Ursodeoxycholic Acid as a Supplementary Treatment in Corrected Biliary Atresia

Early reports suggest that the use of steroids, ursodeoxycholic acid, and chronic intravenous antibiotics may improve bile flow and outcome in infants following the Kasai operation for biliary atresia [[4]].

There is evidence that substances provided orally facilitating the bile flow, could mediate such inflammatory damage. So, we decided to present our brief experience with per os administration of ursodeoxycholic acid in four children with biliary atresia.

All children suffered from extrahepatic biliary atresia, type III and their α‐1 antitrypsin phenotype was Pi-MM. The ages of the children vary from 8 months to 3 years, mean age 1.7 years, and the sexes are equally divided, two boys and two girls. Their postoperative medications included: multivitamins, vitamin E, cholestyramine, spironolactone and cephradine.

One of our patients was treated with steroids (phenobarbitone one dose/day 5 mg/kg), for approximately 6 months after operation until our decision to discontinue the therapy, due to the pure results.

Every child was examined periodically (every 2nd month) in our department and profile biochemical parameters were counted, always including liver function parameters (AST, ALT, γ‐GT, total and direct bilirubin, INR, total protein, total albumin and globulin) and detailed haematological examination. A rapid deterioration of the parameters with high levels of AST, ALT, γ‐GT ten to fifteen times over the normal levels, even if bilirubin levels (total) were less than 1 mg/dl and the poor results with the steroid treatment led us to the oral administration of the sir Ursofalk (ursodeoxycholic acid - galenica). Treatment was 3 doses per day, 15 mg/kg/d, targeting the facilitation of bile flow as a good prognostic factor for the disease's progression. Ursodeoxycholic acid (UDCA) is a bile acid, which is present in human bile at a low concentration of only 3 % of total bile acids. It is a 7beta-hydroxy epimer of the primary bile acid chenodeoxycholic acid (CDCA). Two months after the administration of Ursofalk, the levels of AST, ALT and γ‐GT started decreasing and four, six and eight months later were almost at normal levels. It is fact that even if we have improved biochemical liver function neither the exact way of pharmacokinetics nor histopathological liver specimens can verify that. All children, after the drug administration, are doing very well and no side effects developed.

Every physician wants to determine simple predictors for quality of life (QOL) in long-term jaundice-free survivors after the Kasai operation. It seems that the serum AST and ALT levels represent a simple, strong predicting factor of QOL and liver dysfunction and may prove useful in planning liver transplantation [[2], [6]]. Because the mechanisms that mediate pruritus of cholestasis remain to be determined, the use of empirical therapies continues to be standard practice. Ursodeoxycholic acid may ameliorate pruritus [[1], [3], [5]].

There are many questions regarding the hepato-protective effect of UDCA that should be addressed in the near future. In particular, we do not know how chronic cholestasis induces liver fibrosis and if UDCA can prevent or counteract this process [[1]].

We hope that this therapy could decrease the need for early liver transplantation after Kasai portoenterostomy. Specific to the pediatric patient, optimising growth, development and nutrition, minimizing discomfort and disability, and aiding the child and family in coping with the stress, social, and emotional effects of chronic liver disease remain paramount.

References

• 1 Copaci I, Micu L, Iliescu L, Voiculescu M. New therapeutical indications of ursodeoxycholic acid.  Rom J Gastroenterol. 2005;  14 259-266
• 2 Jiang C B, Lee H C, Yeung C Y. et al . A scoring system to predict the need for liver transplantation for biliary atresia after Kasai portoenterostomy.  Eur J Pediatr. 2003;  162 603-606
• 3 Ishizaki K, Imada T, Tsurufuji M. Hepatoprotective bile acid “ursodeoxycholic acid (UDCA)” Property and difference as bile acids.  Hepatol Res. 2005; 
• 4 Meyers R L, Book L S, O'Gorman M A. et al . High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia.  J Pediatr Surg. 2003;  38 406-411
• 5 Ng V L, Balistreri W F. Treatment Options for Chronic Cholestasis in Infancy and Childhood.  Curr Treat Options Gastroenterol. 2005;  8 419-430
• 6 Uchida K, Urata H, Suzuki H. et al . Predicting factor of quality of life in long-term jaundice-free survivors after the Kasai operation.  J Pediatr Surg. 2004;  39 1040-1044