Risk of Hepatitis B Virus (HBV) Reactivation in HBsAg-Negative, Anti-HBc-Negative Patients Receiving Rituximab for Autoimmune Diseases in HBV Endemic Areas
Ting-Yuan Lan,
Yen-Chun Lin,
Tai-Chung Tseng,
Hung-Chih Yang,
Jui-Hung Kao,
Chiao-Feng Cheng,
Tai-Ju Lee,
Shang-Chin Huang,
Cheng-Hsun Lu,
Ko-Jen Li,
Song-Chou Hsieh
Affiliations
Ting-Yuan Lan
Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
Yen-Chun Lin
Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Douliu, Taiwan
Tai-Chung Tseng
Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Hung-Chih Yang
Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Jui-Hung Kao
Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Douliu, Taiwan
Chiao-Feng Cheng
Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Douliu, Taiwan
Tai-Ju Lee
Division of Rheumatology, Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Shang-Chin Huang
Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
Cheng-Hsun Lu
Division of Rheumatology, Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Ko-Jen Li
Division of Rheumatology, Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Song-Chou Hsieh
Division of Rheumatology, Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
Background/Aims: Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (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 outcome and factors associated with HBVr were analyzed. Results: After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions: In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAg-negative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.
