Efficacy and Safety of Pegylated Interferon Alpha-2β in Patients With Hepatitis B-related Hepatocellular Carcinoma After Radical Resection

The goal of this clinical trial is to evaluate the efficacy and safety of peginterferon alfa-2β (Peg-IFN-α-2β) combined with nucleos(t)ide analogues (NAs) in patients aged 18 to 65 years with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after radical resection. The main questions it aims to answer are: * What are the changes in hepatitis B surface antigen (HBsAg) disappearance rate, HBsAg seroconversion rate, HBsAg decline, and hepatitis B virus deoxyribonucleic acid (HBV DNA) levels during treatment and at the end of treatment? * What are the 1-year, 2-year, 3-year, and 5-year recurrence-free survival (RFS) and overall survival (OS) of the included patients? * What are the correlations between changes in HBsAg, T helper 1/T helper 2 (Th1/Th2) subsets, intestinal flora and RFS, OS in these patients? Researchers will compare Peg-IFN-α-2β combined with NAs to NAs alone to see if the combination treatment can improve HBsAg clearance, seroconversion, long-term survival and reduce recurrence in patients after radical resection of hepatitis B-related hepatocellular carcinoma. Participants will: * Receive either Peg-IFN-α-2β combined with first-line NAs (tenofovir disoproxil fumarate \[TDF\], tenofovir alafenamide fumarate \[TAF\], tenofovir amibufen fumarate \[TMF\]) or first-line NAs alone * Undergo regular assessments including HBsAg, HBV DNA, liver and renal function, blood routine, thyroid function, autoantibodies, and tumor markers * Provide stool samples for intestinal flora analysis at specified time points * Complete long-term survival follow-up for up to 5 years

Sex

All

Minimum age

18 Years

Maximum age

65 Years

Inclusion Criteria:

* Age 18 to 65 years, male or female.
* Confirmed diagnosis of hepatitis B virus-related hepatocellular carcinoma (HCC) by pathology or contrast-enhanced CT/MRI.
* Underwent radical resection or local ablation therapy; CNLC (Chinese Liver Cancer Classification) stage Ia, Ib, or IIa; no residual tumor confirmed by imaging within 1-3 months postoperation.
* HBsAg positive and HBsAg level \< 2000 IU/mL.
* No prior systemic chemotherapy, immunotherapy, or targeted therapy before enrollment.
* Able to provide written informed consent and comply with the follow-up schedule.
* For women of childbearing potential: negative pregnancy test and effective contraception during treatment and for 24 weeks after the last dose.

Exclusion Criteria:

* Recurrent or metastatic HCC at enrollment.
* Contraindication to peginterferon alfa-2b treatment.
* WBC \< 3.5×10⁹/L or platelet count \< 100×10⁹/L.
* ALT \> 3×ULN or total bilirubin (TBIL) \> 2×ULN.
* Child-Pugh score \> 5 points.
* INR \> 1.5.
* History of organ transplantation or planned transplantation.
* Hypersensitivity to peginterferon alfa-2b or any excipient of the study drug.
* Pregnant or breastfeeding women.
* Participation in another interventional clinical trial.
* History of significant alcoholism or drug abuse.
* Genetic or metabolic liver disease (Wilson disease, hemochromatosis, etc.).
* Coinfection with HAV, HCV, HEV, EBV, CMV , or other viral hepatitis that may interfere with study evaluation.
* Unable to comply with study procedures and follow-up.
* Other conditions deemed inappropriate by the investigator.