A Comprehensive Narrative Review on the Underlying Mechanisms Diagnosis and Updated Guidelines for Managing Hepatitis B Virus Reactivation during Immunosuppressive Therapy

Abstract

This narrative review aimed to examine the underlying mechanisms of HBV reactivation, identify major risk factors, and review current strategies for diagnosis, risk stratification, antiviral prophylaxis, monitoring, and management. Literature searches were conducted through PubMed/MEDLINE and Google Scholar using terms related to HBV, HBV reactivation, immunosuppressive therapy, diagnosis, prophylaxis, monitoring, chemotherapy, B-cell-depleting therapy, hematopoietic stem cell transplantation, and newer immunomodulatory agents. Original studies, observational studies, systematic reviews, meta-analyses, guidelines, consensus statements, and relevant clinical reviews were considered, with emphasis on recent evidence. The reviewed evidence indicates that HBV reactivation results from impaired immune control, allowing renewed viral replication from persistent HBV reservoirs, followed in some cases by hepatitis during immune restoration. Risk varies according to HBV serological status, baseline viral activity, underlying disease, and the type and intensity of immunosuppression, with particularly high risk associated with B-cell-depleting therapies and hematopoietic stem cell transplantation. Diagnosis requires assessment of HBsAg, anti-HBc, HBV DNA, alanine aminotransferase, and clinical findings before and during therapy. Current evidence supports risk-based antiviral prophylaxis with potent nucleos(t)ide analogues, particularly entecavir or tenofovir, while selected lower-risk patients may undergo regular monitoring. Updated EASL and AGA guidelines provide guidance for screening, prophylaxis, and post-treatment monitoring, although uncertainty remains for several newer immunomodulatory therapies. Individualized risk assessment and continued surveillance are essential to reduce HBV reactivation-related morbidity and mortality.