The Clinical Cure Project of Chronic Hepatitis B in China

NCT04035837 | Active Not Recruiting Phase 4

• 1 other identifier: ZhuFeng Project
• Study Type: interventional
• Target: 30,000
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic hepatitis B is a global public health problem, with nearly 700,000 deaths each year because of hepatitis B-related diseases. Recent studies have found that some patients who have used nucleot(s)ide analogues(NAs) for some period can achieve higher hepatitis B surface antigen(HBsAg) clearance rate(which is called clinical cure or functional cure) by using pegylated interferon. Patients who achieve clinical cure will further reduce liver inflammation, fibrosis and risks of liver cirrhosis and cancer in the future. This study was initiated in May 2018 and plans to recruit 30,000 eligible patients. The enrollment conditions are as follows: 1. according with the diagnosis of chronic hepatitis B in the guideline of China in 2015; 2.18-60 years old; 3. more than 1 year history of NAs therapy with HBsAg ≤1500 IU/ml, negative hepatitis e antigen and hepatitis B virus DNA\<100 IU/ml; 4. no contraindications of interferon. For the above patients, pegylated interferon was used for 1-2 years(combined with NAs for at least 3 months).The primary goal of this study is to find out the optimal treatment for clinical cure.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• hepatitis B surface antigen

  hepatitis B surface antigen should be tested by the reagents from Roche or Abbott, which is expressed by using IU/ml.

  up to 48 weeks

Secondary Outcomes (1)

• hepatitis B surface antibody

  up to 48 weeks

Study Arms (3)

short-course combination group

EXPERIMENTAL

Nucleoside analogue is used during the first 3 months.

Drug: pegylated interferon-alfa

full-course combination group

EXPERIMENTAL

Nucleoside analogue is used during all the course of study.

Drug: pegylated interferon-alfa

Monotherapy group

EXPERIMENTAL

Only Peg-IFN is used during all the course of study.

Drug: pegylated interferon-alfa

Interventions

pegylated interferon-alfa DRUG

All the patients in this study will receive pegylated interferon for all course.

Monotherapy group; full-course combination group; short-course combination group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• according with the diagnosis of chronic hepatitis B in the guideline of China in 2015
• years old
• more than 1 year history of nucleot(s)ide analogues therapy with HBsAg ≤1500 IU/ml, negative HBeAg and HBV DNA\<100 IU/ml
• no contraindications of interferon

You may not qualify if:

• Allergy to interferon
• Alanine transaminase \>10 times of upper limit of normal(ULN) or total bilirubin \>2 times of ULN
• existing or previous decompensated liver cirrhosis
• White blood cells or Platelet below the lower limit of normal
• existing severe organ injury
• combined with autoimmune diseases, psychiatric diseases, diabetes or thyroidism
• confirmed or suspected malignant tumors
• before or after transplantation
• using immunosuppressor
• pregnant or having a planned parenthood in 2 years
• alcohol or drug addicted
• infected by HIV
• any conditions that is unsuitable to interferon therapy according to the doctors' judgement

Sponsors & Collaborators

• Third Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

Department of Infectious Diseases, The Third Affliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510630, China

Location

Related Publications (13)

• Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008 Feb;48(2):335-52. doi: 10.1016/j.jhep.2007.11.011. Epub 2007 Dec 4.

  PMID: 18096267 BACKGROUND

• Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009 Feb 14;373(9663):582-92. doi: 10.1016/S0140-6736(09)60207-5.

  PMID: 19217993 BACKGROUND

• Brunetto MR. A new role for an old marker, HBsAg. J Hepatol. 2010 Apr;52(4):475-7. doi: 10.1016/j.jhep.2009.12.020. Epub 2010 Jan 30. No abstract available.

  PMID: 20185190 BACKGROUND

• Liu J, Lee MH, Batrla-Utermann R, Jen CL, Iloeje UH, Lu SN, Wang LY, You SL, Hsiao CK, Yang HI, Chen CJ. A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection. J Hepatol. 2013 May;58(5):853-60. doi: 10.1016/j.jhep.2012.12.006. Epub 2012 Dec 13.

  PMID: 23246508 BACKGROUND

• Tseng TC, Liu CJ, Su TH, Wang CC, Chen CL, Chen PJ, Chen DS, Kao JH. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology. 2011 Aug;141(2):517-25, 525.e1-2. doi: 10.1053/j.gastro.2011.04.046. Epub 2011 Apr 28.

  PMID: 21672542 BACKGROUND

• Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, Dauvergne A, Cardoso AC, Asselah T, Nicolas-Chanoine MH, Vidaud M, Valla D, Bedossa P, Marcellin P. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol. 2009 Jun;50(6):1084-92. doi: 10.1016/j.jhep.2009.01.016. Epub 2009 Mar 9.

  PMID: 19376603 BACKGROUND

• Dietary effects on diurnal variation in lipogenesis. Nutr Rev. 1987 May;45(5):157-8. doi: 10.1111/j.1753-4887.1987.tb06353.x. No abstract available.

  PMID: 3601258 BACKGROUND

• European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012 Jul;57(1):167-85. doi: 10.1016/j.jhep.2012.02.010. Epub 2012 Mar 20. No abstract available.

  PMID: 22436845 BACKGROUND

• Thompson AJ, Nguyen T, Iser D, Ayres A, Jackson K, Littlejohn M, Slavin J, Bowden S, Gane EJ, Abbott W, Lau GK, Lewin SR, Visvanathan K, Desmond PV, Locarnini SA. Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology. 2010 Jun;51(6):1933-44. doi: 10.1002/hep.23571.

  PMID: 20512987 BACKGROUND

• Ning Q, Han M, Sun Y, Jiang J, Tan D, Hou J, Tang H, Sheng J, Zhao M. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014 Oct;61(4):777-84. doi: 10.1016/j.jhep.2014.05.044. Epub 2014 Jun 7.

  PMID: 24915612 BACKGROUND

• Chang LJ, Hao CQ, Rao GR, Xu LL, Li J, Cheng Y, Zheng LJ, Wu CW, Chen HX, Chen ZR, Lian JQ, Wu SH, Luo LM, Zhang WL, Zhang Y. Recurrence risk factors for chronic hepatitis B virus-infected patients who achieve functional cure with pegylated interferon-alpha-2b-based therapy: a multicenter pilot study. Virol J. 2025 May 19;22(1):146. doi: 10.1186/s12985-025-02761-3.

  PMID: 40390028 DERIVED

• Wang Z, Wang X, Zhou L, Shi S, Hua Y, Feng Y. Safety and efficacy of 48-week pegylated interferon-alpha-2b therapy in patients with hepatitis B virus-related compensated liver cirrhosis: a pilot observational study. Front Med (Lausanne). 2024 Dec 4;11:1489671. doi: 10.3389/fmed.2024.1489671. eCollection 2024.

  PMID: 39697201 DERIVED

• Huang Q, Xiao X, Zhuang X, Chen W, Huang Y, Liao J, Wang W, Wang Y, Lu L, Liu Z, Huang J. Peripheral Circulating Exosomal-miRNAs Potentially Mediate the Sensitivity to Interferon Treatment in Chronic Hepatitis B Virus Patients. Viral Immunol. 2023 Apr;36(3):209-221. doi: 10.1089/vim.2022.0130. Epub 2023 Mar 21.

  PMID: 36944116 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Zhiliang Gao

  Third Affiliated Hospital, Sun Yat-Sen University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The director of the infectious diseases department

Study Record Dates

• First Submitted: July 13, 2019
• First Posted: July 29, 2019
• Study Start: May 16, 2018
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 13, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)