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

Official title

A Non-randomized Controlled, Prospective, Real-world Study to Evaluate the Efficacy and Safety of Pegylated Interferon Alpha-2β in Patients With Hepatitis B-related Hepatocellular Carcinoma After Radical Resection

Overview

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

Interventions

• Drug Peginterferon alfa-2b
  Peginterferon alfa-2b injection administered subcutaneously
• Drug TDF
  Tenofovir disoproxil fumarate
• Drug TAF
  Tenofovir alafenamide
• Drug TMF
  Tenofovir amibufenamide

Primary outcome measures

• Concentration of Hepatitis B Surface Antigen (Hepatitis B Surface Antigen, HBsAg) [Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240]
• Proportion of patients with HBsAg loss [Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240]
• Proportion of patients with HBsAg seroconversion [Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240]

Secondary outcome measures (11)

• Concentration of HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) [Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240]
• Concentration of Hepatitis B e Antigen (HBeAg) [Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240]
• Composition and diversity of intestinal microbiota [Time frame: Baseline, Week 24, Week 48]
• Recurrence-Free Survival (RFS) [Time frame: Years 1, 2, 3, 5]
• Overall survival (OS) [Time frame: Years 1, 2, 3, 5]
• Concentration of Interleukin-2 (IL-2) [Time frame: Baseline, Week 24, Week 48]
• Concentration of Interleukin-4 (IL-4) [Time frame: Baseline, Week 24, Week 48]
• Concentration of Interleukin-6 (IL-6) [Time frame: Baseline, Week 24, Week 48]
• Concentration of Interleukin-10 (IL-10) [Time frame: Baseline, Week 24, Week 48]
• Concentration of Tumor Necrosis Factor-α (TNF-α) [Time frame: Baseline, Week 24, Week 48]
• Concentration of Interferon-γ (IFN-γ) [Time frame: Baseline, Week 24, Week 48]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Shulan (Hangzhou) Hospital — Hangzhou
• Ningbo Medical Center Lihuili Hospital — Ningbo
• Ningbo Mingzhou Hospital (Affiliated to Zhejiang University) — Ningbo
• Ningbo No.2 Hospital — Ningbo

Identifiers

NCT: NCT07553767 · PJ-NBEY-KY-2025-215-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗