Abstract

Reactivation of overt or occult HBV infection (HBVr) is a well-known, potentially life-threatening event which can occur during the course of immunosuppressive treatments. Although it has been described mainly in subjects receiving therapy for oncological or hematological diseases, the increasing use of immunosuppressant agents in non-oncological patients observed in recent years has raised concerns about the risk of reactivation in several other settings. However, few data can be found in the literature on the occurrence of HBVr in these populations, and few clear recommendations on its management have been defined. The present paper was written to provide an overview of the risk of HBV reactivation in non-neoplastic patients treated with immunosuppressive drugs, particularly for rheumatological, gastrointestinal, dermatological and neurological diseases, and for COVID-19 patients receiving immunomodulating agents; and to discuss the potential strategies for prevention and treatment of HBVr in these settings.

Highlights

  • Hepatitis B virus (HBV) represents one of the most important threats for public health.According to the WHO estimates, approximately 3.5% of the global population was living with a chronic HBV infection in 2015, and about 900,000 people died during the same year from HBV-related cirrhosis or hepatocellular carcinoma [1]

  • As a systematic review recently published by our group estimated a prevalence of occultHBV infection” (OBI) in Western countries ranging from 19% to 51% [4], and considering the incidence of immunosuppressive diseases and/or the use of immunosuppressive treatments, the risk of HBV reactivation (HBVr) has become high

  • As previously described, after the HBsAg clearance, the viral genome can still remain detectable in the liver or plasma, defining the “HBsAg-negative phase” or “occult B infection”; several data suggest that the persistence of low-level replication in patients with occult infections can contribute to the advancement of liver fibrosis and the development of hepatocellular cancer in patients with other etiologies of liver disease, hepatitis C virus (HCV) infections [13,14]

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Summary

Introduction

Hepatitis B virus (HBV) represents one of the most important threats for public health. The increasing use of immunosuppressive treatments has led to a growing incidence of HBV reactivation (HBVr) in patients with overt or occult infection [3]. Life-threatening reactivation episodes have frequently been described in subjects undergoing immune suppression for oncological or hematological diseases [5,6]; little is known about the risk of HBVr in patients treated with immunosuppressants in other settings, such as rheumatological, gastroenterological, neurological, or dermatological diseases, and most recently for SARS-CoV-2 pneumonia. The present paper was written to provide an overview of the risk of reactivation of HBV infection in non-oncological and non-hematological settings, and to discuss the strategies for preventing and treating these life-threatening events

Epidemiology of HBV Infection
Natural History of HBV Infection
HBV Reactivation following Immunosuppressive Treatments
Strategies for the Prevention and Treatment of HBV Reactivation
Risk of HBV Reactivation in Gastroenterological Diseases
Risk of HBV Reactivation in Dermatological Diseases
Risk of Reactivation in Rheumatological Diseases
Risk of HBV Reactivation in Neurological Diseases
Study Design
Conversion of serum HBV DNA results from negative to positive
Increase in HBV DNA
Risk of HBV Reactivation in COVID-19 Patients
Findings
Conclusions

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