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P-102 Secondary fibrinolysis is paramount event in liver cirrhosis
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Posters/International Hepatoiogy Communications 3 Suppl. (1995) $37-S169
P-101 EXPERIMENTAL HEPATIC OSTEODYSTROPHY IN THE RAT WITH CARBON TETRACHLORIDE-INDUCED CIRRHOSIS ,~Nakano, 1 T.Kanda,2 Y.Shimizu 2 and H.Abe 1 1The Research Institute of Oriental Medicine, Kinki Univ. and 2Department of Internal Medicine, Division of Gastroenterology and Metabolism, Osaka prefectural General Hospital, Osaka, Japan We investigated the pathogenesis of osteopenia in the rat cirrhotic model by biochemical and histomorphometrie methods. [Methods] Male Wistar rats of 24 weeks old were divided into 2 groups as follows: Group I was controls; Group II was exposed to CC14 vapor twice a week for 24 weeks and cirrhotic liver was induced. We collected urine for one day. Twenty-four hours afler the last exposure to CC14, blood was drawn and liver, jejunum, tibiae and femora were resected from rats treated ether. We measured biochemical and histomorphometrie parameters [Results] Bone volume of the tibia (BV) in Group II was significantly (P<0.01) lower than that in Group I. In Group II, cortical total ratio, osteoid thickness, osteoid volume and tetracycline labeling ratio were lower (P<0.05) while the fractional resorption surface was higher than those in Group I (}'<0.05). Bone ash, Ca and Pi content in the tibia of Group II were lower than those in Group I (P< 0.05). In Group II, serum total Ca, product Ca and Pi were lower (P< 0.05) and urine Ca/Cr ratio was higher (P<0.05) than those in Group I. There were no significant differences in Ca flee index, serum 25(OH)D3, serum 24,25(OH)2D3 and serum 1,25(OH)2D3 between the two Groups. In Group II, serum albumin correlated with BV (R=0.614, P<0.05) and AST and ALT negatively correlated with BV. The number of goblet cell in the villus also correlated with Ca content in the tibia. [ C o n c l u s i o n ] In this model, we showed that osteopenia was complicated by cirrhosis and the pathological feature was not osteomalacia but osteoporosis due to a combination of both high resorption rates and low formation rates. The intestinal villi atrophy related to the bone loss. Vitamin D metabolism did not affect the bone loss much. From thease results, we conduded that serum albumin was the most important factor in pathogenesis of hepatic osteodystrophy. Index words: Experimental liver cirrhosis, Osteopenia, Calcium metabolism
P-103
EGF RECEPTORS DYNAMIC EXPERIMENTAL LIVER CIRRHOSIS (I.C)
IN
F. Marotta, *D.H.Chui, * J.Wu, +P.Safran, L . B o n c i n e l l i , A. C o l o m b o , G. B a r b i . GI S e r v i c e , S. A n n a H o s p . , Como. * I n t e r n . Med. Dept., N. B e t h u n e Univ., Changchun, China; +Econum, Villeneuve d'Ascq, France. The aim of this study was to provide a time-course mapping of EGF binding in LC. Rats underwent LC by inhaling twice a week C C L 4 - s a t u r a t e d air w h i l e d r i n k i n g w a t e r added with 0.5 g/l phenobarbital.Eats were sacrificed weekly and liver microsome fraction was obtained. EGF binding was measured by iodinated r-human EGF and total EGF receptor concentration W. Blot. LC w a s n o t e d starting the 6th week. S c a t c h a r d plot showed a linear relation. EGF max. b i n d i n g c a p a c i t y in LC s h o w e d a t i m e - c o u r s e d e c r e a s e s i g n i f i c a n t l y lower than in controls but no change occurred of the ~iz~clati~:~ ~ t ~ n t . ~7 W. B]c~ EGF r e c e p t o r c o n c e n t r a t i o n was c o m p a r a b l e to control.These results suggest the presence of s i n g u l a r EGF r e c e p t o r s with a s i m i l a r affinity. D u r i n g the d e v e l o p m e n t of LC a significant decrease of EGF binding occurs w i t h o u t a n y r e l e v a n t c h a n g e in b i n d i n g affinity or in EGF receptor concentration. Thus, such failure seems to be due to an receptor disarray, regeneration mechanism or occupancy by endogenous substances.
r-xv~ SECONDARY FIBRINOLYSIS IS PARAMOLINT EVENT IN LIVER CIRRHOSIS Y. Takikawa, H. lnaba. "[ Katsurashima. Y Sakashita. S. Sato. M Iwai. R. Endo, I. Nakadate. "E Kashiwabara. K. Suzuki and S. Sato First Dept. of Medicine. lwate Medical University, Morioka. 020 Japan A I M: To determine whether fibrinolysis seen in patients with liver cirrhosis is primary event or secondm-y to coagulation, we nveasured the concentrations of plasma fibrin degradation products (FbDP) zmd fibrinogen denudation products (FgDP) in cirrhotics. The association between these products and various molecular markers of coagulation and fiblyno(geno)lysis was also investigated. M E T H O D S : We measured plasma levels of FbDP and FgDP by recently developed ELISA kzts It:ibfinoslJca FbDP and FgDP, Organon Teknika) in 29 patients with liver cirrhosis Normal values of FgDP and FbDP were set as 389 + 127 and 246 ~ 98 ng/ ml (mean-+S D./. respectwely (H. Takahashn " Thromb tiaemostat 63: 340344.1990. ). R E S U L T S : Plasma concentration of FbDP wa~ sigmficantly increased (991 [292-2280] ng/ml, median 125-75 perceutdel. ~hile that of FgDP were nmstly w~thin nnrmal limits (423 [212-701] ng/ml). FgDP level correlated more closely with plasmm-c~2plasmin inhibitor complex (PIC; r=0.827, p< 0.()01 ) than with thrombmantithrombin III complex (TAT: r=0.439, p< 0.05). On the other hand. FbDP was equally correlated with PIC (r=0.627. p<0 001 ) and TAT (r=0.671. p<0.001). None of FgDP. FbDP and PIC correhaed v, ith tissue plasminogen activator and its inhibitor and no correlation between PIC and TAT was detected C O N C L U S I O N S : In the cirrhotics, secon&wy fibrinolysis following to coagulation is the paramount e~ent although mild fibrinogenolysis could also occur concurrently irrespective of coagulation There seems to be no apparent correlation between plasmin production ~u-d plsma levels of tissue plasminogen activator or its inhibitor
P-104
LIVER VOLUME IN PATIENTS WITH OR WITHOUT LIVER DISEASES X.Z. Lin, B.S. Sheu, Y.H. Liu, Y.N. Sun, C.Y. Chen, J.S. Shin, H.M. Tsai, C.L. Shen. Department of Internal Medicine l, Radiology 3, Anatomy 4, and Information Engineering 2, National Cheng Kung University and Hospital, Tainan, Taiwan. Liver size is a very important clinical indicator of liver disease. However, estimation by percussion is subjective and not reliable. In this study, liver volume was studied in patients with or without chronic liver diseases. By using three-dimensional reconstruction technique for computed tomography scans, we prove that the volume change correlated with different etiologies and various disease severity. Thirty-three patients without liver diseases were in control group and forty patients with chronic liver disease were recruited (hepatitis B, 23, hepatitis C, 8, and alcoholic hepatitis 9) in this study. The liver volume was calculated from digitized CT scan images. Techniques of planimetry and summation-of-areas were applied during three-dimensional reconstruction for volume estimation. The method is validated from in vivo piglet study. The demographic factors of patients in control group were analyzed to establish a prediction model to estimate liver volume, which was: liver vohime(ml) = [13 x height(cm)] + [12 x weight(Kg)] - 1530. The predicted liver volumes of patients with hepatitis B, C and alcoholism were statistically the same. However, the volume ratio (volume from reconstructed image x 100%/predicted volume) of alcoholic patient was 135.9±25.8, which was significantly higher than that of chronic hepatitis B (74.54-15.4) and chronic hepatitis C (84.9~22.7). There were no differences between patients with chronic hepatitis B and C. The volume ratio of Child-Pugh A B, and C are 98.1±13.9, 81.24-13.2, and 66.24-14.7, respectively. We concluded that in patients without liver disease, the volume can be estimated by body size. In patients with chronic viral hepatitis, the volume ratio is significantly lower than that of patients in control group and patients with alcoholic hepatitis. Moreover, the volume ratio inversely correlates very well with the disease severity in patients with chronic viral disease.
Posters/International Hepatoiogy Communications 3 Suppl. (1995) $37-S169
P-101 EXPERIMENTAL HEPATIC OSTEODYSTROPHY IN THE RAT WITH CARBON TETRACHLORIDE-INDUCED CIRRHOSIS ,~Nakano, 1 T.Kanda,2 Y.Shimizu 2 and H.Abe 1 1The Research Institute of Oriental Medicine, Kinki Univ. and 2Department of Internal Medicine, Division of Gastroenterology and Metabolism, Osaka prefectural General Hospital, Osaka, Japan We investigated the pathogenesis of osteopenia in the rat cirrhotic model by biochemical and histomorphometrie methods. [Methods] Male Wistar rats of 24 weeks old were divided into 2 groups as follows: Group I was controls; Group II was exposed to CC14 vapor twice a week for 24 weeks and cirrhotic liver was induced. We collected urine for one day. Twenty-four hours afler the last exposure to CC14, blood was drawn and liver, jejunum, tibiae and femora were resected from rats treated ether. We measured biochemical and histomorphometrie parameters [Results] Bone volume of the tibia (BV) in Group II was significantly (P<0.01) lower than that in Group I. In Group II, cortical total ratio, osteoid thickness, osteoid volume and tetracycline labeling ratio were lower (P<0.05) while the fractional resorption surface was higher than those in Group I (}'<0.05). Bone ash, Ca and Pi content in the tibia of Group II were lower than those in Group I (P< 0.05). In Group II, serum total Ca, product Ca and Pi were lower (P< 0.05) and urine Ca/Cr ratio was higher (P<0.05) than those in Group I. There were no significant differences in Ca flee index, serum 25(OH)D3, serum 24,25(OH)2D3 and serum 1,25(OH)2D3 between the two Groups. In Group II, serum albumin correlated with BV (R=0.614, P<0.05) and AST and ALT negatively correlated with BV. The number of goblet cell in the villus also correlated with Ca content in the tibia. [ C o n c l u s i o n ] In this model, we showed that osteopenia was complicated by cirrhosis and the pathological feature was not osteomalacia but osteoporosis due to a combination of both high resorption rates and low formation rates. The intestinal villi atrophy related to the bone loss. Vitamin D metabolism did not affect the bone loss much. From thease results, we conduded that serum albumin was the most important factor in pathogenesis of hepatic osteodystrophy. Index words: Experimental liver cirrhosis, Osteopenia, Calcium metabolism
P-103
EGF RECEPTORS DYNAMIC EXPERIMENTAL LIVER CIRRHOSIS (I.C)
IN
F. Marotta, *D.H.Chui, * J.Wu, +P.Safran, L . B o n c i n e l l i , A. C o l o m b o , G. B a r b i . GI S e r v i c e , S. A n n a H o s p . , Como. * I n t e r n . Med. Dept., N. B e t h u n e Univ., Changchun, China; +Econum, Villeneuve d'Ascq, France. The aim of this study was to provide a time-course mapping of EGF binding in LC. Rats underwent LC by inhaling twice a week C C L 4 - s a t u r a t e d air w h i l e d r i n k i n g w a t e r added with 0.5 g/l phenobarbital.Eats were sacrificed weekly and liver microsome fraction was obtained. EGF binding was measured by iodinated r-human EGF and total EGF receptor concentration W. Blot. LC w a s n o t e d starting the 6th week. S c a t c h a r d plot showed a linear relation. EGF max. b i n d i n g c a p a c i t y in LC s h o w e d a t i m e - c o u r s e d e c r e a s e s i g n i f i c a n t l y lower than in controls but no change occurred of the ~iz~clati~:~ ~ t ~ n t . ~7 W. B]c~ EGF r e c e p t o r c o n c e n t r a t i o n was c o m p a r a b l e to control.These results suggest the presence of s i n g u l a r EGF r e c e p t o r s with a s i m i l a r affinity. D u r i n g the d e v e l o p m e n t of LC a significant decrease of EGF binding occurs w i t h o u t a n y r e l e v a n t c h a n g e in b i n d i n g affinity or in EGF receptor concentration. Thus, such failure seems to be due to an receptor disarray, regeneration mechanism or occupancy by endogenous substances.
r-xv~ SECONDARY FIBRINOLYSIS IS PARAMOLINT EVENT IN LIVER CIRRHOSIS Y. Takikawa, H. lnaba. "[ Katsurashima. Y Sakashita. S. Sato. M Iwai. R. Endo, I. Nakadate. "E Kashiwabara. K. Suzuki and S. Sato First Dept. of Medicine. lwate Medical University, Morioka. 020 Japan A I M: To determine whether fibrinolysis seen in patients with liver cirrhosis is primary event or secondm-y to coagulation, we nveasured the concentrations of plasma fibrin degradation products (FbDP) zmd fibrinogen denudation products (FgDP) in cirrhotics. The association between these products and various molecular markers of coagulation and fiblyno(geno)lysis was also investigated. M E T H O D S : We measured plasma levels of FbDP and FgDP by recently developed ELISA kzts It:ibfinoslJca FbDP and FgDP, Organon Teknika) in 29 patients with liver cirrhosis Normal values of FgDP and FbDP were set as 389 + 127 and 246 ~ 98 ng/ ml (mean-+S D./. respectwely (H. Takahashn " Thromb tiaemostat 63: 340344.1990. ). R E S U L T S : Plasma concentration of FbDP wa~ sigmficantly increased (991 [292-2280] ng/ml, median 125-75 perceutdel. ~hile that of FgDP were nmstly w~thin nnrmal limits (423 [212-701] ng/ml). FgDP level correlated more closely with plasmm-c~2plasmin inhibitor complex (PIC; r=0.827, p< 0.()01 ) than with thrombmantithrombin III complex (TAT: r=0.439, p< 0.05). On the other hand. FbDP was equally correlated with PIC (r=0.627. p<0 001 ) and TAT (r=0.671. p<0.001). None of FgDP. FbDP and PIC correhaed v, ith tissue plasminogen activator and its inhibitor and no correlation between PIC and TAT was detected C O N C L U S I O N S : In the cirrhotics, secon&wy fibrinolysis following to coagulation is the paramount e~ent although mild fibrinogenolysis could also occur concurrently irrespective of coagulation There seems to be no apparent correlation between plasmin production ~u-d plsma levels of tissue plasminogen activator or its inhibitor
P-104
LIVER VOLUME IN PATIENTS WITH OR WITHOUT LIVER DISEASES X.Z. Lin, B.S. Sheu, Y.H. Liu, Y.N. Sun, C.Y. Chen, J.S. Shin, H.M. Tsai, C.L. Shen. Department of Internal Medicine l, Radiology 3, Anatomy 4, and Information Engineering 2, National Cheng Kung University and Hospital, Tainan, Taiwan. Liver size is a very important clinical indicator of liver disease. However, estimation by percussion is subjective and not reliable. In this study, liver volume was studied in patients with or without chronic liver diseases. By using three-dimensional reconstruction technique for computed tomography scans, we prove that the volume change correlated with different etiologies and various disease severity. Thirty-three patients without liver diseases were in control group and forty patients with chronic liver disease were recruited (hepatitis B, 23, hepatitis C, 8, and alcoholic hepatitis 9) in this study. The liver volume was calculated from digitized CT scan images. Techniques of planimetry and summation-of-areas were applied during three-dimensional reconstruction for volume estimation. The method is validated from in vivo piglet study. The demographic factors of patients in control group were analyzed to establish a prediction model to estimate liver volume, which was: liver vohime(ml) = [13 x height(cm)] + [12 x weight(Kg)] - 1530. The predicted liver volumes of patients with hepatitis B, C and alcoholism were statistically the same. However, the volume ratio (volume from reconstructed image x 100%/predicted volume) of alcoholic patient was 135.9±25.8, which was significantly higher than that of chronic hepatitis B (74.54-15.4) and chronic hepatitis C (84.9~22.7). There were no differences between patients with chronic hepatitis B and C. The volume ratio of Child-Pugh A B, and C are 98.1±13.9, 81.24-13.2, and 66.24-14.7, respectively. We concluded that in patients without liver disease, the volume can be estimated by body size. In patients with chronic viral hepatitis, the volume ratio is significantly lower than that of patients in control group and patients with alcoholic hepatitis. Moreover, the volume ratio inversely correlates very well with the disease severity in patients with chronic viral disease.