A case of synthetic oestrogen‐induced autoimmune hepatitis with microvesicular steatosis

Summary What is known and objective Drug‐induced liver injury ( DILI ) is a leading cause of acute liver failure in developed countries. Hepatotoxicity is a well‐recognized adverse effect associated with synthetic oestrogens, which can cause cholestasis. The current report describes ethinyloestradiol ( EE 2)‐associated highly unusual adverse effects of autoimmune hepatitis ( AIH ) and microvesicular steatosis ( MS ). DILI that fulfils the criteria for AIH is referred to as drug‐induced autoimmune hepatitis ( DIAIH ). MS is a potentially severe liver lesion that results from mitochondrial dysfunction. We explore the pathophysiological mechanisms underlying DIAIH and MS . Case summary A 51‐year‐old woman presented with jaundice, increased liver enzymes and IgG, and positive ANA . She had been taking EE 2 for 3 years. Liver biopsy showed prominent interface hepatitis with MS . A drug‐lymphocyte stimulation test ( DLST ) using EE 2 was positive. The liver biochemical parameters had normalized after the EE 2 discontinuation; however, they exacerbated 5 months post‐onset. Repeated liver biopsy showed interface hepatitis with no MS . Considering EE 2‐induced DIAIH , corticosteroids treatment was initiated. Then, all liver biochemical parameters had normalized, and the corticosteroids were successfully withdrawn. The patient continued to be in complete remission over the next 3 years. What is new and conclusion Five remarkable points should be emphasized: (i) a long latency interval, despite the acute presentation; (ii) exacerbation of liver biochemical parameters, even after drug cessation; (iii) the paired liver biopsies indicating continuing inflammation and disappearance of toxic features; (iv) a positive DLST and the absence of fibrosis consistent with DIAIH and not AIH ; and (v) a rare histological feature of MS . Intense immunoallergic reactions were likely triggers of MS in the current case. A possibility of DIAIH should be considered in cases of DILI which exhibit overt jaundice, autoantibodies, intense histological inflammation and a long latency period.