Hepatitis B Virus (HBV) Reactivation In Anti-HB Core Antigen (anti-HBc) Positive Patients with Hematological Malignancies: A Prospective Multicenter Study
Authors: Basso Maria , Hohaus Stefan , Bosco Giulia , Grieco Antonio , Laurenti Luca , Mansueto Giovanna , Pagano Livio , Rapaccini G. Lodovico , Sica Simona , Farina Giuliana , Valentini Giovanna , D'Andrea Mariella , Morrone Aldo , Nosotti Lorenzo , Paviglianiti A. , Petti Maria Concetta , Annino Luciana , Cortese S. , Fenu Susanna , Leone Giuseppe , Pompili Maurizio 
Published: October 2019

Abstract
Abstract 4911
Patients with haematological malignancies and overt hepatitis B (HB) infection defined by the presence of HB surface antigen (HBsAg) are at risk of hepatitis reactivation, and antiviral prophylaxis is generally recommended. HBV reactivation can also occur during immunosuppressive therapy in patients who are HBsAg negative, but are positive for antibodies to HB core antigen (anti-HBc) which suggests prior contact with HBV and potential occult infection. The risk of HBV reactivation for these patients who have evidence of viral clearance (HBV-DNA negative) and developed potential immunity (anti-HBs positive) is not clear, and there are no clear guidelines for prophylaxis in this subset of patients. We therefore performed a multicenter prospective observational study to determine the risk of HBV seroreversion in anti-HBc positive patients with or without anti-HBs and with hematological malignancies undergoing intensive immunosuppressive chemotherapy and/or hematopoietic stem cell transplantation (HSCT). Patients underwent monitoring of HBV serum markers including HBV-DNA serum levels, while patients who started antiviral prophylaxis concomitant to the cytotoxic therapy were excluded. Between 1/2008 and 12/2008, 25 consecutive HBsAg -/antiHBc +/antiHBs + patients (pts) from 3 hematological centers were enrolled into the study (20 pts with lymphoma, 2 pts with acute myeloid leukaemia, 3 with myeloma). Before starting anticancer therapy, all pts had undetectable HBV-DNA levels, 21 were anti-HBs positive, and 12 had also anti-HBe. Moreover, 3 pts had HCV co-infection. All patients underwent intense immunosuppressive therapy including rituximab in 15 pts, and HSCT in 10 pts (7 autologous and 3 allogeneic). HBV markers were monitored during immunosuppressive treatment and for 18 months after end of therapy. At present, 18 pts have completed the planned follow-up period, and other 7 pts have at least 12 months of post-treatment follow-up. Among the 25 patients, we observed 3 cases of seroreversion with positive HBV-DNA levels. All 3 seroversions occurred in patients following allogeneic HSCT despite high anti-HBs levels at baseline. The 3 seroreverted patients showed a progressive decline in anti-HBs titers during the phase of monitoring, and HBV reactivated between the 7th and 9th month after allogeneic HSCT. The pts responded to treatment with antinucleoside analogues (entecavir in 2 cases, lamivudine in 1 case), i.e. HBV-DNA decreased of at least 1 log within three months from treatment start. Moreover, we detected one case of transient anti-HBs disappearance, and one case of persistent anti-HBe loss without seroreversion. None of the HCV co-infected pts presented acute hepatitis. No seroreversions were observed in 15 lymphoma patients undergoing immunochemotherapy including rituximab. In conclusion, patients with occult HBV infection are at risk of HBV reactivation during continuous immunosuppressive therapy following allogeneic HSCT even in the presence of anti-HBs levels at baseline, while the risk appears low in patients undergoing transient immunosuppressive therapy, as immunochemotherapy including rituximab, for the treatment of lymphoma.

Disclosures:
No relevant conflicts of interest to declare.