Lithocholic Acid As a Toxic Endobiotic In Intrahepatic Cholestasis of Pregnancy: Clinical Aspects And Effects Of Ursodeoxicholic Acid Therapy.

CASTANO G; LUCANGIOLI SILVIA,; TRIPODI VALERIA,; SOOKOIAN S

San Francisco, USA,

Congreso; Annual meetting of the American Association for the Study of Liver Diseases; 2008

AASLD

Intrahepatic cholestasis of pregnancy (ICP) has been associated with increased fetal complications and perinatal mortality. Lithocholic acid (LCA) administration causes intrahepatic cholestasis and embriotoxicity in animals. We hypothesized that ICP patients’ with elevated serum LCA present more frequency of fetal complications. Aims: 1) To establish a cut off level of LCA for fetal complications, 2) To analyze the clinical consequences of high levels of LCA in ICP patients and their newborns, and 3) To evaluate the effects of ursodeoxicholic acid (UDCA) therapy administration on SBA profiles in this population. Patients and methods: Forty-nine ICP patients were studied. Medical, obstetrical and perinatal data were recorded. Liver functions tests, total serum bile acids (SBA), cholic acid, deoxycholic acid, chenodeoxycholic acid, LCA and UDCA, in their free, glyco and tauro derivative forms were assessed by capillary electrophoresis at baseline in 49 patients and after UDCA administration in 13 ones. Receiver Operating Characteristic (ROC) curves analysis were used to define cut-off points, with newborn complications as classification variable. Signs of fetal distress, low birth weight, preterm, small-for-gestational age and Apgar score at minute 1 less than 7 were assessed as newborn complications. Results: The area under the curve for LCA was 0.64 (95%CI: 0.49 to 0.78.). Cut-off values of 3.1 mM for LCA and of 23.7 mM for total SBA levels with sensibility of 80% were selected. Complications were associated with higher total SBA levels (47.6 ± 44.5 vs. 27.1 ± 18.2 mM; p=0.03). Elevated LCA was present in 32/ 39 patients. Patients with elevated LCA showed higher total and free SBA levels, and higher relation between free/ conjugated SBA. A high proportion (14/ 17) of the patients with newborn complications showed elevated baseline LCA. ICP patients with elevated LCA had a higher proportion of newborns with low birth weight or small for gestational age (7 vs. 0; p<0.05) and fetal distress (5 vs. 1). UDCA administration induced a significative reduction in liver function tests, in LCA (from 21.5± 23 to 2.4± 4.3 mM, p = 0.0003) and DCA levels (from 12.8± 19 to 2.9± 5.5 mM, p= 0.04). Conclusions: 1) LCA may act as a toxic endobiotic in ICP patients affecting newborns outcome. 2) UDCA had a beneficial effect in the liver function tests and in SBA profile in ICP patients with elevated LCA.