THE EFFECTS OF STEROID ADMINISTRATION ON SERUM ICAM-1 LEVELS IN PATIENTS WITH BILIARY ATRESIA: AN INDICATION OF FUTURE POSSIBILITIES
P. Dillon, A. Devenyi, G. Allison, D. Fields, R. Cilley
Penn State University Children's Hospital, Hershey, Pennsylvania, USA,

Purpose: With the realization that immunologic pathways of inflammation involving ICAM-1 expression may contribute to the pathogenesis of biliary atresia (BA), the possibility exists for altering the disease process by modulating this adhesion molecule's expression. However, role of anti-inflammatory agents for BA has never been explored. Thus, we investigated the effects of steroid therapy on serum ICAM-1 levels in patients with BA.
Methods: Patients with confirmed BA undergoing an hepatoportoenterostomy were started on Prednisone therapy with the resumption of oral intake. The initial dose was 4 mg/kg/day with a tapering schedule of 2 mg/kg/day x 2wks,then 1 mg/kg/day x 2 wks, then 0.5 mg/kg/day x 2 wks, then off. Serum was collected from each patient at the time of diagnosis and at varying time points following surgery and stored at -80°C until assayed. Levels of sICAM-1 were measured in duplicate utilizing an ELISA method (Biosource International).
Results: A total of 3 patients with follow-up>1 yr were studied. Mean duration of follow-up was 20+2; months. sICAM-1 levels were significantly elevated in all patients when compared to controls at the time of diagnosis (533+282 vs 78+12 ng/ml). sICAM-1 levels tended to increase immediately following surgery. By 1 yr after surgery, 2 of the 3 infants had sICAM-1 levels significantly below those found at the time of diagnosis (289+10 vs 1197+l24 ng/ml) and lower than untreated historical controls. All had normal bilirubin levels at 1 yr of follow-up.
Conclusion: In this small group our results indicate that relatively short term steroid therapy following a Kasai procedure may exert an influence on ICAM-1 expression and its serum levels in biliary atresia and have a positive impact on the clinical course of the disease. These results point to the potential benefit of long term suppression of ICAM-1 expression in treating this devastating process.

---

THE EFFECT OF URSODEOXYCHOLIC ACID (UDCA) THERAPY IN BILIARY ATRESIA: A RANDOMIZED, DOUBLE-BLIND, CONTROLLED TRIAL
Frederick C. Ryckman, Maria A. Alonso., Hesham A-Kader, William F. Balistreri
Children's Hospital; Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229

We hypothesized that ursodeoxycholic acid (UDCA), a choleretic and cytoprotective bile acid, would improve the outcome for patients with biliary atresia. We, therefore, carried out a double-blind, randomized, placebo-controlled trial of UDCA in 23 patients (each below the age of 4 months) with documented biliary atresia following hepatoportoenterostomy. The patient received either UDCA (15 mg/kg/day) or placebo. Biliary enrichment with UDCA measured at one month was significantly higher; in UDCA recipients (16.4%, range 9.6 to 21.9%, vs 3.8%, range 0.9 to 4.9%; p<0.05). UDCA therapy was associated with relief of pruritus, which worsened following cessation of therapy; placebo recipients experienced relief of pruritus, when switched to UDCA at the end of the study. In UDCA recipients, aspartate aminotransferase (AST) levels decreased from a mean of 245 to 149 IU/L (p< 0.05) and alanine aminotransferase (ALT) levels decreased from a mean of 201 to 72 IU/I (p< 0.01) with no significant improvement in the placebo group.
There was no significant improvement in bilirubin levels. There were no discernable differences in weight gain or clinical outcome between UDCA and placebo recipients. Eight of the twelve UDCA recipients and 7 of the 11 placebo recipients underwent liver transplantation at a mean age/weight of 14.3 months/7.2 kg and 11.1 months and 6.4 kg respectively. No side effects were observed. We conclude that UDCA in a dose of 15 mg/kg/day may improve biochemical indices and relieve pruritus in patients with biliary atresia.

>> TOP