Hepatitis B, ChronicNCT06041022
A Non-invasive Model to Predict Antiviral Therapy in Gray Zone of Chronic Hepatitis B
An observational study of Hepatitis B, Chronic, run by Qilu Hospital of Shandong University.
Trial summary
Establishment and validation of the non-invasive model to predict antiviral therapy in the gray zone of chronic hepatitis B Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Exposure factors
- How many people
- 1,000 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2023to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The minimum sample size required for the study was calculated to be 417, and it was estimated that almost 1000 patients with chronic hepatitis B underwent hepatic puncture biopsy in the seven hospitals from 2010 to 2022, and all patients will be included in the study.
Who may be able to join
- HBeAg positive, normal serum alanine aminotransferase(ALT) level，HBVDNA≤10^6 IU/ml
- HBeAg positive, elevated serum ALT, HBVDNA≤2*10^4 IU/ml
- HBeAg negative, elevated serum ALT, HBVDNA≤2*10^3 IU/ml
- HBeAg negative, normal serum ALT, HBVDNA≥2*10^3 IU/ml
- Normal upper limit of ALT is 35 U/L for male and 25 U/L for female.
Who cannot join
- Concurrent with other liver diseases such as autoimmune hepatitis, Hepatitis C virus infectious, liver cirrhosis, HCC, or unexplained liver function abnormalities
- Patients with incomplete clinical data
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Non-invasive Model to Predict Antiviral Therapy in Patients With Gray Zone of Chronic Hepatitis B: a Multi-center, Retrospective Study
Establishment and validation of the non-invasive model to predict antiviral therapy in the gray zone of chronic hepatitis B
Read the detailed description
Chronic hepatitis B virus (HBV) infection continues to be a major public health problem worldwide today. According to statistics, the prevalence of chronic HBV infection assessed globally in 2016 was 3.5%, or 257 million people with chronic infection. In China, it is estimated that about 70 million people are chronically infected with HBV in 2019, including about 20-30 million people with chronic hepatitis B (CHB). CHB is a major risk factor for cirrhosis, and hepatocellular carcinoma (HCC). 12-20% of patients with chronic hepatitis B will develop cirrhosis, and of these, around 20% will further develop decompensated cirrhosis and 6-15% will develop HCC, with hepatitis B accounting for approximately 50% of HCC cases worldwide. Therefore, strongly and exact management of chronic hepatitis B is extremely important for the control of HBV progression. Current domestic and international clinical guidelines generally divide the natural history of chronic hepatitis B into four immune phases based on HBV DNA levels, liver injury, and HBeAg status: immune active, immune tolerant, inactive HBsAg carriers, and reactive stage. The guidelines of American Association for the Study of Liver Diseases (AASLD) recommend the use of antiviral therapy for patients in the immune active and reactive phases, and also provide a detailed follow-up plan for patients in other phases. However, a significant number of patients with chronic hepatitis B cannot be classified in any of these four phases, who falls into a gray area with uncertainty of formal management. According to the 2018 AASLD Hepatitis B Guidelines criteria for antiviral therapy, patients in the gray zone still do not have clarity on the need for antiviral therapy based only on clinical indicators. A recent study showed that nearly 40% of patients with chronic hepatitis B were in the indeterminate stage. At long-term follow-up assessment, half of these patients were still in the indeterminate phase and one-fifth had transitioned to the immune active phase. Patients in the indeterminate phase were 14 times more likely to develop HCC than those with inactive hepatitis B. Therefore, the management of antiviral therapy in patients with CHB in the "gray zone" is crucial and should be demonstrated. The aim of the investigators is to investigate the clinical characteristics of patients with uncertain treatment in the "gray zone" of CHB and to develop a non-invasive predictive model for the indication of antiviral therapy. This will provide guidance for the clinical management of patients in the "gray zone" of CHB, thereby reducing the incidence of cirrhosis and liver cancer and improving their quality of life.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Exposure factors
- Keywords
- Antiviral therapy, Liver biopsy, Gray zone, Model, Chronic hepatitis B
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure factorsOther
Including demographical data, laboratory features and liver histological indicators.
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with the antiviral therapy as assessed by AASLD guideline
The criteria of antiviral therapy:
- Immune-active CHB: an elevation of ALT≥2 the upper limit of normal (ULN)plus elevated HBV DNA above 2,000 IU/mL (HBeAg negative) or above 20,000 IU/mL (HBeAg positive).
- Immune-active CHB and cirrhosis if HBV DNA is >2,000 IU/mL.
- Immune-active CHB with ALT < 2 the ULN and HBV DNA below thresholds (less than 2,000 IU/mL if HBeAg negative or less than 20,000 IU/mL if HBeAg positive) are as follows: 1) Age: older age (>40 years). 2) Family history of cirrhosis or HCC. 3) Previous treatment history. 4) Presence of extrahepatic manifestations. 5) Presence of cirrhosis.
- Immune tolerance CHB with the moderate-to-severe necroinflammation or fibrosis on a liver biopsy specimen.
Measured: From Jan 1st,2010 to Aug 31,2023
Number of participants with significant liver histology as assessed by Metavia scoring system
Significant liver histology showing significant hepatic inflammation ≥G2 and/or fibrosis ≥S2 as assessed by Metavir scoring system
The fibrosis score is used to describe the amount of inflammation (the intensity of inflammation/breakdown of tissue) in the liver:
F0: No fibrosis F1: Portal fibrosis without septa F2: Portal fibrosis with few septa F3: Numerous septa without cirrhosis F4: Cirrhosis
The activity score is a prediction about how rapidly the degree of fibrosis is progressing:
G0: No activity G1: Mild activity G2: Moderate activity G3: Severe activity
Measured: From Jan 1st,2010 to Aug 31,2023
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2023
- Study start1 Oct 2023 (estimated)
- Primary completion1 Nov 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by Qilu Hospital of Shandong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Qilu Hospital of Shandong University
- Sponsor type
- University, hospital or other
- Collaborators
- Linyi People's Hospital, First Affiliated Hospital Xi'an Jiaotong University, First Affiliated Hospital of Wenzhou Medical University, Third Affiliated Hospital, Sun Yat-Sen University, Sir Run Run Shaw Hospital, First Affiliated Hospital of Zhejiang University
- Responsible party
- Sponsor
- Investigators
- Yu-Chen Fan, MD,PhD, Study chair, Qilu Hospital of Shandong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06041022
- Sponsor's protocol ID
- KYLL-202301-030
- Status last verified
- Sep 2023
- First submitted
- 3 Sep 2023
- Last updated
- 18 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26231459Wang G, Duan Z. Guidelines for Prevention and Treatment of Chronic Hepatitis B. J Clin Transl Hepatol. 2021 Oct 28;9(5):769-791. doi: 10.14218/JCTH.2021.00209. Epub 2021 Sep 28.
PubMed 34722192Huang DQ, Lim SG. Hepatitis B: Who to treat? A critical review of international guidelines. Liver Int. 2020 Feb;40 Suppl 1:5-14. doi: 10.1111/liv.14365.
PubMed 32077616Terrault 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.
PubMed 29405329Ma HY, Yang XY, Tian YX, Li XD, He YL, Yang Q, Zheng MH, Zheng YB, Yu Y, Xu LY, Wang QN, Zhang T, Shi Y, Fan YC. Performance of the AASLD, EASL, and APASL Clinical Practice Guidelines in"grey zone"stages of Chinese patients with chronic hepatitis B. Hepatol Int. 2025 Aug;19(4):796-808. doi: 10.1007/s12072-025-10833-3. Epub 2025 May 14.
PubMed 40360826Yang XY, Li XD, Wu BY, Yang Q, Zheng YB, Zheng MH, Wu YP, Ma HY, Zuo J, Jia RX, Yu Y, Xu LY, Tian YX, An Q, Zhang T, He YL, Shi Y, Fan YC. A Model to Identify Gray Zone Patients With Chronic Hepatitis B Requiring Antiviral Therapy: A Multicenter Retrospective Study. J Infect Dis. 2025 Aug 14;232(2):485-498. doi: 10.1093/infdis/jiaf070.
PubMed 39960318
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-invasive Model to Predict Antiviral Therapy in Patients With Gray Zone of Chronic Hepatitis B: a Multi-center, Retrospective Study
- ClinicalTrials.gov ID
- NCT06041022
- Acronym / sponsor ID
- KYLL-202301-030
- Conditions
- Hepatitis B, Chronic
- Keywords
- Antiviral therapy, Liver biopsy, Gray zone, Model, Chronic hepatitis B
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Qilu Hospital of Shandong UniversityUniversity, hospital or other
- Collaborators
- Linyi People's Hospital, First Affiliated Hospital Xi'an Jiaotong University, First Affiliated Hospital of Wenzhou Medical University, Third Affiliated Hospital, Sun Yat-Sen University, Sir Run Run Shaw Hospital, First Affiliated Hospital of Zhejiang University
- Study start
- 1 Oct 2023 (estimated)
- Primary completion
- 1 Nov 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 18 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Establishment and validation of the non-invasive model to predict antiviral therapy in the gray zone of chronic hepatitis B
Detailed description
Chronic hepatitis B virus (HBV) infection continues to be a major public health problem worldwide today. According to statistics, the prevalence of chronic HBV infection assessed globally in 2016 was 3.5%, or 257 million people with chronic infection. In China, it is estimated that about 70 million people are chronically infected with HBV in 2019, including about 20-30 million people with chronic hepatitis B (CHB). CHB is a major risk factor for cirrhosis, and hepatocellular carcinoma (HCC). 12-20% of patients with chronic hepatitis B will develop cirrhosis, and of these, around 20% will further develop decompensated cirrhosis and 6-15% will develop HCC, with hepatitis B accounting for approximately 50% of HCC cases worldwide. Therefore, strongly and exact management of chronic hepatitis B is extremely important for the control of HBV progression. Current domestic and international clinical guidelines generally divide the natural history of chronic hepatitis B into four immune phases based on HBV DNA levels, liver injury, and HBeAg status: immune active, immune tolerant, inactive HBsAg carriers, and reactive stage. The guidelines of American Association for the Study of Liver Diseases (AASLD) recommend the use of antiviral therapy for patients in the immune active and reactive phases, and also provide a detailed follow-up plan for patients in other phases. However, a significant number of patients with chronic hepatitis B cannot be classified in any of these four phases, who falls into a gray area with uncertainty of formal management. According to the 2018 AASLD Hepatitis B Guidelines criteria for antiviral therapy, patients in the gray zone still do not have clarity on the need for antiviral therapy based only on clinical indicators. A recent study showed that nearly 40% of patients with chronic hepatitis B were in the indeterminate stage. At long-term follow-up assessment, half of these patients were still in the indeterminate phase and one-fifth had transitioned to the immune active phase. Patients in the indeterminate phase were 14 times more likely to develop HCC than those with inactive hepatitis B. Therefore, the management of antiviral therapy in patients with CHB in the "gray zone" is crucial and should be demonstrated. The aim of the investigators is to investigate the clinical characteristics of patients with uncertain treatment in the "gray zone" of CHB and to develop a non-invasive predictive model for the indication of antiviral therapy. This will provide guidance for the clinical management of patients in the "gray zone" of CHB, thereby reducing the incidence of cirrhosis and liver cancer and improving their quality of life.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The minimum sample size required for the study was calculated to be 417, and it was estimated that almost 1000 patients with chronic hepatitis B underwent hepatic puncture biopsy in the seven hospitals from 2010 to 2022, and all patients will be included in the study.
Key inclusion criteria (5 listed)
- HBeAg positive, normal serum alanine aminotransferase(ALT) level，HBVDNA≤10^6 IU/ml
- HBeAg positive, elevated serum ALT, HBVDNA≤2*10^4 IU/ml
- HBeAg negative, elevated serum ALT, HBVDNA≤2*10^3 IU/ml
- HBeAg negative, normal serum ALT, HBVDNA≥2*10^3 IU/ml
- Normal upper limit of ALT is 35 U/L for male and 25 U/L for female.
Key exclusion criteria (2 listed)
- Concurrent with other liver diseases such as autoimmune hepatitis, Hepatitis C virus infectious, liver cirrhosis, HCC, or unexplained liver function abnormalities
- Patients with incomplete clinical data
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exposure factorsIncluding demographical data, laboratory features and liver histological indicators. | Other | – |
Primary outcome
Number of participants with the antiviral therapy as assessed by AASLD guideline
Time frame: From Jan 1st,2010 to Aug 31,2023
The criteria of antiviral therapy: 1. Immune-active CHB: an elevation of ALT≥2 the upper limit of normal (ULN)plus elevated HBV DNA above 2,000 IU/mL (HBeAg negative) or above 20,000 IU/mL (HBeAg positive). 2. Immune-active CHB and cirrhosis if HBV DNA is >2,000 IU/mL. 3. Immune-active CHB with ALT < 2 the ULN and HBV DNA below thresholds (less than 2,000 IU/mL if HBeAg negative or less than 20,000 IU/mL if HBeAg positive) are as follows: 1) Age: older age (>40 years). 2) Family history of cirrhosis or HCC. 3) Previous treatment history. 4) Presence of extrahepatic manifestations. 5) Presence of cirrhosis. 4. Immune tolerance CHB with the moderate-to-severe necroinflammation or fibrosis on a liver biopsy specimen.
Number of participants with significant liver histology as assessed by Metavia scoring system
Time frame: From Jan 1st,2010 to Aug 31,2023
Significant liver histology showing significant hepatic inflammation ≥G2 and/or fibrosis ≥S2 as assessed by Metavir scoring system The fibrosis score is used to describe the amount of inflammation (the intensity of inflammation/breakdown of tissue) in the liver: F0: No fibrosis F1: Portal fibrosis without septa F2: Portal fibrosis with few septa F3: Numerous septa without cirrhosis F4: Cirrhosis The activity score is a prediction about how rapidly the degree of fibrosis is progressing: G0: No activity G1: Mild activity G2: Moderate activity G3: Severe activity
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2023.
- Background: PubMed 26231459Schweitzer 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.
- Background: PubMed 34722192Wang G, Duan Z. Guidelines for Prevention and Treatment of Chronic Hepatitis B. J Clin Transl Hepatol. 2021 Oct 28;9(5):769-791. doi: 10.14218/JCTH.2021.00209. Epub 2021 Sep 28.
- Background: PubMed 32077616Huang DQ, Lim SG. Hepatitis B: Who to treat? A critical review of international guidelines. Liver Int. 2020 Feb;40 Suppl 1:5-14. doi: 10.1111/liv.14365.
- Background: PubMed 29405329Terrault 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.
- Derived from this study: PubMed 40360826Ma HY, Yang XY, Tian YX, Li XD, He YL, Yang Q, Zheng MH, Zheng YB, Yu Y, Xu LY, Wang QN, Zhang T, Shi Y, Fan YC. Performance of the AASLD, EASL, and APASL Clinical Practice Guidelines in"grey zone"stages of Chinese patients with chronic hepatitis B. Hepatol Int. 2025 Aug;19(4):796-808. doi: 10.1007/s12072-025-10833-3. Epub 2025 May 14.
- Derived from this study: PubMed 39960318Yang XY, Li XD, Wu BY, Yang Q, Zheng YB, Zheng MH, Wu YP, Ma HY, Zuo J, Jia RX, Yu Y, Xu LY, Tian YX, An Q, Zhang T, He YL, Shi Y, Fan YC. A Model to Identify Gray Zone Patients With Chronic Hepatitis B Requiring Antiviral Therapy: A Multicenter Retrospective Study. J Infect Dis. 2025 Aug 14;232(2):485-498. doi: 10.1093/infdis/jiaf070.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yu-Chen Fan, MD,PhD study chair
Qilu Hospital of Shandong University
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis B, Chronic, run by Qilu Hospital of Shandong University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yu-Chen Fan, MD,PhD (18560082065, fanyuchen@sdu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with the antiviral therapy as assessed by AASLD guideline (time frame: From Jan 1st,2010 to Aug 31,2023). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06041022, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2023.