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

April 20, 2026 updated by: Liyun Fu, Ningbo No.2 Hospital

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

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

156

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310022
        • Shulan (Hangzhou) Hospital
        • Contact:
        • Contact:
      • Ningbo, Zhejiang, China, 315000
        • Ningbo Medical Center Lihuili Hospital
        • Contact:
        • Contact:
      • Ningbo, Zhejiang, China, 315000
        • Ningbo NO.2 Hospital
        • Contact:
        • Contact:
      • Ningbo, Zhejiang, China, 315000
        • Ningbo Mingzhou Hospital (Affiliated to Zhejiang University)
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Peginterferon alfa-2b combined with NAs
Patients receive peginterferon alfa-2b (Pegintron®) combined with first-line nucleos(t)ide analogues (TDF/TAF/TMF)
Drug: Peginterferon alfa-2b
Peginterferon alfa-2b injection administered subcutaneously
Drug: TDF
Tenofovir disoproxil fumarate
Drug: TAF
Tenofovir alafenamide
Drug: TMF
Tenofovir amibufenamide
Active Comparator: NAs alone
Patients receive first-line nucleos(t)ide analogues (TDF/TAF/TMF) alone
Drug: TDF
Tenofovir disoproxil fumarate
Drug: TAF
Tenofovir alafenamide
Drug: TMF
Tenofovir amibufenamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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

Serum HBsAg concentration assessed by Chemiluminescent Microparticle Immunoassay (CMIA).

Unit: IU/mL
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 loss (HBsAg < 0.05 IU/mL) determined by CMIA. Unit: % of patients
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

Proportion of patients with HBsAg loss (HBsAg < 0.05 IU/mL) and anti-HBs seropositivity (anti-HBs ≥ 10 mIU/mL) determined by CMIA.

Unit: % of patients
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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

Serum HBV DNA viral load quantified by a TaqMan-based real-time quantitative polymerase chain reaction (qPCR) assay.

Unit: IU/mL
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
Serum HBeAg concentration assessed by CMIA. Unit: S/CO
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
Intestinal microbiota analyzed by 16S rRNA gene high-throughput sequencing. Unit: Relative abundance (%) and alpha diversity index
Baseline, Week 24, Week 48
Recurrence-Free Survival (RFS)
Time Frame: Years 1, 2, 3, 5

Time to first hepatocellular carcinoma (HCC) recurrence or death from any cause, which is confirmed by contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI).

Unit: Months
Years 1, 2, 3, 5
Overall survival (OS)
Time Frame: Years 1, 2, 3, 5
Time from enrollment to death from any cause, regardless of the cause of death. Unit: Months
Years 1, 2, 3, 5
Concentration of Interleukin-2 (IL-2)
Time Frame: Baseline, Week 24, Week 48
Serum levels of IL-2 will be measured using cytometric bead array (CBA). Unit: pg/mL
Baseline, Week 24, Week 48
Concentration of Interleukin-4 (IL-4)
Time Frame: Baseline, Week 24, Week 48
Serum levels of IL-4 will be measured using cytometric bead array (CBA). Unit: pg/mL
Baseline, Week 24, Week 48
Concentration of Interleukin-6 (IL-6)
Time Frame: Baseline, Week 24, Week 48
Serum levels of IL-6 will be measured using cytometric bead array (CBA). Unit: pg/mL
Baseline, Week 24, Week 48
Concentration of Interleukin-10 (IL-10)
Time Frame: Baseline, Week 24, Week 48
Serum levels of IL-10 will be measured using cytometric bead array (CBA). Unit: pg/mL
Baseline, Week 24, Week 48
Concentration of Tumor Necrosis Factor-α (TNF-α)
Time Frame: Baseline, Week 24, Week 48
Serum levels of TNF-α will be measured using cytometric bead array (CBA). Unit: pg/mL
Baseline, Week 24, Week 48
Concentration of Interferon-γ (IFN-γ)
Time Frame: Baseline, Week 24, Week 48
Serum levels of IFN-γ will be measured using cytometric bead array (CBA). Unit: pg/mL
Baseline, Week 24, Week 48

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Levels of Thyroid Stimulating Hormone (TSH)
Time Frame: Baseline, Weeks 12, 24, 36, 48
TSH measured by chemiluminescent immunoassay (CLIA). Unit: mIU/L
Baseline, Weeks 12, 24, 36, 48
The Levels of Free Triiodothyronine (FT3)
Time Frame: Baseline, Weeks 12, 24, 36, 48
FT3 measured by chemiluminescent immunoassay (CLIA). Unit: pmol/L
Baseline, Weeks 12, 24, 36, 48
The Levels of Free Thyroxine (FT4)
Time Frame: Baseline, Weeks 12, 24, 36, 48
FT4 measured by chemiluminescent immunoassay (CLIA). Unit: pmol/L
Baseline, Weeks 12, 24, 36, 48
The Levels of Thyroglobulin Antibody (TgAb)
Time Frame: Baseline, Weeks 12, 24, 36, 48
TgAb measured by chemiluminescent immunoassay (CLIA). Unit: IU/mL
Baseline, Weeks 12, 24, 36, 48
The Levels of Thyroid Peroxidase Antibody (TPOAb)
Time Frame: Baseline, Weeks 12, 24, 36, 48
TPOAb measured by chemiluminescent immunoassay (CLIA). Unit: IU/mL
Baseline, Weeks 12, 24, 36, 48
Concentration of Alpha-fetoprotein (AFP)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 96, 144, 192
AFP measured by CLIA. Unit: ng/mL
Baseline, Weeks 12, 24, 36, 48, 96, 144, 192
Serum levels of Protein induced by vitamin K absence-II (PIVKA-II)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
PIVKA-II measured by chemiluminescence immunoassay (CLIA). Unit: mAU/mL
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Levels of Red Blood Cell count (RBC)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
RBC measured by automated hematology analyzer. Unit: ×10¹²/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Levels of White Blood Cell (WBC)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
WBC measured by automated hematology analyzer. Unit: ×10⁹/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Levels of Platelet (PLT)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
PLT measured by automated hematology analyzer. Unit: ×10⁹/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Levels of Absolute Neutrophil Count (ANC)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
ANC measured by automated hematology analyzer. Unit: ×10⁹/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Levels of Absolute Lymphocyte Count (ALC)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
ALC measured by automated hematology analyzer. Unit: ×10⁹/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Levels of Absolute Monocyte Count (AMC)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
AMC measured by automated hematology analyzer. Unit: ×10⁹/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Levels of Hemoglobin (Hb)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Hb measured by automated hematology analyzer. Unit: g/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Alanine Aminotransferase (ALT)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
ALT measured by automated biochemical analyzer. Unit: IU/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Aspartate Aminotransferase (AST)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
AST measured by automated biochemical analyzer. Unit: IU/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Alkaline Phosphatase (ALP)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
ALP measured by automated biochemical analyzer. Unit: IU/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Gamma-Glutamyl Transferase (GGT)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
GGT measured by automated biochemical analyzer. Unit: IU/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Total Bilirubin (TBil)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
TBil measured by automated biochemical analyzer. Unit: μmol/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Direct Bilirubin (DBil)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
DBil measured by automated biochemical analyzer. Unit: μmol/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Indirect Bilirubin (IBil)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
IBil measured by automated biochemical analyzer. Unit: μmol/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Alpha-L-Fucosidase (AFU)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
AFU measured by automated biochemical analyzer. Unit: U/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Albumin (ALB)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
ALB measured by automated biochemical analyzer. Unit: g/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Levels of Estimated Glomerular Filtration Rate (eGFR)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
eGFR measured by automated biochemical analyzer. Unit: ml/min
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum Levels of Creatinine (Cr)
Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Cr measured by automated biochemical analyzer. Unit: μmol/L
Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
The Levels of Antinuclear Antibody (ANA)
Time Frame: Baseline, Weeks 12, 24, 36, 48
ANA detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Antimitochondrial Antibody (AMA)
Time Frame: Baseline, Weeks 12, 24, 36, 48
AMA detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Smooth Muscle Antibody (SMA)
Time Frame: Baseline, Weeks 12, 24, 36, 48
SMA detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Anti-Liver-Kidney Microsomal Antibody 1 (Anti-LKM1)
Time Frame: Baseline, Weeks 12, 24, 36, 48
Anti-LKM1 detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Anti-Soluble Liver Antigen / Liver-Pancreas Antigen (Anti-SLA/LP)
Time Frame: Baseline, Weeks 12, 24, 36, 48
Anti-SLA/LP detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Anti-Neutrophil Cytoplasmic Antibody (ANCA)
Time Frame: Baseline, Weeks 12, 24, 36, 48
ANCA detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Anti-Glycoprotein 210 (Anti-gp210)
Time Frame: Baseline, Weeks 12, 24, 36, 48
Anti-gp210 detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Anti-Nuclear Pore Protein 100 (Anti-sp100)
Time Frame: Baseline, Weeks 12, 24, 36, 48
Anti-sp100 detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Antimitochondrial Antibody M2 (AMA-M2)
Time Frame: Baseline, Weeks 12, 24, 36, 48
AMA-M2 detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Anti-Sjogren Syndrome B Antibody (Anti-SS-B)
Time Frame: Baseline, Weeks 12, 24, 36, 48
Anti-SS-B detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48
The Levels of Anti-Sjogren Syndrome A Antibody (Anti-SS-A)
Time Frame: Baseline, Weeks 12, 24, 36, 48
Anti-SS-A detected by indirect immunofluorescence assay (IFA). Unit: Positive or Negative; Titer
Baseline, Weeks 12, 24, 36, 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ningbo No.2 Hospital

Collaborators

Ningbo Medical Center Lihuili Hospital
Shulan (Hangzhou) Hospital
Ningbo Mingzhou Hospital (Affiliated to Zhejiang University)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 31, 2026

Primary Completion (Estimated)

December 31, 2034

Study Completion (Estimated)

December 31, 2035

Study Registration Dates

First Submitted

March 29, 2026

First Submitted That Met QC Criteria

April 20, 2026

First Posted (Actual)

April 28, 2026

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 20, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PJ-NBEY-KY-2025-215-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD sharing is not planned for this investigator-initiated study. Data will be used only for the primary study analysis and reporting.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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