Fulminant hepatic failure with massive necrosis as a result of hepatitis a infection

Fulminant hepatic failure as a result of hepatitis A is a rarely diagnosed complication entity in developed countries. With the advent of specific serologic markers for acute hepatitis A virus infection, the incidence and pathology of fulminant hepatitis A can be more clearly defined. We describe four patients (one adult, three children; two males and two females, ages 2 ½-58 years) referred to our institution for orthotopic liver transplantation subsequent to fulminant hepatic failure following hepatitis A infection. All of these patients had a history of residence in or travel to hepatitis A endemic areas. Hepatitis A infection was documented by the presence of serum IgM against hepatitis A virus prior to transplantation. Infection with hepatitis B virus, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus was excluded by clinical and specific serologic examinations. All patients presented with varying degrees of encephalopathy, progressing to coma. Coagulopathy in the form of prolonged prothrombin time and partial thromboplastin time was present in all patients. Peak liver parenchymal enzymes increased to greater than ten times the upper limit of the normal range. Total and direct bilirubin levels increased to >20 and 10 mg/dl, respectively. Histologic evaluation of the explanted livers showed a spectrum of changes ranging from periportal hepatocellular necrosis with focal parenchymal collapse and prominent bile duct proliferation to massive necrosis with complete loss of hepatic architecture. In two cases (Cases 1 and 4), prominent microvesicular and macrovesicular steatosis was seen within residual hepatocytes. No evidence of preexisting disease (i.e., parenchymal scarring) was present. Two of the four patients (Cases 1 and 4) are alive and well, 3 and 4 years post-transplant. Two children died posttransplant of complications of fulminant hepatic failure; marked cerebral edema, necrosis, and brainstem herniation were confirmed at autopsy. Hepatitis A appears to be an important cause of fulminant hepatic failure, especially in endemic areas. Orthotopic liver transplantation performed prior to irreversible brain injury may save a significant number of patients with fulminant hepatic failure.