Archives of Disease itn Childhood, 1979, 54, 367-370
Serum 25-hydroxy-vitamin D in hepatobiliary disease in infancy AKIO KOBAYASHI, SAKAE KAWAI, MICHIKO OHKUBO, AND YOSHIRO OHBE Department of Paediatrics, National Children's Hospital, Tokyo
Serum 25-hydroxy-vitamin D (25-OHD) concentrations were measured in 49 patients with hepatobiliary disease in infancy. Low mean values were found in groups of patients with biliary atresia, neonatal hepatitis, choledochal cyst, and chronic intrahepatic cholestatic syndrome. In the group of patients with surgically repaired biliary atresia, the mean value did not differ from normal. Parenteral vitamin D increased 25-OHD in serum in patients with biliary atresia, but did not do so in one patient with neonatal hepatitis. In contrast, oral vitamin D did not increase serum 25-OHD concentrations in patients with biliary atresia. It is concluded that the reduction of serum 25-OHD seen in biliary atresia was largely due to the malabsorption of vitamin D, while in neonatal hepatitis it was due to impairment of 25-hydroxylation of the vitamin. SUMMARY
Although rickets is a common complication in hepatobiliary disease in infancy (Yu et al., 1971; Kobayashi et al., 1974a), the mechanism underlying its pathogenesis is poorly understood. It can be postulated that the impairment of 25-hydroxylation of vitamin D in the liver may contribute to the pathogenesis of hepatic rickets. On the other hand, rickets in hepatobiliary disease may result from defective absorption of fat-soluble vitamin D because of deficient or absent bile flow into the intestine. The present study was undertaken to assess serum 25-hydroxy-vitamin D (25-OHD) con-
centrations in patients with hepatobiliary disease in infancy and to investigate the pathogenesis of hepatic rickets.
Subjects and methods The subjects were 14 patients with biliary atresia, 22 with biliary atresia who had been successfully repaired by hepatic portojejunostomy and had no jaundice (Kobayashi et al., 1976), 7 infants with neonatal hepatitis, 5 patients with chronic intrahepatic cholestatic syndrome, and one infant with choledochal cyst. All patients with biliary atresia had laparotomy Department of Paediatrics, Section of Gastroenterology, National Children's Hospital, Tokyo AKIO KOBAYASHI, clinical paediatrician SAKAE KAWAT, clinical paediatrician MICHIKO OHKUBO, clinical paediatrician YOSHIRO OHBE, chief clinical paediatrician
and the diagnosis was confirmed. Diagnosis of neonatal hepatitis was on clinical and laboratory grounds, excluding other diseases causing obstructive jaundice during infancy. Of 5 patients with chronic intrahepatic cholestatic syndrome, 3 had intrahepatic biliary hypoplasia (Alagille et al., 1975) and the other 2 had recurrent intrahepatic cholestasis (Summerskill and Walshe, 1959). One infant with choledochal cyst had a laparotomy and the diagnosis was confirmed. Radiological evidence of rickets was found in 7 (50%) of 14 patients with biliary atresia at the time of determination of serum 25-OHD. No lesions were observed in 22 patients with surgically repaired biliary atresias. In neonatal hepatis 3 (43 %) of 7 patients had the lesion. In the group of patients with chronic intrahepatic cholestatic syndrome one patient with intrahepatic biliary hypoplasia had rickets. The infant with choledochal cyst had no radiological signs of rickets. The lesions in the present series were florid. Serum 25-OHD was measured by a modified method of Belsey et al. (1974), using competitive protein-binding assay.
Results Serum 25-OHD concentrations of control group. Serum 25-OHD was measured in 17 healthy infants and children. The mean value from age 2 months to 1 11/12 years was 22-4 ng/ml (n = 11, SD 9 5), with a range of 8 3 to 42 0. In the group above 2 367
368 Kobayashi, Kawai, Ohkubo, and Ohbe years of age it was 18 * 9 ng/ml (n = 6, SD 7 6), with a range of 12 5 to 30 0. There was no significant difference between the two age groups. -
Serum 25-OHD concentrations in hepatobiliary disease (Fig. 1). In 14 patients with biliary atresia serum 25-OHD concentrations were conspicuously reduced with the mean value of 8 2 ng/ml (SD 5 2, range 2 0 to 17 5), which was significantly lower than normal (P , , 0 ("-
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Serum 25-hydroxy-vitamin D in hepatobiliary disease in infancy AKIO KOBAYASHI, SAKAE KAWAI, MICHIKO OHKUBO, AND YOSHIRO OHBE Department of Paediatrics, National Children's Hospital, Tokyo
Serum 25-hydroxy-vitamin D (25-OHD) concentrations were measured in 49 patients with hepatobiliary disease in infancy. Low mean values were found in groups of patients with biliary atresia, neonatal hepatitis, choledochal cyst, and chronic intrahepatic cholestatic syndrome. In the group of patients with surgically repaired biliary atresia, the mean value did not differ from normal. Parenteral vitamin D increased 25-OHD in serum in patients with biliary atresia, but did not do so in one patient with neonatal hepatitis. In contrast, oral vitamin D did not increase serum 25-OHD concentrations in patients with biliary atresia. It is concluded that the reduction of serum 25-OHD seen in biliary atresia was largely due to the malabsorption of vitamin D, while in neonatal hepatitis it was due to impairment of 25-hydroxylation of the vitamin. SUMMARY
Although rickets is a common complication in hepatobiliary disease in infancy (Yu et al., 1971; Kobayashi et al., 1974a), the mechanism underlying its pathogenesis is poorly understood. It can be postulated that the impairment of 25-hydroxylation of vitamin D in the liver may contribute to the pathogenesis of hepatic rickets. On the other hand, rickets in hepatobiliary disease may result from defective absorption of fat-soluble vitamin D because of deficient or absent bile flow into the intestine. The present study was undertaken to assess serum 25-hydroxy-vitamin D (25-OHD) con-
centrations in patients with hepatobiliary disease in infancy and to investigate the pathogenesis of hepatic rickets.
Subjects and methods The subjects were 14 patients with biliary atresia, 22 with biliary atresia who had been successfully repaired by hepatic portojejunostomy and had no jaundice (Kobayashi et al., 1976), 7 infants with neonatal hepatitis, 5 patients with chronic intrahepatic cholestatic syndrome, and one infant with choledochal cyst. All patients with biliary atresia had laparotomy Department of Paediatrics, Section of Gastroenterology, National Children's Hospital, Tokyo AKIO KOBAYASHI, clinical paediatrician SAKAE KAWAT, clinical paediatrician MICHIKO OHKUBO, clinical paediatrician YOSHIRO OHBE, chief clinical paediatrician
and the diagnosis was confirmed. Diagnosis of neonatal hepatitis was on clinical and laboratory grounds, excluding other diseases causing obstructive jaundice during infancy. Of 5 patients with chronic intrahepatic cholestatic syndrome, 3 had intrahepatic biliary hypoplasia (Alagille et al., 1975) and the other 2 had recurrent intrahepatic cholestasis (Summerskill and Walshe, 1959). One infant with choledochal cyst had a laparotomy and the diagnosis was confirmed. Radiological evidence of rickets was found in 7 (50%) of 14 patients with biliary atresia at the time of determination of serum 25-OHD. No lesions were observed in 22 patients with surgically repaired biliary atresias. In neonatal hepatis 3 (43 %) of 7 patients had the lesion. In the group of patients with chronic intrahepatic cholestatic syndrome one patient with intrahepatic biliary hypoplasia had rickets. The infant with choledochal cyst had no radiological signs of rickets. The lesions in the present series were florid. Serum 25-OHD was measured by a modified method of Belsey et al. (1974), using competitive protein-binding assay.
Results Serum 25-OHD concentrations of control group. Serum 25-OHD was measured in 17 healthy infants and children. The mean value from age 2 months to 1 11/12 years was 22-4 ng/ml (n = 11, SD 9 5), with a range of 8 3 to 42 0. In the group above 2 367
368 Kobayashi, Kawai, Ohkubo, and Ohbe years of age it was 18 * 9 ng/ml (n = 6, SD 7 6), with a range of 12 5 to 30 0. There was no significant difference between the two age groups. -
Serum 25-OHD concentrations in hepatobiliary disease (Fig. 1). In 14 patients with biliary atresia serum 25-OHD concentrations were conspicuously reduced with the mean value of 8 2 ng/ml (SD 5 2, range 2 0 to 17 5), which was significantly lower than normal (P , , 0 ("-
-b
6r to
0
el
h i;. -C 4p.Q,Q, -fi
6
210
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5 Duration of therapy (weeks)
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