This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.

Chronic hepatitis B (CHB) infection remains a global health treat. The ideal end point of therapy is HBsAg loss or HBsAg seroconversion, indicating a complete remission of CHB. In patients with HBeAg-positive CHB, sustained HBeAg seroconversion is also a desirable end point. Current therapies include pegylated interferon (PegIFN) finite and nucleos(t)ide analogues (NUCs) longterm therapy. However, only 30-40% of patients may achieve HBeAg seroconversion on PegIFN monotherapy, whereas 15-20% of patients on entecavir (ETV). Recently, accumulating evidence had shown that optimization of switching or combining PegIFN in patients on long-term ETV therapy may increase rate of HBeAg seroconversion and even lead to the complete eradication of HBV. However, these two regimens has not been tested adequately in patients with low HBsAg/HBeAg titers on long-term ETV therapy.

This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.

Inclusion Criteria:

• Male and female patients > 18 and ≤ 60 years of age;
• Positive HBsAg for more than 6 months;
• Patients receiving previous ETV therapy ≥2 years;
• Patients who have achieved undetectable HBV DNA, HBsAg <1500IU/mL and HBeAg <200S/CO prior to switch or S-C therapy;
• ALT<=10*ULN and TB<2*ULN;
• Patients who have been assigned to treatment with PegIFN (S-C or switch) or continuous ETV after previous ETV therapy

Exclusion Criteria:

• Evidence of decompensated cirrhosis or hepatocellular carcinoma;
• Serological evidence of co-infection with HCV, HDV or HIV;
• Pregnant or breast-feeding women;
• Patients with diseases that might contraindicate to PegIFN therapy including severe psychiatric diseases, immunological diseases, severe retinopathy, thyroid dysfunction, leukocytopenia, thrombopenia, etc
• Patients receiving concomitant therapy with telbivudine;
• A history of drug or alcohol abuse;
• Other conditions that investigates consider not suitable for participate

Chronic Hepatitis B Patients with Low HBsAg and HBeAg Titers after Long-term Entecavir Therapy