sequential peg-ifn for hbv after ending rna-targeted regimens

Conditions: Hepatitis B, Chronic

Summary: the goal of this clinical trial is to compare sequential peg-ifnα therapy strategies in chronic hepatitis b (chb) patients previously treated with aso/sirna. the main questions it aims to answer are: 1. does sequential peg-ifnα therapy (vs. deferred/no treatment) improve hbsag clearance rates? 2. what are the hbsag clearance and relapse rates after 24 weeks of peg-ifnα therapy? 3. is intermittent peg-ifnα therapy as effective and safe as continuous therapy? researchers will compare: • group a (immediate 24-week peg-ifnα + 24-week follow-up) vs. group b (24-week observation + 24-week peg-ifnα) in phase 1 to see if sequential peg-ifnα therapy will improve hbsag loss rate . researchers will describe: * the response rate of ifn treatment in non-responders (hbsag-positive) in phase 2. * the relaspe rate of responders (hbsag-negative). participants will: phase 1 (0-48 weeks): * group a: receive peg-ifnα for 24 weeks, followed by 24-week treatment-free follow-up. * group b: undergo 24-week observation, then receive peg-ifnα for 24 weeks. phase 2 (48-96 weeks): * hbsag-positive at week 48 patients either from group a or group b : receive 24-week peg-ifnα therapy, followed by 24-week follow-up. * hbsag-negative at week 48 patients either from group a or group b: enter 24-week follow-up without treatment. all participants will undergo: • hbsag quantification, hbv dna, liver function, and safety monitoring (every 12 weeks).


Eligibility criteria:
inclusion criteria: * age ≥18 years. * chronic hbv infection (documented hbsag positivity for \>6 months). * prior participation in aso or sirna clinical trials: * received ≥1 dose of aso/sirna (or matched placebo, if applicable). * achieved ≥1 log10 iu/ml hbsag decline from baseline during prior therapy. * discontinued aso/sirna therapy before screening. * screening hbsag: 0.05-500 iu/ml. * no prior interferon (ifn) therapy within 6 months before enrollment. * willingness to comply with study-related treatments, tests, and procedures. * commitment to contraception during the study. * voluntary participation with signed informed consent. exclusion criteria: * decompensated cirrhosis or hepatic malignancy (evidenced by imaging or histology within 6 months before/during screening). * elevated afp: screening afp \>100 ng/ml; afp 20-100 ng/ml with imaging-confirmed hepatocellular carcinoma (ultrasound/ct/mri). * coinfection with hepatitis a virus (hav), hepatitis c virus (hcv), hepatitis d virus (hdv), hepatitis e virus (hev), or human immunodeficiency virus (hiv). * recent immunomodulatory therapy: systemic corticosteroids, thymosin, or other potent immunomodulators for \>2 weeks within 6 months before enrollment. * pregnancy, lactation, or plans for pregnancy during the study. * autoimmune hepatitis. * active autoimmune diseases (e.g., psoriasis, systemic lupus erythematosus). * uncontrolled cardiovascular disease (e.g., unstable angina, myocardial infarction within 6 months). * poorly controlled endocrine disorders (e.g., diabetes mellitus, thyroid dysfunction). * severe psychiatric disorders: history of depression, anxiety, bipolar disorder, schizophrenia, or family history of psychiatric conditions (especially depression). * substance abuse: alcohol (\>40 g/day for males; \>20 g/day for females) or illicit drug use. * severe retinopathy or ophthalmologic disorders. * renal diseases: chronic nephritis, renal insufficiency, nephrotic syndrome. * major organ dysfunction (e.g., heart, lung, pancreas). * organ transplant recipients or candidates. * hypersensitivity to interferon or excipients. * concurrent participation in other hbv-related interventional trials. * other conditions deemed unsuitable by investigators (e.g., non-compliance risk).