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

Abstract

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 HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

Chronic hepatitis B in rheumatic diseases: issues of screening and reactivation of infection: A review

“…Исходно положительный результат на анти-HBS был связан с более низким риском HBV-r. Существенных различий риска HBV-r между РА и другими аутоиммунными заболеваниями не выявлено. Среди анти-HBcor-негативных пациентов, не вакцинированных против HBV, отмечена более высокая частота HBV-r (4/368, 1,1%) по сравнению с теми, кто получил вакцину (0/126, 0%) [43].…”

Reactivation of Chronic Hepatitis B in a Patient with Rheumatoid Arthritis

“…Lan и соавт. подтвердили, что РТМ часто вызывает HBV-р даже у полностью серонегативных больных [36]. Недавно опубликована самая крупная на сегодняшний день серия случаев HBV-р, развившейся при применении АБА.…”

HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: a systematic review and meta-analysis

“…For patients living with an AIIRD, HBVr risk seems higher in patients receiving B cell–depleting therapies like rituximab, even though this risk is probably lower when compared with that of patients with lymphoma [ 1 , 3 , 10–12 ]. The use of TNF inhibitors also poses a considerable risk, as does the prolonged use of CSs, especially in high doses [ 1 , 5 , 13–15 ], while HBVr risk seems to be low in patients under conventional DMARDs [ 1 , 5 ].…”