Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc–positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study

Varisco, V.; Viganò, Mauro; Batticciotto, Alberto; Lampertico, Pietro; Marchesoni, Antonio; Gibertini, P.; Pellerito, Raffaele; Rovera, Guido; Caporali, Roberto; Todoerti, Monica; Covelli, M.; Notarnicola, A.; Atzeni, Fabiola; Sarzi-Puttini, Piercarlo

doi:10.3899/jrheum.151105

Cited by 56 publications

(32 citation statements)

References 30 publications

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“…The differences in findings between the few reports available may result from differences in follow-up time, sample size, monitoring policy, the definition of HBV reactivation and race. In an Italian multicenter study of patients receiving a median of 3 cycles of RTX (range, 1-8) over 34 months of follow-up (range, 0-80), the risk of HBV reactivation was 3% (1/33) in HBsAg − /HBcAb + patients 16 . A cohort study from Taiwan with a follow-up of 3.4 ± 1.7 years from RTX initiation reported an HBV reactivation rate of approximately 9.1% (4/44) 15 , consistent with that observed in our study (8%; 4/50).…”

Section: Discussionmentioning

confidence: 99%

“…In a cohort study conducted in a regional hospital in Taiwan, approximately 9.1% of HBsAg − /HBcAb + RA patients (4/44) experienced HBV reactivation approximately 2 years after receiving RTX 15 . In a retrospective multicenter Italian study, the HBV reactivation rate was low (3%; 1/33) in HBsAg − /HBcAb + patients 16 . Only one patient became positive for HBV DNA after 6 months of RTX treatment and was effectively treated with lamivudine, which prevented hepatitis flare-ups.…”

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confidence: 94%

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Moderate Risk of Hepatitis B Virus Reactivation in HBsAg−/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis

Kuo

Tseng

Lee

et al. 2020

Sci Rep

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to investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg) − / HBV core antibody (HBcAb) + patients who underwent rituximab (RtX) therapy for rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg − /HBcAb + patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg − /HBcAb + RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1-4 years after the first dose of RTX and 0.5-1.5 years after the last one. In HBsAg − /HBcAb + patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb) − at baseline than in those who were HBsAb + (30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg − /HBcAb + RA patients receiving RtX therapy. the reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 94%

Moderate Risk of Hepatitis B Virus Reactivation in HBsAg−/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis

Kuo

Tseng

Lee

et al. 2020

Sci Rep

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“…Although a previous study demonstrated no rHBV in RTX‐treated rheumatic patients with resolved HBV infection, rHBV has recently been recognized as a complication characterized by a seroreversion of HBsAg in HBsAg‐negative patients receiving RTX therapy . Despite these findings, there are limited data or even conflicting results on rHBV in RTX‐treated patients . In addition, the risk factors of rHBV in HBsAg‐negative, HBcAb‐positive RA patients with prior HBV infection have yet to be defined.…”

Section: Introductionmentioning

confidence: 99%

Reactivation of hepatitis B virus infection following rituximab treatment in HBsAg‐negative, HBcAb‐positive rheumatoid arthritis patients: A long‐term, real‐world observation

et al. 2019

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Aim: Longitudinal data of the reactivation of hepatitis B virus (rHBV) and serial serological markers or HBV-DNA has been limited. This study aimed to investigate the temporal course of rHBV development in rheumatoid arthritis (RA) patients undergoing long-term rituximab therapy. Methods: The occurrence of rHBV was examined in 157 RA patients during rituximab therapy. Serum levels of HBV surface antigen (HBsAg), HBV core antibody (HBcAb), and HBsAb were determined by electrochemiluminescence immunoassays, and viral loads by real-time polymerase chain reaction assay. Results: Among 157 patients undergoing rituximab therapy, 103 (65.6%) were HBsAg-negative and HBcAb-positive. Before rituximab therapy, 20 (19.4%) of these 103 patients were HBsAb-negative, while 83 (80.1%) were HBsAb-positive. Five (20%) HBsAb-negative patients developed rHBV after rituximab therapy. Among 83 HBsAb-positive patients, 4 (4.8%) developed rHBV. Among 9 patients with rHBV, 7 (77.7%) exhibited HBsAg seroreversion. Significant decline of HBsAb titers (mean ± SD, 296.0 ± 417.3 mIU/mL at baseline vs 187.0 ± 332.5 mIU/mL after rituximab therapy, P < 0.001) was observed in HBsAg-/HBsAb + patients. All HBsAgnegative patients who developed rHBV during rituximab therapy were characterized by baseline HBsAb titers < 100 mIU/mL and negative HBsAb at the time of rHBV.HBsAb positivity was an independent protective factor for rHBV (hazards ratio: 0.14, 95% CI: 0.03-0.62, P = 0.009). Conclusion:Baseline HBsAb positivity was a significant protective factor for rHBV in HBsAg-negative, HBcAb-positive RA patients receiving rituximab therapy. K E Y W O R D SHBsAg seroreversion, hepatitis B virus reactivation, rheumatoid arthritis, rituximab therapy

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“…A multi-center study concluded that combination of rituximab and DMARDs in patients with Rheumatoid arthritis (RA) had a negligible risk of HBVr. They therefore recommended serum monitoring but not prophylaxis in these patients 7 . Thus, the decision of using anti-viral prophylaxis to prevent reactivation of HBV infection remains controversial, although strong evidence exists in the favor of prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B Screening before Immunosuppressive Therapy: A statewide survey of current practice

Ali

Hayat

Fazili

et al. 2019

Preprint

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Background: Reactivation of Hepatitis B virus (HBVr) in patients on immunosuppressive therapy (IST) can be prevented by screening for HBV and preemptive antiviral therapy in patients with prior exposure. Some internal medicine (IM) subspecialty guidelines recommend screening for HBV in all patients prior to starting IST while other guidelines do not and there is no consensus. Methods: We conducted a cross sectional survey to assess the current practice of IM sub-specialty physicians in Oklahoma regarding screening for HBV prior to starting IST. Results: There were seventy respondents from different clinical practice settings; 47.2% (33/70) free-standing specialty clinic, 18.6% (20/70) university hospital/VA hospital, 12.9% (9/70) community hospital and 21.4% (15/70) private hospital. Gastroenterologists accounted for 34.3% (24/70), rheumatologists 25.7% (18/70), hematology-oncologists 21.4% (15/70), and dermatologists 18.6% (13/70). Mean number of years of clinical practice was 27.7(SD 11.9 years). The majority of respondents 91.4% (64/70) were aware of an existing guideline within their respective specialty about screening for HBV prior to prescribing IST. There was a statistically significant difference in practice by subspecialty regarding the choice of serological tests for HBV screening and practice regarding care of screening positive patients (P<0.05). Conclusion: There was significant variation in clinical practice regarding HBV screening, choice of HBV serological tests and management of screening positive patients. The extent to which our results are influenced by divergent subspecialty guidelines is unclear. However, it highlights an unmet need for physician education at IM sub-specialty level and a need for consensus on guidelines for prevention of HBVr.

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Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc–positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study

Abstract: The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.

Cited by 56 publications

References 30 publications

Moderate Risk of Hepatitis B Virus Reactivation in HBsAg−/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis

Moderate Risk of Hepatitis B Virus Reactivation in HBsAg−/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis

Reactivation of hepatitis B virus infection following rituximab treatment in HBsAg‐negative, HBcAb‐positive rheumatoid arthritis patients: A long‐term, real‐world observation

Hepatitis B Screening before Immunosuppressive Therapy: A statewide survey of current practice

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