Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts

Tamori, Akihiro; Koike, Tatsuya; Goto, Hitoshi; Wakitani, Shigeyuki; Tada, Masahiro; Morikawa, Hiroyasu; Enomoto, Masaru; Inaba, Masaaki; Nakatani, Tatsuya; Hino, Masayuki; Kawada, Norifumi

doi:10.1007/s00535-010-0367-5

Cited by 141 publications

(132 citation statements)

References 43 publications

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“…21,[38][39][40] Several studies reported that elevated HBV viral load subsequently leads to active hepatitis. 24,25 A recent study analyzing patients with inflammatory arthritis also revealed an increased risk of HBV reactivation associated with anti-TNF therapy in patients with chronic HBV infection. 41 However, due to limited wellcontrolled studies, the association between TNF-a blockage and HBV reactivation remains uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23] However, there are limited reports on its effect on HBV persistence and reactivation in chronic HBV infection during anti-TNF therapy. 24,25 The role of anti-TNF therapy in chronic HBV infection is still not clear, and detailed analysis of HBV infection under TNF-a blockage therapy is essential for the prophylaxis and therapy for HBV reactivation and recurrence.…”

Section: Introductionmentioning

confidence: 99%

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Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

Chyuan

Tsai²,

Tzeng

et al. 2015

Cell Mol Immunol

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Hepatitis B virus (HBV) reactivation and recurrence are common in patients undergoing immunosuppression therapy. Tumor necrosis factor (TNF) blockage therapy is effective for the treatment of many autoimmune inflammatory diseases. However, the role of TNF-a blockage therapy in the innate and adaptive immune responses against HBV is still not clear. A detailed analysis of HBV infection under TNF-a blockage therapy is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV clearance and T-cell responses were analyzed in a HBV-transfected mouse model under anti-TNF blockage therapy. Our results demonstrated that under TNF-a blockage therapy, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose-and temporal-dependent manner. The impairment of HBV clearance under anti-TNF-a blockage therapy occurred at early time points after HBV infection. In addition, TNF-a blockade maintained a higher serum HBV viral load and increased the number of intrahepatic programmed cell death (PD)-1 high CD127 low exhausted T cells. Furthermore, TNF-a blockade abolished Toll-like receptor 9 (TLR9) ligand-induced facilitation of HBV viral clearance. Taken together, TNF-a blockade impairs HBV clearance and enhances viral load, and these effects depend on early administration after HBV infection. Our results here demonstrate that early TNF-a blockade reduces viral clearance and persistently maintains elevated HBV viral load in a mouse model, suggesting that HBV may reactivate during therapy with TNF-a-blocking agents.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

Chyuan

Tsai²,

Tzeng

et al. 2015

Cell Mol Immunol

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“…22,23 Additional host risk factors for HBV reactivation have been reported as male sex, 6 diagnosis of lymphoma, 3 absence of anti-HBs at baseline, 6,24 and decrease of anti-HBs titers after immunosuppressive therapy. 25 The risk classification for HBV reactivation according to serum HBV markers and the intensity of immunosuppressive therapy can be determined based on the current evidence ( Figure 1). 7 HBV reactivation in HBsAg-positive patients after anti-B-cell therapy HBV reactivation often occurs in HBsAg-positive patients after immunosuppressive therapy even if steroid alone is given.…”

Section: Risk Of Hbv Reactivation After Immunosuppressive Therapymentioning

confidence: 99%

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

Kusumoto

Tobinai

2014

Hematology

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Reactivation of hepatitis B virus (HBV) is a potentially fatal complication after anti-B-cell therapy. It can develop not only in patients seropositive for hepatitis B surface antigen (HBsAg), but also in those with resolved HBV infection who are seronegative for HBsAg but seropositive for antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs). The risk of HBV reactivation depends on the balance between replication of the virus and the immune response of the host. Anti-CD20 monoclonal antibody-rituximab in combination with steroid-containing chemotherapy (R-CHOP: rituximab ϩ cyclophosphamide ϩ hydroxydaunorubicin ϩ vincristine ϩ prednisone/prednisolone)-is an important risk factor for HBV reactivation in HBsAg-negative patients. More obviously, HBsAg-positive patients are considered to be at very high risk for HBV reactivation and, in the rituximab era, 59%-80% of these patients develop HBV reactivation after R-CHOP-like chemotherapy. Patients with resolved HBV infection should also be considered at high risk of HBV reactivation, the incidence of which is reported to be 9%-24% in such lymphoma patients. All patients should be screened to identify risk groups for HBV reactivation before initiating anti-B-cell therapy by measuring serum HBV markers including HBsAg, anti-HBc and anti-HBs. To prevent the development of hepatitis due to HBV reactivation after anti-B-cell therapy, antiviral prophylaxis is recommended for HBsAg-positive patients and/or patients in whom HBV DNA is detectable at baseline, whereas regular monitoring of HBV DNA-guided preemptive antiviral therapy is a reasonable and useful approach for patients with resolved HBV infection. Learning Objectives• To become familiar with the risk of HBV reactivation in patients who receive anti-B-cell therapy • To manage such high-risk patients successfully using antiviral prophylaxis or by HBV DNA-monitoring-guided preemptive antiviral therapy

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“…The uses of biological agents in HBV patients are still uncertain. TNF alpha level is increased in both serum and hepatocytes of patients with chronic HBV (12). In transgenic animal models, TNF alpha produced by HBV-specific cytotoxic T lymphocytes downregulated HBV replication in hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Current antiviral practice and course of Hepatitis B virus infection in inflammatory arthritis: a multicentric observational study (A + HBV study)

et al. 2015

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Objective: The reactivation of hepatitis B virus (HBV) infection is a well-known event in hepatitis B surface antigen (HbsAg)-positive patients receiving immunosuppressive therapy. The objective of this study was to assess the antiviral practice and course of HBV infection in inflammatory arthritis. Material and Methods:Nineteen rheumatology centers participated in this retrospective study. HbsAg-positive patients who were taking disease-modifying antirheumatic drugs and who were being tested for HBV viral load at a minimum of two different time points were included. The case report form (CRF) consisted of demographic data, rheumatic diseases, treatment profiles, transaminase levels, viral hepatitis serological markers, and HBV viral load. The reactivation of HBV was defined as the abrupt rise in HBV replication by an increase in serum HBV DNA levels in a patient with a previously inactive HBV infection. Results:In total, the data of 101 (female 50.5%) patients were included (76 patients with inactive HBV carriers and 25 patients with chronic HBV infection). The mean age of patients was 44±12 years, and the mean follow-up duration was 31±22 months. Of the 101 patients, 70 (69.3%) received antiviral treatment. HBV reactivation was detected in 13 of 76 (17.1%) patients with inactive HBV carriers. HBV reactivation was observed less frequently, not although significantly, in those patients receiving antiviral prophylaxis compared with those not receiving prophylaxis [5/41 (12.2%) vs. 8/33 (24.2%), p=0.17]. Forty-two patients (31 patients had inactive HBV carriers) were using anti-tumor necrosis factor agents. HBV reactivation was detected in 6 of the 31 (19.3%) patients. Twenty-five patients had chronic hepatitis, and five (20%) of them had not received antiviral prophylaxis. HBV viral loads were persistently elevated in 7 (28%) of 25 patients (three patients under and four patients not under antiviral treatment).Conclusion: HBV reactivation was observed in approximately 17% of patients under immunosuppressive treatments. HBV reactivation was more frequently observed in those who did not receive antiviral prophylaxis.

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Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts

Cited by 141 publications

References 43 publications

Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

Current antiviral practice and course of Hepatitis B virus infection in inflammatory arthritis: a multicentric observational study (A + HBV study)

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