Lithocholic acid hepatotoxicity

When chenodeoxycholic acid therapy was first introduced, there was some anxiety that this bile acid, or its bacterial metabolite lithcholic acid, might cause liver damage in man. This possible complication has not eventuated. Lithocholic acid is toxic to the liver in many animal species but in man, it is converted to sulfolithocholate and excreted (A5). Nevertheless, up to one-third of patients undergoing chenodeoxycholic acid treatment do show transient rises in serum levels of aspartate aminotransferase activity. The mechanism of this hypertransaminasemia is obscure, although it could possibly be related to lithocholate formation (D8). In any case, hepatotoxicity very rarely occurs at a clinically significant level (SI4). 

Neomycin is a polybasic, poorly absorbed antibiotic which forms insoluble precipitates with bile salts (99). It lowers serum cholesterol concentrations in man (100-102) and chickens (99) and increases fecal bile acid excretion. It inhibits the hepatotoxic effects of lithocholic acid ingestion in chickens (99) and prevents bacterial conversion of cholate to deoxycho-late (103). Neomycin, 6-12 g/day, induces a malabsorption syndrome, with mucosal changes similar to those of sprue (104). Bile salt metabolism is thus affected in at least three ways by neomycin (1) a binding effect similar to that of cholestyramine, (2) suppression of deconjugation and secondary bile formation caused by antimicrobial properties, and (3) possible impairment of absorption of bile salts by intestinal mucosa. The first probably accounts for most of the increased fecal excretion of bile salts. 

Lithocholic acid, however, although hepatotoxic in the experimental animal, should not produce liver damage in man. The human liver, in fact, sulphates efficiently lithocholic acid and sihde sulphated bile acids are malabsorbed, man should be protected from potential hepatotoxicity of this secondary bile acid. 

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