This is a real-world, prospective, multicenter, non-randomized, controlled study. It aims to investigate the efficacy and safety of pegylated interferon α-2b (PEG IFN α-2b) monotherapy versus its combination with nucleos(t)ide analogs (NAs) regarding hepatitis B surface antigen (HBsAg) clearance in interferon-experienced patients with chronic hepatitis B (CHB). Subjects will receive either interferon-based therapy or NAs monotherapy based on their personal willingness and physicians' professional recommendations, with a uniform 48-week treatment course for all enrolled patients.

Inclusion Criteria:

• • Voluntary participation and ability to understand and provide written informed consent.

  • Age 18-65 years (inclusive), either gender.
  • Documented HBsAg positivity for at least 6 months, or other evidence confirming chronic hepatitis B (CHB).
  • Prior interferon therapy before enrollment (treatment discontinuation ≥ 3 months), with HBsAg level at the end of prior treatment reduced by ≥ 50% from baseline.
  • HBsAg ≤ 500 IU/mL at screening, and HBsAg rebound at screening not exceeding 50% of the baseline HBsAg level during the first-round interferon therapy.
  • Negative pregnancy test within 24 hours prior to the first dose (for women of childbearing potential); all subjects (male and female) must use effective contraceptive measures during the study.

Exclusion Criteria:

• • Pregnant or lactating women, or subjects with a pregnancy plan during the study period.

  • Subjects with neuropsychiatric disorders, in particular a history of depression, anxiety, mania, schizophrenia, or a family history of psychiatric disorders (especially a history of depression or depressive tendency).
  • Concurrent active infection with hepatitis A, hepatitis C, hepatitis E and/or HIV, or chronic liver disease due to other causes (e.g., alcoholic hepatitis, drug-induced liver injury, autoimmune liver disease, etc.).
  • Evidence of acute severe liver damage: e.g., ALT > 10 × ULN, or marked ALT elevation accompanied by significant hyperbilirubinemia.
  • Evidence of decompensated liver disease: e.g., ascites, esophagogastric variceal bleeding, sepsis, hepatic encephalopathy, hepatorenal syndrome, etc.; or prior evidence of decompensated cirrhosis.
  • Evidence of hepatocellular carcinoma (HCC), or AFP > 1 × ULN.
  • Renal diseases: acute or chronic nephritis, renal insufficiency, nephrotic syndrome, etc.; or serum creatinine > 1 × ULN at screening.
  • Neutrophil count < 1.5 × 10⁹/L, platelet count < 90 × 10⁹/L, or serum phosphorus < 0.8 mmol/L during the screening period.
  • Autoimmune diseases (e.g., psoriasis, systemic lupus erythematosus, etc.), endocrine disorders (e.g., thyroid diseases, diabetes, etc.), hypertension poorly controlled by prescription medications (blood pressure ≥ 140/90 mmHg), a history of severe heart disease (especially poorly controlled within 6 months), severe retinopathy or other serious ophthalmologic diseases, or other organic lesions or dysfunction of vital organs.
  • Subjects planning to undergo or having previously undergone organ transplantation.
  • Subjects with hypersensitivity to the investigational product or its excipients, or meeting any contraindication listed in the prescribing information of the investigational product.
  • Other conditions deemed inappropriate for enrollment by the investigator

Chronic hepatitis B patients who received pegylated interferon alpha for the first time and achieved a good response.