HBV ReactivationHBV-post HSCTNCT07644026
HBV Reactivation Prediction Model in Allo-HSCT
An observational study of HBV Reactivation and HSCT, run by Xiao Hui Zhang.
Trial summary
Hepatitis B virus (HBV) reactivation is a serious complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT), particularly in patients with resolved HBV infection (HBsAg-negative, anti-HBc-positive). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HBV Reactivation, HSCT
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- 20 Jun 2026to 30 Jun 2029
- How long will I take part?
- 3 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: he study population will include HBsAg-negative/anti-HBc-positive patients undergoing first allogeneic hematopoietic stem cell transplantation at the participating centers. Patients will be prospectively enrolled before conditioning and followed for subsequent hepatitis B virus (HBV) reactivation (defined as HBsAg reappearance and/or HBV DNA ≥10 IU/mL) and post-transplant outcomes, including hepatitis due to HBV reactivation, hepatic failure, HBV-related mortality, and HBsAg seroclearance after reactivation. Baseline recipient/donor HBV serology (anti-HBs titers, anti-HBc titers), antiviral prophylaxis practice, graft-versus-host disease, and cytomegalovirus reactivation will be collected to describe the incidence, timing, risk factors, and clinical course of HBV reactivation in this high-risk population.
Who may be able to join
- Patients must meet all of the following criteria to be enrolled in the study:
- Planned allogeneic HSCT: Scheduled to undergo first allogeneic hematopoietic stem cell transplantation (allo-HSCT) for any hematologic malignancy or non-malignant hematologic disorder. Any donor type is permitted.
- Resolved HBV infection: Documentation of both of the following serological markers on a blood sample collected within 30 days prior to the start of conditioning:
- Hepatitis B surface antigen (HBsAg): negative Antibody to hepatitis B core antigen (anti-HBc): positive Note: Patients may be either positive or negative for anti-HBs at baseline. Willingness to follow protocol-defined monitoring: Patients (or legally authorized representatives) must agree to adhere to the study-specific HBV monitoring schedule as outlined in the protocol.
- Informed consent: Written informed consent obtained from the patient or a legally authorized representative prior to any study-related procedures.
Who cannot join
- Patients meeting any of the following criteria will be excluded from the study:
- Co-infection with other hepatotropic viruses:
- Positive serology for hepatitis C virus (HCV) (anti-HCV antibody positive with detectable HCV RNA) Positive serology for hepatitis D virus (HDV) (anti-HDV antibody positive) Positive serology for human immunodeficiency virus (HIV)
- Pre-existing advanced liver disease:
- Clinical or histological evidence of liver cirrhosis (METAVIR stage F4, or imaging showing nodular liver surface/splenomegaly/varices) History of hepatic encephalopathy or variceal bleeding History of hepatocellular carcinoma (HCC) Prior solid organ transplantation (including kidney, liver, heart, or lung transplantation).
- Previous allogeneic HSCT (patients receiving a second or subsequent allo-HSCT are excluded; prior autologous HSCT is allowed).
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- Active uncontrolled infection at the time of enrollment that, in the opinion of the treating physician, would preclude safe participation.
- Pregnancy or lactation at the time of enrollment. Female patients of childbearing potential must have a negative pregnancy test within 7 days before starting conditioning.
- Life expectancy <6 months due to underlying disease or comorbid conditions, as judged by the treating physician.
- Inability to comply with follow-up due to geographic, psychiatric, or social reasons.
- Enrollment in another interventional trial that prohibits co-enrollment in observational studies (at the discretion of the principal investigator).
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Development and External Validation of a Nomogram for Predicting Hepatitis B Virus Reactivation in HBsAg-Negative/Anti-HBc-Positive Patients Undergoing Allogeneic Haematopoietic Stem Cell Transplantation: A Multicentre Prospective Study
Hepatitis B virus (HBV) reactivation is a serious complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT), particularly in patients with resolved HBV infection (HBsAg-negative, anti-HBc-positive). The incidence ranges from 10% to 40%, and severe reactivation can lead to hepatitis flare, hepatic failure, and death.
Several risk factors have been identified: low recipient anti-HBs titre, donor anti-HBs negativity, recipient age ≥50 years, chronic GVHD, and use of rituximab. However, no validated clinical prediction model exists for this specific population. The only available study (Zhang et al., BBMT 2020) performed risk factor analysis but did not develop a predictive nomogram, and the sample size was limited (only 16 reactivation events). Therefore, we aim to develop and externally validate a robust nomogram using a large multicentre retrospective cohort and then validate its performance in a prospective cohort
- Conditions
- HBV Reactivation, HSCT
- Being tested
- No Intervention: Observational Cohort
- Keywords
- HBV Reactivation, HSCT, A Multicentre Prospective Observational Study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No Intervention: Observational CohortOther
No study-specific intervention will be administered. Participants will receive standard clinical care after allo-HSCTaccording to institutional practice and treating physician discretion. This multicenter study will prospectively collect observational data on HBV reactivation and associated clinical outcomes in HBsAg-negative/anti-HBc-positive patients for at least 36 months post-transplant.
| Study group | Role | What they receive |
|---|---|---|
| Multicenter prospective observational cohort | This is a multicenter, prospective, observational cohort study. Patients who are HBsAg-negative and anti-HBc-positive prior to allo-HSCT will be enrolled from multiple clinical centers and prospectively followed. Resolved HBV infection will be confirmed by two separate negative HBsAg tests and positive anti-HBc before initiation of conditioning. No investigational intervention is assigned; all participants receive routine clinical care per local practice. Baseline data include demographic characteristics, transplant-related variables (conditioning regimen, donor type, GVHD prophylaxis), recipient and donor HBV serological markers (anti-HBs titre, anti-HBc titre, HBeAg/anti-HBe, HBV DNA). Post-transplant complications (acute and chronic GVHD, CMV reactivation) and subsequent HBV reactivation (defined as reappearance of HBsAg and/or detectable HBV DNA ≥10 IU/mL) will be recorded. All patients will be followed for at least 36 months af Receives: Other: No Intervention: Observational Cohort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatitis B Virus (HBV) Reactivation
HBV reactivation is defined according to the American Association for the Study of Liver Diseases (AASLD) 2018 guidance as the occurrence of any of the following events in patients who are HBsAg-negative/anti-HBc-positive at baseline:
Serological reactivation: Reappearance of hepatitis B surface antigen (HBsAg) from negative to positive (confirmed by two consecutive tests at least one week apart); OR Virological reactivation: Reappearance of detectable HBV DNA (≥10 IU/mL) in a patient who had undetectable HBV DNA at baseline; OR Virological flare: In patients with detectable HBV DNA at baseline, an increase in HBV DNA level of ≥10-fold (1 log₁₀ IU/mL) above baseline level, confirmed on two consecutive measurements within a 2-week period.
For patients receiving preemptive or prophylactic antiviral therapy, reactivation is defined as above, with the additional requirement that HBV DNA ≥10 IU/mL is confirmed on at least two consecutive measurements to exclude transient low-level dete
Measured: Within 36 months after allo-HSCT
Secondary outcomes (6)
Time to HBV Reactivation
The time interval (in days) from the date of allogeneic hematopoietic stem cell transplantation (allo-HSCT) to the date of first occurrence of HBV reactivation. Patients without reactivation are censored at the date of last follow-up, death, or 36 months post-HSCT, whichever occurs first.
Measured: From date of allo-HSCT until date of first documented HBV reactivation (as defined in primary outcome), assessed up to 36 months
Hepatitis Due to HBV Reactivation
Hepatitis due to HBV reactivation is defined as the occurrence of all of the following criteria in a patient with documented HBV reactivation (as defined in the primary outcome):
Alanine aminotransferase (ALT) elevation >3 times the upper limit of normal (ULN) or >3 times baseline value if baseline was already elevated;
Exclusion of other causes of liver injury, including:
Acute or chronic graft-versus-host disease (GVHD) involving the liver (requires histologic confirmation or typical clinical presentation with other organ involvement);Drug-induced liver injury (DILI) - assessed by Roussel Uclaf Causality Assessment Method (RUCAM) score; Cytomegalovirus (CMV) or Epstein-Barr virus (EBV) hepatitis; Hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS); Iron overload; Sepsis or ischemic hepatopathy.
Measured: Within 36 months after allo-HSCT
HBV-Related Mortality
Death directly attributable to HBV reactivation or its hepatic complications, including:
Death from hepatic failure as defined above; Death from cirrhosis-related complications (variceal hemorrhage, spontaneous bacterial peritonitis, hepatorenal syndrome) occurring after HBV reactivation; Death from hepatocellular carcinoma diagnosed after HBV reactivation (if no other etiology identified).
Deaths from other causes (relapse of underlying hematologic disease, infection, GVHD, etc.) will be considered competing events.
Measured: Within 36 months after allo-HSCT
HBsAg Seroclearance After HBV Reactivation
In patients who experience HBV reactivation and receive antiviral treatment (entecavir, tenofovir, or other nucleos[t]ide analogues), HBsAg seroclearance is defined as:
Two consecutive negative HBsAg tests at least 4 weeks apart; and Confirmation by a third negative test at 12 weeks after the first negative test.
The proportion of patients achieving HBsAg seroclearance among those with HBV reactivation will be reported, along with the median time from reactivation to seroclearance.
Measured: Within 36 months after HBV reactivation
Comparison of HBV Reactivation Incidence by Prophylaxis Status
The cumulative incidence of HBV reactivation will be compared between:
Patients receiving antiviral prophylaxis (entecavir, tenofovir, or lamivudine) started at or before conditioning; versus Patients not receiving antiviral prophylaxis.
The analysis will adjust for baseline differences using propensity score matching or multivariable regression. The types, doses, and durations of prophylaxis will be descriptively summarized.
Measured: Within 36 months after allo-HSCT
Overall Survival (OS) and Non-Relapse Mortality (NRM)
Overall Survival: Time from allo-HSCT to death from any cause. Non-Relapse Mortality: Death from any cause other than relapse of the underlying hematologic malignancy. NRM will be estimated using cumulative incidence functions treating relapse as a competing risk.
These outcomes will be compared between patients with and without HBV reactivation.
Measured: At 1, 2, and 3 years after allo-HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2026
- Study start20 Jun 2026 (estimated)
- Primary completion30 Jul 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HBV ReactivationStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
- Target duration
- 3 Years
Sponsor and investigators
- Lead sponsor
- Xiao Hui Zhang
- Sponsor type
- University, hospital or other
- Collaborators
- Xinqiao Hospital of Chongqing, First Affiliated Hospital of Zhejiang University, Tang-Du Hospital, Institute of Hematology & Blood Diseases Hospital, China
- Responsible party
- Sponsor-investigator, Xiao Hui Zhang, Peking University People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07644026
- Sponsor's protocol ID
- HBV-HSCT
- Acronym
- HBV-post HSCT
- Status last verified
- Jun 2026
- First submitted
- 8 Jun 2026
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development and External Validation of a Nomogram for Predicting Hepatitis B Virus Reactivation in HBsAg-Negative/Anti-HBc-Positive Patients Undergoing Allogeneic Haematopoietic Stem Cell Transplantation: A Multicentre Prospective Study
- ClinicalTrials.gov ID
- NCT07644026
- Acronym / sponsor ID
- HBV-post HSCT / HBV-HSCT
- Conditions
- HBV Reactivation, HSCT
- Keywords
- HBV Reactivation, HSCT, A Multicentre Prospective Observational Study
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Xiao Hui ZhangUniversity, hospital or other
- Collaborators
- Xinqiao Hospital of Chongqing, First Affiliated Hospital of Zhejiang University, Tang-Du Hospital, Institute of Hematology & Blood Diseases Hospital, China
- Study start
- 20 Jun 2026 (estimated)
- Primary completion
- 30 Jul 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 12 Jun 2026 (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.
Hepatitis B virus (HBV) reactivation is a serious complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT), particularly in patients with resolved HBV infection (HBsAg-negative, anti-HBc-positive). The incidence ranges from 10% to 40%, and severe reactivation can lead to hepatitis flare, hepatic failure, and death.
Several risk factors have been identified: low recipient anti-HBs titre, donor anti-HBs negativity, recipient age ≥50 years, chronic GVHD, and use of rituximab. However, no validated clinical prediction model exists for this specific population. The only available study (Zhang et al., BBMT 2020) performed risk factor analysis but did not develop a predictive nomogram, and the sample size was limited (only 16 reactivation events). Therefore, we aim to develop and externally validate a robust nomogram using a large multicentre retrospective cohort and then validate its performance in a prospective cohort
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 3 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multicenter prospective observational cohort | – | Other: No Intervention: Observational CohortThis is a multicenter, prospective, observational cohort study. Patients who are HBsAg-negative and anti-HBc-positive prior to allo-HSCT will be enrolled from multiple clinical centers and prospectively followed. Resolved HBV infection will be confirmed by two separate negative HBsAg tests and positive anti-HBc before initiation of conditioning. No investigational intervention is assigned; all participants receive routine clinical care per local practice. Baseline data include demographic characteristics, transplant-related variables (conditioning regimen, donor type, GVHD prophylaxis), recipient and donor HBV serological markers (anti-HBs titre, anti-HBc titre, HBeAg/anti-HBe, HBV DNA). Post-transplant complications (acute and chronic GVHD, CMV reactivation) and subsequent HBV reactivation (defined as reappearance of HBsAg and/or detectable HBV DNA ≥10 IU/mL) will be recorded. All patients will be followed for at least 36 months af |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- he study population will include HBsAg-negative/anti-HBc-positive patients undergoing first allogeneic hematopoietic stem cell transplantation at the participating centers. Patients will be prospectively enrolled before conditioning and followed for subsequent hepatitis B virus (HBV) reactivation (defined as HBsAg reappearance and/or HBV DNA ≥10 IU/mL) and post-transplant outcomes, including hepatitis due to HBV reactivation, hepatic failure, HBV-related mortality, and HBsAg seroclearance after reactivation. Baseline recipient/donor HBV serology (anti-HBs titers, anti-HBc titers), antiviral prophylaxis practice, graft-versus-host disease, and cytomegalovirus reactivation will be collected to describe the incidence, timing, risk factors, and clinical course of HBV reactivation in this high-risk population.
Key inclusion criteria (5 listed)
- Patients must meet all of the following criteria to be enrolled in the study:
- Planned allogeneic HSCT: Scheduled to undergo first allogeneic hematopoietic stem cell transplantation (allo-HSCT) for any hematologic malignancy or non-malignant hematologic disorder. Any donor type is permitted.
- Resolved HBV infection: Documentation of both of the following serological markers on a blood sample collected within 30 days prior to the start of conditioning:
- Hepatitis B surface antigen (HBsAg): negative Antibody to hepatitis B core antigen (anti-HBc): positive Note: Patients may be either positive or negative for anti-HBs at baseline. Willingness to follow protocol-defined monitoring: Patients (or legally authorized representatives) must agree to adhere to the study-specific HBV monitoring schedule as outlined in the protocol.
- Informed consent: Written informed consent obtained from the patient or a legally authorized representative prior to any study-related procedures.
Key exclusion criteria (11 listed)
- Positive serology for hepatitis C virus (HCV) (anti-HCV antibody positive with detectable HCV RNA) Positive serology for hepatitis D virus (HDV) (anti-HDV antibody positive) Positive serology for human immunodeficiency virus (HIV)
- Clinical or histological evidence of liver cirrhosis (METAVIR stage F4, or imaging showing nodular liver surface/splenomegaly/varices) History of hepatic encephalopathy or variceal bleeding History of hepatocellular carcinoma (HCC) Prior solid organ transplantation (including kidney, liver, heart, or lung transplantation).
- Previous allogeneic HSCT (patients receiving a second or subsequent allo-HSCT are excluded; prior autologous HSCT is allowed).
- Active uncontrolled infection at the time of enrollment that, in the opinion of the treating physician, would preclude safe participation.
- Pregnancy or lactation at the time of enrollment. Female patients of childbearing potential must have a negative pregnancy test within 7 days before starting conditioning.
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 |
|---|---|---|
| No Intervention: Observational CohortNo study-specific intervention will be administered. Participants will receive standard clinical care after allo-HSCTaccording to institutional practice and treating physician discretion. This multicenter study will prospectively collect observational data on HBV reactivation and associated clinical outcomes in HBsAg-negative/anti-HBc-positive patients for at least 36 months post-transplant. | Other | Multicenter prospective observational cohort |
Primary outcome
Hepatitis B Virus (HBV) Reactivation
Time frame: Within 36 months after allo-HSCT
HBV reactivation is defined according to the American Association for the Study of Liver Diseases (AASLD) 2018 guidance as the occurrence of any of the following events in patients who are HBsAg-negative/anti-HBc-positive at baseline: Serological reactivation: Reappearance of hepatitis B surface antigen (HBsAg) from negative to positive (confirmed by two consecutive tests at least one week apart); OR Virological reactivation: Reappearance of detectable HBV DNA (≥10 IU/mL) in a patient who had undetectable HBV DNA at baseline; OR Virological flare: In patients with detectable HBV DNA at baseline, an increase in HBV DNA level of ≥10-fold (1 log₁₀ IU/mL) above baseline level, confirmed on two consecutive measurements within a 2-week period. For patients receiving preemptive or prophylactic antiviral therapy, reactivation is defined as above, with the additional requirement that HBV DNA ≥10 IU/mL is confirmed on at least two consecutive measurements to exclude transient low-level dete
6 secondary outcomes
Time to HBV Reactivation
Time frame: From date of allo-HSCT until date of first documented HBV reactivation (as defined in primary outcome), assessed up to 36 months
Hepatitis Due to HBV Reactivation
Time frame: Within 36 months after allo-HSCT
HBV-Related Mortality
Time frame: Within 36 months after allo-HSCT
HBsAg Seroclearance After HBV Reactivation
Time frame: Within 36 months after HBV reactivation
Comparison of HBV Reactivation Incidence by Prophylaxis Status
Time frame: Within 36 months after allo-HSCT
Overall Survival (OS) and Non-Relapse Mortality (NRM)
Time frame: At 1, 2, and 3 years after allo-HSCT
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of HBV Reactivation and HSCT, run by Xiao Hui Zhang.
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 11 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: opening soon, as of the sponsor's last update on 12 Jun 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yun He (+8615201099254, heyun04@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatitis B Virus (HBV) Reactivation (time frame: Within 36 months after allo-HSCT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jun 2026.