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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 300
Study Overview
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
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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).
Investigators
Xiao Hui Zhang
Professor
Peking University People's Hospital