CORRECTION OF MATERNAL SERUM BILE-ACID PROFILE DURING URSODEOXYCHOLICACID THERAPY IN CHOLESTASIS OF PREGNANCY

Background/Aims: Intrahepatic cholestasis of pregnancy is characterize d by pruritus and increased levels of serum bile acids, and is often a ssociated with premature delivery, fetal distress, and perinatal morta lity. The aims of the present study were: (i) to better define the ser um bile acid profile in intrahepatic cholestasis of pregnancy and its potential usefulness for differential diagnosis; (ii) to investigate t he effect of ursodeoxycholic acid treatment on the bile acid pool; and (iii) to investigate possible adverse effects of therapy. Methods: Fi fteen patients with intrahepatic cholestasis of pregnancy were enrolle d in this study. Ursodeoxycholic acid (14 mg/kg body weight per day) w as administered for 13+/-5 days. Twenty normal pregnant women served a s controls. Serum bile acid profile was analyzed by high-performance l iquid chromatography.Results: Patients with cholestasis of pregnancy s howed significant alterations in the proportion of primary bile acids, with an increase in cholic acid (64.0+/-3.0% vs. 32.2+/-1.8%, p<0.01) , and a decrease in chenodeoxycholic acid (20.8+/-1.4% vs, 31.9+/-1.3% , p<0.01), as compared to controls, resulting in a marked elevation in the cholic/chenodeoxycholic acid ratio (3.4+/-0.5 vs. 1.1+/-0.1, p<0. 01), The glycine/taurine ratio was reduced in cholestasis of pregnancy (0.8+/-0.1 vs. 1.4+/-0.1, p<0.01), During ursodeoxycholic acid admini stration its proportion in serum increased from 1.4+/-0.6% (0.6+/-0.2 mu mol/l) at baseline to 24.7+/-2.3% (5.9+/-1.9 mu mol/l) with therapy (p<0.01). This increment was accompanied by a significant decrease in the percentage of cholic acid (28.2+/-2.6%, p<0.01) and an elevation in chenodeoxycholic acid proportion (25.0+/-1.9%, N.S.). Although lith ocholic acid concentration in serum was maintained with treatment (1.2 +/-0.2 mu mol/l vs. 1.7+/-0.5 mu mol/l), there was a significant incre ase in lithocholic acid proportion (p<0.01) from 3.3+/-0.5% at baselin e to 7.4+/-1.3% during therapy, The glycine/taurine ratio of serum bil e acid pool returned to normal after ursodeoxycholic acid administrati on (1.7+/-0.3). Conclusions: These results establish the importance of ursodeoxycholic acid treatment for the correction of maternal serum b ile acid profile in cholestasis of pregnancy, indicating that ursodeox ycholic acid may improve fetal prognosis.