Document Type

Conference Proceeding

Publication Date

5-1-2026

Abstract

Hepatitis B virus (HBV) reactivation remains a critical concern in immunosuppressed oncology and hematopoietic stem cell transplant (HSCT) patients, yet the optimal duration of antiviral prophylaxis is unresolved. Current guidelines recommend 12–18 months of prophylaxis after HSCT or B-cell depleting therapy for patients who are isolated anti-HBc positive, based on documented cases of late reactivation beyond the traditional 12-month threshold. However, these recommendations largely derive from studies in HBsAg-positive patients or those receiving rituximab-containing regimens, with limited data addressing the broader range of high-risk scenarios encountered in practice. We present two vignettes highlighting this gap. Patient 1 is a 60-year-old woman with relapsed follicular non-Hodgkin’s lymphoma who underwent haploidentical PBSCT in May 2018. Pretransplant evaluation revealed isolated anti-HBc positivity with low-level anti-HBs, but negative HBV PCR and surface antigen. Infectious disease consultation recommended monitoring rather than prophylaxis. She remained clinically stable posttransplant, without GVHD or hepatic complications, though she developed chronic digital neuropathy and finger erythema. In October 2024, routine labs for a life insurance application revealed HBV viremia with a PCR of 496 million copies, despite being asymptomatic and off immunosuppression for over five years. Entecavir was initiated, and her viral load gradually declined over 14 months but remained detectable (~4000 copies). Patient 2 is a 68-year-old man with EBV-positive refractory diffuse large B-cell lymphoma involving the bowel, rectum, spleen, and pelvic nodes. He experienced multiple infectious complications requiring antibiotics, colostomy, and nephrostomy tubes. After failing R-CHOP, he enrolled in a trial with epcoritamab plus GDP chemotherapy. Screening revealed isolated anti-HBc positivity with low-level anti-HBs (27 copies), and he was started on Entecavir prophylaxis. Following additional therapy with loncastuximab tesirine, he achieved complete remission by August 2024. Entecavir was discontinued in November 2024, one year after his last rituximab dose. He remained well until fall 2025, when mild transaminitis (ALT/AST ~120) prompted evaluation revealing HBV reactivation with viremia (peak 18,700 copies), surface antigenemia, and positive HBeAg. Entecavir was restarted, leading to gradual viral decline, though HBV DNA remained detectable (136 copies after three months). These cases underscore the risk of late HBV reactivation in HSCT and lymphoma patients, even years after transplant or beyond standard prophylaxis duration. AASLD guidelines recommending 12–18 months of prophylaxis for anti-HBc positive patients may be insufficient, as reactivation has been documented up to 75 months post-HSCT. The first patient’s reactivation six years posttransplant without prophylaxis, and the second patient’s relapse after discontinuation at 12 months, highlight the limitations of fixed-duration strategies. Recent ECIL-9 guidelines advocate indefinite monitoring rather than arbitrary cessation of prophylaxis. Specifically, monthly then quarterly HBV DNA surveillance when prophylaxis is discontinued in anti-HBc positive patients, acknowledging the ongoing risk. This represents a paradigm shift from time-based to risk-based management. A personalized, risk-stratified approach is needed, incorporating factors such as anti-HBs levels, type and intensity of immunosuppression, GVHD status, and time since last immunosuppressive exposure to guide prophylaxis duration and monitoring frequency. These vignettes illustrate the importance of individualized strategies to prevent late HBV reactivation in vulnerable populations.

Comments

American College of Physicians Michigan Chapter and Society of Hospital Medicine Michigan Chapter 2026 Resident and Medical Student Day, May 1, 2026, Troy, MI

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