Antiviral prophylaxis for hepatitis B virus in COVID-19 patients treated with immunosuppressive drug therapy

To The Editor,

We read with great interest the review on COVID-19 and hepatitis B infection by Alqahtani SA and Buti M [1] underlining the need for screening and possible prophylaxis for HBV in patients with COVID-19 receiving corticosteroids and other immunosuppressive agents.The risk of HBV reactivation in patients with HBV surface antigen (HBsAg)−/HBV core antibody (HBcAb)+ is estimated to be between 1 and 10% if they are taking moderate-dose (10–20 mg prednisone or equivalent) or high dose (>20 mg prednisone daily or equivalent) of corticosteroids daily for >4 weeks [2]. Hepatitis B virus reactivation can occur in HBsAg-negative patients who have only markers of previous exposure to HBV (HBcAb-positive with or without hepatitis B surface antibody [HBsAb]) [3].To investigate retrospectively the incidence of HBV reactivation in HBsAg−/HBcAb+ patients, we reviewed the medical files of 450 patients with Covid-19 admitted at “Annunziata” Hub Hospital, a tertiary care hospital in Cosenza, Italy, between 6 March 2020 and 6 July 2021. Hepatitis B virus virologic indicators were determined at baseline. A total of 60 (34 males and 26 females; median age 69 year, range: 39–87) COVID-19 patients showed evidence of resolved HBV (HBsAg-negative, HBsAb-positive, HBcAb-positive). fifty-five of them patients had at least one comorbidity (most commonly hypertension, diabetes mellitus type 2, and cardiovascular diseases). Forty of the 60 patients met the criteria for severe COVID-19. Five were treated in ICU. Out of these 60 patients, all patients were given corticosteroids, 95 patients received tocilizumab, 40 patients received baricitinib, 30 patients were given anakinra, and 16 patients were treated with canakinumab. Hepatitis B virus virologic indicators were determined at baseline. There were no deaths. They all underwent antiviral prophylaxis with tenofovir disoproxil fumarate, for an average duration of 20 days (14–46 days). They also received antiviral therapy to treat the COVID-19 (remdesivir 50 and lopinavir/ritonavir 10 patients). Ten of those 60 patients had ALT above normal range (i.e. >45 IU/L). In 12 patients with normal values of ALT at the time of admission there was a rise of ALT above normal range during hospitalization. With recovery from COVID-19, liver function gradually returned to baseline. None of the 60 patients with resolved HBV infection developed clinical evidence of HBV reactivation during 3–6 months of follow-up. We did not observe slower SarsCov2 viral clearance in these patients, while patients with higher HBsAb titers developed higher anti-SarsCov2 antibody titers. There were no adverse events attributable to anti HBV viral prophylaxis. Hepatitis B virus reactivation in subjects undergoing immunosuppressive treatment is recognized as a serious clinical problem. Although the risk of HBV reactivation has been estimated to be low in COVID-19 patients [4], the possibility of HBV reactivation associated with the use of immunosuppressive therapies in hospitalized Covid-19 patients should never be underestimated [5–6]. Aldhaleei et al. [7] reported a case of transient HBV reactivation in a 36-year-old patient successfully treated with Entecavir [7]. Authors from Qatar presented the case of a 24-year-old patient who died because of COVID-19 and HBV related fulminant hepatitis [8]. Based on our experience, we suggest that COVID-19 patients with past HBV infection undergoing therapy with corticosteroids and/or other immunosuppressant agents, may benefit from antiviral prophylaxis. We also advocate that careful monitoring of routine HBV virological and liver injury indicators should be carried out in hospitalized patients with COVID-19.