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is terminated, although progression to a chronic biliary cirrhosis-like illness can occur rarely, even if the drug is withdrawn. Steroid-type cholestasis is a pure reaction with little or no hepatocellular inflammation. Gradual onset of cholestasis without systemic symptoms is usual. Alkaline phosphatase is elevated, but aminotransferase levels are usually unimpressive, and liver biopsy shows only centrizonal bile stasis with little portal reaction or hepatocellular disarray.
Complete resolution follows drug withdrawal.
This type of cholestasis is produced by oral contraceptives, methyltestosterone, and related drugs, most of which are C-17 alkylated steroids. The reaction appears to be an exaggeration of the physiologic effect of sex hormones on bile formation, rather than an immunologic sensitivity or membrane cytotoxicity. Interference with canalicular water flow, microfilament dysfunction, and altered membrane fluidity may be responsible, but the exact mechanism of cholestasis is uncertain. Lovastatin and related cholesterol-regulating drugs not uncommonly produce subclinical aminotransferase elevations, although major liver injury is infrequent. The illness may begin as an acute hepatitis or more insidiously.