A 55-year-old woman comes to the emergency department with nausea, fever, fatigue, and anorexia. She returned a week ago from a trip to Mexico, where she underwent an emergency cholecystectomy without complications. Her temperature is 38.3 C (101 F), blood pressure is 100/60 mm Hg, pulse is 90/min, and respirations are 12/min. The patient is alert and answers questions but appears extremely weak and slightly icteric. She has no other medical problems and takes no medications. She does not use tobacco, alcohol, or illicit drugs. The patient is admitted to the hospital, but her condition worsens and she dies 2 days later. Postmortem viral serologies are negative. Gross examination of the liver on autopsy is shown in the image below.
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Which of the following additional findings would have most likely been found in this patient?
This patient presents after a recent surgery with signs and symptoms consistent with drug-induced liver injury, most likely due to inhaled anesthetic use. Inhaled anesthetic hepatotoxicity is most frequently associated with halothane, which remains one of the most commonly used inhaled anesthetics worldwide. In the United States, halothane has been largely replaced with other halogenated anesthetics, such as enflurane, isoflurane, desflurane, and sevoflurane. Although these agents are safer than halothane, there have been reports of associated hepatotoxicity.
Halogenated inhaled anesthetics predominantly cause a hepatocellular pattern of liver injury. This can range from mild asymptomatic aminotransferase elevation to fulminant hepatitis with a 50% fatality rate. In severe cases, extensive hepatocellular damage causes the liver to rapidly atrophy and appear shrunken on autopsy. Histologically, widespread centrilobular necrosis and inflammation of the portal tracts and parenchyma are observed, making the condition indistinguishable from fulminant viral hepatitis. The underlying mechanism is thought to be a hypersensitivity reaction to the drug that causes an immune-mediated attack against hepatocytes.
Patients suffering from inhaled-anesthetic hepatotoxicity typically have fever, anorexia, nausea, myalgias, arthralgias, and rash. Tender hepatomegaly (reflecting widespread liver inflammation) and jaundice can be present on physical examination. Laboratory findings typically include markedly elevated serum aminotransferase levels, prolonged prothrombin time, leukocytosis, and eosinophilia. The prolonged prothrombin time is due to failure of hepatic synthetic function and deficiency of factor VII (which has the shortest half-life of all the procoagulant factors).
(Choice A) Decreased serum albumin levels are commonly seen in patients with chronic, end-stage liver disease as the remaining hepatocytes have reduced functionality. However, acute liver injury presents with normal albumin levels due to the long half-life of albumin (~20 days).
(Choices B and D) Distended abdominal veins with ascites and palmar erythema are usually seen in patients with end-stage liver disease (eg, cirrhosis). These findings are not associated with acute hepatic failure.
(Choice C) A markedly elevated alanine aminotransferase level would be expected with fulminant hepatic failure.
(Choice F) Splenomegaly develops secondary to portal hypertension and can be seen in cirrhotic patients. It is not associated with acute hepatitis.
Educational objective:
Inhaled anesthetics, such as halothane, can be associated with a highly lethal fulminant hepatitis that cannot be distinguished histologically from acute viral hepatitis. Patients have significantly elevated aminotransferase levels due to massive hepatocellular injury and a prolonged prothrombin time due to failure of hepatic synthetic function.