Low risk of hepatitis B reactivation in patients with severe COVID-19 who receive immunosuppressive therapy

J Viral Hepat. 2021 Jan;28(1):89-94. doi: 10.1111/jvh.13410. Epub 2020 Oct 12.


A significant proportion of patients infected with SARS-CoV-2 develop severe respiratory symptoms due to an excessive immune response. Treatment of this condition may include immunosuppressive therapies, such as IL-6 receptor antagonists and corticosteroids, which pose a risk for patients with active or past hepatitis B virus (HBV) infection. In this prospective cohort study, we analysed the risk of HBV reactivation in patients with severe COVID-19 and resolved HBV infection undergoing immunosuppressive therapy. From 15th March to 30th April 2020, 600 patients with severe COVID-19 were admitted to our hospital and treated with immune modulators. Data regarding HBV infection were available in 484, of whom 69 (14%) were HBsAg negative/anti-HBc positive. For these patients, HBV reactivation prophylaxis with entecavir was strongly recommended. Complete follow-up was available in 61 patients: 72% were male, median age was 67 years, and anti-HBs was >10 IU/mL in 72%. The immunosuppressive drug most used was tocilizumab (72%). Despite HBV prophylaxis recommendation, 38 (62%) patients received entecavir and 23 (38%) did not. Baseline features of both groups were similar. At follow-up, we found no cases of HBsAg seroreversion and only 2 (3%) patients (no prophylaxis group) had detectable serum HBV-DNA (<15 IU/mL). Both were anti-HBs negative and had normal aminotransferase levels. Our data show that the risk of HBV reactivation in patients with severe COVID-19 and resolved HBV infection undergoing immunosuppressive treatment is low. However, if a systematic follow-up after hospital discharge is unfeasible in patients without anti-HBs, a short course of antiviral prophylaxis may be a safe option.

Keywords: COVID-19; hepatitis B; immunotherapy; reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiviral Agents / therapeutic use
  • COVID-19 / complications
  • COVID-19 Drug Treatment*
  • DNA, Viral / blood
  • Female
  • Hepatitis B / complications
  • Hepatitis B / prevention & control
  • Hepatitis B / virology*
  • Hepatitis B Antibodies / blood
  • Hepatitis B Core Antigens / immunology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / immunology
  • Hepatitis B virus / physiology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk
  • SARS-CoV-2
  • Virus Activation / drug effects*


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Immunosuppressive Agents