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


From 15th March to 30th April 2020, 600 patients with severe COVID-19 were admitted into our Hospital and were treated with an immune modulator. Data of HBV infection status were available in 490 (81%) patients, 3 of whom (0.6%) were HBsAg positive and 69 (14%) were HBsAg negative/anti-HBc positive (Figure 1). As expected in our geographical area, the prevalence of anti-HBc increased with age and was higher than 15% in individuals over 60 years (Figure S1).

Figure 1.

Flow chart of the study

Among the 69 patients with isolated anti-HBc, eight died during the admission and follow-up was not available. Thus, the final study cohort consisted in 61 HBsAg-negative/anti-HBc-positive patients. Their baseline features are depicted in Table 1: 72% were men, median age 67 (59–75) years, the most frequent comorbidities were arterial hypertension (62%), diabetes mellitus (36%) and dyslipidemia (33%). Fifty-three (87%) patients had abnormal ALT levels, 35 (57%) with values three times above the ULN. Regarding HBV infection markers, 44 (72%) of the 61 patients were anti-HBs positive. The most frequently used immunosuppressant drug was tocilizumab (72%); 7 (11%) patients had received a second drug (anakinra). Twenty-five patients (41%) received high doses of steroids (methylprednisolone 250 mg/d for 3 days) alone (n = 5) or in combination with other immune modulators (n = 20). Twenty-two patients (36%) received 0.5 mg/kg/d of prednisone for 1 month or longer due to suspected organizing pneumonia; 15 of them had undergone high-dose steroid therapy (Table 1).

Thirty-eight (62%) patients received entecavir prophylaxis, and 23 (38%) did not (Figure 1). Although the hospital protocol recommended NUC prophylaxis for anti-HBc-positive patients undergoing immune modulator treatments, the decision to indicate HBV prophylaxis depended on the treating physician. As shown in Table 1, relevant baseline features of both groups (prophylaxis/no prophylaxis) were similar regarding age, gender, presence of comorbidities, immune modulator regimen and laboratory tests. After being discharged, 19 (31%) patients were transferred to a nursing home or rehabilitation centre for continuing their recovery; the proportion was similar in patients who did or did not receive entecavir prophylaxis.

Follow-up data after hospital discharge were available in 57 (93%) of the 61 patients (4 patients were lost after discharge). Among these 57 patients, we did not identify a single case of HBsAg seroreversion (positive HBsAg), and we only detected two cases of positive HBV-DNA. In both, HBV viral load was below the quantification limit (<10 IU/mL). None of these two patients had undergone entecavir prophylaxis, and both were negative for anti-HBs. One case (male, 77 years old) had received siltuximab and methylprednisolone 250 mg/d (3 days) followed by prednisone 0.5 mg/kg due to suspected organizing pneumonia, whereas the second case (male, 64 years old) was treated with a single dose of tocilizumab.

Concerning aminotransferase elevations, the proportion of patients with abnormal ALT levels (above the ULN) decreased from 87% (peak during hospitalization) to only 35% at follow-up (4% with ALT values three times above ULN). ALT values were within the normal range in the 2 individuals with detectable HBV-DNA.

Regarding the three HBsAg-positive patients, two had positive HBV-DNA (109 IU/mL and 15 IU/mL, respectively) whereas one patient (who was coinfected with HIV undergoing tenofovir therapy) had undetectable HBV-DNA. Entecavir prophylaxis was initiated in the two patients with positive HBV-DNA, and they are currently followed at our liver clinic.