Abstract

Introduction: Tocilizumab (TCZ) is an interleukin 6 (IL-6) receptor inhibitor well known as an immunomodulatory agent used in rheumatic disease that has currently gained greater relevance as an investigational agent in SARS-COV-2 patients. TCZ results in a profound immunosuppressive state, impairing the IL-6 physiologic effects in protective processes such as the HBV infection clearance, HBV replication suppression, and prevention of the accumulation of HBV covalently. We present a case of TCZ-associated HBV reactivation with acute hepatitis in a patient with SARS-COV-2 disease. Case Description/Methods: A 55-year-old Vietnamese man with a history of inactive chronic hepatitis B since childbirth presented in view of progressive shortness of breath. He was diagnosed with SARS-COV-2, placed on supplemental oxygen with no favorable clinical response. The patient was subsequently admitted to the intensive care unit and started in high-flow ventilation, dexamethasone, and apixaban in view of acute respiratory disease syndrome. He received convalescent plasma with no improvement. Therefore, a trial of TCZ was given. The patient gradually showed signs of respiratory and functional status improvement. Supplemental oxygen was de-escalated to a nasal cannula and the patient was discharged to acute rehabilitation. Laboratory workup after discharge revealed elevated liver tests with normal bilirubin and INR. HBV panel showed a rise in the DNA levels to 10 million IU/ml (table 1). Serologies for viral hepatitis were negative (Table 1). Imaging ruled out hepatocellular carcinoma but showed cirrhosis. The patient was started on Tenofovir with gradual improvement in liver enzymes and reduction in HBV viral load >1 log (figure 1). Discussion: TCZ interferes with IL-6 which plays a protective role in the HBV infection with inversely proportional disease severity correlation in HBV infection. Guidelines regarding HBV reactivation reports that TCZ has a moderate risk of reactivation in patients with HBsAg positive. Guidelines regarding therapeutic approaches of Hepatitis B virus recommend preventive therapy for those patients considered at high risk of re-activation such as undergoing immunosuppressive therapy, regardless of the duration, or previous HBV status. Hepatitis B reactivation is often seen within 2 weeks and up to 1 year after the onset of immunosuppressive therapy. No previous cases exist to our knowledge looking at short and long-term effects of TCZ in SARS-COV-2 patients with HBV infection.Figure 1.: Liver enzymes trend pre and post-Tocilizumab and Tenofovir therapies.Table 1.: Hepatitis viral serologies pre and post-Tocilizumab and Tenofovir therapies.

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