Clinical Outcomes of HBeAg-negative CHB Patients With Indeterminate Phase
PILOT
1 other identifier
observational
4,500
1 country
5
Brief Summary
Chronic hepatitis B virus (HBV) infection remains a global public health burden around the world. Investigating the disease process of chronic hepatitis B (CHB) is essential to individual management in clinical practice. According to American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidance, CHB can be classified into four phases: immune-tolerant CHB, HBeAg-positive immune active CHB, inactive CHB and hepatitis B e antigen (HBeAg)-negative immune active CHB. Antiviral therapy is recommended in patients with HBeAg-positive or -negative immune active CHB patients to reduce the incidence of liver cirrhosis and hepatocellular carcinoma, while periodic monitoring is recommended for inactive carrier and immune-tolerant CHB patients. However, a substantial proportion of patients fall into an indeterminate phase whose serum HBV DNA and alanine aminotransferase levels do not fit well into these well-described phases. Most of CHB patients with indeterminate phase are HBeAg negative. However, the clinical outcomes of these patients remain unclear. Therefore, the purpose of this study is to investigate the clinical outcomes of HBeAg-negative chronic hepatitis B patients with indeterminate phase.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Dec 2022
Longer than P75 for all trials
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 13, 2022
CompletedStudy Start
First participant enrolled
December 1, 2022
CompletedFirst Posted
Study publicly available on registry
December 22, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2028
December 22, 2022
December 1, 2022
5.2 years
August 13, 2022
December 21, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
The incidence of hepatocellular carcinoma at 240 weeks
240 weeks
The HBsAg clearance rate at 240 weeks
240 weeks
Study Arms (2)
Observation cohort
Treatment cohort
Interventions
Receive first-line antiviral treatment, including entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, tenofovir amibufenamide or peginterferon
Eligibility Criteria
HBeAg-negative chronic hepatitis B patients with indeterminate phase
You may qualify if:
- Hepatitis B surface antigen (HBsAg) positive over 6 months
- Age ≥18 years
- Treatment-naïve
- HBeAg negative, anti-HBe positive
- HBV DNA \>2000 IU/mL
- Persistently normal alanine transaminase (ALT)
- Liver inflammation \<G2 or A2 and liver fibrosis \<S2 or F2 before enrollment, or liver stiffness \>8 kilopascals (kPa)
- No family history of liver cirrhosis or hepatocellular carcinoma
You may not qualify if:
- Coinfection with hepatitis A virus, hepatitis C virus, hepatitis D virus, hepatitis E virus or human immunodeficiency virus;
- Coexisting of hepatocellular carcinoma and other malignancy, or alpha-fetoprotein \>upper limit of normal at enrollment;
- Presence of liver cirrhosis;
- Alcohol abuse within the last year (ethanol: male \>40 g/d, female \>20 g/d; or heavy drinking within 2 weeks before enrollment: ethanol \>80 g/d), or history of drug abuse;
- Participating in other clinical trials in the last 3 months;
- Coexisting of autoimmune liver diseases;
- Pregnant or planned pregnancy in a short term or lactation patients;
- History of severe heart disease, mental disease;
- Uncontrolled diabetes, hypertension, thyroid dysfunction, retinopathy, autoimmune diseases;
- Neutrophil count \<2×10\^9/L and/or platelet count \<100×10\^9/L;
- History of organ transplantation or preparing for organ transplantation;
- Using immunosuppressive drugs;
- Undergone organ transplantation or preparing for organ transplantation;
- Receiving immunosuppressive agents;
- Patients thought by the investigators not suitable to participate in this study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
The Third Hospital of Changzhou
Changzhou, Jiangsu, 213001, China
Huai'an No.4 People's Hospital
Huai'an, Jiangsu, 223300, China
Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008, China
Suqian People's Hospital
Suqian, Jiangsu, 223800, China
The Fifth People's Hospital of Suzhou
Suzhou, Jiangsu, 215007, China
Related Publications (8)
Liu J, Liang W, Jing W, Liu M. Countdown to 2030: eliminating hepatitis B disease, China. Bull World Health Organ. 2019 Mar 1;97(3):230-238. doi: 10.2471/BLT.18.219469. Epub 2019 Jan 28.
PMID: 30992636RESULTTerrault 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. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.
PMID: 29405329RESULTHuang DQ, Li X, Le MH, Le AK, Yeo YH, Trinh HN, Zhang J, Li J, Wong C, Wong C, Cheung RC, Yang HI, Nguyen MH. Natural History and Hepatocellular Carcinoma Risk in Untreated Chronic Hepatitis B Patients With Indeterminate Phase. Clin Gastroenterol Hepatol. 2022 Aug;20(8):1803-1812.e5. doi: 10.1016/j.cgh.2021.01.019. Epub 2021 Jan 16.
PMID: 33465482RESULTYao K, Liu J, Wang J, Yan X, Xia J, Yang Y, Wu W, Liu Y, Chen Y, Zhang Z, Li J, Huang R, Wu C. Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the grey zone. J Viral Hepat. 2021 Jul;28(7):1025-1033. doi: 10.1111/jvh.13511. Epub 2021 Apr 26.
PMID: 33797145RESULTEuropean 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: 28427875RESULTChen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.
PMID: 16391218RESULTBonacci M, Lens S, Marino Z, Londono MC, Rodriguez-Tajes S, Mas A, Garcia-Lopez M, Perez-Del-Pulgar S, Sanchez-Tapias JM, Forns X. Anti-viral therapy can be delayed or avoided in a significant proportion of HBeAg-negative Caucasian patients in the Grey Zone. Aliment Pharmacol Ther. 2018 May;47(10):1397-1408. doi: 10.1111/apt.14613. Epub 2018 Mar 25.
PMID: 29577350RESULTChoi GH, Kim GA, Choi J, Han S, Lim YS. High risk of clinical events in untreated HBeAg-negative chronic hepatitis B patients with high viral load and no significant ALT elevation. Aliment Pharmacol Ther. 2019 Jul;50(2):215-226. doi: 10.1111/apt.15311. Epub 2019 May 28.
PMID: 31135074RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
August 13, 2022
First Posted
December 22, 2022
Study Start
December 1, 2022
Primary Completion (Estimated)
February 1, 2028
Study Completion (Estimated)
May 1, 2028
Last Updated
December 22, 2022
Record last verified: 2022-12