Highly Sensitive HBsAg, Anti-HBc and Anti HBsAg Titres in Early Diagnosis of HBV Reactivation in Anti-HBc-Positive Onco-Haematological Patients.

Carlotta Cerva,William Arcese,Ada Bertoli,Elisabetta Teti,Mohammad Alkhatib,Gavin Cloherty,Jeff Gersch,Romina Salpini,Maria Cantonetti,Lorenzo Piermatteo,Loredana Sarmati,Ludovica Ferrari,Campogiani Laura,Massimo Andreoni,Vera Holzmayer,Vincenzo Malagnino,Francesca Ceccherini‐Silberstein ,Mary C Kuhns ,V Svicher ,A Battisti ,Carlo Federico Perno

doi:10.3390/biomedicines10020443

Abstract

The role of novel HBV markers in predicting Hepatitis B virus reactivation (HBV-R) in HBsAg-negative/anti-HBc-positive oncohaematological patients was examined. One hundred and seven HBsAg-negative/anti-HBc-positive oncohaematological patients, receiving anti-HBV prophylaxis for >18 months, were included. At baseline, all patients had undetectable HBV DNA, and 67.3% were anti-HBs positive. HBV-R occurred in 17 (15.9%) patients: 6 during and 11 after the prophylaxis period. At HBV-R, the median (IQR) HBV-DNA was 44 (27–40509) IU/mL, and the alanine aminotransferase upper limit of normal (ULN) was 44% (median (IQR): 81 (49–541) U/L). An anti-HBc > 3 cut-off index (COI) plus anti-HBs persistently/declining to <50 mIU/mL was predictive for HBV-R (OR (95% CI): 9.1 (2.7–30.2); 63% of patients with vs. 15% without this combination experienced HBV-R (p < 0.001)). The detection of highly sensitive (HS) HBsAg and/or HBV-DNA confirmed at >2 time points, also predicts HBV-R (OR (95% CI): 13.8 (3.6–52.6); 50% of positive vs. 7% of negative patients to these markers experienced HBV-R (p = 0.001)). HS-HBs and anti-HBc titration proved to be useful early markers of HBV-R. The use of these markers demonstrated that HBV-R frequently occurs in oncohaematological patients with signs of resolved HBV infection, raising issues of proper HBV-R monitoring.

Highlights

HBsAg-negative/anti-HBc-positive patients with oncohaematological diseases are at high risk of hepatitis B virus reactivation (HBV-R)
This study aims to (i) evaluate the rate of Hepatitis B virus reactivation (HBV-R) in HBsAg-negative/antiHBc-positive oncohaematological patients undergoing antiviral prophylaxis for >18 months; and (ii) define the role of highly sensitive detection of HBsAg (HS-HBs) and quantitative anti-HBc titres in predicting HBV-R in the setting of haematological malignancies
This study shows the occurrence of HBV-R in almost 16% of oncohaematological antiHBc-positive/HBsAg-negative patients

Summary

Introduction

HBsAg-negative/anti-HBc-positive patients with oncohaematological diseases are at high risk of hepatitis B virus reactivation (HBV-R). HBV-R has a negative impact on the clinical course of oncohaematological patients, since it is associated with liver injury and with delayed administration or premature termination of immunosuppressive treatments, contributing to worsening prognosis [1]. For this reason, most international guidelines recommend starting antiviral prophylaxis in oncohaematological patients at high HBV-R risk. HBV-R cases, occurring even several years after the last immunosuppressive therapy, have been frequently reported, in patients undergoing haematological stem cell transplantation (HSCT), as a consequence of deep and long-lasting immunosuppression [6] This highlights the need to better define proper antiviral prophylaxis in this special population

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