Low Risk of Hepatitis B Reactivation in Patients With Severe COVID-19 Who Receive Immunosuppressive Therapy

Sergio Rodríguez-Tajes; Anna Miralpeix; Josep Costa; Ester López-Suñé; Montserrat Laguno; Anna Pocurull; Sabela Lens; Zoe Mariño; Xavier Forns


J Viral Hepat. 2020;28(1):89-94. 

In This Article

Patients and Methods

This is a prospective cohort study conducted in a single centre (Hospital Clínic of Barcelona). All patients admitted to our centre from 15th March to 30th April 2020 with a diagnosis of COVID-19 who had an indication for immune modulatory therapy were tested for markers of present (HBsAg) or past (anti-HBc) hepatitis B virus infection. HBsAg- or anti-HBc-positive patients were included in the study.

The following drugs were considered as immunosuppressive therapy: (a) interleukin-6 receptor antagonists (tocilizumab, siltuximab); (b) interleukin-1 receptor antagonists (anakinra); (c) Janus kinase inhibitors (baricitinib); and (d) high-dose corticosteroids. Tocilizumab was administered in a single dose of 400 mg (600 mg if weight >75 kg); some patients received a second dose within the next 24 hours if there was an unfavourable clinical course. Siltuximab was administered as a single dose of 800 mg. Anakinra was administered at a dose of 200 mg/12 h the first day and 200 mg/d the following 2 days. Baricitinib was administered at a dose of 4 mg/d for 3 days. Regarding corticosteroid therapy, methylprednisolone was dosed at 250 mg/d for 3 days, followed by 30 mg/d for a week. In patients with suspected organizing pneumonia, treatment with prednisone 0.5 mg/kg/d was initiated and extended for at least 1 month.

Due to the complex and rapidly evolving situation during the pandemic's peak, the immunosuppressive treatment regimen was decided according to the physicians' criteria, availability of drugs at the time of admission, or based on inclusion in ongoing clinical trials.

HBV Reactivation Prophylaxis

Hepatitis B virus reactivation prophylaxis was mandatory for HBsAg-positive patients and strongly recommended for those who were HBsAg-negative/anti-HBc-positive (independently of their anti-HBs status). For HBsAg-positive patients, we indicated entecavir 0.5 mg/d for at least 6 months. For patients with isolated positive anti-HBc markers, entecavir 0.5 mg/d was administered for 1 month. Doses of entecavir were adjusted if renal failure was present according to label.

For HBsAg-negative/anti-HBc-positive patients, HBV reactivation was defined as: (a) detectable HBV-DNA or (b) reverse HBsAg seroconversion (reappearance of HBsAg).[9]


Between 1 and 2 months after the last dose of the immune modulator therapy, all HBsAg-positive or HBsAg-negative/anti-HBc-positive patients at hospital admission underwent a blood test including liver enzymes and HBV infection markers (HBsAg, HBeAg, anti-HBe, anti-HBc, anti-HBs and HBV viral load). HBsAg, HBeAg, anti-HBc, anti-HBe and anti-HBs were determined by Atellica (Siemens); HBV-DNA was determined by real-time PCR with a lower limit of quantification of 10 and a lower limit of detection of 3 IU/mL (Cobas-HBV; Roche).


The study was approved by the Hospital Ethics Committee. All patients gave oral consent to participate in the study. Once patients were discharged from the centre, a written informed consent form was provided to all patients in order to obtain their signature.