The goal of this clinical trial is to learn if peginterferon alfa-2b can reduce the recurrence of HBV-related liver cancer in patients who have undergone radical treatment. The study will also explore the potential benefits of peginterferon alfa-2b in achieving clinical cure and its impact on reducing liver cancer recurrence. The trial is designed as a single-center, non-randomized, open-label study. Participants will be HBV-related liver cancer patients who have received radical treatment. The study will compare two groups: one receiving nucleos(t)ide analogues (NAs) alone and the other receiving NAs combined with peginterferon alfa-2b. The main question it aims to answer is: Can peginterferon alfa-2b lower the 3-year recurrence rate in HBV-related liver cancer patients after radical treatment? Participants will undergo regular follow-ups, including imaging studies and blood tests, to monitor for cancer recurrence and assess the safety of the treatment.
1. 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. 2. 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 3. 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. 4. 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.
Study Type
OBSERVATIONAL
Enrollment
332
Participants will receive standard NAs therapy, which may include entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), or tenofovir amibufenamide (TMF). NAs are antiviral medications used to suppress HBV replication and manage chronic hepatitis B infection.
Participants will receive Peg-IFNα-2b in addition to NAs therapy. Peg-IFNα-2b is an antiviral medication that works by boosting the immune system and has additional antiviral, antifibrotic, and anti-tumor effects. It is used to treat chronic hepatitis B and may help reduce the recurrence of liver cancer.
3-Year Cumulative Recurrence Rate via MRI (LI-RADS)
1. Measurement Tool: Liver Imaging Reporting and Data System (LI-RADS v2018) 1.1 Primary modality: Dynamic contrast-enhanced MRI 1.2 Confirmatory criteria: 1.2.1 LI-RADS 5 (definite HCC): 1.2.1.1 Arterial hyperenhancement + 1.2.1.2 Portal venous washout ± 1.2.1.3 Capsule/threshold growth 1.2.2 Histopathology (biopsy) for equivocal cases 2. Definition: Proportion of participants with new intrahepatic lesions meeting LI-RADS 5 criteria or histologically confirmed HCC metastases within 3 years post-radical treatment. 3. Clinical Significance: Recurrence defined as: 3.1 Local (original site) 3.2 Intrahepatic (\>2 cm from resection margin) 3.3 Extrahepatic (metastases with biopsy confirmation)
Time frame: 3 years post-radical treatment.
2-Year HBsAg Seroclearance Rate
* Measurement Tool: Architect HBsAg QT Assay * Definition: Proportion with HBsAg loss (\<0.05 IU/mL) * Directionality: Lower HBsAg levels indicate better response * Confirmation: Required at two timepoints ≥24 weeks apart
Time frame: 2 years post-treatment initiation.
2-Year HBV DNA undetectable rate
* Measurement Tool: COBAS® TaqMan HBV Test v2.0 * Definition: Proportion of participants achieving HBV DNA \<10 IU/mL (LLOQ) in two consecutive tests ≥6 months apart * Directionality: Lower values indicate better virological control
Time frame: 2 years post-treatment initiation.
Incidence of Adverse Events (AEs)
* Measurement Tool: CTCAE v5.0 grading system * Definition: Frequency of all-cause AEs, categorized by: * Severity: Grade 1 (mild) to 5 (death) * Relatedness: Definite/probable/possible vs. unrelated * Range: 1-5 scale (higher grade = worse severity) * Reporting Threshold: All events ≥Grade 2
Time frame: Throughout the 3-year follow-up period.
Serious Adverse Event (SAE) Rate
* Measurement Tool: CTCAE v5.0 * Definition: Events meeting ≥1 SAE criterion: Death/life-threatening Hospitalization/prolonged hospitalization Persistent disability Congenital anomaly -Causality Assessment: Using WHO-UMC system
Time frame: Throughout the 3-year follow-up period.
Liver Function Deterioration Rate
* Measurement tool: Change in Child-Pugh score ≥ 2 points * Range: 5 - 15 points (the higher the score, the worse the liver function) * Definition: The proportion of patients with an increase in Child-Pugh score of ≥ 2 points during treatment compared to the baseline.
Time frame: Throughout the 3-year follow-up period.
Quality of Life Change
* Measurement tool: EORTC QLQ-C30 * Range: 0-100 (higher scores on functional dimensions indicate better status; higher scores on symptom dimensions indicate worse status) * Definition: Change from baseline in global health status/QoL over 3 years, analyzed with a mixed-effects linear model.
Time frame: Throughout the 3-year follow-up period.
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