SELECTIVITY AND SENSITIVITY OF CHANGES IN SERUM BILE-ACIDS DURING INDUCTION OF CIRRHOSIS IN RATS

Because some patients with cirrhosis have serum transaminase levels wi thin the normal range, a prospective study was undertaken to determine whether the concentration of individual serum bile acids would be a s ensitive indicator of development of cirrhosis. The choline-deficient rat has been used as a model for study of these changes. Using high-pe rformance liquid chromatography, we measured the concentrations of ind ividual serum bile acids at 3, 6, 10, 20 and 30 wk of dietary intake. Serum levels of total glycine- and taurine-conjugated bile acids were elevated at all stages tested as compared with levels in control group s (choline supplemented). Similarly, unconjugated bile acids and, part icularly, cholic acid showed significantly higher levels at all stages except with the occurrence of cirrhosis at 30 wk, at which time there was a significantly lower level for unconjugated bile acids (0.48 +/- 0.11 vs. 1.40 +/- 0.36 in controls) and for cholic acid (0.17 +/- 0.0 5 vs. 0.91 +/- 0.39 in controls). The ratio of serum cholic acid to se rum chenodeoxycholic acid changed in temporal relationship to progress ion in the histological lesions in livers of these rats. The ratio was at its highest at 78 +/- 3 at 3 wk (no histological change) and decre ased with increasing time and changes in histological appearance until 30 wk, at which time it was down to 1.6 +/- 0.6. The routinely used m arkers of liver injury (serum ALT, alkaline phosphatase and bilirubin) , however, did not match the progression of hepatic histological chang es. The relationship of the increase in serum bile acids to the cirrho tic process is supported by qualitatively similar findings in a second rat model. Thus the hepatic pathological changes in cirrhotic rats we re reflected by the changes in the individual serum bile acids togethe r with the ratio of serum cholic acid to serum chenodeoxycholic acid, but not with other standard tests of liver function.