Etanercept-Induced Autoimmune Hepatitis

Abstract

Introduction: Drug-induced autoimmune hepatitis (AIH) is a rare adverse event of tumor necrosis factor alpha antagonist (anti-TNFa) therapy. A patient on etanercept presented with characteristic complaints plus serologic and histologic findings, significant for rarity of the condition and implication of etanercept as the causal agent. Case: 36 y/o female with 10 yr hx of psoriatic arthritis, intolerant of infliximab, was initiated on weekly etanercept 50mg injections. After 20 doses, she developed anorexia, dark urine, lethargy, acholic stools and jaundice. Testing documented negative Hepatitis A, B and C serologies, AST 575 U/L, ALT 417 U/L, Alk Phos 230 U/L, bilirubin 7.2 mg/dL. ANA positive, 1:320, speckled, and elevated serum IgG, 1951 mg/dL. Abdominal US was unremarkable; MRCP demonstrated heterogeneous hepatic enhancement, periportal edema. Liver biopsy revealed chronic hepatitis, severely active, consistent with autoimmune type injury pattern with mild portal and extensive Space of Disse fibrosis. Clinical condition and labs improved; she was discharged on prednisone. On follow up, she endorsed clinical improvement. Liver associated enzymes improved. She was initiated on azathioprine for steroid-sparing therapy in the setting of drug-induced AIH. Discussion: Anti-TNFa agents are used in the treatment of various autoimmune conditions. Serious adverse events are drug-induced liver injury (DILI) and, rarely, drug-induced AIH. A combination of positive autoantibodies, elevated immunoglobulins and characteristic histology allows for distinguishing AIH from DILI. Infliximab is traditionally implicated in AIH, but this case is attributed to etanercept. Research is required to delineate if etanercept is a less likely causal agent or a less commonly used therapy. This patient presented clinically, whereas prior reports emphasized distinction between the induction of autoimmunity, and, less commonly, clinically apparent autoimmune disease [1]. Clinicians must be aware of AIH in patients on immune system modulators. Anti-TNFa agents differ in molecular structure, lacking cross reactivity, but autoimmunity induction appears to be a class effect. AIH has risk of relapse after cessation of immunosuppressive therapy and treatment decisions underscore the importance of accurate diagnosis.Figure 1