The study is to guide clinical cure of peginterferon alfa-2a treatment in patients with chronic hepatitis B based on the detection of interferon gene mutation (IFNA2p.Ala120Thr) and interferon-stimulated genes (ISGs) detection gene spectrum.

It is estimated that more than 400 million people are infected with hepatitis B virus (HBV) globally.How to make more patients with chronic hepatitis B get clinical treatment through the existing anti-viral treatment is an urgent problem to be solved.This study is a random, multi-center and open experiment,the collaborators includes the second people's hospital of zhongshan city, the eighth people's hospital of guangzhou city, and the first people's hospital of foshan city.

Patients with chronic hepatitis B who were treated with NAs for over 1 year,HBsAg quantification≤1500 IU/mL, HBeAg negative and serum HBV DNA quantification <100 IU/mL were enrolled in this study. In our study, the enrolled patient's IFNA2p.Ala120Thr without variation and ISGs>0.05 were divided into two groups. After informed consent , patients were grouped according to their treatment intentions,in one group, patients continued NAs for another 48 weeks. In another group , patients were treated with peg-interferon-2a and NAs for 48 weeks.Patient's BMI, genotype, family history, smoking history, drinking history, other medical history, suspected transmission channels, types and time of use were recorded in this study.Moreover, Patients were assessed every 12 weeks,included liver and kidney function, blood routine, HBV cccDNA, HBeAg quantification, HBsAg quantification, pgRNA and so on.In addition,liver imaging examination and liver hardness test were assessed every six months.

In this study, we will analyze whether clinical cure rates differed between patients with chronic hepatitis B treated with peginterferon alfa-2a and NAs;Bisedes,the baseline interferon variant site variants and changes in interferon-stimulated gene profile expression were analyzed to determine whether they could be used as molecular markers to predict clinical cure with interferon.

Inclusion Criteria:

• Age between 18 and 60 years old;
• HBsAg positive, HBsAg quantification≤1500 IU/mL;
• Serum HBV DNA quantification <100 IU/mL;
• HBeAg negative.

Exclusion Criteria:

• Treated with interferon in the past six months;
• Liver cirrhosis or HCC and other associated tumors;
• Women during pregnancy or lactation;
• With liver disease caused by other causes;
• Combination infection of HIV or other immunodeficiency diseases;
• With diabetes, autoimmune diseases and other organ dysfunction or failure;
• Combination of other serious complications (infection, hepatic encephalopathy,gastrointestinal bleeding, hepatorenal syndrome, etc.);
• Others who cannot be treated with interferon;
• Anyone cannot return to the hospital for follow-up and follow-up visits regularly as planned

Active Comparator:nucleotide analogues(NAs) patients continue to use NAs

Experimental: peg-interferon alfa-2a patients switch to sequential peg-interferon α-2a