that people with a family history of cirrhosis and liver cancer at this stage could be treated with antiviral therapy even if they did not meet the indications of antiviral therapy. According to Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2019) of China, antiviral therapy is still recommended for some patients with inactive HBsAg carrier status who are HBV DNA positive and meet the treatment indications. Studies have shown that some patients in immune tolerance stage may enter the immune clearance stage and have hepatitis flare. Patients of inactive CHB have the potential to develop HBeAg-negative CHB, and studies of long-term follow-up in this population have indicated the risk of hepatocellular carcinoma. With the popularization of the concept of functional cure for chronic hepatitis B, more and more people with inactive CHB have a strong desire for treatment. In recent years, several studies have demonstrated that Pegylated-interferon therapy can achieve high functional cure rate in patients with inactive CHB.

The purpose of this study is to establish a national multi-center, prospective real world study to compare the efficacy of different antiviral treatment regimens for patients with inactive CHB and seek for the factors of functional cure.

Inclusion Criteria:

• Age 18-60, no gender limitation
• HBsAg is positive for more than 6 months
• Hepatitis B e antigen(HBeAg) is negative and anti-HBe is positive
• Serum HBV DNA is less than 2000 IU/mL
• Alanine aminotransferase(ALT) and/or Aspartate aminotransferase(AST) is normal
• No antiviral durg (including nucleos(t)ide analogue and interferon) was used before enrollment
• Good compliance and voluntarily signed informed consent

Exclusion Criteria:

• Allergic to pegylated interferon α-2b
• Any indication of liver cirrhosis
• Coinfection with hepatitis A virus(HAV), hepatitis C virus(HCV), hepatitis D virus(HDV), hepatitis E virus(HEV) or human immunodeficiency virus(HIV)
• Combined with other liver diseases (including drug-related, alcoholic, autoimmune, genetic metabolic liver diseases, etc.)
• There are serious lesions in the important organs, such as heart, lung, kidney, brain and fundus
• Patients with autoimmune diseases, unstable diabetes or thyroid diseases(hyperthyroidism or hypothyroidism)
• Confirmed or suspected liver cancer or other malignant tumors
• Patients after or preparing for organ transplantation
• Peripheral blood white blood cell count < 3.5×109/L and/or platelet count < 80×109/L
• Under immunosuppressant treatment
• Pregnant or planned pregnancy in a short term or lactation patients
• Alcohol abuse (average alcohol intake is more than 40 g/d in males or 20g/d in women) or drug addicts
• Present or past history of mental or psychological diseases
• Other conditions that the investigators deem inappropriate for the study.

Individual participant data would be available to other researchers with the approval of the ethics committee