of 1 /1
SEQt~ENTIAL STUDIES ON FASTING AND POST-PRANDIAL PLASMA AMMONIA AND AMINO ACIDS IN CIRRHOSIS AFTER WARREN'S SHUNT. F.Trevisani, M.Bernardim R.De Palmat A.Simone, F.Grilli, P.Casanova t A.Mazziot ti*, A.Cavallari*~ S.Piazzi#~ D.Patrono#, G.Gozzetti*t G.Gasbarrini. Patol.Medica I,*Clin.Chirurgica II, #Lab.Centr., University of Bologna, Italy. Hyperam~onemia and amino acid pattern imbalance of cirrhosis are quickly worsened by non- selective portasystemic shunts. To evaluate possible changes induced by Warren's shunt (WS) in nitrogen metabolism, fasting plasma insulin (IRI), glucagon (IRG), ammonia (NH3), amino acid (AA) profile and their 5 hour plasma responses (AUC) to a protein meal (240 g of meat) were determined before, 3 months and 1 year after WS in 7 cirrhotics maintained on a standard diet. Shunt patency was ascertained by ultrasonography. The significant changes seen after 3 months, were an increase in fasting IRG (p<0.02), NH3 (p<0.025) and tyrosine (p<0.005), and a decrease in valine (p<0.005), leucine (p<0.01), isoleucine (p<0.01) and BCAA/AAA r a t i o (p<0.005). No changes in the AUC of IRI, IRG, NH3 and AA were found. After 1 year, fasting NH3 did not underwent a further significant increase, while phenylalanine (p<0.02) rose and a further increase in tyrosine was noted (p<0.001). As a result, the BCAA/AAA ratio decreased with respect to the 3 months value (p<0.05). An increase was also found in fasting metionine (p<0.05) and in GAA: alanine (0.1>p>0.05), arginine (p<0.05), glycine (p<0.02) and lysine (p<0.02). No changes in the AUC of IRI, IRG, NH3, BCAA and AAA were found, while the AUC of GAA alanine, arginine, glycine, serine and threonine rose (p<0.05 or less). A correlation between IRG and NH3 (r=0.95; p<0.001) was only found under pre-shunt conditions. WS led to an early worsening of the fasting imbalance of plasma AA and hyper---,onemia, while the clearance capacity of an exogenous nitrogen load was long preser- ved. The late increase in the AUC of GAA suggests that gluconeogenesis is the metabolic pathway to be primarily involved, possibly due to the shunt of most pancreatic venous blood around the liver. Finally, post-shunt fasting hyper--,-onemia could not be related to the enhanced hyperglucugonamia. SERUM LAMININ P1 CONCENTRATIONS AND CHRONICITY OF LIVER DISEASE IN CHILDHOOD. PLTrivedi. *B. Portmann & A.P. Mowat. Department of Child Health & ~The Liver Unit, Kings College Hospital, London. Elevated serum concentrations of laminin PI (P1), a major constituent of basement membrane, occuring in alcoholic hepatitis with cirrhosis may reflect sinusoidal capillarization. To investigate the role of P1 in paediatric liver disorders, we have measured P| by RIA (Hoescht) in 492 serum samples from 108 children (24 biliary atresia [BA]; 20 idiopathic hepatitis of infancy [IHI]; 38 ~l-antitrypsin deficiency [ ~IATD]; 18 autoimmune chronic active hepatitis (CAH) & 8 primary sclerosing cholangitis [PSC]). In 64 healthy subjects, Pl showed no variation between I month and 16 years of age (mean sd=l.53±O.33U/l). Elevated P1 levels occured in the first 4 months of life in 80% with EHBA, 85% with IHI and 73% with ~IATD; Pl remained raised at one year of age in 80% with EHBA but only in 30% with IHI and none with ~IATD, all raised levels returning to normal over the next four years. The incidence of chronic liver disease in BA was 100%, in IHI 5% and in ~IATD 85%. In children with CAH and PSC, elevated P1 occured in 12/15 and 4/6 untreated patients respectively; on immunosuppressive therapy PI fell to normal in all but 3 with uncontrolled CA~ In 20 patients studied, hepatic prolyl hydroxylase activity (PH) showed a significant correlation with P1 (rffi0.735; p<0.001), suggesting PI may be a non-invasive indicator of hepatic connective tissue synthesis. PI did not correlate with any biochemical liver function test, semi-quantitative assessment of histological abnormality or cirrhosis. P1 gave no guide to prognosis. The raised levels of PI observed in infants in this study, together with our previous data on elevated PH and serum type III procollagen peptides in cholestatic infants, suggests that turnover of connective tissue and/or serum clearance of connective tissue metabolites may differ between infants and children with liver disease. S170

Serum laminin P1 concentrations and chronicity of liver disease in childhood

  • Upload
    vankhue

  • View
    214

  • Download
    0

Embed Size (px)

Citation preview

SEQt~ENTIAL STUDIES ON FASTING AND POST-PRANDIAL PLASMA AMMONIA AND AMINO ACIDS IN CIRRHOSIS AFTER WARREN'S SHUNT. F.Trevisani, M.Bernardim R.De Palmat A.Simone, F.Grilli, P.Casanova t A.Mazziot ti*, A.Cavallari*~ S.Piazzi#~ D.Patrono#, G.Gozzetti*t G.Gasbarrini. Patol.Medica I,*Clin.Chirurgica II, #Lab.Centr., University of Bologna, Italy.

Hyperam~onemia and amino a c i d p a t t e r n imbalance o f c i r r h o s i s a r e q u i c k l y worsened by non- s e l e c t i v e p o r t a s y s t e m i c s h u n t s . To e v a l u a t e p o s s i b l e changes induced by War ren ' s shun t (WS) in n i t r o g e n metabol i sm, f a s t i n g plasma i n s u l i n ( IR I ) , g lucagon (IRG), ammonia (NH3), amino a c i d (AA) p r o f i l e and t h e i r 5 hour plasma r e s p o n s e s (AUC) t o a p r o t e i n meal (240 g o f meat) were de t e rmined b e f o r e , 3 months and 1 year a f t e r WS in 7 c i r r h o t i c s m a i n t a i n e d on a s t a n d a r d d i e t . Shunt pa t ency was a s c e r t a i n e d by u l t r a s o n o g r a p h y . The s i g n i f i c a n t changes seen a f t e r 3 months, were an i n c r e a s e in f a s t i n g IRG (p<0.02) , NH3 (p<0.025) and t y r o s i n e (p<0.005) , and a d e c r e a s e in v a l i n e (p<0.005) , l e u c i n e (p<0.01) , i s o l e u c i n e (p<0.01) and BCAA/AAA r a t i o (p<0.005) . No changes in t he AUC o f IRI, IRG, NH3 and AA were found. A f t e r 1 y e a r , f a s t i n g NH3 d id no t underwent a f u r t h e r s i g n i f i c a n t i n c r e a s e , w h i l e p h e n y l a l a n i n e (p<0.02) r o s e and a f u r t h e r i n c r e a s e in t y r o s i n e was n o t e d (p<0.001) . As a r e s u l t , t h e BCAA/AAA r a t i o d e c r e a s e d w i t h r e s p e c t t o t h e 3 months va lue (p<0.05) . An i n c r e a s e was a l s o found in f a s t i n g m e t i o n i n e (p<0.05) and in GAA: a l a n i n e (0 .1>p>0.05) , a r g i n i n e (p<0.05) , g l y c i n e (p<0.02) and l y s i n e (p<0.02) . No changes in t h e AUC o f IRI, IRG, NH3, BCAA and AAA were found, wh i l e t he AUC o f GAA a l a n i n e , a r g i n i n e , g l y c i n e , s e r i n e and t h r e o n i n e r o s e (p<0.05 or l e s s ) . A c o r r e l a t i o n between IRG and NH3 (r=0.95; p<0.001) was on ly found under p r e - s h u n t c o n d i t i o n s . WS l ed to an e a r l y worsen ing o f t he f a s t i n g imbalance o f plasma AA and hyper- - - ,onemia , w h i l e t h e c l e a r a n c e c a p a c i t y o f an exogenous n i t r o g e n load was long p r e s e r - ved. The l a t e i n c r e a s e in t he AUC o f GAA s u g g e s t s t h a t g l u c o n e o g e n e s i s i s t he m e t a b o l i c pathway to be p r i m a r i l y i nvo lved , p o s s i b l y due t o t h e shun t o f most p a n c r e a t i c venous b lood around t h e l i v e r . F i n a l l y , p o s t - s h u n t f a s t i n g hyper - - , -onemia cou ld no t be r e l a t e d to t h e enhanced hyperglucugonamia.

SERUM LAMININ P1 CONCENTRATIONS AND CHRONICITY OF LIVER DISEASE IN CHILDHOOD.

PLTrivedi. *B. Portmann & A.P. Mowat. Department of Child Health & ~The Liver Unit, Kings College Hospital, London.

Elevated serum concentrations of laminin PI (P1), a major constituent of basement membrane, occuring in alcoholic hepatitis with cirrhosis may reflect sinusoidal capillarization. To investigate the role of P1 in paediatric liver disorders, we have measured P| by RIA (Hoescht) in 492 serum samples from 108 children (24 biliary atresia [BA]; 20 idiopathic hepatitis of infancy [IHI]; 38 ~l-antitrypsin deficiency [ ~IATD]; 18 autoimmune chronic active hepatitis (CAH) & 8 primary sclerosing cholangitis [PSC]). In 64 healthy subjects, Pl showed no variation between I month and 16 years of age (mean sd=l.53±O.33U/l). Elevated P1 levels occured in the first 4 months of life in 80% with EHBA, 85% with IHI and 73% with ~IATD; Pl remained raised at one year of age in 80% with EHBA but only in 30% with IHI and none with ~IATD, all raised levels returning to normal over the next four years. The incidence of chronic liver disease in BA was 100%, in IHI 5% and in ~IATD 85%. In children with CAH and PSC, elevated P1 occured in 12/15 and 4/6 untreated patients respectively; on immunosuppressive therapy PI fell to normal in all but 3 with uncontrolled CA~ In 20 patients studied, hepatic prolyl hydroxylase activity (PH) showed a significant correlation with P1 (rffi0.735; p<0.001), suggesting PI may be a non-invasive indicator of hepatic connective tissue synthesis. PI did not correlate with any biochemical liver function test, semi-quantitative assessment of histological abnormality or cirrhosis. P1 gave no guide to prognosis. The raised levels of PI observed in infants in this study, together with our previous data on elevated PH and serum type III procollagen peptides in cholestatic infants, suggests that turnover of connective tissue and/or serum clearance of connective tissue metabolites may differ between infants and children with liver disease.

S170