Risk of Hepatitis B Virus Reactivation in HBsAg-negative, Anti-HBc-negative Patients Receiving Rituximab for Autoimmune Diseases in Hepatitis B Virus Endemic Areas

Abstract Background Rituximab is known to be associated with a high resolved hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation in rheumatic patients receiving rituximab is limited. Aims To assess the HBV reactivation in HBsAg-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcomes and factors associated with HBV reactivation were analyzed. Results After a median follow-up period of 3.3 years, 21 patients developed HBV reactivation, among which 17 patients were positive for anti-HBc and 4 were negative. Thirteen patients had clinical hepatitis flare, while 8 patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, and undetectable serum anti-HBs level at rituximab initiation were associated with HBV reactivation. There was no significant difference in the HBV reactivation risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBV reactivation (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions In HBV endemic areas, patients with negative anti-HBc, especially those without vaccination at birth, were still at risk for HBV reactivation after receiving rituximab. Regular monitoring of HBV serology should be considered for all HBsAg-negative patients receiving rituximab for autoimmune diseases.