HEPATITIS B CHRONIC, Hepatitis B Chronic Infection, Hepatocellular Carcinoma
Conditions
Keywords
Peg-IFN-α-2b, hepatitis B, hepatocellular carcinoma, prognosis
Brief summary
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
DRUGPeginterferon alfa-2b
Peginterferon alfa-2b injection administered subcutaneously
DRUGTDF
Tenofovir disoproxil fumarate
DRUGTAF
Tenofovir alafenamide
DRUGTMF
Tenofovir amibufenamide
Sponsors
Ningbo No.2 Hospital
Ningbo Medical Center Lihuili Hospital
Ningbo Mingzhou Hospital (Affiliated to Zhejiang University)
Shulan (Hangzhou) Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Hepatitis B Surface Antigen (Hepatitis B Surface Antigen, HBsAg) | 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 |
| Proportion of patients with HBsAg loss | 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 |
| Proportion of patients with HBsAg seroconversion | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) | 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 |
| Concentration of Hepatitis B e Antigen (HBeAg) | Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240 | Serum HBeAg concentration assessed by CMIA. Unit: S/CO |
| Composition and diversity of intestinal microbiota | Baseline, Week 24, Week 48 | Intestinal microbiota analyzed by 16S rRNA gene high-throughput sequencing. Unit: Relative abundance (%) and alpha diversity index |
| Recurrence-Free Survival (RFS) | 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 |
| Overall survival (OS) | Years 1, 2, 3, 5 | Time from enrollment to death from any cause, regardless of the cause of death. Unit: Months |
| Concentration of Interleukin-2 (IL-2) | Baseline, Week 24, Week 48 | Serum levels of IL-2 will be measured using cytometric bead array (CBA). Unit: pg/mL |
| Concentration of Interleukin-4 (IL-4) | Baseline, Week 24, Week 48 | Serum levels of IL-4 will be measured using cytometric bead array (CBA). Unit: pg/mL |
| Concentration of Interleukin-6 (IL-6) | Baseline, Week 24, Week 48 | Serum levels of IL-6 will be measured using cytometric bead array (CBA). Unit: pg/mL |
| Concentration of Interleukin-10 (IL-10) | Baseline, Week 24, Week 48 | Serum levels of IL-10 will be measured using cytometric bead array (CBA). Unit: pg/mL |
| Concentration of Tumor Necrosis Factor-α (TNF-α) | Baseline, Week 24, Week 48 | Serum levels of TNF-α will be measured using cytometric bead array (CBA). Unit: pg/mL |
| Concentration of Interferon-γ (IFN-γ) | Baseline, Week 24, Week 48 | Serum levels of IFN-γ will be measured using cytometric bead array (CBA). Unit: pg/mL |
Countries
China
Contacts
CONTACTLiyun Fu
CONTACTMengyuan Hu
Outcome results
None listed