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Bleeding as the first symptom of extrahepatic biliary atresia
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THREE S E R O L O G I C A L M A R K E R S OF C O N N E C T I V E TISSUE M E T A B O L I S M AS INDICATORS OF SEVERE HEPATIC FIBROSIS IN INDIAN C H I L D H O O D C I R R H O S I S . . . L.R1stell . * • -* , M . S . T a n n e r** . S.Bhave " t P.~rlvedl. , J.R1stell , A . P a n d i t " & A . P . M o w a t . King's C o l l e g e Hospital, London, UK. * • ** . . • Collagen Research Unlt, Oulu, FINLAND. U n l v e r s l t y of Lelcester, UK. SKing Edward Memorial Hospital, Pune, INDI~ Although serum type III procollagen peptides (PIIIP) have been considered as indicators of hepatic pathology in adults, our studies to date have not confirmed this in children. To clarify this and to determine the role of PIIIP and of serum basement membrane antigens in the a s s e s s m e n t of hepatic c o n n e c t i v e tissue accumulation in children, we have m e a s u r e d serum concentrations of PIIIP, the 7S domain of type IV collagen (7S) and the Pl fragment of l a m i n i n (Pl) in patients aged 0.75-3.0yrs w i t h a p a r t i c u l a r l y a g g r e s s i v e form of cirrhosis, Indian Childhood Cirrhosis (ICC). Serum PIIIP, 7S and Pl were each compared with semi- quantitative histological analysis of liver biopsy specimens. PIIIP, 7S and PI were all significantly increased in ICC (p<0.001) when compared to healthy siblings and age-matched controls; 7S was raised above the upper limit of normal for age (mean+2xsd) in 95% of children with ICC, Pl in 91% and PlIIP in 76%. PIIIP (sds-a~e corrected) 7S (ugll) P1 ~U/I) (49) C a u c a s i a n controls 0 ± 1.02 (55) <13 (36) 1.58 f 0.36 H e a l t h y siblings 0.23 ± 1.03 (17) <13 ( 7) 1.61 ± 0.21 (12) ICC 12.58 ± 12.70 (34) 95 ± 63 (22) 6.29 ± 2.49 (23) Serum 7S and PI each s h o w e d a significant c o r r e l a t i o n with the degree of i n t r a l o b u l a r fibrosis in ICC (p
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BLEEDING AS THE FIRST SYMPTOMOF EXTRAHEPATICBILIARY ATRESIA R.H.J. Houwen, J. Bouquet*, C.M.A. Bijleveld Dept. of Pediatrics, University Hospital Groningen and * Sophia Childrens Hospital Rotterdam
Extrahepatic b i l i a r y atresia is a rare disease with an incidence of 1 in 10.000 newborns. I t is characterized by a total occlusion of the bile ducts outside the l i v e r . So these infants generally present with cholestatic jaundice in the f i r s t months of l i f e . We did a retrospective analysis of 100 patients with extrahepatic b i l i a r y atresia. Twelve infants presented with haemorrhagic phenomena rather than with jaundice. Mean age at presentation of these 12 was 23 days (range 9-45 days). Five patients had an intracranial bleeding, four umbilical bleeding and three extensive haematomata. Coagulation studies were indicative of vitamin K deficiency. Ten patients were treated with vitamin K, which stopped the bleeding. The other two patients were transfused with fresh blood or clotting factors. In these 12 patients jaundice was observed only after the bleeding episode. We assume that mild cholestasis and thus vitamin K malabsorption was already present before the bleeding occurred. Moreover all twelve infants had breast feeding, which has a low vitamin K content. So in these children the low vitamin K intake due to the breast feeding was aggravated by the malabsorption due to the cholestasis. This led to the increased bleeding tendency. The same mechanism, vitamin K deficiency due to cholestasis causing an increased bleeding tendency also occurs in =l-antitrypsin deficiency and in neonatal hepatitis. The incidence of bleeding as the f i r s t symptom of extrahepatic b i l i a r y atresia is 1-2:100.000. The same applies to e l - a n t i t r y p s i n deficiency and possibly neonatal hepatitis. So the overall incidence of bleeding as the f i r s t symptom of cholestatic l i v e r disease in the neonatal period w i l l be 3-6:100.000. The incidence of severe bleeding in a l l newborns is 20-50:100.000. So at least 6% of severe bleeding in infants is due to cholestasis induced vitamin K malabsorption. Therefore cholestatic l i v e r disease should be considered in each infant with haemorrhagic phenomena.
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THREE S E R O L O G I C A L M A R K E R S OF C O N N E C T I V E TISSUE M E T A B O L I S M AS INDICATORS OF SEVERE HEPATIC FIBROSIS IN INDIAN C H I L D H O O D C I R R H O S I S . . . L.R1stell . * • -* , M . S . T a n n e r** . S.Bhave " t P.~rlvedl. , J.R1stell , A . P a n d i t " & A . P . M o w a t . King's C o l l e g e Hospital, London, UK. * • ** . . • Collagen Research Unlt, Oulu, FINLAND. U n l v e r s l t y of Lelcester, UK. SKing Edward Memorial Hospital, Pune, INDI~ Although serum type III procollagen peptides (PIIIP) have been considered as indicators of hepatic pathology in adults, our studies to date have not confirmed this in children. To clarify this and to determine the role of PIIIP and of serum basement membrane antigens in the a s s e s s m e n t of hepatic c o n n e c t i v e tissue accumulation in children, we have m e a s u r e d serum concentrations of PIIIP, the 7S domain of type IV collagen (7S) and the Pl fragment of l a m i n i n (Pl) in patients aged 0.75-3.0yrs w i t h a p a r t i c u l a r l y a g g r e s s i v e form of cirrhosis, Indian Childhood Cirrhosis (ICC). Serum PIIIP, 7S and Pl were each compared with semi- quantitative histological analysis of liver biopsy specimens. PIIIP, 7S and PI were all significantly increased in ICC (p<0.001) when compared to healthy siblings and age-matched controls; 7S was raised above the upper limit of normal for age (mean+2xsd) in 95% of children with ICC, Pl in 91% and PlIIP in 76%. PIIIP (sds-a~e corrected) 7S (ugll) P1 ~U/I) (49) C a u c a s i a n controls 0 ± 1.02 (55) <13 (36) 1.58 f 0.36 H e a l t h y siblings 0.23 ± 1.03 (17) <13 ( 7) 1.61 ± 0.21 (12) ICC 12.58 ± 12.70 (34) 95 ± 63 (22) 6.29 ± 2.49 (23) Serum 7S and PI each s h o w e d a significant c o r r e l a t i o n with the degree of i n t r a l o b u l a r fibrosis in ICC (p
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BLEEDING AS THE FIRST SYMPTOMOF EXTRAHEPATICBILIARY ATRESIA R.H.J. Houwen, J. Bouquet*, C.M.A. Bijleveld Dept. of Pediatrics, University Hospital Groningen and * Sophia Childrens Hospital Rotterdam
Extrahepatic b i l i a r y atresia is a rare disease with an incidence of 1 in 10.000 newborns. I t is characterized by a total occlusion of the bile ducts outside the l i v e r . So these infants generally present with cholestatic jaundice in the f i r s t months of l i f e . We did a retrospective analysis of 100 patients with extrahepatic b i l i a r y atresia. Twelve infants presented with haemorrhagic phenomena rather than with jaundice. Mean age at presentation of these 12 was 23 days (range 9-45 days). Five patients had an intracranial bleeding, four umbilical bleeding and three extensive haematomata. Coagulation studies were indicative of vitamin K deficiency. Ten patients were treated with vitamin K, which stopped the bleeding. The other two patients were transfused with fresh blood or clotting factors. In these 12 patients jaundice was observed only after the bleeding episode. We assume that mild cholestasis and thus vitamin K malabsorption was already present before the bleeding occurred. Moreover all twelve infants had breast feeding, which has a low vitamin K content. So in these children the low vitamin K intake due to the breast feeding was aggravated by the malabsorption due to the cholestasis. This led to the increased bleeding tendency. The same mechanism, vitamin K deficiency due to cholestasis causing an increased bleeding tendency also occurs in =l-antitrypsin deficiency and in neonatal hepatitis. The incidence of bleeding as the f i r s t symptom of extrahepatic b i l i a r y atresia is 1-2:100.000. The same applies to e l - a n t i t r y p s i n deficiency and possibly neonatal hepatitis. So the overall incidence of bleeding as the f i r s t symptom of cholestatic l i v e r disease in the neonatal period w i l l be 3-6:100.000. The incidence of severe bleeding in a l l newborns is 20-50:100.000. So at least 6% of severe bleeding in infants is due to cholestasis induced vitamin K malabsorption. Therefore cholestatic l i v e r disease should be considered in each infant with haemorrhagic phenomena.
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