Long-term Outcomes of Anti-viral Therapies in Patients With Chronic Viral Hepatitis B

NCT04896255 | Recruiting

• 1 other identifier: KY2020-911
• Study Type: observational
• Target: 33,000
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational, multicenter , real-world study is to evaluate the long-term outcomes of different antiviral therapies in adults with chronic hepatitis B (CHB). The main questions it aims to answer are: What is the 5-year incidence of hepatocellular carcinoma (HCC) under various treatment regimens? How do rates of HBsAg seroclearance, decompensated cirrhosis, liver fibrosis progression, and other virological and clinical outcomes compare across regimens? Researchers will compare real-world treatment arms-including nucleos(t)ide analogue (NA) monotherapy (e.g., entecavir, tenofovir), PegIFN based regimen (e.g., PegIFN monotherapy, PegIFN plus NA combinations)-to identify optimal strategies for reducing HCC risk and improving functional cure rates. Participants will undergo routine clinical care with no study-imposed interventions; data on demographics, medical history, symptoms, laboratory tests (e.g., HBsAg, HBV DNA, liver function), imaging (e.g., ultrasound, elastography), and clinical events will be collected prospectively (for up to 5 years in some cohorts) or retrospectively from medical records at baseline and scheduled follow-up visits (e.g., every 3-12 months initially, then annually).

Conditions

Chronic Hepatitis b

Outcome Measures

Primary Outcomes (1)

• rate of hepatocellular carcinoma at 5 year from baseline

  Rate of hepatocellular carcinoma will be evaluated as an end-stage liver disease event at 5 years from baseline

  5 year from baseline

Secondary Outcomes (10)

• rate of HBsAg loss

  24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline

• rate of decompensated cirrhosis

  1year, 2 year, 3 year, 4 year and 5 year from baseline

• rate of cirrhosis

  1 year, 2 year, 3 year, 4year, and 5 year from baseline

• rate of fibrosis progression

  24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline

• rate of fibrosis regression

  24 weeks, 48 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks, 168 weeks, 192 weeks, 216 weeks, 240 weeks from baseline

Other Outcomes (1)

• demographic characteristics

  baseline

Study Arms (3)

Prospective

CHB patients enrolled pre-Protocol v3.0 (Dec 2023), planned or on antiviral therapy, followed prospectively for 5 years post-consent. Treatments: routine NA monotherapy, or PegIFN based regimens, per clinical guidelines. Data: baseline and 5 -year follow-up via routine visits.

Drug: peginterferon alpha based regimen; Drug: nucleos(t)ide

Retrospective-Prospective

CHB patients with baseline (≥Sep 2020) pre-v3.0, consenting post-v3.0. Retrospective data from baseline to consent; prospective for 5 years from baseline. Treatments: NAs monotherapy, or PegIFN based regimens. Data: retrospective before consent; prospective from visit matching baseline-consent interval. Missing routine data noted.

Drug: peginterferon alpha based regimen; Drug: nucleos(t)ide

Retrospective

CHB patients with records from Sep 2020 to v3.0 (Dec 2023), collected retrospectively. Treatments: NAs monotherapy, or PegIFN based regimens, per historical practice. Data: extracted from the electronic healthcare record; missing routine data recorded.

Drug: peginterferon alpha based regimen; Drug: nucleos(t)ide

Interventions

peginterferon alpha based regimen DRUG

peginterferon alpha based regimen or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study

Prospective; Retrospective; Retrospective-Prospective

nucleos(t)ide DRUG

peginterferon alpha based regimen or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study

Prospective; Retrospective; Retrospective-Prospective

Eligibility Criteria

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

Study Population

patients with chronic hepatitis B under anti-viral treatment of peginterferon alpha based regimen or nucleos(t)ide alone.

You may qualify if:

• Male and female patients with age ≥18; subjects who are over 70 years of age must be in generally stable health conditions.
• There should be evidences that HBsAg has been positive for more than 6 months or HBV-related histological changes.
• Planned or currently receiving potent low-resistance NAs \[entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), or tenofovir amibufenamide (TMF)\], or planned to receive PegIFNα-2b, either treated or treatment-naïve.
• Agree to participate in the study and sign the patient informed consent form.

You may not qualify if:

• Hepatocellular carcinoma (diagnosed or planned for treatment) or liver failure at baseline
• Concurrently participating in other interventional clinical trials.
• Any other conditions deemed unsuitable by investigators or preventing compliance with study requirements.

Sponsors & Collaborators

• Huashan Hospital: lead
• Chinese Foundation for Hepatitis Prevention and Control: collaborator
• The Third People's Hospital of Taiyuan: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator
• Beijing YouAn Hospital: collaborator
• Henan Provincial People's Hospital: collaborator
• Yunnan Provincial No.1 Hospital: collaborator
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• The First Affiliated Hospital of Xiamen University: collaborator
• Beijing Ditan Hospital: collaborator
• Tianjing No.2 People's Hospital: collaborator
• Qingdao No.6 People's Hospital: collaborator
• The Fourth Affiliated Hospital of Zhejiang University School of Medicine: collaborator
• Ningbo Beilun District Traditional Chinese Medicine Hospital: collaborator
• Wuxi No.5 People's Hospital: collaborator
• Taicang No.1 People's hospital: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator

Study Sites (1)

Huashan Hospital

Shanghai, 200040, China

RECRUITING

Related Publications (15)

• Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X. Epub 2015 Jul 28.

  PMID: 26231459 BACKGROUND

• Shin EC, Sung PS, Park SH. Immune responses and immunopathology in acute and chronic viral hepatitis. Nat Rev Immunol. 2016 Aug;16(8):509-23. doi: 10.1038/nri.2016.69. Epub 2016 Jul 4.

  PMID: 27374637 BACKGROUND

• Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015 Dec;64(12):1972-84. doi: 10.1136/gutjnl-2015-309809. Epub 2015 Jun 5.

  PMID: 26048673 BACKGROUND

• Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA. 2018 May 1;319(17):1802-1813. doi: 10.1001/jama.2018.3795.

  PMID: 29715359 BACKGROUND

• Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Clin Liver Dis (Hoboken). 2018 Aug 22;12(1):33-34. doi: 10.1002/cld.728. eCollection 2018 Jul. No abstract available.

  PMID: 30988907 BACKGROUND

• European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.

  PMID: 28427875 BACKGROUND

• Lim TH, Gane E, Moyes C, Borman B, Cunningham C. HBsAg loss in a New Zealand community study with 28-year follow-up: rates, predictors and long-term outcomes. Hepatol Int. 2016 Sep;10(5):829-37. doi: 10.1007/s12072-016-9709-6. Epub 2016 Mar 8.

  PMID: 26957439 BACKGROUND

• Hu P, Shang J, Zhang W, Gong G, Li Y, Chen X, Jiang J, Xie Q, Dou X, Sun Y, Li Y, Liu Y, Liu G, Mao D, Chi X, Tang H, Li X, Xie Y, Chen X, Jiang J, Zhao P, Hou J, Gao Z, Fan H, Ding J, Zhang D, Ren H. HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog: New Switch Study. J Clin Transl Hepatol. 2018 Mar 28;6(1):25-34. doi: 10.14218/JCTH.2017.00072. Epub 2018 Mar 17.

  PMID: 29577029 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

• Mak LY, Wong DK, Pollicino T, Raimondo G, Hollinger FB, Yuen MF. Occult hepatitis B infection and hepatocellular carcinoma: Epidemiology, virology, hepatocarcinogenesis and clinical significance. J Hepatol. 2020 Oct;73(4):952-964. doi: 10.1016/j.jhep.2020.05.042. Epub 2020 Jun 3.

  PMID: 32504662 BACKGROUND

• Shiels MS, Engels EA, Yanik EL, McGlynn KA, Pfeiffer RM, O'Brien TR. Incidence of hepatocellular carcinoma among older Americans attributable to hepatitis C and hepatitis B: 2001 through 2013. Cancer. 2019 Aug 1;125(15):2621-2630. doi: 10.1002/cncr.32129. Epub 2019 Apr 12.

  PMID: 30980394 BACKGROUND

• Hsu YC, Wong GL, Chen CH, Peng CY, Yeh ML, Cheung KS, Toyoda H, Huang CF, Trinh H, Xie Q, Enomoto M, Liu L, Yasuda S, Tanaka Y, Kozuka R, Tsai PC, Huang YT, Wong C, Huang R, Jang TY, Hoang J, Yang HI, Li J, Lee DH, Takahashi H, Zhang JQ, Ogawa E, Zhao C, Liu C, Furusyo N, Eguchi Y, Wong C, Wu C, Kumada T, Yuen MF, Yu ML, Nguyen MH. Tenofovir Versus Entecavir for Hepatocellular Carcinoma Prevention in an International Consortium of Chronic Hepatitis B. Am J Gastroenterol. 2020 Feb;115(2):271-280. doi: 10.14309/ajg.0000000000000428.

  PMID: 31634265 BACKGROUND

• Miyake Y, Kobashi H, Yamamoto K. Meta-analysis: the effect of interferon on development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Gastroenterol. 2009;44(5):470-5. doi: 10.1007/s00535-009-0024-z. Epub 2009 Mar 25.

  PMID: 19308310 BACKGROUND

• Shiffman ML. Approach to the patient with chronic hepatitis B and decompensated cirrhosis. Liver Int. 2020 Feb;40 Suppl 1:22-26. doi: 10.1111/liv.14359.

  PMID: 32077612 BACKGROUND

• Jang JW, Choi JY, Kim YS, Yoo JJ, Woo HY, Choi SK, Jun CH, Lee CH, Sohn JH, Tak WY, Lee YR, Han KH. Effects of Virologic Response to Treatment on Short- and Long-term Outcomes of Patients With Chronic Hepatitis B Virus Infection and Decompensated Cirrhosis. Clin Gastroenterol Hepatol. 2018 Dec;16(12):1954-1963.e3. doi: 10.1016/j.cgh.2018.04.063. Epub 2018 May 9.

  PMID: 29753085 BACKGROUND

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

• Wenhong Zhang, MD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

• Jiming Zhang, MD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

• Feng Sun, MD

  Huashan Hospital

  STUDY CHAIR

• Qiran Zhang, MD

  Huashan Hospital

  STUDY DIRECTOR

Central Study Contacts

Wenhong Zhang, Professor

CONTACT

13801844344; zhangwenhong@fudan.edu.cn

Feng Sun, doctor

CONTACT

15921403893; aaronsf1125@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: May 21, 2021
• Study Start: September 9, 2020
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 31, 2031
• Last Updated: October 6, 2025

Record last verified: 2025-09

Locations

CN (1)