Hepatitis B Virus (HBV) Reactivation in Patients Receiving Tumor Necrosis Factor (TNF)-Targeted Therapy

Pérez-Álvarez, R.; Díaz-Lagares, Cándido; García–Hernández, Francisco J.; López-Rosés, Leopoldo; Brito-Zerón, Pilar; Pérez-de-Lis, M.; Retamozo, Soledad; Bové, Albert; Bosch, Xavier; Sánchez-Tapias, José-Marı́a; Forns, Xavier; Ramos-Casals, Manuel

doi:10.1097/md.0b013e3182380a76

Cited by 262 publications

(220 citation statements)

References 60 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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“…According to a recent meta-analysis (5) and a case series (6), HBV reactivation rate ranges from 15% to 39% in HBsAg-positive RA patients receiving tumor necrosis factor (TNF) inhibitors, and 3% to 5% in HBsAg-negative patients receiving this class of medication. Reactivation also occurs in those receiving nonbiologic DMARDs (7-9) and a non-TNF biologic agent, abatacept (10,11).…”

Section: Introductionmentioning

confidence: 99%

Practice Pattern of Hepatitis B Testing in Rheumatoid Arthritis Patients: A Cross‐National Comparison Between the US and Taiwan

Lin

Hashemi

Kim

et al. 2017

Arthritis Care & Research

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Objective. The hepatitis B virus (HBV) testing rates and patterns in rheumatoid arthritis (RA) patients starting disease-modifying antirheumatic drugs (DMARDs) have not been well studied. We describe and compare the practice patterns of HBV testing among RA patients in the US and Taiwan. Methods. We conducted a retrospective cohort study, including RA patients starting a first DMARD in the US or Taiwan. The first date patients newly received any DMARD was defined as the index date, and the 1-year period before the index date was the baseline period. HBV testing was defined as any of the following tests 1 year before or after the index date: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, hepatitis B envelope antigen, hepatitis B envelope antibody, or HBV DNA. We calculated the HBV testing rate by year and used Poisson regression to calculate the testing rate ratio. Results. We identified 14,568 RA patients in the US and 46,265 in Taiwan. The overall testing rate was 20.3% in the US and 24.5% in Taiwan, and gradually increased over the study period from 13.1-23.0% in the US and 16.8-30.0% in Taiwan. More than one type of HBV test was used in 43.4% of patients in the US and 16.3% of patients in Taiwan receiving tests. Results of Poisson regression found Taiwan had a 17% higher testing rate over the US during the followup period (crude rate ratio 1.17 [95% confidence interval 1.12-1.22]). Conclusion. We found small differences in the HBV testing rates across the US and Taiwan. Although the rate gradually increased in the past decade, it remained low in both countries.

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“…A recent review of reported cases found that reactivation occurred in 39% (35 of 89) of HBsAg-positive individuals including four fatal cases of acute liver failure and reactivation occurred in 5% (9 of 168) of those who were HBsAg-negative, anti-HBc-positive before starting anti-TNF therapy, including 1 fatal case. 15 Most studies have found the risk to be highest in patients receiving infliximab compared with etanercept or adalimumab. 15,16 Reactivation has also been reported with azathioprine, 6-mercaptopurine, and methotrexate used in nononcologic settings.…”

Section: Hbv Reactivation In Nononcologic Settingsmentioning

confidence: 99%

“…15 Most studies have found the risk to be highest in patients receiving infliximab compared with etanercept or adalimumab. 15,16 Reactivation has also been reported with azathioprine, 6-mercaptopurine, and methotrexate used in nononcologic settings. 17 There have been individual case reports with targeted kinase inhibitors 18 but no published reports of HBV reactivation with inhibitors of vascular growth endothelial factor.…”

Section: Hbv Reactivation In Nononcologic Settingsmentioning

confidence: 99%

HBV treatment in a patient who will be receiving immunosuppressive therapy

Feld

2013

Clinical Liver Disease

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Despite an effective vaccine, hepatitis B virus (HBV) infection remains an enormous global public health problem with up to 400 million people chronically infected and as many as 2 billion people with evidence of exposure to the virus worldwide. 1,2 The virus is noncytopathic, with hepatic injury occurring as a result of the host immune response against the virus. 1 As a result, the interaction between HBV and the immune system is critical in determining the outcome of infection.After perinatal or early childhood infection, >90% of individuals will progress to chronic infection, initially characterized by normal liver tests and histology despite high levels of HBV replication, the so-called immunotolerant phase of infection. 2 Patients eventually develop an immune response against HBV, leading to flares of hepatitis with the potential for progressive liver damage. Ultimately, most immunocompetent patients will gain immune control of HBV, with suppression of viral replication, normalization of liver enzymes, and loss of circulating HBeAg. 2 Persistence of this inactive carrier state depends on immune function. Even those with undetectable HBV DNA in the serum continue to harbor replication-competent HBV in infected liver cells. With immunosuppression, immune control may be lost, resulting in reactivation of HBV replication with the potential for severe flares of hepatitis, often at the time of restoration of immune function. Reactivation has variable clinical consequences ranging from asymptomatic increases in serum HBV DNA to potentially fulminant and even fatal flares of hepatitis. 3,4 Reactivation may also lead to interruptions or premature discontinuation of immunosuppressive therapy, including cancer chemotherapy with potential negative consequences. 5

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Hepatitis B Virus (HBV) Reactivation in Patients Receiving Tumor Necrosis Factor (TNF)-Targeted Therapy

Cited by 262 publications

References 60 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

Practice Pattern of Hepatitis B Testing in Rheumatoid Arthritis Patients: A Cross‐National Comparison Between the US and Taiwan

HBV treatment in a patient who will be receiving immunosuppressive therapy

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