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Retention of a bile acid analogue in the enterohepatic circulation (EHC) in primary biliary cirrhosis (PBC): Comparison with normal controls and effect of bile acid treatment
HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995
AASLD ABSTRACTS
1209 DIAGNOSIS OF CIRRHOSIS IN PATIENTS WITH CONGESTIVE HEART FAILURE BY TRANSYUGULAR LIVER BIOPSY: PREDICTIVE VALUE OF LIVER DAMAGE BY ECHOCARDIOGRAM AND HEPATIC PRESSURES. A de Hoyos, R: Mal~, MA Martinez:Rioa, M GiI-Moreno, MC Lacy, JA Kuri, J Mdrtinez-Redinfl, M Uribe, J V~.quez-Sanchez, S P6rez-Santander, ML Lomdo, A Aranda-Frausto, M Cardenas-Loiza. Instituto Nacional de Cardiologia "lgnacio Chavez", Mexico City. INTRODUCTION: Patients (pts) with congestive head failure (CHF) who developed cirrhosis, have poor prognosis for cardiovascualr surgery. METHODS. We included ten patients 8F and 2M. Average age 44.9 y/o (14-56). Fifty percent of the pts had mild elevation of indirect bilirubin (1-2 mg/dl). The rest of the liver function tests (LFTs) were normal in all but two patients. The primary cardiac disease was rheumatic cardiomyopathy. All pts had some degree of tricuspid insufficiency (TI) by echocardiogram and by hemodynamic measurements, Seven pts had severe TI (tricuspid valve gradient > 25 mm/hg). Three pts had moderate TI (tricuspid valve gradient 10-25 mm/hg). The cardiac disease had diagnosed 18.6 years (3-32) before the time of the liver biopsy. All pts had wedge hepatic, sinusoidal and free pressure determinations dudng the transyugular liver biopsy. RESULTS: Liver biopsy showed cirrhosis in 30%, fibrosis in 30% and no specific findings in 60% (dilatation and congestion of the central veins, steatosis or cholestasis). Wedge hepatic pressure (WHP) was >12 mm/hg in 50%, corresponding to the high free pressure secondary to the CHF, Sinusoidal pressure was normal (<4mm/hg) in all pts but one (6mm/hg). The pt with elevated sinusoidal pressure was the one with amyloidosis, and he did not have cirrhosis or fibrosis although the WHP and the free pressure were elevated (20 mm/hg). The degree of fibrosis in the liver had no correlation with the WHP, TI severity and cardiopathy diagnosis time. CONCLUSIONS: 1) Cirrhosis or fibrosis of the liver are common in CHF (60%). 2)LFTs, the cardiopathy progress and the degree of TI have not predictive value to determine the degree of liver damage in CHF. 3) Liver biopsy, specially by the transyugular approach, is safe for the diagnosis of liver disease in pts with CHF. 4) Portal hypertension in pts with CHF even with cirrhosis is uncommon.
1211
PERCUTANEOUS ETHANOL INJECTION (PEI) OF HEPATOCELLULAR CARCINOMA(HCC) IN LIVER C I R R H O S I S : L O N G T E R M F O L L O W U P IN 72 P A T I E N T S I. de Sio, L. Castellano, M. C a l a n d r a , S . Scotto di Santolo, A. De Luca, C. Guerriero, M. P e r s i c o *, C. Del V e c c h i o - B l a n c o Gastroenterology Unit- *Internal Medicine-2nd U n i v e r s i t y of N a p l e s , I t a l y PEI has recently been proposed as a new therapeutical approach for HCC in liver c i r r h o s i s . W e h e r e b y r e p o r t the r e s u l t s of PEI in 72 HCC patients. Patients and methods:72 p a t i e n t s ( 5 6 M a n d 15 F, m e d i a n a g e 66 yrs, r a n g e 54-77 y r s ) . F i f t y five p a t i e n t s w e r e in the C h i l d A and 17 in the C h i l d B class. F o r t y n i n e p a t i e n t s h a d a s i n g l e l e s i o n < 5 cm; 3 a s i n g l e l e s i o n > 5 cm; a n d 20 h a d 2 o r 3 l e s i o n s each one < 4 cm. S u r v i v a l c u r v e s w e r e c a l c u l a t e d a c c o r d i n g t h e Kaplan-Meier method and the WilcoxOn test was u s e d to c a l c u l a t e d i f f e r e n c e in s u r v i v a l b e t w e e n patients. Results:l) the survival rate for all p a t i e n t s w a s 89%, 79%, 55%, 36% a n d 29% at 1 yr, 2 yr, 3 yr, 4 yr and 5 yr r e s p e c t i v e l y ; 2) the s u r v i v a l r a t e in p a t i e n t s w i t h a s i n g l e l e s i o n was 9 1 % , 8 4 % , 6 2 % , 3 4 % and 23% at i yr, 2 yr, 3 yr, 4 yr and 5 yr respectively;3) in this latter g r o u p the s u r v i v a l r a t e at 1 yr, 2 yr and 3 yr was s i g n i f i c a n t l y h i g h e r in s u b j e c t s in the Child A c l a s s t h a n i n t h o s e w h o w e r e in the C h i l d B c l a s s ( 9 6 % , 9 0 % and 69% vs 79%, 68% a n d 41%, p< 0.05 );4) in the g r o u p of p a t i e n t s w i t h m u l t i p l e lesions, the s u r v i v a l r a t e was 83%, 63% and 35% at 1 yr, 2 yr and 3 yr r e s p e c t i v e l y ( p< 0.05 vs the survival rate of patients with single lesions).Conclusion: PEI is a safe and efficacious alternative therapy for the m a n a g e m e n t of H C C in liver cirrhosis.
409A
1210 SUBCUTANEOUS OCTREOTIDE FOR THE TREATMENT OF VARICEAL BLEEDING: A PHARMACOKINETIC STUDY V ~te L6dinehen. MP Riuauh. N Raffoux. S Bououet. C Silvain. M B e a u c h a n t . Hepatology Unit and Pharmacology Unit, Poitiers University, France Octreotide, a synthetic analog of somatostatin, is known m be effective for the control of variceal bleeding in cirrhosis, and the minimal dose recommended was a 25p.g/h intravenous (IV) continuous infusion. Few studies delt on the subcutaneous way of administration which appeared preferential in the prevention of early rebleeding. The aim of this study was to compare plasma octreotide concentrations (C) obtained after IV infusion and subcutaneous (SC) injection in patients with cirrhosis. Six patients (6M, Pugh's A=2, B=2, C=2) with alcoholic cirrhosis received a 25 ~tg/h IV infusion of octreotide for variceal bleeding. Plasma C W were obtained at 12 and 16h (C W steady state) from start of infusion. After a 24h wash out period, the same patient received a 500ktg octreotide SC injection. Octreotide plasma C s c was measured by radioimmunoassay at 0,1.5,8 and 14h after dosin~oResults: SD m
Civss (pg/ml) 4622 1800
Csc max CLT/F sc T I/2el sc (pg/ml) (l/h) (h) 13058 2'368
4,9 0,99
5,08 1,32
Vdss sc (i) 34 8,5
In most patients octreotide plasma C s c only remained above CIvo. within the first 8h. Assuming that a line~a: pharmacokinetic model c6u~d be applied to octreotide, theoretical mean plasma CSC after 100 and 200 pg/ml subcutaneous injection would be respectively 2610 and 5221 pg/ml at 90mn, and 921 and 1842 pg/ml at 8h. Conclusion: Assuming that 25 Ixg/h IV:infusion is the minimal dose required to control variceal bleeding, these results suggest that the optimal subcutaneous octreotide dose would be 500 ~tg every 8 hours for prevention of early variceal rebleeding.
1212 RETENTION
OF A BILE ACID ANALOGUE IN THE ENTEROHEPATIC CIRCULATION (EHC) IN PRIMARY BILIARY CIRRHOSIS (PBC): COMPARISON WITH NORMAL CONTROLS AND EFFECT OF BILE ACID TREATMENT. M. De Tavonatti, M.B. Panarotto,* G. Maim*. F. Fmnceschini§, F. Lanzarotto, A. Lanzini. Medicine 1, Nuclear Medicine* and Immunology§, Spedali Civili. Brescia. Italy.
The gamma-emitting bile acid analogue selena homocholic acid-taurine (SeHCAT) behaves as a natural bile acid in man (Gastroenterology 1988; 95:164), and we reasoned that in chronic cholestasis it may be retained in the EHC longer than in health. Furthermore, Sis retention may be reduced by chronic administration of ursodeoxycholie acid (UDCA), as suggested by studies in healthy subjects (Hepatology 1990; 12:1206). The aims of our study were to compare SeHCAT retention time in PBC patients with fimctioning gallbladders before (n=10) and during (n=5) UDCA administration, with that of matched healthy controls (n=8). We used tanrine conjugated UDCA (TUDCA, 10 mg/kg/day) to enhance bioavailability of this bile acid. SeHCAT retention time was expressed as half-time (T1/2) of the exponential decline of activity over the gallbladder area as measured by gamma camera counting on 5 successive days. SeHCAT T 1/2 ranged between 53 and 220 h in PBC patients, and between 40 and 59 h in controls. Mean T1/2 value was significantly higher in PBC patients (125 + 18 h, SEM) than in control subjects (47+ 2 h, p<0.002, by unpaired t test). TI/2 was l 14 vs 44h, 89 vs 33 h, 141 vs 31 h, 220 vs 4 lh and 64 vs 78h in the 5 patients studied before and during TUDCA. Mean T1/2 value decreased from 126 + 27 to 45 + 9 during TUDCA treatment (p=0.065, paired t test). There was no correlation (r = -0.08) between histological PBC grading and pretreatment SeHCAT T1/2. We conclude that in PBC i) retention of SeHCAT in the EHC is increased by comparison with healthy controls; that ii) this increase is not related to histological stage; and that iii) TUDCA reduces SeHCAT retention to the same values as in healthy subjects.
AASLD ABSTRACTS
1209 DIAGNOSIS OF CIRRHOSIS IN PATIENTS WITH CONGESTIVE HEART FAILURE BY TRANSYUGULAR LIVER BIOPSY: PREDICTIVE VALUE OF LIVER DAMAGE BY ECHOCARDIOGRAM AND HEPATIC PRESSURES. A de Hoyos, R: Mal~, MA Martinez:Rioa, M GiI-Moreno, MC Lacy, JA Kuri, J Mdrtinez-Redinfl, M Uribe, J V~.quez-Sanchez, S P6rez-Santander, ML Lomdo, A Aranda-Frausto, M Cardenas-Loiza. Instituto Nacional de Cardiologia "lgnacio Chavez", Mexico City. INTRODUCTION: Patients (pts) with congestive head failure (CHF) who developed cirrhosis, have poor prognosis for cardiovascualr surgery. METHODS. We included ten patients 8F and 2M. Average age 44.9 y/o (14-56). Fifty percent of the pts had mild elevation of indirect bilirubin (1-2 mg/dl). The rest of the liver function tests (LFTs) were normal in all but two patients. The primary cardiac disease was rheumatic cardiomyopathy. All pts had some degree of tricuspid insufficiency (TI) by echocardiogram and by hemodynamic measurements, Seven pts had severe TI (tricuspid valve gradient > 25 mm/hg). Three pts had moderate TI (tricuspid valve gradient 10-25 mm/hg). The cardiac disease had diagnosed 18.6 years (3-32) before the time of the liver biopsy. All pts had wedge hepatic, sinusoidal and free pressure determinations dudng the transyugular liver biopsy. RESULTS: Liver biopsy showed cirrhosis in 30%, fibrosis in 30% and no specific findings in 60% (dilatation and congestion of the central veins, steatosis or cholestasis). Wedge hepatic pressure (WHP) was >12 mm/hg in 50%, corresponding to the high free pressure secondary to the CHF, Sinusoidal pressure was normal (<4mm/hg) in all pts but one (6mm/hg). The pt with elevated sinusoidal pressure was the one with amyloidosis, and he did not have cirrhosis or fibrosis although the WHP and the free pressure were elevated (20 mm/hg). The degree of fibrosis in the liver had no correlation with the WHP, TI severity and cardiopathy diagnosis time. CONCLUSIONS: 1) Cirrhosis or fibrosis of the liver are common in CHF (60%). 2)LFTs, the cardiopathy progress and the degree of TI have not predictive value to determine the degree of liver damage in CHF. 3) Liver biopsy, specially by the transyugular approach, is safe for the diagnosis of liver disease in pts with CHF. 4) Portal hypertension in pts with CHF even with cirrhosis is uncommon.
1211
PERCUTANEOUS ETHANOL INJECTION (PEI) OF HEPATOCELLULAR CARCINOMA(HCC) IN LIVER C I R R H O S I S : L O N G T E R M F O L L O W U P IN 72 P A T I E N T S I. de Sio, L. Castellano, M. C a l a n d r a , S . Scotto di Santolo, A. De Luca, C. Guerriero, M. P e r s i c o *, C. Del V e c c h i o - B l a n c o Gastroenterology Unit- *Internal Medicine-2nd U n i v e r s i t y of N a p l e s , I t a l y PEI has recently been proposed as a new therapeutical approach for HCC in liver c i r r h o s i s . W e h e r e b y r e p o r t the r e s u l t s of PEI in 72 HCC patients. Patients and methods:72 p a t i e n t s ( 5 6 M a n d 15 F, m e d i a n a g e 66 yrs, r a n g e 54-77 y r s ) . F i f t y five p a t i e n t s w e r e in the C h i l d A and 17 in the C h i l d B class. F o r t y n i n e p a t i e n t s h a d a s i n g l e l e s i o n < 5 cm; 3 a s i n g l e l e s i o n > 5 cm; a n d 20 h a d 2 o r 3 l e s i o n s each one < 4 cm. S u r v i v a l c u r v e s w e r e c a l c u l a t e d a c c o r d i n g t h e Kaplan-Meier method and the WilcoxOn test was u s e d to c a l c u l a t e d i f f e r e n c e in s u r v i v a l b e t w e e n patients. Results:l) the survival rate for all p a t i e n t s w a s 89%, 79%, 55%, 36% a n d 29% at 1 yr, 2 yr, 3 yr, 4 yr and 5 yr r e s p e c t i v e l y ; 2) the s u r v i v a l r a t e in p a t i e n t s w i t h a s i n g l e l e s i o n was 9 1 % , 8 4 % , 6 2 % , 3 4 % and 23% at i yr, 2 yr, 3 yr, 4 yr and 5 yr respectively;3) in this latter g r o u p the s u r v i v a l r a t e at 1 yr, 2 yr and 3 yr was s i g n i f i c a n t l y h i g h e r in s u b j e c t s in the Child A c l a s s t h a n i n t h o s e w h o w e r e in the C h i l d B c l a s s ( 9 6 % , 9 0 % and 69% vs 79%, 68% a n d 41%, p< 0.05 );4) in the g r o u p of p a t i e n t s w i t h m u l t i p l e lesions, the s u r v i v a l r a t e was 83%, 63% and 35% at 1 yr, 2 yr and 3 yr r e s p e c t i v e l y ( p< 0.05 vs the survival rate of patients with single lesions).Conclusion: PEI is a safe and efficacious alternative therapy for the m a n a g e m e n t of H C C in liver cirrhosis.
409A
1210 SUBCUTANEOUS OCTREOTIDE FOR THE TREATMENT OF VARICEAL BLEEDING: A PHARMACOKINETIC STUDY V ~te L6dinehen. MP Riuauh. N Raffoux. S Bououet. C Silvain. M B e a u c h a n t . Hepatology Unit and Pharmacology Unit, Poitiers University, France Octreotide, a synthetic analog of somatostatin, is known m be effective for the control of variceal bleeding in cirrhosis, and the minimal dose recommended was a 25p.g/h intravenous (IV) continuous infusion. Few studies delt on the subcutaneous way of administration which appeared preferential in the prevention of early rebleeding. The aim of this study was to compare plasma octreotide concentrations (C) obtained after IV infusion and subcutaneous (SC) injection in patients with cirrhosis. Six patients (6M, Pugh's A=2, B=2, C=2) with alcoholic cirrhosis received a 25 ~tg/h IV infusion of octreotide for variceal bleeding. Plasma C W were obtained at 12 and 16h (C W steady state) from start of infusion. After a 24h wash out period, the same patient received a 500ktg octreotide SC injection. Octreotide plasma C s c was measured by radioimmunoassay at 0,1.5,8 and 14h after dosin~oResults: SD m
Civss (pg/ml) 4622 1800
Csc max CLT/F sc T I/2el sc (pg/ml) (l/h) (h) 13058 2'368
4,9 0,99
5,08 1,32
Vdss sc (i) 34 8,5
In most patients octreotide plasma C s c only remained above CIvo. within the first 8h. Assuming that a line~a: pharmacokinetic model c6u~d be applied to octreotide, theoretical mean plasma CSC after 100 and 200 pg/ml subcutaneous injection would be respectively 2610 and 5221 pg/ml at 90mn, and 921 and 1842 pg/ml at 8h. Conclusion: Assuming that 25 Ixg/h IV:infusion is the minimal dose required to control variceal bleeding, these results suggest that the optimal subcutaneous octreotide dose would be 500 ~tg every 8 hours for prevention of early variceal rebleeding.
1212 RETENTION
OF A BILE ACID ANALOGUE IN THE ENTEROHEPATIC CIRCULATION (EHC) IN PRIMARY BILIARY CIRRHOSIS (PBC): COMPARISON WITH NORMAL CONTROLS AND EFFECT OF BILE ACID TREATMENT. M. De Tavonatti, M.B. Panarotto,* G. Maim*. F. Fmnceschini§, F. Lanzarotto, A. Lanzini. Medicine 1, Nuclear Medicine* and Immunology§, Spedali Civili. Brescia. Italy.
The gamma-emitting bile acid analogue selena homocholic acid-taurine (SeHCAT) behaves as a natural bile acid in man (Gastroenterology 1988; 95:164), and we reasoned that in chronic cholestasis it may be retained in the EHC longer than in health. Furthermore, Sis retention may be reduced by chronic administration of ursodeoxycholie acid (UDCA), as suggested by studies in healthy subjects (Hepatology 1990; 12:1206). The aims of our study were to compare SeHCAT retention time in PBC patients with fimctioning gallbladders before (n=10) and during (n=5) UDCA administration, with that of matched healthy controls (n=8). We used tanrine conjugated UDCA (TUDCA, 10 mg/kg/day) to enhance bioavailability of this bile acid. SeHCAT retention time was expressed as half-time (T1/2) of the exponential decline of activity over the gallbladder area as measured by gamma camera counting on 5 successive days. SeHCAT T 1/2 ranged between 53 and 220 h in PBC patients, and between 40 and 59 h in controls. Mean T1/2 value was significantly higher in PBC patients (125 + 18 h, SEM) than in control subjects (47+ 2 h, p<0.002, by unpaired t test). TI/2 was l 14 vs 44h, 89 vs 33 h, 141 vs 31 h, 220 vs 4 lh and 64 vs 78h in the 5 patients studied before and during TUDCA. Mean T1/2 value decreased from 126 + 27 to 45 + 9 during TUDCA treatment (p=0.065, paired t test). There was no correlation (r = -0.08) between histological PBC grading and pretreatment SeHCAT T1/2. We conclude that in PBC i) retention of SeHCAT in the EHC is increased by comparison with healthy controls; that ii) this increase is not related to histological stage; and that iii) TUDCA reduces SeHCAT retention to the same values as in healthy subjects.