A rare but important cause of fulminant hepatic failure

A 79 year-old Caucasian man presented to our institution with jaundice and dark urine having fallen from a ladder in his stables three days prior to admission. The fall had left him with some discomfort for which he had self-medicated with paracetamol. He denied having exceeded the recommended dose of paracetamol. There was no past medical history of liver disease, illicit drug use, drugs known to cause liver failure, or any history of foreign travel. Physical examination revealed icterus in the absence of clinical stigmata of chronic liver disease. Haematological and biochemical parameters were consistent with acute hepatitis. The synthetic function of the liver showed a rapidly worsening trend with an initial albumin of 33 g/L that worsened to 18 g/L and an initial INR of 1.4 that deteriorated to 2.5. Serology was negative for hepatitis A, hepatitis B, hepatitis C, EpsteinBarr virus and cytomegalovirus. HIV status was not tested. Autoantibodies, alpha 1 antitrypsin, immunoglobins, ferritin and copper were in the normal range. Serum paracetamol was undetectable. An electrocardiogram did not show any ischaemic features. An abdominal computed tomography scan did not demonstrate any abnormality in the liver, with a patent hepatic vein and no radiological evidence of portal hypertension or cirrhosis. Initially, the working diagnosis was paracetamol induced subfulminant liver failure as a result of therapeutic misadventure. Intravenous N-acetyl cysteine therapy was commenced. Despite these and general supportive measures the patient continued to deteriorate with worsening liver function tests. Subsequently he became encephalopathic and developed renal failure and pneumonia and was considered too unstable for consideration of an orthotopic liver transplant. He failed to respond to further treatment and died two weeks after presentation. Hepatitis E virus (HEV) serology taken ante-mortem was positive for anti-HEV IgM and anti-HEV IgG thus suggesting a diagnosis of acute HEV infection. A postmortem liver biopsy demonstrated histological changes consistent with an acute hepatitis with submassive necrosis.