Megan Brooks

November 04, 2009

November 4, 2009 (Boston, Massachusetts) — Two commercially available multivitamin preparations containing fat-soluble vitamins do not prevent fat-soluble vitamin deficiencies in infants with biliary atresia, particularly those with ongoing cholestasis.

That finding comes from an interim analysis of a prospective multicenter study, the Biliary Atresia Research Consortium, presented during a plenary session here at The Liver Meeting 2009: American Association for the Study of Liver Diseases 60th Annual Meeting.

The 2 supplements — ADEKs and AquADEKs — contain increased amounts of fat-soluble vitamins combined with tocopheryl polyethylene glycol-1000 succinate, which is rapidly absorbed, independent of bile flow, Benjamin L. Shneider, MD, the study's principal investigator from Children's Hospital Pittsburgh in Pennsylvania, explained in an interview with Medscape Gastroenterology.

"These multivitamin supplements are often used in clinical practice in infants with cholestasis because they are more convenient than giving individual vitamins and they are perceived to be effective," Dr. Shneider said. "However, much to our surprise, we found that they don't work as well as one would have thought."

The findings come from a study of 57 infants enrolled in a placebo-controlled trial of corticosteroid therapy following hepatoportoenterostomy (HPE) for biliary atresia. All of the infants received ADEKs/AquADEKs (2 mL daily), coadministered with vitamin K (2.5 mg, 3 times weekly), and were monitored at 1, 3, and 6 months after HPE.

Despite multivitamin supplementation, "40 of the 57 infants required additional fat-soluble vitamin supplementation at some point in time as treatment for fat-soluble deficiency," write Dr. Shneider and colleagues in a meeting abstract.

At 1, 3, and 6 months after HPE, the frequency of vitamin A deficiency (retinol <20 µg/dL) in infants tested was 17%, 31%, and 27%, respectively, and the frequency of vitamin D deficiency (25-OH vitamin D <15 ng/mL) was 29%, 21% and 35%, respectively.

For vitamin E deficiency (α tocopherol <3.8 µg/mL), the frequencies were 8%, 5%, and 5%, respectively, and for vitamin K deficiency (international normalized ratio >1.2), the frequencies were 10%, 23%, and 21%, respectively.

"When we looked at bilirubin level vs bile acid level as a predictor of any vitamin deficiency, we found a better correlation with bilirubin than with bile acids," Dr. Shneider noted. "Our data suggest that children with bilirubin levels greater than 2 are at greatest risk for vitamin deficiencies."

Three months after HPE, fat-soluble deficiencies were seen in 44% of infants with a total bilirubin level of 2 mg/dL or more, and in none of the infants with a total bilirubin level of less than 2 mg/dL, the researchers reported.

"The bottom line is that these multivitamin supplements, although theoretically useful, don't appear to be effective in children whose bilirubin levels are greater than 2," Dr. Shneider said, "so one is faced with going back, perhaps, to the method of using multiple individual supplements."

"Just as important, I think we all need to be monitoring these children more closely for vitamin deficiencies. Clearly, just putting them on these vitamin preparations is not enough," Dr. Shneider told Medscape Gastroenterology.

Meeting attendee Shikha S. Sundaram, MD, from the Children's Hospital in Denver, Colorado, who was not involved in the study, said: "I think this is seminal work because we've always supplemented vitamin levels in these patients but no one has ever really systematically looked at this issue."

Although rare, affecting 1 in 13,000 to 14,000 American children, biliary atresia is the most common indication for liver transplantation in children.

The study was supported by the National Institutes Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Axcan Pharma supplied ADEK and Ursodiol under a Cooperative Research and Development Agreement with the National Institutes of Health. Dr. Shneider and Dr. Sundaram have disclosed no relevant financial relationships.

The Liver Meeting 2009: American Association for the Study of Liver Diseases (AASLD) 60th Annual Meeting: Abstract 698. Presented November 1, 2009.


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