Peginterferon Treatment Study for Inactive Chronic Hepatitis B Patients

Official title

Real World Study of Peginterferon Alpha-2b Treatment for Inactive Chronic Hepatitis B Patients: E-Cure Study

Overview

There are about 400 million chronic hepatitis B virus (HBV) infection patients worldwide, posing a serious threat to global public health security. In China, HBV infection occured mainly in the perinatal period or infants, and about 10% of patients in the immune tolerance stage spontaneously transit to the immune clearance stage every year and become HBeAg-negative chronic HBV infection, resulting in a significant increase in the number of inactive chronic hepatitis B (CHB) patients. In recent years, different guidelines have not reached consensus on the need to initiate antiviral therapy for inactive CHB patients: In the guidelines of Asian Pacific Association for The Study of Liver(APASL)-2015 and American Association for the Study of Liver Diseases(AASLD)-2018, antiviral therapy is generally not recommended for this group of patients, and regular outpatient follow-up is recommended. Guideline of European Association for the Study of the Liver(EASL)-2017 suggests that people with a family history of cirrhosis and liver cancer at this stage could be treated with antiviral therapy even if they did not meet the indications of antiviral therapy. According to Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2019) of China, antiviral therapy is still recommended for some patients with inactive HBsAg carrier status who are HBV DNA positive and meet the treatment indications. Studies have shown that some patients in immune tolerance stage may enter the immune clearance stage and have hepatitis flare. Patients of inactive CHB have the potential to develop HBeAg-negative CHB, and studies of long-term follow-up in this population have indicated the risk of hepatocellular carcinoma. With the popularization of the concept of functional cure for chronic hepatitis B, more and more people with inactive CHB have a strong desire for treatment. In recent years, several studies have demonstrated that Pegylated-interferon therapy can achieve high functional cure rate in patients with inactive CHB. The purpose of this study is to establish a national multi-center, prospective real world study to compare the efficacy of different antiviral treatment regimens for patients with inactive CHB and seek for the factors of functional cure.

Interventions

• Drug Peginterferon Alfa-2B
  Different usage of peginterferon Alfa-2B and/or Nucleos(t)ide analogs in arm/group descriptions are depended on the wishes of the patient and the advice of the attending doctor.
• Drug Nucleoside Analogs
  Nucleos(t)ide analogs refer to one of the first-line drugs, including ETV, TDF and TAF.

Primary outcome measures

• HBsAg clearance rate [Time frame: From date of the beginning of treatment until the date of the end of treatment, assessed up to 96 weeks]

Secondary outcome measures (4)

• HBsAg serological conversion rate [Time frame: From date of the beginning of treatment until the date of the end of treatment, assessed up to 96 weeks]
• The magnitude of HBsAg decline from baseline [Time frame: through treatment completion, an anticipated period of 96 weeks]
• The magnitude of HBV-DNA decline from baseline and the undetectable rate [Time frame: through treatment completion, an anticipated period of 96 weeks]
• HBsAg clearance rate, HBsAg serological conversion rate and maintenance response rate of HBsAg clearance [Time frame: through follow-up completion, an anticipated period of 144 weeks]

Eligibility criteria

Inclusion criteria

• Age 18-60, no gender limitation
• HBsAg is positive for more than 6 months
• Hepatitis B e antigen(HBeAg) is negative and anti-HBe is positive
• Serum HBV DNA is less than 2000 IU/mL
• Alanine aminotransferase(ALT) and/or Aspartate aminotransferase(AST) is normal
• No antiviral durg (including nucleos(t)ide analogue and interferon) was used before enrollment
• Good compliance and voluntarily signed informed consent

Exclusion criteria

• Allergic to pegylated interferon α-2b
• Any indication of liver cirrhosis
• Coinfection with hepatitis A virus(HAV), hepatitis C virus(HCV), hepatitis D virus(HDV), hepatitis E virus(HEV) or human immunodeficiency virus(HIV)
• Combined with other liver diseases (including drug-related, alcoholic, autoimmune, genetic metabolic liver diseases, etc.)
• There are serious lesions in the important organs, such as heart, lung, kidney, brain and fundus
• Patients with autoimmune diseases, unstable diabetes or thyroid diseases(hyperthyroidism or hypothyroidism)
• Confirmed or suspected liver cancer or other malignant tumors
• Patients after or preparing for organ transplantation
• Peripheral blood white blood cell count < 3.5×109/L and/or platelet count < 80×109/L
• Under immunosuppressant treatment
• Pregnant or planned pregnancy in a short term or lactation patients
• Alcohol abuse (average alcohol intake is more than 40 g/d in males or 20g/d in women) or drug addicts
• Present or past history of mental or psychological diseases
• Other conditions that the investigators deem inappropriate for the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

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

Publications

• Li MH, Xie Y, Zhang L, Lu Y, Shen G, Wu SL, Chang M, Mu CQ, Hu LP, Hua WH, Song SJ, Zhang SF, Cheng J, Xu DZ. Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a. World J Hepatol. 2016 May 28;8(15):637-43. doi: 10.4254/wjh.v8.i15.637. PMID 27239256
• Cao Z, Liu Y, Ma L, Lu J, Jin Y, Ren S, He Z, Shen C, Chen X. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha. Hepatology. 2017 Oct;66(4):1058-1066. doi: 10.1002/hep.29213. Epub 2017 Aug 26. PMID 28407271
• Wu F, Lu R, Liu Y, Wang Y, Tian Y, Li Y, Li M, Wang W, Zhang X, Jia X, Dang S. Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers. Liver Int. 2021 Sep;41(9):2032-2045. doi: 10.1111/liv.14897. Epub 2021 May 26. PMID 33896094
• 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
• Huang Y, Qi M, Liao C, Xun J, Zou J, Huang H, Long LY, Chen J, Fan X, Chen R. Analysis of the Efficacy and Safety of PEGylated Interferon-alpha2b Treatment in Inactive Hepatitis B Surface Antigen Carriers. Infect Dis Ther. 2021 Dec;10(4):2323-2331. doi: 10.1007/s40121-021-00511-w. Epub 2021 Aug 4. PMID 34350562
• Zeng QL, Yu ZJ, Shang J, Xu GH, Sun CY, Liu N, Li CX, Lv J, Liu YM, Liang HX, Li ZQ, Pan YJ, Hu QY, Li W, Zhang DW, Wang FS. Short-term Peginterferon-Induced High Functional Cure Rate in Inactive Chronic Hepatitis B Virus Carriers With Low Surface Antigen Levels. Open Forum Infect Dis. 2020 Jun 3;7(6):ofaa208. doi: 10.1093/ofid/ofaa208. eCollection 2020 Jun. PMID 32626791
• 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

Identifiers

NCT: NCT05182463 · [2021]02-373-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗