Research of congenital biliary atresia using analysis of DELTA^4-3-oxo-bile acids in urine

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Normal values of urinary DELTA^4-3-oxo-bile acids were established in the present from neonates to adults. Activity of 3-oxo-DELTA^4-steroid 5beta-reductase (5beta-reductase) increased immediately after birth, and thereafter the urinary DELTA^4-3-oxo-bile acids gradually decreased until 3 months of age. However, after 1 year of age we again detected small amounts of DELTA^4-3-oxo-bile acids in the urine, DELTA^4-3-oxo-bile acids produced in the intestine by bacterial flora.The percentage of DELTA^4-3-oxo-bile acids in total bile acids (TBAs) in urine of biliary atresia significantly exceeded that of neonatal cholestasis or healthy controls (p<0.05). However, biliary atresia could not be distinguished from idiopathic neonatal hepatitis based on the percentage of DELTA^4-3-oxo-bile acids in TBAs in urine.In this study, moreover, analysis of DELTA^4-3-oxo-bile acids in patients with 5beta-reductase, fulminant hepatie failure, and cirrhosis showcd that these patients exhibited a higher percentage of 7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid in TBAs than 7alpha, 12alpha-dihydroxy-3-oxochol-4-en-24-oic acid and 12alpha-hydroxy-3-oxochola-4,6-dien-24-oic acid. These patients were positively correlated with poor prognosis. This finding suggests that a reduction in 5beta-reductase activity due to severe liver damage leads to reduction in 12alpha-hydroxylase.We reported the first Japanese patient with 5beta-reductase deficiency during this study. It will very important to determine whether this disease should be defined as primary or secondary 5beta-reductase deficiency.In conclusion, to determine the profile of unusual urinary bile acids, such as DELTA^4-3-oxo-bile acids, at an early stage of liver disease is important to define prognosis and/or treatment. We also think that analysis of urinary DELTA^4-3-oxo-bile acids is very useful to identify inborn errors in bile acid synthesis.