HBV Reactivation Prediction Model in Allo-HSCT

N/ANot Yet RecruitingNCT07644026

Xiao Hui Zhang300 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

300

Conditions

HBV Reactivation HSCT

Interventions

No Intervention: Observational Cohort

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

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

Time frame: Within 36 months after allo-HSCT

Secondary Outcomes

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.

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

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: At 1, 2, and 3 years after allo-HSCT

HBV Reactivation Prediction Model in Allo-HSCT

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts