A 36-year-old, alcoholic woman presents with a 1-week history of yellow skin and sclerae. She has suffered persistent headaches. Her vital signs are normal. Physical examination reveals jaundice. Laboratory studies disclose markedly elevated levels of AST and ALT (956 and 1,400 U/L, respectively). A few days later, she develops hepatic encephalopathy and renal failure. A liver biopsy shows prominent centrilobular necrosis. Which of the following is the most likely diagnosis?

Correct Answer: Acetaminophen toxicity
Description: Drug toxicity should be suspected in all cases of acute hepatitis. In this case, centrilobular necrosis suggests acetaminophen toxicity. The toxic dose of acetaminophen after a single acute ingestion is in the range of 150mg/kg in children and 7 g in adults. Acetaminophen is rapidly absorbed from the stomach and small intestine and conjugated in the liver to nontoxic agents, which then are eliminated in the urine. In cases of acute overdose, normal pathways of acetaminophen metabolism become saturated. Excess acetaminophen is then metabolized in the liver via the mixed function oxidase P450 system, yielding oxidative metabolites that cause predictable, hepatocellular necrosis. The centrilobular zones are particularly affected (centrilobular necrosis). Centrilobular necrosis is not seen in the other choices. Reye syndrome (choice D) occurs in children. Fatty liver of pregnancy (choice B) features micro vesicular steatosis.Diagnosis: Acetaminophen toxicity, hepatorenal syndrome
Category: Pathology
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