Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported.

A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d.

COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.

Hepatitis B virus (HBV) reactivation occurs primarily when body immunity declines due to the use of chemotherapy, long-term glucocorticoids, or immunosuppressive therapy[1]. Coronavirus disease 2019 (COVID-19) is an emerging global viral infectious disease. The pathogenesis of COVID-19 is still unclear[2]. Whether HBV reactivation occurs in COVID-19 patients has not yet been reported.

COVID-19 and hepatitis B virus infection.

After admission, the patient was treated with recombinant interferon-alpha-2b and lopinavir/ritonavir. Following this, he was treated with methylprednisolone (40 mg once daily). His lymphocyte count continued its downtrend to 0.89 × 10⁹/L, CD4+ T cells further declined to 27.14%, and liver enzymes ALT and AST showed no significant changes. HBV DNA was increased to 1.11 × 10² IU/mL, although it was actually negative before this admission (Figure 1). Hence, tenofovir fumarate was added for possible HBV reactivation.

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Figure 1 Time-course of CD4+ T cells, lymphocyte count, alanine aminotransferase, aspartate transaminase, and hepatitis B virus DNA. A: CD4+ T cells, lymphocyte count, and hepatitis B virus (HBV) DNA; B: Alanine aminotransferase, aspartate transaminase, and HBV DNA. ALT: Alanine aminotransferase; AST: Aspartate transaminase; HBV: Hepatitis B virus.

The patient started to be afebrile, and liver enzymes ALT and AST decreased to 42 U/L and 17 U/L, respectively. The nucleic acid test for COVID-19 became negative twice then. HBV DNA became lower than the detection limit (30 IU/mL). HBV drug resistance gene of the HBV P region was negative too. Then, the patient was discharged. Both liver enzymes and HBV DNA were within normal range after discharge from hospital.

As we know, unstandardized administration of nucleos(t)ide analog, glucocorticoids, chemotherapy drugs, and new biological agents such as monoclonal antibodies and antiviral drugs of hepatitis B virus can cause HBV reactivation[1]. This patient had used adefovir dipivoxil and entecavir for antiviral therapy for a long time. His HBV DNA was negative before the development of COVID-19. He had elevated liver enzymes and increased HBV DNA during the treatment of COVID-19. Thus, according to American Association for the Study of Liver Diseases guideline about the definition of HBV reactivation, he met the criteria for HBV reactivation. Besides, the long term usage of antiviral drugs that may cause HBV resistance to NAs is also possible[3]. However, his HBV resistance gene was tested and negative for entecavir and adefovir dipivoxil. Noncompliance is another reason that causes HBV reactivation[3], but our patient was followed in the clinic regularly, and he did not discontinue or reduce dose without physician’s advice. Therefore, it could be possible that HBV reactivation in this patient was caused by COVID-19 or related treatment. The mechanism of HBV reactivation is not yet fully understood. Once the immune homeostasis between the virus and the body is disturbed, HBV reactivation may occur[4]. Previous studies have shown that COVID-19 patients may have impaired immune function and lower lymphocyte count, especially CD4+ T lymphocytes[2]. And glucocorticoid usage may decrease cellular immune function sharply. As a novel infectious disease, the pathogenesis of COVID-19 is yet unclear. This is the first case report of COVID-19 complicated with HBV reactivation.

For COVID-19 patients complicated with hepatitis B, HBV reactivation may happen, and glucocorticoids need to be used cautiously.