Hepatitis B virus reactivation in rheumatoid arthritis and ankylosing spondylitis patients treated with anti-TNF alpha agents: A retrospective analysis of 49 cases

Abstract

Clinical guidelines regarding anti-viral prophylaxis for HBV surface antigen (HBsAg) carriers starting anti-TNF alpha agents are not yet fully established, even in endemic regions of HBV infection. We retrospectively collected the clinical data of 52 HBsAg carriers with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) that had been administered anti-TNF alpha treatment at seven medical centers in South Korea. Periodic data of liver function tests and serum HBV DNA were both utilized to assess HBV reactivation. The YMDD motif mutation of HBV DNA polymerase was tested in lamivudine-treated patients with elevated HBV DNA. Three of the 52 patients were excluded from the analysis. Of the 49 analyzed patients, 20 patients received anti-viral prophylaxis (15 lamivudine, five entecavir) with anti-TNF alpha treatment. The remaining 29 patients were treated with anti-viral agents if needed at the discretion of the clinician and did not receive prophylaxis. Of the 29 patients who did not receive primary prophylaxis, two (6.9%) developed viral reactivation within a year of anti-TNF alpha treatment. In the prophylaxis group, one patient developed viral reactivation at week 64 of anti-TNF alpha therapy attributed to YMDD mutation caused by lamivudine. Patients with HBV reactivation all responded well to antiviral therapy. In summary, anti-viral prophylaxis helped preventing HBV reactivation in HBsAg carriers with RA or AS starting anti-TNF alpha, yet mutation in the YMDD motif of HBV DNA polymerase could be detrimental to some patients under long-term lamivudine prophylaxis.