- Email: [email protected]
Effects of verapamil on porto-hepatic gradient and metabolic activity of the liver in alcoholic cirrhosis
430
EFFECTS OF VERAPAMIL ON PORTO-HEPATIC GRADIENT AND METABOLIC ACTIVITY OF THE LIVER IN ALCOHOLIC CIRRHOSIS.
J.P.Vinel,
J.P.Caucanas,
P.Cales,
J.P.Pascal.
Service
d'h~pato-gastro-
e n t d r o l o g i e - CHU PURPAN, )i059 TOULOUSE CEDEX - FRANCE.
Verapamil has been shown to improve hepatic function in rats with cirrhosis and to decrease intra-hepatic vascular resistance (3.Reichen, J. Clin. Invest. 1986, 78 : 448-455). The present study aimed to investigate the effects of Verapamil on hepatic function and porto-hepatic gradient in patients with alcoholic cirrhosis. Methods : after an overnight fast, indocyanine green was infused at a constant rate of 0.15 mg.min-I after a bolus injection of i0 rag, in 6 patients (4 males and 2 females, mean age : 63+-6 years) with biopsy proven alcoholic cirrhosis (Child-Pugh's = 9 in 3 and = I0 in 3). Before and i hour after the iv injection of 10 mg of Verapamil (V) : l-hepatic blood flow (HBF), hepatic extraction (El and intrinsic hepatic clearance (IHC) of ICG according to the sinusoidal model were calculated. 2-Free and wedged hepatic vein pressures were recorded. Statistical analysis used the paired t-test. Rdsults : Porto-hepatic E H B F I H C gradient (mm Hg) (%) (ml .min-l) (ml .min-I ) : :
B e f o r e Verapamil A f t e r V~rapamil
: :
21.4 + 5.8 1 9 . 5 +- 4 . 2
: :
1 5 . 1 +_ 5 . 6 16 +- 5 . 8
: :
739 +_ 286 744 +- 308
: :
1 0 9 . 1 +_ 1 6 . 5 1 1 5 . 3 _+ 1 6 . 5
: :
: p : N.S. : N.S. : N.S. : < 0.05 : Conclusions : in patients with alcoholic cirrhosis, intra-venous Verapamil at a dose within the therapeutic range : 1-significantly improved the metabolic activity of the liver. However as a mean, intrinsic hepatic clearance increase was only 5.6 %. 2-had no effect on porto-hepatic gradient. These results suggest that Verapamil should probably not be recommended for the treatment of portal hypertension in cirrhotic patients.
431
S I G N I F I C A N C E AND C O R R E L A T I O N B E T W E E N SERUM HBV DNA AND H E P A T I T I S B e A N T I G E N / A N T I B O D Y : A L O N G I T U D I N A L STUDY IN P A T I E N T S WITH CHRONIC H E P A T I T I S B. E. Walter, H.E. Blum, B. MSller*, W.-B. O f f e n s p e r g e r , S. Offensperker, U. Hopf*, W. Gerok. Depts. of Medicine, Univ. of Freiburg, FRG and *Univ. C l i n i c C h a r l o t t e n b u r g , Free Univ., Berlin.
The d e t e c t i o n of h e p a t i t i s 8 virus DNA in serum by n u c l e i c acid h y b r i d i z a tion p r o v i d e s a d i r e c t and h i g h l y s e n s i t i v e m a r k e r of viral r e p l i c a t i o n . In a l o n g i t u d i n a l study we a n a l y z e d the sera from 19 H B s A g - p o s i t i v e p a t i e n t s with c h r o n i c h e p a t i t i s B for HBV DNA by spot blot h y b r i d i z a t i o n and for viral m a r k e r s by r a d i o i m m u n o a s s a y s (Abbott) to d e t e r m i n e the s i g n i f i c a n c e and t e m p o r a l c o r r e l a t i o n of t h e s e p a r a m e t e r s . A v e r a g e time of f o l l o w - u p was 38.2 m o n t h s (ranging from 13 to 57 months). All p a t i e n t s had h i s t o l o g i c a l l y p r o v e n c h r o n i c active h e p a t i t i s B. (I) H B e A ~ - p o s i t i v e p a t i e n t s : 6/8 (75%) R B e A g - p o s i t i v e p a t i e n t s were c o n t i n u ously HBV DNA p o s i t i v e , 2/8 (25%) were i n t e r m i t t e n t l y HBV DNA positive, i.e. all c o n t i n u o u s l y H B e A g - p o s i t i v e p a t i e n t s were also HBV DNA p o s i t i v e at least at some point in time. (II) A n t i - H B e - p o s i t i v e p a t i e n t s : i/8 (12%) a n t i - H B e - p o s i t i v e p a t i e n t s had HBV DNA d e t e c t a b l e d u r i n g the f o l l o w - u p period of 33 months, while 7/8 (88%) a n t i - H B e - p o s i t i v e p a t i e n t s were HBV DNA negative. (III) P a t i e n t s with HBeAg/ a n t i - H B e or a n t i - H B e / HBeAg s e r o c o n v e r s i o n : In all 3 p a t i e n t s f o l l o w e d no HBV DNA was d e t e c t a b l e at any point in time. C o n c l u s i o n : W h i l e in the m a j o r i t y of p a t i e n t s the p r e s e n c e and a b s e n c e of HBV DNA in serum c o r r e l a t e s w i t h the HBeAg and a n t i - H B e status, r e s p e c t i v e ly, there is a s i g n i f i c a n t n u m b e r of i n d i v i d u a l s f o l l o w e d l o n g i t u d i n a l l y with d i s c o r d a n c e of HBeAg/ a n t i - H B e and HBV DNA.
$221
EFFECTS OF VERAPAMIL ON PORTO-HEPATIC GRADIENT AND METABOLIC ACTIVITY OF THE LIVER IN ALCOHOLIC CIRRHOSIS.
J.P.Vinel,
J.P.Caucanas,
P.Cales,
J.P.Pascal.
Service
d'h~pato-gastro-
e n t d r o l o g i e - CHU PURPAN, )i059 TOULOUSE CEDEX - FRANCE.
Verapamil has been shown to improve hepatic function in rats with cirrhosis and to decrease intra-hepatic vascular resistance (3.Reichen, J. Clin. Invest. 1986, 78 : 448-455). The present study aimed to investigate the effects of Verapamil on hepatic function and porto-hepatic gradient in patients with alcoholic cirrhosis. Methods : after an overnight fast, indocyanine green was infused at a constant rate of 0.15 mg.min-I after a bolus injection of i0 rag, in 6 patients (4 males and 2 females, mean age : 63+-6 years) with biopsy proven alcoholic cirrhosis (Child-Pugh's = 9 in 3 and = I0 in 3). Before and i hour after the iv injection of 10 mg of Verapamil (V) : l-hepatic blood flow (HBF), hepatic extraction (El and intrinsic hepatic clearance (IHC) of ICG according to the sinusoidal model were calculated. 2-Free and wedged hepatic vein pressures were recorded. Statistical analysis used the paired t-test. Rdsults : Porto-hepatic E H B F I H C gradient (mm Hg) (%) (ml .min-l) (ml .min-I ) : :
B e f o r e Verapamil A f t e r V~rapamil
: :
21.4 + 5.8 1 9 . 5 +- 4 . 2
: :
1 5 . 1 +_ 5 . 6 16 +- 5 . 8
: :
739 +_ 286 744 +- 308
: :
1 0 9 . 1 +_ 1 6 . 5 1 1 5 . 3 _+ 1 6 . 5
: :
: p : N.S. : N.S. : N.S. : < 0.05 : Conclusions : in patients with alcoholic cirrhosis, intra-venous Verapamil at a dose within the therapeutic range : 1-significantly improved the metabolic activity of the liver. However as a mean, intrinsic hepatic clearance increase was only 5.6 %. 2-had no effect on porto-hepatic gradient. These results suggest that Verapamil should probably not be recommended for the treatment of portal hypertension in cirrhotic patients.
431
S I G N I F I C A N C E AND C O R R E L A T I O N B E T W E E N SERUM HBV DNA AND H E P A T I T I S B e A N T I G E N / A N T I B O D Y : A L O N G I T U D I N A L STUDY IN P A T I E N T S WITH CHRONIC H E P A T I T I S B. E. Walter, H.E. Blum, B. MSller*, W.-B. O f f e n s p e r g e r , S. Offensperker, U. Hopf*, W. Gerok. Depts. of Medicine, Univ. of Freiburg, FRG and *Univ. C l i n i c C h a r l o t t e n b u r g , Free Univ., Berlin.
The d e t e c t i o n of h e p a t i t i s 8 virus DNA in serum by n u c l e i c acid h y b r i d i z a tion p r o v i d e s a d i r e c t and h i g h l y s e n s i t i v e m a r k e r of viral r e p l i c a t i o n . In a l o n g i t u d i n a l study we a n a l y z e d the sera from 19 H B s A g - p o s i t i v e p a t i e n t s with c h r o n i c h e p a t i t i s B for HBV DNA by spot blot h y b r i d i z a t i o n and for viral m a r k e r s by r a d i o i m m u n o a s s a y s (Abbott) to d e t e r m i n e the s i g n i f i c a n c e and t e m p o r a l c o r r e l a t i o n of t h e s e p a r a m e t e r s . A v e r a g e time of f o l l o w - u p was 38.2 m o n t h s (ranging from 13 to 57 months). All p a t i e n t s had h i s t o l o g i c a l l y p r o v e n c h r o n i c active h e p a t i t i s B. (I) H B e A ~ - p o s i t i v e p a t i e n t s : 6/8 (75%) R B e A g - p o s i t i v e p a t i e n t s were c o n t i n u ously HBV DNA p o s i t i v e , 2/8 (25%) were i n t e r m i t t e n t l y HBV DNA positive, i.e. all c o n t i n u o u s l y H B e A g - p o s i t i v e p a t i e n t s were also HBV DNA p o s i t i v e at least at some point in time. (II) A n t i - H B e - p o s i t i v e p a t i e n t s : i/8 (12%) a n t i - H B e - p o s i t i v e p a t i e n t s had HBV DNA d e t e c t a b l e d u r i n g the f o l l o w - u p period of 33 months, while 7/8 (88%) a n t i - H B e - p o s i t i v e p a t i e n t s were HBV DNA negative. (III) P a t i e n t s with HBeAg/ a n t i - H B e or a n t i - H B e / HBeAg s e r o c o n v e r s i o n : In all 3 p a t i e n t s f o l l o w e d no HBV DNA was d e t e c t a b l e at any point in time. C o n c l u s i o n : W h i l e in the m a j o r i t y of p a t i e n t s the p r e s e n c e and a b s e n c e of HBV DNA in serum c o r r e l a t e s w i t h the HBeAg and a n t i - H B e status, r e s p e c t i v e ly, there is a s i g n i f i c a n t n u m b e r of i n d i v i d u a l s f o l l o w e d l o n g i t u d i n a l l y with d i s c o r d a n c e of HBeAg/ a n t i - H B e and HBV DNA.
$221