Tocilizumab-Induced Acute Liver Injury in Adult Onset Still’s Disease

Abstract

Background. Tocilizumab, a monoclonal humanized anti-IL-6 receptor antibody, is used in treatment of refractory adult onset Still's disease (AOSD). Mild to moderate liver enzyme elevation is a well-known side effect, but severe liver injury has only been reported in 3 cases in the literature. Case. A young female suffering from corticoid and methotrexate refractory AOSD was treated by tocilizumab. After 19 months of consecutive treatment, she developed acute severe liver injury. Liver biopsy showed extensive hepatocellular necrosis with ballooned hepatocytes, highly suggestive of drug-induced liver injury. No other relevant drug exposure beside tocilizumab was recorded. She recovered totally after treatment discontinuation and an initial 3-day course of intravenous N-acetylcysteine with normalization of liver function tests after 6 weeks. Conclusion. Acute severe hepatitis can be associated with tocilizumab as documented in this case. Careful monitoring of liver function tests is warranted during tocilizumab treatment.

Mechanisms, biomarkers and targets for adult-onset Still’s disease

“…h Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, potentially induced by IL-1 or IL-6 or another immunosuppressive agent, is a differential diagnosis that should always be ruled out because it can be responsible for a fulminant hepatitis and mimic AoSD systemic manifestations. i Keeping in mind that tocilizumab-induced hepatic injury has also been reported 175 . have to be made on the basis of clinical, biological or imaging characteristics.…”

Tocilizumab, a Potent Interleukin-6 Receptor Inhibitor, Decreases Bone Resorption and Increases the Rate of Bacterial Infection After Tooth Extraction in Rats

“…Hepatotoxicity is a limiting factor to TCZ treatment in patients with rheumatoid arthritis, 41 which has been described in case reports of severe hepatitis after TCZ use. 42 It is probable that the indispensable axis involving IL-6 and hepatocyte growth factor is partly responsible for this toxicity. 42 , 43 …”

Biologic and Checkpoint Inhibitor‐Induced Liver Injury: A Systematic Literature Review

“…Tocilizumab is a humanized monoclonal antibody to the interleukin (IL)‐6 receptor that has been used for RA. A hepatocellular pattern of liver injury has been documented in several case reports, with liver biopsies showing focal necrosis with steatosis and early fibrosis with other etiologies of injury excluded . In one case, tocilizumab was continued given normalization of liver enzymes and remained stable at 6 months of follow‐up.…”