Macrophage activation syndrome with acute hepatitis E during tocilizumab treatment for rheumatoid arthritis

Leroy, Marie; Coiffier, Guillaume; Pronier, Charlotte; Triquet, Louise; Perdriger, Aleth; Guggenbuhl, Pascal

doi:10.1016/j.jbspin.2015.01.018

Cited by 15 publications

(3 citation statements)

References 11 publications

(13 reference statements)

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“…The search of the FAERS database and medical literature retrieved 254 unique reports, including 14 published articles 26–39 . The majority of the excluded reports that did not meet the case selection criteria reported mild abnormalities of serum aminotransferases or contained insufficient information to fully assess the report.…”

Section: Resultsmentioning

confidence: 99%

A case series analysis of serious exacerbations of viral hepatitis and non‐viral hepatic injuries in tocilizumab‐treated patients

Biehl

Harinstein

Brinker

et al. 2020

Liver International

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Background and Aims Reports of moderate to severe liver injury associated with tocilizumab, an interleukin‐6 (IL‐6) receptor antagonist, have been reported in the post‐marketing setting. This case series aims to characterize cases of tocilizumab‐associated clinically significant hepatic injury. Methods We analysed cases of severe acute liver injury associated with tocilizumab reported in the FDA Adverse Event Reporting System and the medical literature. Results We identified 12 cases in which tocilizumab was a suspected primary cause of liver injury and eight cases in which serious sequelae of underlying or coincident viral hepatitis were temporally associated with its use. Using the Drug‐Induced Liver Injury Network (DILIN) severity scale, five of 12 cases were Grade 5 (two liver transplants, three deaths), one was Grade 4 (liver failure) and six were Grade 3 (serious events with elevated bilirubin). Two cases reported liver atrophy with low hepatocellular expression of Ki‐67, a marker of cellular proliferation. Among the eight cases of tocilizumab‐associated viral hepatitis exacerbation, three were scored as DILIN severity Grade 5 (one liver transplant, two deaths), one was Grade 4 (liver failure), and four were Grade 3. The reported viral hepatitis events were hepatitis B virus (HBV) reactivation (n = 3), hepatitis C virus (HCV) flare (n = 1), cytomegalovirus (CMV)‐induced liver failure (n = 1), Epstein‐Barr virus hepatitis (n = 1), acute hepatitis E (HEV, n = 1) and HEV‐induced macrophage activation syndrome (n = 1). Conclusion Tocilizumab may be a primary cause of severe liver injury, as well as exacerbate underlying viral hepatitis. The disruption by tocilizumab of IL‐6‐mediated immune protection and hepatocyte regeneration may aggravate clinical outcomes in some cases.

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Section: Resultsmentioning

confidence: 99%

A case series analysis of serious exacerbations of viral hepatitis and non‐viral hepatic injuries in tocilizumab‐treated patients

Biehl

Harinstein

Brinker

et al. 2020

Liver International

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“…Few cases of HEV-related hemophagocytic syndrome have been documented. [69][70][71] Also, HEV infection has been detected in patients with CD30 (+) cutaneous T cell lymphoproliferative disorder 72 and monoclonal gammopathy of undetermined significance (MGUS). However, the relation between MGUS and HEV remains uncertain.…”

Section: Thrombocytopeniamentioning

confidence: 99%

Extrahepatic manifestations of hepatitis E virus: An overview

2020

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Hepatitis E virus (HEV) is a significant health problem with approximately 20 million individuals infected annually. HEV infection has been associated with a wide spectrum of extrahepatic manifestations, including neurological, hematological and renal disorders. Guillain-Barré syndrome and neuralgic amyotrophy are the most frequent neurological manifestations. In addition, HEV infection has been observed with other neurological diseases, such as encephalitis, myelitis and Bell's palsy. Hematologic manifestations include anemia due to glucose-6-phospate dehydrogonase deficiency, autoimmune hemolytic anemia and severe thrombocytopenia. Membranoproliferative glomerulonephritis and relapse IgA nephropathy with or without coexisting cryoglobulinemia appear to be the most common renal injuries related with HEV infection. Also, HEV infection has been associated with acute pancreatitis and other immune-mediated manifestations, such as arthritis and myocarditis. However, the pathophysiologic mechanisms of HEV-related extrahepatic manifestations are still largely unclear.

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“…In France, two cases of haemophagocytic syndrome (HPS) have been reported in patients with HEV infection, both of whom had underlying comorbidities (splenic lymphoma and rheumatoid arthritis on tocilizumab infusion) (Leroy et al , ; Bazerbachi et al , ). Dual infection with hepatitis A virus and HEV has also been associated with HPS (Kaur et al , ).…”

Section: Haematological Manifestations As Features Of Hepatitis E Virmentioning

confidence: 99%

Hepatitis E virus – key points for the clinical haematologist

2018

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In recent years there has been a paradigm shift in our understanding of the epidemiology and clinical features of hepatitis E virus (HEV) infection. Once classically described as an acute hepatitis associated with waterborne outbreaks in areas of poor sanitation, HEV is now recognised to be endemic in Europe and is probably zoonotic in origin. Evidence for transfusion-transmitted HEV has prompted the introduction of blood donor screening in a number of countries, but the risk to the haematology patient from food sources remains. The aim of this review therefore, is to equip the clinical haematologist with the knowledge required to diagnose HEV infection and to aid decision-making in patient management. The article also provides information on addressing patient concerns about their risk of acquiring hepatitis E and how this risk can be mitigated.

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Macrophage activation syndrome with acute hepatitis E during tocilizumab treatment for rheumatoid arthritis

Cited by 15 publications

References 11 publications

A case series analysis of serious exacerbations of viral hepatitis and non‐viral hepatic injuries in tocilizumab‐treated patients

A case series analysis of serious exacerbations of viral hepatitis and non‐viral hepatic injuries in tocilizumab‐treated patients

Extrahepatic manifestations of hepatitis E virus: An overview

Hepatitis E virus – key points for the clinical haematologist

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