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402A 1181 AASLD ABSTRACTS HEPATOLOGY October 1995 PORTAL VEIN THROMBOSIS (PVT) IN CIRRHOSIS BEFORE LIVER TRANSPLANTATION (LT) : THE IMPACT OF TRANSJUGULAR PORTOSYSTEMIC INTRAHEPATIC SHUNT (TIPS).P. Castellani, 1. Portal, JM Bartoli*, D Bemardini, C. Wartelle G. Moulin*,AP. Gauthier, D.Botta- Fridlund. Hepatology unit Conception hospital Marseilles, Radiological unit Timone hospital Marseilles*. 1182 IMPROVEMENT OF LIVER GRAFT VIABILITY PRIOR TO TRANSPLANTATION BY HYPOTHERMIC REPERFUSION. Changani. K.K.. Fuller, B.J., ~Bryant, D.J.. ~'Bell. J.D. #Ala-Koroela, M., Moore, D.P. #Taylor-Robinson, S. and Davidson. B.R. Department of Surgery, Royal Free Hospital School of Medicine, London. #NMR Unit, Hammersmith Hospital, London. The occurence of PVT in cirrhosis worsens hepatic dysfunction and increases the risk and the severity of gastro-intestinal bleeding. When extented to spleno- mesenteric confluent (SMC), LT can be difficult or even impossible. TIPS is now an established procedure for controlling gastro-intestinal bleeding due to portal hypetension (PHT) and can be used as a bridge to LT. We report our experience in two patients waiting for LT with recent PVT where a TIPS procedure was performed to prevent total occlusion of the portal system. First patient was a 39 years old man, with a posthepatitie C cirrhosis, Child-Pugh B, waiting for LT, with grade 3 oesophageal and gastric varices, with no history of bleeding episod. Sonography showed a partial SMC thrombosis extending to PV and splenic vein. PV flow by Doppler US was slow and directed towards the liver. TIPS was successfully performed. Follow-up Doppler studies showed a good stent permeability, a progressive p v r decrease and a good PV flow. 9 months later, sonography showed a good stent permeability and the regression of SMC thrombosis. The second patient was a 33 years old man, with a cryptegenie cirrhosis, Child-Pugh B, with a previous variceal hemorrhage in 1992. He was listed for LT in 9/94. Gastroscopy showed grade 2 oesophageal variccs and PHT gastropathy. Doppler US showed a SMC thrombosis extending to the PV. PV flow was slow and directed towards the liver. TIPS was successfully performed in 2/95. Colttrol sonography showed a good stent permeability and a normal PV flow. SMC thrombosis did not extend. Both patients are still waiting for LT in good condition. In our experience, (1) TIPS is a feasable procedure in patient with recent PVT. (2) It prevents the extension of the thrombosis allowing to wait for LT in better condition. Liver transplantation has proved to be a highly successful treatment for end- stage liver disease. However, its success has placed an increasing demand for liver donors and harvesting techniques, which optimise liver viability. This study has used the non-invasive technique of 3T magnetic resonance spectroscopy (MRS) to synchronously measure, in real time, ATP, inorganic phosphate (PO, pbosphomonoesters (PME) and phosphodiesters (PDE), following a period of hypothermic reperfusion (HtR) of harvested pig livers. Pig livers (n=4) were stored on ice following in situ perfusion with citrate buffer and University of Wisconsin preservation solution. The liver was positioned in the bore of a 1.5 Tesla Picker Prototype MRS machine and phosphorus spectra collected at 26MHz. Spectra took 2 rain to acquire. The liver was HtR with an oxygenated buffer containing sodium gluconate (100mM), raffinose (30raM), CaCI~ (0.5mM), glycine (5mM) and MgSO4 (5raM). HtR was subsequently stopped after 90 min. All values were calculated with respect to methelenediphosphonic acid standard. During the period of HtR I~-ATF levels increased linearly by 30% over the first 6 rain of HtR, followed by a further 20% linear increase over the next 64 rain. The P~ reduced by 75% over the first 14 rain of HtR and then by a further 25% over the next 56 min. The PME fell by 100% whereas the PDE increased by approximately 100% over the first 40 min of HtR. This study has shown for the first time that ATP regeneration can be achieved and monitored in vivo, following a period of HtR in the pig liver. ATP regeneration occurred with two distinct flux rates, the former being 16 times faster than the latter. Furthermore it has shown that various metabolite fluxes can simultaneously be monitored in the intact tissue by the non-invasive technique of MRS. Hypothermic reperfusion may be a method of optimising human donor livers prior to transplantation. 1183 Predictive value of liver iron for the occurrence of hepatocellular carcinoma (HCC) in 151 prospectively followed patients with cirrhosis. Chapel F I, Ganne-Carri~ N 2, Chastang Cl3t Trinchet JC 2, Beau@rand M2t Guettier C 1 . Iservice d'Anatomie Pathologique. 2Service d'H~patogastroent~rologie, HSpital Jean Verdier, avenue du 14 juillet, 93143 Bondy Cedex. 3D4partement de Biostatistique, HSpital Saint-Louis, 1 avenue Claude Vellefaux, 75010 Paris (France). Iron could favor the formation of free radicals and DNA damage. Recently a case-control study has shown that hepatic iron content was higher in patients with HCC occurring in non cirrhotic liver than in patients without HCC. However, experimental data suggested that a high iron content of the liver was not associated with an increased risk of carcinogenesis.To explore the influence of liver iron content on the occurrence of HCC in patients with cirrhosis, we studied the initial hepatic biopsy samples from 151 patients with cirrhosis, prospectively screened for the occurrence of HCC. Cirrhosis was viral-related in 28, alcohol-related in 71, both in 22, and from other causes in 30. 31 patients experienced HCC during the follow up (follow-up: 51~26 months, annual incidence of HCC:5%). Hepatic iron content has been assessed histologically by 2 observers using a semiquantitative scoring system. Patients were classified in 3 groups : 13 had a very high score. 63 a high score, 76 a low score. The predictive value of liver iron was studied by the Cox Model incorporating clinical and biological variables previously shown to be associated with a high risk of HCC in the same population : age, sex, prothrombine activity, serum AFP, presence of large esophageal varices (stade II or III). The Cox Model demonstrated the additional predictive value of liver iron score (P <0.02). In patients with cirrhosis, the relation ship between liver iron content and a high risk of HCC suggests a role for iron in hepatic carcinogenesis. 1184 DIFFERENTIAL EXPRESSION OF BCL-2-AND PCNA IN APOPTOSIS OF ALCOHOLIC LIVER DISEASE. A. Chedid, TR Morgan, M. Eichorst & VACS #352. Departments of Pathology and Medicine; FUHS/Chicago Medical School, North Chicago, IL., Long Beach, CA and Hines, IL. VA Hospitals. Apoptosis and mitosis have often been considered opposite phenomena in the life of cells. Apoptosis is common in liver disease but has not been reported properly because of its confusion with necrosis and difficulty in histological identification. The genes controlling apoptosis and cell proliferation are known to be variously expressed in the liver. In this investigation we studied the expression of the genes involved in apoptosis and cell proliferation at different stages of alcoholic liver disease. MATERIALS AND METHODS: Forty six patients with alcoholic cirrhosis from nationwide medical centers were entered into the study after initial biopsy. Seven cases of alcoholic hepatitis, 10 of fatty liver and 4 livers with nonspecific changes from our local hospital were included as controls. The ABC method with antibodies from commercial sources was used for the immtmohistochemistry. We chose to study the following markers: Bel-2, Bax, Bcl-x and ICE for apoptosis, and p53 and PCNA as indicators of cell proliferation. RESULTS: In cirrhosis bcl-2 was expressed in 42/46 cases on lymphocytes about the areas of piecemeal necrosis and in 6 cases on bile ducts. Bax and ICE were weakly expressed on hepatocytes (9 cases) and on bile duct cells in 4 cases. PCNA was strongly expressed on the nuclei of regenerating hepatocytes (31/46), small bile ducts and ductules (12/46). PCNA and bcl-2 were expressed in 3/7 cases of alcoholic hepatitis. In fatty livers bcl-2 was found in 4 cases while PCNA was expressed in all. No marker was seen in nonspecific changes, p53 and Bcl-x were absent from all livers. Iron and ceroid stained with PCNA, Bax and ICE. CONCLUSIONS: The striking expression of bcl-2 in the proximity of piecemeal necrosis supports a role for this protein in apoptosis. The minimal expression of Bax and ICE in hepatocytes contrasts with reports in rat liver. The generalized presence of PCNA suggests that this protein is expressed nonspecifically in any type of injury.

Portal vein thrombosis (PVT) in cirrhosis before liver transplantation (LT): The impact of transjugular portosystemic intrahepatic shunt (TIPS) . Hepatology unit Conception hospital

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402A

1181

AASLD ABSTRACTS HEPATOLOGY O c t o b e r 1995

PORTAL VEIN THROMBOSIS (PVT) IN CIRRHOSIS BEFORE LIVER TRANSPLANTATION (LT) : THE IMPACT OF TRANSJUGULAR PORTOSYSTEMIC INTRAHEPATIC SHUNT (TIPS).P. Castellani, 1. Portal, JM Bartoli*, D Bemardini, C. Wartelle G. Moulin*,AP. Gauthier, D.Botta- Fridlund. Hepatology unit Conception hospital Marseilles, Radiological unit Timone hospital Marseilles*.

1182 IMPROVEMENT OF LIVER GRAFT VIABILITY PRIOR TO TRANSPLANTATION BY HYPOTHERMIC REPERFUSION. Changani. K.K.. Fuller, B.J., ~Bryant, D.J.. ~'Bell. J.D. #Ala-Koroela, M., Moore, D.P. #Taylor-Robinson, S. and Davidson. B.R. Department of Surgery, Royal Free Hospital School of Medicine, London. #NMR Unit, Hammersmith Hospital, London.

The occurence of PVT in cirrhosis worsens hepatic dysfunction and increases the risk and the severity of gastro-intestinal bleeding. When extented to spleno- mesenteric confluent (SMC), LT can be difficult or even impossible. TIPS is now an established procedure for controlling gastro-intestinal bleeding due to portal hypetension (PHT) and can be used as a bridge to LT. We report our experience in two patients waiting for LT with recent PVT where a TIPS procedure was performed to prevent total occlusion of the portal system. First patient was a 39 years old man, with a posthepatitie C cirrhosis, Child-Pugh B, waiting for LT, with grade 3 oesophageal and gastric varices, with no history of bleeding episod. Sonography showed a partial SMC thrombosis extending to PV and splenic vein. PV flow by Doppler US was slow and directed towards the liver. TIPS was successfully performed. Follow-up Doppler studies showed a good stent permeability, a progressive p v r decrease and a good PV flow. 9 months later, sonography showed a good stent permeability and the regression of SMC thrombosis. The second patient was a 33 years old man, with a cryptegenie cirrhosis, Child-Pugh B, with a previous variceal hemorrhage in 1992. He was listed for LT in 9/94. Gastroscopy showed grade 2 oesophageal variccs and PHT gastropathy. Doppler US showed a SMC thrombosis extending to the PV. PV flow was slow and directed towards the liver. TIPS was successfully performed in 2/95. Colttrol sonography showed a good stent permeability and a normal PV flow. SMC thrombosis did not extend. Both patients are still waiting for LT in good condition. In our experience, (1) TIPS is a feasable procedure in patient with recent PVT. (2) It prevents the extension of the thrombosis allowing to wait for LT in better condition.

Liver transplantation has proved to be a highly successful treatment for end- stage liver disease. However, its success has placed an increasing demand for liver donors and harvesting techniques, which optimise liver viability. This study has used the non-invasive technique of 3T magnetic resonance spectroscopy (MRS) to synchronously measure, in real time, ATP, inorganic phosphate (PO, pbosphomonoesters (PME) and phosphodiesters (PDE), following a period of hypothermic reperfusion (HtR) of harvested pig livers.

Pig livers (n=4) were stored on ice following in situ perfusion with citrate buffer and University of Wisconsin preservation solution. The liver was positioned in the bore of a 1.5 Tesla Picker Prototype MRS machine and phosphorus spectra collected at 26MHz. Spectra took 2 rain to acquire. The liver was HtR with an oxygenated buffer containing sodium gluconate (100mM), raffinose (30raM), CaCI~ (0.5mM), glycine (5mM) and MgSO4 (5raM). HtR was subsequently stopped after 90 min.

All values were calculated with respect to methelenediphosphonic acid standard. During the period of HtR I~-ATF levels increased linearly by 30% over the first 6 rain of HtR, followed by a further 20% linear increase over the next 64 rain. The P~ reduced by 75% over the first 14 rain of HtR and then by a further 25% over the next 56 min. The PME fell by 100% whereas the PDE increased by approximately 100% over the first 40 min of HtR.

This study has shown for the first time that ATP regeneration can be achieved and monitored in vivo, following a period of HtR in the pig liver. ATP regeneration occurred with two distinct flux rates, the former being 16 times faster than the latter. Furthermore it has shown that various metabolite fluxes can simultaneously be monitored in the intact tissue by the non-invasive technique of MRS. Hypothermic reperfusion may be a method of optimising human donor livers prior to transplantation.

1183 Predictive value of liver iron for the occurrence of hepatocellular carcinoma (HCC) in 151 prospectively followed patients with cirrhosis.

Chapel F I, Ganne-Carri~ N 2, Chastang Cl3t Trinchet JC 2,

Beau@rand M2t Guettier C 1 . Iservice d'Anatomie

Pathologique. 2Service d'H~patogastroent~rologie, HSpital Jean Verdier, avenue du 14 juillet, 93143 Bondy Cedex.

3D4partement de Biostatistique, HSpital Saint-Louis, 1 avenue Claude Vellefaux, 75010 Paris (France).

Iron could favor the formation of free radicals and DNA damage. Recently a case-control study has shown that hepatic iron content was higher in patients with HCC occurring in non cirrhotic liver than in patients without HCC. However, experimental data suggested that a high iron content of the liver was not associated with an increased risk of carcinogenesis.To explore the influence of liver iron content on the occurrence of HCC in patients with cirrhosis, we studied the initial hepatic biopsy samples from 151 patients with cirrhosis, prospectively screened for the occurrence of HCC. Cirrhosis was viral-related in 28, alcohol-related in 71, both in 22, and from other causes in 30. 31 patients experienced HCC during the follow up (follow-up: 51~26 months, annual incidence of HCC:5%). Hepatic iron content has been assessed histologically by 2 observers using a semiquantitative scoring system. Patients were classified in 3 groups : 13 had a very high score. 63 a high score, 76 a low score. The predictive value of liver iron was studied by the Cox Model incorporating clinical and biological variables previously shown to be associated with a high risk of HCC in the same population : age, sex, prothrombine activity, serum AFP, presence of large esophageal varices (stade II or III). The Cox Model demonstrated the additional predictive value of liver iron score (P <0.02). In patients with cirrhosis, the relation ship between liver iron content and a high risk of HCC suggests a role for iron in hepatic carcinogenesis.

1184 D I F F E R E N T I A L E X P R E S S I O N OF B C L - 2 - A N D PCNA IN APOPTOSIS OF A L C O H O L I C L I V E R DISEASE. A. Chedid, TR Morgan, M. Eichorst & VACS #352. Departments of Pathology and Medicine; FUHS/Chicago Medical School, North Chicago, IL., Long Beach, CA and Hines, IL. VA Hospitals.

Apoptosis and mitosis have often been considered opposite phenomena in the life of cells. Apoptosis is common in liver disease but has not been reported properly because of its confusion with necrosis and difficulty in histological identification. The genes controlling apoptosis and cell proliferation are known to be variously expressed in the liver. In this investigation we studied the expression of the genes involved in apoptosis and cell proliferation at different stages of alcoholic liver disease. MATERIALS AND METHODS: Forty six patients with alcoholic cirrhosis from nationwide medical centers were entered into the study after initial biopsy. Seven cases of alcoholic hepatitis, 10 of fatty liver and 4 livers with nonspecific changes from our local hospital were included as controls. The ABC method with antibodies from commercial sources was used for the immtmohistochemistry. We chose to study the following markers: Bel-2, Bax, Bcl-x and ICE for apoptosis, and p53 and PCNA as indicators of cell proliferation. RESULTS: In c i r rhos i s bcl-2 was expressed in 42/46 cases on lymphocytes about the areas of piecemeal necrosis and in 6 cases on bile ducts. Bax and ICE were weakly expressed on hepatocytes (9 cases) and on bile duct cells in 4 cases. PCNA was strongly expressed on the nuclei of regenerating hepatocytes (31/46), small bile ducts and ductules (12/46). PCNA and bcl-2 were expressed in 3/7 cases of alcoholic hepatit is. In fat ty livers bcl-2 was found in 4 cases while PCNA was expressed in all. No marker was seen in nonspecific changes, p53 and Bcl-x were absent from all livers. Iron and ceroid stained with PCNA, Bax and ICE. CONCLUSIONS: The striking expression of bcl-2 in the proximity of piecemeal necrosis supports a role for this protein in apoptosis. The minimal expression of Bax and ICE in hepatocytes contrasts with reports in rat liver. The generalized presence of PCNA suggests that this protein is expressed nonspecifically in any type of injury.