non syndromatic paucity of interlobular bile ducts in adult

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436 NON SYNDROHATICPAUCITY OF INTERLOBULAR BILE DUCTS IN ADULT. ES. ZAFRANI, B. GUIGUI, C. DOUVIN, D. LARREY, P. MASSARI, JM. METREAU, JP. BENHAMOU, D. DHUMEAUX. Department of Pathology, H6pital Henri Mondor, Cr~teil ; Hepatology Unit, H6pital Beaujon, Clichy ; Department of Hepatology, H6pital Henri Mondor, 94010 Cr~teil Cedex, France. Non syndromatic intrahepatic cholestatic syndrome with paucity of in~erlobular bile ducts (ILBD) is known in infancy and childhood. The purpose of the present study is to describe a similar syndrome that occurred in adults. The 5 patients were 2 men and 3 women, including 2 siblings in 2 families. They were aged from 18 zo 32 yrs at onset of disease, which was revealed by pruritus and/or jaundice. At this time, serum ASAT ranged from 1 to lOxN, alkaline phosphatases from 2 to 15xN, and total bilirubin from 27 to 150 Nmol/l. Initial liver biopsy showed mild to moderate fibrosis with mild inflammatory infiltrate, cholangiolar proliferation, and, in 4 cases, reduction in the number of ILBD. Antimitochondrial antibodies were absent and common bile duct was normal after opacification. Four of the 5 patients were followed-up for 3 to II yrs. Three of them experienced bouts of jaundice, and liver biopsy obtained after 2,4 and 5 yrs showed aggravation of the lesions with development of biliary type cirrhosis ; ILBD were absent, even in the case in which they were initially normal. Two of these 3 patienzs died of complications of cirrhosis, 3 and II yrs after revelation of disease, and the ~hird patient, with persistent jaundice, is to be transplanted. The fourth patient has anicteric cholestasis, and a liver biopsy performed after 3 yrs showed marked increase in fibrosis. In conclusion, our study shows that chronic cholestatic syndrome with paucity of ILBD may be revealed at an adult age. This syndrome, possibly familial, may rapidly progress towards severe hepatic disease, leading to discuss early transplantation. 437 IMMUNOGENICITY OF RECOMBINANT YEAST HEPATITIS B VACCINES A.R.Zanetti,E.Tanzi,S.Perin,A.Pozzl,A.Car@nel,P.Vlgan~,F.Bergamini. Institute of Virology, University of Milan and ~Hospital L.Sacco, Milan. Recombinant hepatitis B vaccine prepared from antigen expressed in yeast was given to 89 healthy medical students and clinical laboratory staff mem- bers. Of these individuals, 59 (45 males, 14 females; mean age 26.4 years, range 22-42 years) received vaccine made by Smith Kline-Rit (group I) and 30 subjects (10 males, 20 females; mean age 24.4 years, range 20-35 years) were injected with vaccine prepared by Merck Sharp & Dohme Labs. (group II) . Befo- re the study, all participants were negative for HBsAg, anti-HBc, anti-HBs, showed normal ALT level and had no history of allergic diseases. Each indivi- dual was given three i.m. (deltoid region) injections of vaccine (subjects of group I received doses of 20 mcg and those of group II received doses of 10 mcg) at time 0, I and 6 months. After completion of the vaccination schedule, 50.8% of individuals assigned to group I showed anti-HBs titers higher than 1000 mIU/ml, 32.2% between 100 and 1000 mIU/ml, 15.3% between 10 and 99 mIU/ ml, while one subject showed a very poor response (lower than 10 mIU/ml). Among individuals of group II, 41.4% developed titers greater than 1000 mIU/ ml, 48.3% between 100 and 1000 and 10.3% between 10 and 99 mIU/ml. During the follow-up, none of the vaccine recipients developed HBsAg and/or anti-HBc. No serious adverse reactions occurred during the study. These data indicate that both recombinant hepatitis B vaccines used are immunogenic and safe. $224

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436 NON SYNDROHATIC PAUCITY OF INTERLOBULAR BILE DUCTS IN ADULT.

ES. ZAFRANI, B. GUIGUI, C. DOUVIN, D. LARREY, P. MASSARI, JM. METREAU, JP. BENHAMOU, D. DHUMEAUX. Department of Pathology, H6pital Henri Mondor, Cr~tei l ; Hepatology Unit , H6pital Beaujon, Cl ichy ; Department of Hepatology, H6pital Henri Mondor, 94010 Cr~tei l Cedex, France.

Non syndromatic in t rahepat ic cho lesta t ic syndrome with paucity of in~er lobular b i l e ducts (ILBD) is known in infancy and childhood. The purpose of the present study is to describe a s imi la r syndrome that occurred in adults.

The 5 pat ients were 2 men and 3 women, inc lud ing 2 s ib l ings in 2 fami l ies . They were aged from 18 zo 32 yrs at onset of disease, which was revealed by p rur i tus and/or jaundice. At t h i s time, serum ASAT ranged from 1 to lOxN, a lka l ine phosphatases from 2 to 15xN, and to ta l b i l i r u b i n from 27 to 150 Nmol/ l . I n i t i a l l i v e r biopsy showed mild to moderate f i b ros i s with mild inflammatory i n f i l t r a t e , cholangiolar p r o l i f e r a t i o n , and, in 4 cases, reduction in the number of ILBD. Ant imitochondrial antibodies were absent and common b i le duct was normal a f te r opac i f i ca t ion . Four of the 5 pat ients were fol lowed-up for 3 to I I yrs. Three of them experienced bouts of jaundice, and l i v e r biopsy obtained a f ter 2,4 and 5 yrs showed aggravation of the lesions with development of b i l i a r y type c i r rhos is ; ILBD were absent, even in the case in which they were i n i t i a l l y normal. Two of these 3 patienzs died of complications of c i r rhos is , 3 and I I yrs a f ter reve la t ion of disease, and the ~hird pat ient , with pers is tent jaundice, is to be transplanted. The four th pat ient has an ic ter ic cholestasis, and a l i v e r biopsy performed af ter 3 yrs showed marked increase in f i b ros i s .

In conclusion, our study shows that chronic cho lesta t ic syndrome with paucity of ILBD may be revealed at an adult age. This syndrome, possibly f a m i l i a l , may rap id ly progress towards severe hepatic disease, leading to discuss ear ly t ransp lanta t ion .

437 IMMUNOGENICITY OF RECOMBINANT YEAST HEPATITIS B VACCINES

A.R.Zanetti,E.Tanzi,S.Perin,A.Pozzl,A.Car@nel,P.Vlgan~,F.Bergamini.

Institute of Virology, University of Milan and ~Hospital L.Sacco, Milan.

Recombinant hepatitis B vaccine prepared from antigen expressed in yeast was given to 89 healthy medical students and clinical laboratory staff mem- bers. Of these individuals, 59 (45 males, 14 females; mean age 26.4 years, range 22-42 years) received vaccine made by Smith Kline-Rit (group I) and 30 subjects (10 males, 20 females; mean age 24.4 years, range 20-35 years) were injected with vaccine prepared by Merck Sharp & Dohme Labs. (group II) . Befo- re the study, all participants were negative for HBsAg, anti-HBc, anti-HBs, showed normal ALT level and had no history of allergic diseases. Each indivi- dual was given three i.m. (deltoid region) injections of vaccine (subjects of group I received doses of 20 mcg and those of group II received doses of 10 mcg) at time 0, I and 6 months. After completion of the vaccination schedule, 50.8% of individuals assigned to group I showed anti-HBs titers higher than 1000 mIU/ml, 32.2% between 100 and 1000 mIU/ml, 15.3% between 10 and 99 mIU/ ml, while one subject showed a very poor response (lower than 10 mIU/ml). Among individuals of group II, 41.4% developed titers greater than 1000 mIU/ ml, 48.3% between 100 and 1000 and 10.3% between 10 and 99 mIU/ml. During the follow-up, none of the vaccine recipients developed HBsAg and/or anti-HBc. No serious adverse reactions occurred during the study. These data indicate that both recombinant hepatitis B vaccines used are immunogenic and safe.

$224