Real-world Study Evaluating the Long-term Outcomes of Pegylated Interferon α-2b Treatment in the Families With Clusters of HBV Infection and Unfavorable Prognosis - A Prospective, Controlled, Multicenter, Cohort Study

NCT07079150 | Recruiting

• 1 other identifier: XJTU1AF2024LSYY-468
• Study Type: observational
• Target: 1,500
• Locations: 1 country
• Sites: 2

Brief Summary

Chronic hepatitis B can develop into cirrhosis and liver cancer, which seriously endangers the life and health of people. In China, HBV is mainly transmitted from mother to child, showing the phenomenon of family clusters. Similarly, cirrhosis and hepatocellular carcinoma occur in familial clusters. Familial clusters of HBV infection with unfavorable prognoses refers to HBV-infected patients from two consecutive generations of blood relatives, with at least one family member diagnosed with hepatitis B-related cirrhosis or hepatocellular carcinoma (HCC). Previous family investigations have shown that the risk and harm of HBV-related cirrhosis and hepatocellular carcinoma are significantly higher in families with familial clusters of HBV infection with unfavorable prognoses than in the general population. Currently, antiviral drugs used for CHB mainly include nucleoside analogues (NAs) and interferon-alpha (mainly pegylated interferon-alpha, Peg IFN). NAs mainly inhibits viral replication by blocking the reverse transcription process, but it cannot effectively inhibit the expression of viral proteins such as HBsAg, and rarely achieves clinical cure. Multiple clinical studies have shown that the use of NAs reduces the incidence of cirrhosis decompensation, HCC, and death in patients with CHB compared to untreated or placebo-treated patients. Despite long-term treatment with first-line NAs drugs, CHB patients continue to be at risk of developing hepatocellular carcinoma. Peg IFN α-2b injection is the first-line drug of choice for antiviral treatment of chronic hepatitis B, and its main mechanism of action includes anti-HBV, anti-fibrosis, anti-tumor and regulation of immune response. In 2024, a randomized controlled multicenter study showed that Peg IFN α-2b combined with NAs therapy could effectively prevent hepatocellular carcinoma in CHB patients. There is sufficient evidence in clinical practice that long-term antiviral therapy, whether NAs or Peg IFN α-2b, reduces the risk of cirrhosis, hepatocellular carcinoma, and death in patients with CHB. In conclusion, early antiviral therapy can reduce the risk of developing hepatitis B cirrhosis and hepatocellular carcinoma in CHB patients with familial clusters of HBV infection with unfavorable prognoses. The goal of this observational study is to explore the evaluation of pegylated interferon α-2b combined with first-line NAs on the long-term outcome of CHB antiviral therapy with cirrhosis and HCC progression as the main observation targets, compared with only use of NAs in the context of familial clusters of HBV infection with unfavorable prognoses. It is intended to provide high-quality evidence-based medical evidence for the treatment and follow-up of CHB, explore optimal clinical decision-making, and provide global clinical data for the improvement and evaluation of this difficult-to-treat population. The main question it aims to answer is: Can Peg IFN-α-2B combined with NAs therapy improve the long-term outcomes of this particular population of familial clusters of HBV infection with unfavorable prognoses compared to first-line NAs monotherapy? Patients with familial clusters of HBV infection with unfavorable prognoses using Peg IFN-α-2B combined with NAs therapy and NAs monotherapy will be collected laboratory and medical examination data at specified follow-up points, and recorded adverse events and drug combinations in detail for 7 years.

Conditions

Hepatitis B, Chronic (CHB); Hepatitis B; Hepatitis B Virus (HBV)

Keywords

hepatitis B; family cluster; interferon; antiviral therapy; cirrhosis; hepatocellular carcinoma

Outcome Measures

Primary Outcomes (2)

• the number and percentage of cases of cirrhosis and HCC occurring in the non-cirrhosis population

  From enrollment to the end of treatment at 5 years and 7 years

• the number and percentage of cases of decompensated cirrhosis and HCC occurring in the compensated cirrhosis population

  From enrollment to the end of treatment at 5 years and 7 years

Secondary Outcomes (5)

• Overall survival time of patients in each treatment subgroup

  From enrollment to the end of treatment at 5 years and 7 years

• the time of cirrhosis and HCC occurring in the non-cirrhosis population

  From enrollment to the end of treatment at 5 years and 7 years

• the time of decompensated cirrhosis and HCC occurring in the compensated-cirrhosis population

  From enrollment to the end of treatment at 5 years and 7 years

• the number and percentage of HBsAg seroconversion cases, the number and percentage of HBeAg seroconversion cases (for those who are HBeAg-positive) per 24 weeks

  From enrollment to the end of treatment at 5 years and 7 years

• HBV DNA levels, HBsAg levels, and HBeAg levels per 24 weeks

  From enrollment to the end of treatment at 5 years and 7 years

Study Arms (4)

Peg IFN-α-2b combined with NAs therapy for non-cirrhotic group

Drug: Peg IFN-α-2b

NAs monotherapy for non-cirrhotic group

Peg IFN-α-2b combined with NAs therapy for cirrhotic group

Drug: Peg IFN-α-2b

NAs monotherapy for cirrhotic group

Interventions

Peg IFN-α-2b DRUG

In the treatment of Peg IFNα-2b combined with NAs (Peg IFN combined treatment group), the treatment of Peg IFNα-2b should be no less than 48 weeks. The initial therapeutic dose of Peg IFNα-2b and the subsequent adjusted dose will be individualized determined by clinicians based on the specific condition of the patients. In the NAs monotherapy group, entecavir (ETV), tenofovir fumarate disoproxil (TDF), tenofovir propofol fumarate (TAF), and emitenofovir (TMF) were used for treatment for no less than 48 weeks, and Peg IFN was not added or switched for treatment.

Peg IFN-α-2b combined with NAs therapy for cirrhotic group; Peg IFN-α-2b combined with NAs therapy for non-cirrhotic group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will be conducted across multiple centers in China, planning to enroll 600 non-cirrhosis and 300 compensated cirrhosis patients with a family history of unfavorable prognoses clustering of HBV infection who also have HBsAg positivity for more than 6 months, and who meet the inclusion criteria and do not meet the exclusion criteria. In the non-cirrhosis cohort, the Peg IFN α-2b combination therapy group plans to enroll 300 patients, and the nucleos(t)ide group plans to enroll 300 patients; in the compensated cirrhosis cohort, the Peg IFN α-2b combination therapy group plans to enroll 150 patients, and the nucleos(t)ide group plans to enroll 150 patients.

You may qualify if:

• Meet the criteria for a family cluster of unfavorable prognoses associated with HBV infection: that is, patients with HBV infection in two consecutive generations of blood relatives, and at least one patient with cirrhosis or HCC in two or more generations of blood relatives;
• Chronic HBV-infected individuals from families with unfavorable prognoses clustering (meeting either (1)+(2) or (1)+(3) criteria): (1) Positive for HBsAg for more than 6 months; (2) Treated with nucleos(t)ide analogs (NAs); (3) Compensated cirrhosis due to hepatitis B (for details, see the "Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition)");
• A negative pregnancy test within 24 hours before the first administration of medication in the treatment group (for women of childbearing age);
• No contraindications for interferon treatment.

You may not qualify if:

• Patients diagnosed with liver cancer or other systemic tumors before treatment;
• Patients with contraindications to Peg IFN α-2b use (for details, see the "Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition)");
• Peripheral blood counts: WBC \< 3.0 × 10\^9/L, PLT \< 70 × 10\^9/L;
• Liver function: ALT \> 5 × upper limit of normal (ULN), TBIL \> 2 × ULN; Individuals planning to receive organ transplantation or who have already undergone organ transplantation;
• Those allergic to interferon or with any contraindication listed in the product information;
• Any other conditions deemed unsuitable for enrollment by the investigator.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead

Study Sites (2)

First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi, 710061, China

NOT YET RECRUITING

First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi, 710061, China

RECRUITING

MeSH Terms

Conditions

Hepatitis B; Bronchiolitis Obliterans Syndrome; Fibrosis; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Study Officials

• Yingren Zhao, Professor

  First Affiliated Hospital of Xian Jiaotong University

  STUDY DIRECTOR

Central Study Contacts

Yingren Zhao, Professor

CONTACT

0086-029-85323437; zhaoyingren@mail.xjtu.edu.cn

Ze Zhang

CONTACT

zz082089@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2025
• First Posted: July 22, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): January 1, 2032
• Last Updated: July 22, 2025

Record last verified: 2025-07

Locations

CN (2)