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Treatment with colchicine of experimental liver cirrhosis
144
TREATMENT WITH COLCHICINE OF E X P E R I M E N T A L LIVER CIRRHOSIS PROF. J O S I F E. A D H A M I U n i v e r s i t y ,,Enver Hoxha,~ of T i r a n a A l b a n i a
The object of t h i s w o r k w a s to s t u d y thp effoct of c o l c h i c i n e on c i r r h o t i c rats. The s t u d y w a s c a r r i e d out on 38 rats of the W i s t a r race, w e i g h i n g b e t w e e n 150 a nd 350 g, to w h i c h CCL, 50% in m a i z e oil w a s a d m i n i s t e r e d s u b c u t a n e o u s l y at the dose of 1.3 m l / k g t w i c e a w e e k for t h r e e mont hs . D u r i n g t h a t pe ri od 9 of the rats died. The remainir~g 29 rats w e r e d i v i d e d into 3 g r o u p s : g r o u p I c ons i s t e d of 4 r a t s w h i c h w e r e s a c r i f i c e d i m m e d i a t e l y a f t e r the period of tr~.atm~nt w i t h CCI,. In t h i s g r o u p can also be i nc l u4*d the 9 r a t s t h a t had diod d u r i n ~ t h a t period. G r o u p II c o n t a i n e d 10 r a t s w h i c h w e r e left w i t h o u t t r e a t m e n t for 10 w e e k s and w e r e t h e n sacrificed. G r o u p III w a s composed of 15 r a t s t r e a t e d w i t h c o l c h i c i n e 1.5 l~g/kg by i n t r a m u s c u l a r ini_~ctions threo timo~ a w e e k for 10 w e e k s a nd w e r e t he n sacrificed. Histopath01o3ic findings: Group I ~ S l i g h t ir~filtration of t he p o r t a l areas, also s l i q h t l i n i d d y s t r o p h y , m o r e m a r k e d g r a n u l a r d y s t r o p h y and vpry m a r k e d necrosis of t he hel~atic cells (over 500/0 of t h e he Datocvtes w e r e i n v o l v e d l . T h e r e w a s p r o n o u n c e d fibrosis, p e n o t r a t i n g into t he l i v e r lobules, as w e l l as p e r i c e l l u l a r fibrosis. G r o u p II, t h e true control ~roun. n r e s e n t e d a less~r d e g r e e of i n f i l t r a t i o n of t he p o r t a l ~reas. w h e r e a ~ the g r a n u l a r and lipid d y s t r o n h y a n d t h e ne c ros i s of t he heDatocytes w e r e l i t t l e modi fi e d. Th," fibrosis t~nded to d i m i n i s h i n th,, por'ral area~ but w a s c o n c e n t r a t e d in t he wa11~ of t h e w e s s e l s , w h i l o tho ,~-o,,dolobulo~ of r ~ o n e r a t i o n h a d r e m a i n e d virtu.~llv u n c h a n g e d . Group III, the group t r e a t er w i t h c o l c h i c i n e - - S t a i n i n g w i t h Tricromverd s h o w e d t h a t t he f~brosis w a s n o r m a l i s e d in 7nnt, nf +he earns, th e w a l l s of the v e s s e l s w e r e n o r m a l . D~ourt,~lobul~s w~r~ f'~und onl y in thee,, ca.~e.q a n d h a d d i s a p p e a r e d in th e o t h e r s ; g r a n u l a r and linld dv~tronhv w e r e reduced, n~crosis of t he h e p a t o c y t e s w a s limitpd, and processes of r e p a i r and r e g e n e r a t i o n had a n p e a r e d . Conclusion: The effect of colchicm~ is to roduco th_~ ~ r a n u l ~ r a nd l i pi d ch~n~es of t he b o n a t n cvtes, to l i m i t t h e i r necrosis, to ine~llre n r o c o ~ , * o¢ r~-~'~eration a nd rcr,.".'.'r, t~ e l i m i n a t e t he f i b r o s i s of the p~rtal areas, the sclerosis of the w a l l s of th~ v~ssels a nd tl~e g ~ : u d o l o b u l e s of r e g e n e r a t i o n .
145
DELTA VIRUS
(HDV) A N D
CHRONIC H E P A T O P A T H Y
J O S I F E. ADHAMI, I~ETRIKA' TROJA, J O V A N BASHO, S p i t a l i k h n i k nr. 1. or. 3. U n i v e r s i t y ,,Enver H o x h a * of T i r a n a A l b a n i a The p u r p o s e of this s t u d y is to access the f r e q u e n c y of d e l t a v i r u s in c h r o n i c h e p a t o p a t h i e s a nd the p a r t it p l a y s in c a u s i n g them. The m a t e r i a l c o m p r i s e s 127 p a t i e n t s a t t h e m e a n a ge of 41.2 ___ 14.4 years. Of these, 110 had c h r o n i c h e p a t o p a t h y of w h o m 27 CPH, 14 CAH, 39 AC, 21 n o n - a c t i v e c i r r h o s i s a n d 9 fibr ous h epatitis. In a d d i t i o n , 17 had c h a n g e s such as i n f e c t t i o n of t h e b i l i a r y tract, d y s k i n e s i a of t h e bil i a r y t r a c t etc, w h i c h w e r e used as a c o n t r o l l group. The di a gnos i s , be s i de s t he c l i n i c a l ~nd l a b o r a t o r y f indings, w a s based on l a p a r a s c o p y , p u n c t u r e b i o p s y of t he liver, e c h o g r a p h y , s c i n t i g r a p h y a n d on t he serologic findings. To d e t e c t t h e v i r u s m a r k e r s , t h e f o l l o w i n g m e a n s w e r e us e d: t he IED t e c h n i a u e for the d e t e c t i o n of H B s A g / a n t i - H B s , a n d for t h e n e g a t i v e cases t he h e m a g g l u t i n i n test w i t h r e a g e n t s from the W e l l c o m e f i r m ; a n t i - H B c and a n t i - d e l t a w e r e tes t e d w i t h t he md of t h e A b b o t t c o m m e r m a l ki t s (ELISA). Of t h e 110 cases of c h r o n i c h e p a t o p a t h y , 42 r e s u l t e d HBsAg-pos.itive w h i l e of the c ont rol gr o up of 17 only 5 (X2 ~ 0.48. n.s.). In the p a t i e n t s w i t h H B s A g (-I-) a nd H B s A g (--) a n t i - H B c was s e a r c h e d for a n d w a s found in 100% and 97.05% r e s p e c t i v e l y (X'-' = 0.87. n.s.). The f r e q u e n c y of a nt 2-de l t a in the cases w i t h chronic h e p a t o p a t h y w a s 88.2%, w h e r e a s in t he r e m a i n i n g cases it w a s 47.1°/0 (X~ ~-~ 28.25 p < 0.001). It w a s e n c o u n t e r e d m o r e f r e q u e n t l y in c i r r h o s i s a n d f i b r o u s h e p a t i t i s (94.2%), t h a n m CPH or CAH (p < 0.01). The a n a l y s i s of the i n c i d e n c e of a n t i - d e l t a in all t h e p a t i e n t s of t h e s t u d y s h o w e d t h a t it w a s h i g h e r in p a t i e n t s w i t h H B s A g (-}-) t h a n in t hos e w~th H B s A g (--L b u t w i t h a n t i -HBC (-{-) (91.4% and 77.5o/0 r e s p e c t i v e l y ; p < 0.05). The s e f i n d i n g s dndi c a t e t h a t : 1) in a d d i t i o n to HBV, d e l t a v i r u s p l a y s an i m p o r t a n t role in the d e v e l o p m e n t of c h r o n i c h e p a t o p a t h y (88.2%); 2) HDV w a s m o r e f r e q u e n t in c i r r h o s i s a n d l i v e r f i b r o s i s t h a n in c h r o n i c h e p a t i t i s (p < 0.01); 3) a n t i - d e l t a is m u c h m o r e f r e q u e n t in p a t i e n t s w i t h c h r o n i c h e p a t o p a t h y t h a n in t he control g r o u p (p -: 0.091).
S78
TREATMENT WITH COLCHICINE OF E X P E R I M E N T A L LIVER CIRRHOSIS PROF. J O S I F E. A D H A M I U n i v e r s i t y ,,Enver Hoxha,~ of T i r a n a A l b a n i a
The object of t h i s w o r k w a s to s t u d y thp effoct of c o l c h i c i n e on c i r r h o t i c rats. The s t u d y w a s c a r r i e d out on 38 rats of the W i s t a r race, w e i g h i n g b e t w e e n 150 a nd 350 g, to w h i c h CCL, 50% in m a i z e oil w a s a d m i n i s t e r e d s u b c u t a n e o u s l y at the dose of 1.3 m l / k g t w i c e a w e e k for t h r e e mont hs . D u r i n g t h a t pe ri od 9 of the rats died. The remainir~g 29 rats w e r e d i v i d e d into 3 g r o u p s : g r o u p I c ons i s t e d of 4 r a t s w h i c h w e r e s a c r i f i c e d i m m e d i a t e l y a f t e r the period of tr~.atm~nt w i t h CCI,. In t h i s g r o u p can also be i nc l u4*d the 9 r a t s t h a t had diod d u r i n ~ t h a t period. G r o u p II c o n t a i n e d 10 r a t s w h i c h w e r e left w i t h o u t t r e a t m e n t for 10 w e e k s and w e r e t h e n sacrificed. G r o u p III w a s composed of 15 r a t s t r e a t e d w i t h c o l c h i c i n e 1.5 l~g/kg by i n t r a m u s c u l a r ini_~ctions threo timo~ a w e e k for 10 w e e k s a nd w e r e t he n sacrificed. Histopath01o3ic findings: Group I ~ S l i g h t ir~filtration of t he p o r t a l areas, also s l i q h t l i n i d d y s t r o p h y , m o r e m a r k e d g r a n u l a r d y s t r o p h y and vpry m a r k e d necrosis of t he hel~atic cells (over 500/0 of t h e he Datocvtes w e r e i n v o l v e d l . T h e r e w a s p r o n o u n c e d fibrosis, p e n o t r a t i n g into t he l i v e r lobules, as w e l l as p e r i c e l l u l a r fibrosis. G r o u p II, t h e true control ~roun. n r e s e n t e d a less~r d e g r e e of i n f i l t r a t i o n of t he p o r t a l ~reas. w h e r e a ~ the g r a n u l a r and lipid d y s t r o n h y a n d t h e ne c ros i s of t he heDatocytes w e r e l i t t l e modi fi e d. Th," fibrosis t~nded to d i m i n i s h i n th,, por'ral area~ but w a s c o n c e n t r a t e d in t he wa11~ of t h e w e s s e l s , w h i l o tho ,~-o,,dolobulo~ of r ~ o n e r a t i o n h a d r e m a i n e d virtu.~llv u n c h a n g e d . Group III, the group t r e a t er w i t h c o l c h i c i n e - - S t a i n i n g w i t h Tricromverd s h o w e d t h a t t he f~brosis w a s n o r m a l i s e d in 7nnt, nf +he earns, th e w a l l s of the v e s s e l s w e r e n o r m a l . D~ourt,~lobul~s w~r~ f'~und onl y in thee,, ca.~e.q a n d h a d d i s a p p e a r e d in th e o t h e r s ; g r a n u l a r and linld dv~tronhv w e r e reduced, n~crosis of t he h e p a t o c y t e s w a s limitpd, and processes of r e p a i r and r e g e n e r a t i o n had a n p e a r e d . Conclusion: The effect of colchicm~ is to roduco th_~ ~ r a n u l ~ r a nd l i pi d ch~n~es of t he b o n a t n cvtes, to l i m i t t h e i r necrosis, to ine~llre n r o c o ~ , * o¢ r~-~'~eration a nd rcr,.".'.'r, t~ e l i m i n a t e t he f i b r o s i s of the p~rtal areas, the sclerosis of the w a l l s of th~ v~ssels a nd tl~e g ~ : u d o l o b u l e s of r e g e n e r a t i o n .
145
DELTA VIRUS
(HDV) A N D
CHRONIC H E P A T O P A T H Y
J O S I F E. ADHAMI, I~ETRIKA' TROJA, J O V A N BASHO, S p i t a l i k h n i k nr. 1. or. 3. U n i v e r s i t y ,,Enver H o x h a * of T i r a n a A l b a n i a The p u r p o s e of this s t u d y is to access the f r e q u e n c y of d e l t a v i r u s in c h r o n i c h e p a t o p a t h i e s a nd the p a r t it p l a y s in c a u s i n g them. The m a t e r i a l c o m p r i s e s 127 p a t i e n t s a t t h e m e a n a ge of 41.2 ___ 14.4 years. Of these, 110 had c h r o n i c h e p a t o p a t h y of w h o m 27 CPH, 14 CAH, 39 AC, 21 n o n - a c t i v e c i r r h o s i s a n d 9 fibr ous h epatitis. In a d d i t i o n , 17 had c h a n g e s such as i n f e c t t i o n of t h e b i l i a r y tract, d y s k i n e s i a of t h e bil i a r y t r a c t etc, w h i c h w e r e used as a c o n t r o l l group. The di a gnos i s , be s i de s t he c l i n i c a l ~nd l a b o r a t o r y f indings, w a s based on l a p a r a s c o p y , p u n c t u r e b i o p s y of t he liver, e c h o g r a p h y , s c i n t i g r a p h y a n d on t he serologic findings. To d e t e c t t h e v i r u s m a r k e r s , t h e f o l l o w i n g m e a n s w e r e us e d: t he IED t e c h n i a u e for the d e t e c t i o n of H B s A g / a n t i - H B s , a n d for t h e n e g a t i v e cases t he h e m a g g l u t i n i n test w i t h r e a g e n t s from the W e l l c o m e f i r m ; a n t i - H B c and a n t i - d e l t a w e r e tes t e d w i t h t he md of t h e A b b o t t c o m m e r m a l ki t s (ELISA). Of t h e 110 cases of c h r o n i c h e p a t o p a t h y , 42 r e s u l t e d HBsAg-pos.itive w h i l e of the c ont rol gr o up of 17 only 5 (X2 ~ 0.48. n.s.). In the p a t i e n t s w i t h H B s A g (-I-) a nd H B s A g (--) a n t i - H B c was s e a r c h e d for a n d w a s found in 100% and 97.05% r e s p e c t i v e l y (X'-' = 0.87. n.s.). The f r e q u e n c y of a nt 2-de l t a in the cases w i t h chronic h e p a t o p a t h y w a s 88.2%, w h e r e a s in t he r e m a i n i n g cases it w a s 47.1°/0 (X~ ~-~ 28.25 p < 0.001). It w a s e n c o u n t e r e d m o r e f r e q u e n t l y in c i r r h o s i s a n d f i b r o u s h e p a t i t i s (94.2%), t h a n m CPH or CAH (p < 0.01). The a n a l y s i s of the i n c i d e n c e of a n t i - d e l t a in all t h e p a t i e n t s of t h e s t u d y s h o w e d t h a t it w a s h i g h e r in p a t i e n t s w i t h H B s A g (-}-) t h a n in t hos e w~th H B s A g (--L b u t w i t h a n t i -HBC (-{-) (91.4% and 77.5o/0 r e s p e c t i v e l y ; p < 0.05). The s e f i n d i n g s dndi c a t e t h a t : 1) in a d d i t i o n to HBV, d e l t a v i r u s p l a y s an i m p o r t a n t role in the d e v e l o p m e n t of c h r o n i c h e p a t o p a t h y (88.2%); 2) HDV w a s m o r e f r e q u e n t in c i r r h o s i s a n d l i v e r f i b r o s i s t h a n in c h r o n i c h e p a t i t i s (p < 0.01); 3) a n t i - d e l t a is m u c h m o r e f r e q u e n t in p a t i e n t s w i t h c h r o n i c h e p a t o p a t h y t h a n in t he control g r o u p (p -: 0.091).
S78