Post-Radical Treatment Antiviral Strategies in HBV-Related Liver Cancer: Impact on Tumor Prognosis

• Study Background The 3-year recurrence rate of HBV-related liver cancer after radical surgery is as high as 40% to 70%. This study aims to explore whether the addition of peginterferon alfa-2b (Peg-IFNα-2b) to nucleoside (acid) analogues (NAs) can reduce the risk of recurrence through immune modulation.
• Key Mechanism Hypotheses

Peg-IFNα-2b may reduce the reactivation of micrometastases through:

• Enhancing HBV-specific T-cell responses
• Lowering serum HBsAg levels
• Inhibiting immune suppression in the tumor microenvironment
• Detection Methods

• Imaging Monitoring: Abdominal MRI (using LI-RADS v2018 criteria) every 12 weeks ± 7 days.
• Laboratory Tests:
• HBV DNA: COBAS® TaqMan HBV Test (LLOQ = 10 IU/mL)
• Quantitative HBsAg: Architect HBsAg QT assay
• PBMC Immune Profile: Flow cytometry (proportion of CD8+/PD-1+ T cells)
• Tissue Biomarkers: Postoperative tumor tissue PD-L1 immunohistochemistry (22C3 antibody) and T-cell infiltration score.
• Statistical Design

• Sample size: 332 cases (power 80%, α = 0.05, expected HR = 0.6)
• Primary endpoint analysis: 3-year cumulative recurrence rate (Kaplan-Meier method + Log-rank test)
• Covariate adjustment: Cox model includes age, BCLC stage, and baseline HBsAg level.

Inclusion criteria

• Age: Participants must be between 18 and 70 years of age.
• HBsAg Positive: Participants must be positive for hepatitis B surface antigen (HBsAg).
• Confirmed Hepatocellular Carcinoma (HCC): Participants must have a pathological confirmation of HCC via surgical resection or local ablation.
• BCLC Staging: Participants must have a Barcelona Clinic Liver Cancer (BCLC) staging of 0 or A.
• Liver Function: Participants must have normal or well-compensated liver function, classified as Child-Pugh A.
• Expected Survival: Participants must have an expected survival of more than 3 months.
• Informed Consent: Participants must sign an informed consent form and agree to comply with the study requirements. If a participant is unable to sign the consent form, a legal guardian or agent must do so.

Exclusion criteria

• Prior Systemic Cancer Treatments: Participants who have received prior systemic cancer treatments such as liver transplantation, chemotherapy, targeted therapy, or biological therapy will be excluded.
• Other Active Malignancies: Participants with a history or presence of other active malignancies, except for skin basal cell carcinoma or squamous cell carcinoma that has been cured, or cervical carcinoma in situ, will be excluded.
• Allergies to Interferon: Participants who are allergic to interferon or any of its components, or whom the investigator deems unsuitable for interferon therapy, will be excluded.
• Other Chronic Liver Diseases: Participants with other chronic liver diseases such as hepatitis A, C, D, or E virus infection, alcoholic liver disease, genetic metabolic liver disease, or drug-induced liver disease will be excluded.
• Autoimmune Diseases:Participants with autoimmune diseases,including autoimmune liver disease and psoriasis, will be excluded.
• Severe Liver Dysfunction: Participants with severe liver dysfunction or decompensated cirrhosis will be excluded.
• Renal Impairment: Participants with serum creatinine levels exceeding 1.5 times the upper limit of normal will be excluded.
• Severe Systemic Diseases:Participants with severe systemic diseases affecting the heart,lungs,kidneys,brain,or blood will be excluded.
• Severe Neuropsychiatric Disorders:Participants with severe neuropsychiatric disorders such as epilepsy, depression, mania, or schizophrenia will be excluded.
• Unstable Medical Conditions:Participants with unstable diabetes,hypertension,hyperthyroidism,or other endocrine diseases will be excluded.
• Retinopathy:Participants with a history of severe retinopathy or other evidence of retinopathy will be excluded.
• Substance Abuse:Participants with a history of drug abuse or alcoholism will be excluded.
• Pregnancy or Breastfeeding:Pregnant or breastfeeding women, or women planning to become pregnant during the study period who are unwilling to use contraception, will be excluded.
• Investigator's Judgment:Participants whom the investigator deems unsuitable for the study based on their current medical condition will be excluded.
• Concurrent Participation in Other Trials:Participants who are concurrently involved in other clinical research trials will be excluded.