HBV Reactivation Prediction Model in Allo-HSCT

NCT07644026 | Not Yet Recruiting DMC

• 1 other identifier: HBV-HSCT
• Study Type: observational
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief 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). 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

Keywords

HBV Reactivation; HSCT; A Multicentre Prospective Observational Study

Outcome Measures

Primary Outcomes (1)

• 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

  Within 36 months after allo-HSCT

Secondary Outcomes (6)

• Time to HBV Reactivation

  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

  Within 36 months after allo-HSCT

• HBV-Related Mortality

  Within 36 months after allo-HSCT

• HBsAg Seroclearance After HBV Reactivation

  Within 36 months after HBV reactivation

• Comparison of HBV Reactivation Incidence by Prophylaxis Status

  Within 36 months after allo-HSCT

Study Arms (1)

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

Other: No Intervention: Observational Cohort

Interventions

No Intervention: Observational Cohort OTHER

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.

Multicenter prospective observational cohort

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• Xiao Hui Zhang: lead
• Xinqiao Hospital of Chongqing: collaborator
• Zhejiang University: collaborator
• Tang-Du Hospital: collaborator
• Institute of Hematology & Blood Diseases Hospital, China: collaborator

Central Study Contacts

Yun He

CONTACT

+8615201099254; heyun04@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 12, 2026
• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: June 12, 2026

Record last verified: 2026-06