A snapshot of virological presentation and outcome of immunosuppression‐driven HBV reactivation from real clinical practice: Evidence of a relevant risk of death and evolution from silent to chronic infection

Abstract

The study was undertaken in order to provide a snapshot from real clinical practice of virological presentation and outcome of patients developing immunosuppression‐driven HBV reactivation. Seventy patients with HBV reactivation were included (66.2% treated with rituximab, 10% with corticosteroids and 23.8% with other immunosuppressive drugs). Following HBV reactivation, patients received anti‐HBV treatment for a median (IQR) follow‐up of 31(13‐47) months. At baseline‐screening, 72.9% of patients were HBsAg‐negative and 27.1% HBsAg‐positive. About 71.4% had a diagnosis of biochemical reactivation [median (IQR) HBV DNA and ALT: 6.9 (5.4‐7.8) log IU/mL and 359 (102‐775) U/L]. Moreover, 10% of patients died from hepatic failure. Antiviral prophylaxis was documented in 57.9% and 15.7% of HBsAg‐positive and HBsAg‐negative patients at baseline‐screening (median [IQR] prophylaxis duration: 24[15‐33] and 25[17‐36] months, respectively). Notably, HBV reactivation occurred 2‐24 months after completing the recommended course of anti‐HBV prophylaxis in 35.3% of patients. By analysing treatment outcome, the cumulative probability of ALT normalization and of virological suppression was 97% and 69%, respectively. Nevertheless, in patients negative to HBsAg at baseline‐screening, only 27% returned to HBsAg‐negative status during prolonged follow‐up, suggesting the establishment of chronic infection. In conclusion, most patients received a diagnosis of HBV reactivation accompanied by high ALT and 10% died for hepatic failure, supporting the importance of strict monitoring for an early HBV reactivation diagnosis. Furthermore, HBV reactivation correlates with high risk of HBV chronicity in patients negative for HBsAg at baseline‐screening, converting a silent into a chronic infection, requiring long‐term antiviral treatment. Finally, a relevant proportion of patients experienced HBV reactivation after completing the recommended course of anti‐HBV prophylaxis, suggesting the need to reconsider proper duration of prophylaxis particularly in profound immunosuppression.

Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure

“…HBV reactivation under immunosuppression is becoming an increasingly important issue, as more and more patients are treated with immunosuppressive regimens. Its clinical manifestation can vary from asymptomatic hepatitis to ALF with fatal outcome [2,4]. The aim of our study was to investigate viral and host factors potentially contributing to ALF in patients with HBV reactivation.…”

“…Furthermore, patients with low replicative HBV infection at baseline had an increased risk of developing ALF compared to all other patients. This may be associated with pre-existing liver damage due to HBV in patients with detectable HBsAg at baseline, although in a previous study the percentage of severe/fulminant hepatitis in at baseline HBsAg− and HBsAg+ patients were comparable [22] and in another HBsAg- patients had a greater risk for ALF [4].…”

“…The clinical manifestation of HBV reactivation ranges from asymptomatic to acute liver failure (ALF). Its outcome may be immunological control or persistence of HBV infection [2,4]. HBV reactivation can be divided into three phases as described by Hoofnagle [5]: Firstly, the reappearance of HBsAg or HBV DNA in the serum of previously HBsAg-negative patients or an increase in HBV DNA serum levels in HBsAg-positive patients can be observed.…”

A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition In Vitro

“…In our previous studies, we have analyzed the genetic characteristics of HBV variants in patients experiencing immunosuppression-driven HBV reactivation, highlighting the role of HBsAg genetic variability in its promotion. Furthermore, we have reported the evidence of a peculiar enrichment of HBsAg immune-escape mutations in the setting of HBV reactivation [6,7]. Indeed, immune-escape mutations can affect the structure and the antigenicity of HBsAg, thus contributing to HBV reuptake in the setting of a suboptimal immune system control [8].…”

Hematological Malignancies and HBV Reactivation Risk: Suggestions for Clinical Management

“…These mutants might then go undetected and HBVr unnoticed by common monitoring strategies, during and after immunosuppressive treatments. A specific immune-escape mutation has recently been detected, whose presence significantly correlates with the use of RAb, suggesting that the grade of immunosuppression mediated by powerful drugs, such as the anti-CD-20 group, might progressively weaken the humoral response and favor the emergence of mutant species capable to evade antibodies [79].…”