Unless the drug is stopped, progressive chronic hepatitis and cirrhosis can develop. Whether the reaction is caused by a hypersensitivity mechanism or by hepatotoxic metabolites is uncertain, but most evidence favors the latter. Obesity seems to be a risk factor, possibly because halothane metabolites are stored in adipose tissue. Hepatitis typically develops within a few days to 2 wk after operation, is heralded by fever, and is often severe. Distinction from posttransfusion viral hepatitis is aided by a shorter latency period, negative serologic tests for hepatitis B and C, occasional eosinophilia or skin rash, and sometimes subtle histologic differences.
Mortality is high, but survivors usually recover completely.
Methoxyflurane and enflurane, related anesthetics, can produce the same syndrome. Differentiation from extrahepatic obstruction may be difficult, even by liver biopsy. The reaction seems to result from idiosyncrasy, and eosinophilia and other signs of a sensitivity reaction occur in some cases. Other evidence, however, points to direct toxicity to hepatic canaliculi, possibly via interference with membrane ATPase. Complete resolution is usual when drug administration is terminated, although progression to a chronic biliary cirrhosis-like illness can occur rarely, even if the drug is withdrawn.