Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders

ABSTRACT

Introduction: Targeted therapies have gained popularity in the treatment of several oncologic and immune-mediated diseases. Immunosuppression caused by these drugs has been associated to reactivation of hepatitis B virus (HBV) in both hepatitis B surface antigen (HBsAg) positive patients (overt infection) and HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive carriers (resolved infection), leading to premature discontinuation of therapy and potentially fatal hepatitis.

Areas covered: This review summarizes the evidence of HBV reactivation in patients with overt or resolved HBV infection undergoing targeted therapies for cancer or immune-mediated disorders, providing recommendations for the management of these patients.

Expert opinion: The risk of HBV reactivation relies on the immunosuppressive potency and duration of these therapies, the underlying disease and the virological patient’s profile. However, HBV reactivation is preventable by screening for HBV markers in all patients scheduled to receive targeted therapies, assessing the virological profile and patient’s clinical state, followed by appropriate antiviral treatment or prophylaxis in those patients at high risk of HBV reactivation. Close monitoring of HBV carriers at low risk of reactivation is warranted with the aim to start antiviral therapy as soon as HBV reactivates.

KEYWORDS:

• Anti-TNF-α
• antiviral therapy
• biological therapy
• cancer
• hepatitis B reactivation
• monoclonal antibodies
• rituximab
• targeted therapy

Article highlights

• Targeted therapies are increasingly popular for the treatment of several oncologic and immune-mediated diseases. However, HBV reactivation may occur with a wide variety of immunosuppressive therapies in benign or malignant disease both in patients with overt and resolved infection.

• HBV reactivation may induce not only premature discontinuation of targeted therapies and progression of the underlying disease but, more importantly, potentially fulminant and even fatal hepatitis. However, this complication is preventable by screening for HBV markers (HBsAg, anti-HBc, anti-HBs) all patients scheduled to receive these therapies and by referring those with overt or resolved infection for the proper management.

• Long-term anti-HBV therapy with ETV or TDF is recommended in all active HBV carriers in need of targeted therapies.

• All inactive carriers undergoing targeted therapies for cancer or immune-mediate disorders must undergo anti-HBV prophylaxis. For most of these carriers, LMV for at least 12/18 months after completion of immunosuppressive therapy is the recommended strategy. By converse, for inactive carriers who receive RTX plus other combination therapies with or without high doses of steroids, those with onco-hematological diseases, those for whom long-term biologic therapy can be anticipated or whenever regular HBV DNA monitoring cannot be implemented, ETV or TDF should be preferred.

• Patients with resolved HBV infection receiving RTX, BOR or Carfilzomib for onco-hematological disease both the ‘anti-HBV prophylaxis’ with LMV for at least 12/18 months after the end of chemotherapy or the ‘pre-emptive anti-HBV therapy’ with ETV could be recommended, whereas for all the other settings at low risk of reactivation the ‘pre-emptive anti-HBV therapy’ is the best strategy.

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Declaration of interest

P Lampertico has received funding for participation in speaking bureaus and advisory boards for Bristol-Myers Squibb, Roche, Gilead, MSD and GlaxoSmithKline. M Viganò has received funding for speaking and teaching from Roche, Gilead and Bristol-Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.