HBV Reactivation in Patients with Past Infection Affected by Non-Hodgkin Lymphoma and Treated with Anti-CD20 Antibody Based Immuno-Chemotherapy: A Multicenter Experience.

Michele Clerico,Veronica Peri,Simone Ferrero,Gabriele De Luca,Barbara Botto,Alfredo Marzano,Marcella Battaglini,Federica Cavallo,Vittorio Ruggero Zilioli,Simone Ragaini,Francesco Merli,Wael Al Essa,Loretta Cervi,Paola Ghione,Irene Dogliotti,Daniele Grimaldi

doi:10.3390/jpm12020285

Abstract

Hepatitis B virus reactivation (HBVr) can develop in HBV surface antigen (HBsAg) positive or HBsAg-negative and anti-hepatitis B core antigen antibodies (anti-HBc) positive (past HBV infection) patients receiving immuno-chemotherapy for hematological malignancies. A higher rate of HBVr is associated with the use of rituximab (R) in patients with past HBV infection, thus justifying an antiviral prophylaxis. In this study we evaluated the incidence of HBVr in a real-life cohort of 362 anti-HBc-positive subjects affected by non-Hodgkin lymphoma (NHL), mainly receiving lamivudine (LAM) prophylaxis (93%) and all undergoing a R-containing regimen. A retrospective, multicenter, observational study was conducted in 4 Italian Hematology Departments. The primary endpoint was the incidence of virologic (HBV DNA-positive), serologic (HBsAg-positive) and clinical (ALT increase > 3 × upper limit of normal) HBVr, which occurred in five, four and one patients, respectively, with a total HBVr rate of 1.4%. None of them had to discontinue the chemotherapy program, while two patients required a delay. Treatment-related adverse events (AEs) were reported during LAM prophylaxis in three patients (0.9%). In conclusion, this study confirms the efficacy and safety of LAM prophylaxis in anti-HBc-positive patients undergoing R-containing regimens.

Highlights

Despite that the prevalence of hepatitis B virus (HBV) infection has been globally decreasing during the last decades due to vaccination programs and effective treatments, it remains a major public health issue worldwide [1–3]: it is estimated that more than 240 millions people are chronic HBV surface antigen (HBsAg) carriers and at least two billions show hepatitis B core antigen antibodies, with large regional variations [4].In particular, in the past infection group, patients who require deep immunosuppressive therapy are at risk of virus reactivation, with different possible scenarios, ranging from serum HBV-DNA detection in asymptomatic patients to potentially fatal hepatitis and liver failure [5]
All patients were studied for HBV and hepatitis C virus (HCV) serology
These lasts were not included because the study was aimed to potential occult B infection and not to overt occult B infection (OBI) carriers (HBV DNA-positive)

Summary

Introduction

In the past infection group, patients who require deep immunosuppressive therapy are at risk of virus reactivation, with different possible scenarios, ranging from serum HBV-DNA detection in asymptomatic patients to potentially fatal hepatitis and liver failure [5]. This event was reported in patients receiving immuno-chemotherapy protocols for hematological malignancies or undergoing hematopoietic stem cells transplantation (HSCT) [6–11]. In this context, the highest rates of reactivation are associated with the use of rituximab (R), an anti-CD20 monoclonal antibody widely used against lymphoproliferative disorders [8,10,12,13]. The European Association for the Study of Liver (EASL) Clinical Practice Guidelines (2017) and the recent American Society of Clinical

Objectives

Methods

Results

Discussion

Conclusion