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Lactitol vs. lactulose in the treatment of chronic recurrent portal systemic encephalopathy (PSE)
274
ACUTE AND CHRONIC DELTA HEPATITIS IN WOODCHUCKS INOCULATED WITH HIGHLY DILUTED HDV-CONTAINING WOODCHUCK SERA. C Hele(1), M Rapicetta(2), B Forzani(1), R Rasshofer(3), AN Di Rienzo(2), C La-
varini(1), MF Bonetti(4), G Morace(2), M RoEEendorf(3), F Callea(4), G Verme(1), A Ponzetto(1). (1)Molinette Hospital,Torino. (2)Ist.Sup.Sanit~,Roma. (3)Max-vonPettenkofer-Inst.,Wdnchen. (4)Spedali Civili, Brescia. The Eastern woodchuck (Mar~ota monax) has been shown susceptible to the infection by the Hepatitis Delta Virus (HDV), an ominous human pathoEen known for its deadly potential. The therapeutic approach to HDV-induced liver disease could be Ereatly ameliorated by the use of an animal model. We therefore started to characterize the natural history of chronic HDV infection in the woodchuck animal model. Here we report the establish~ent_~ ofl~cute_~ and chronic Delta Hepatitis induced by inoculation with serial dilutions (i0 to I0 ) of HDVcontainin E woodchuck serum. Seven wild cauEht Woodchuck Hepatitis Virus cart}St animals were injected. Delta infection occurred constantly in each animal up to the I0 serum dilution. Delta hepatitis was ~ndistinEuishable from the acute and chronic disease observed either in humans and chimpanzess. H D V l ~ A was detected by molecular l~ybridisation 4 to 6 weeks after inoculation with I0 to i0 serum dilution and persisted in circulation throughout the entire follow-up of 3 to i0 months post-inoculation. All available liver biopsy samples resulted HDAg-positive durinE both acute and chronic phase of infection. HistoloEy demonstrated early development of chronic active hepatitis with features identical to those observed in human Delta patients. Delta hepatitis in woodchucks is therefore an ideal model for the therapeutic approach to this eludent pathogen.
275
LACTITOL Vs. LACTULOSE IN THE TREATMENTOF CHRONIC RECURRENTPORTALSYSTEMIC ENCEPHALOPATHY (PSE) D. Heredia, J. Ter~s, N. Orteu, J. Rod,s. Liver Unlt, Hospital Clinic i Provincial, Medical School. Barcelona. Spain.
Previous data suggested that l a c t i t o l (beta-galactoside-sorbitol), a new synthetic non absorbable dissacharide, has beneficial effects on chronic and acute PSE. To compare the efficacy and patient acceptability of l a c t i t o l vs. lactulose in chronic recurrent PSE, 25 cirrhotic patients with history of repeated episodes of PSE who required chronic administration of lactulose, were included in a controlled cross-over c l i n i c a l t r i a l in which patients received at random l a c t i t o l (at an i n i t i a l dosage of lOg./6h.) or lactulose (15 ml/6h) during a three months period and then crossed-over to the alternative treatment for the following three months. Doseswere adjusted to obtain two bowel movementsper day.During the study period the daily protein intake was 40-60 g. Clinical and analytical data ( i n cluding amonia levels) as well as EEG, numberconnection test and PSE index, were collected before treatment and monthly until the end of the treatment. During treatment patients f i l l e d a questionnaire with daily dosage, stool frequency and consistency, acceptability (very poor, p o o r , mild, very good) and other incidences. Five patients had to be excluded to the analysis because of early death or lack of follow-up. No significant differences were found between l a c t i t o l and lactulose on the neurological and biological parameters, suggesting that the two treatments could be considered as equally effective. Lactitol was significantly better accepted t h a n lactulose (p=.02) the taste of which being assessed too sweet and provoking nausea. In conclusion, l a c t i t o l is a good alternative to lactulose in patients with chronic recurrent PSE, spetially in those who intolerate the excessive sweetness of lactulose.
S143
ACUTE AND CHRONIC DELTA HEPATITIS IN WOODCHUCKS INOCULATED WITH HIGHLY DILUTED HDV-CONTAINING WOODCHUCK SERA. C Hele(1), M Rapicetta(2), B Forzani(1), R Rasshofer(3), AN Di Rienzo(2), C La-
varini(1), MF Bonetti(4), G Morace(2), M RoEEendorf(3), F Callea(4), G Verme(1), A Ponzetto(1). (1)Molinette Hospital,Torino. (2)Ist.Sup.Sanit~,Roma. (3)Max-vonPettenkofer-Inst.,Wdnchen. (4)Spedali Civili, Brescia. The Eastern woodchuck (Mar~ota monax) has been shown susceptible to the infection by the Hepatitis Delta Virus (HDV), an ominous human pathoEen known for its deadly potential. The therapeutic approach to HDV-induced liver disease could be Ereatly ameliorated by the use of an animal model. We therefore started to characterize the natural history of chronic HDV infection in the woodchuck animal model. Here we report the establish~ent_~ ofl~cute_~ and chronic Delta Hepatitis induced by inoculation with serial dilutions (i0 to I0 ) of HDVcontainin E woodchuck serum. Seven wild cauEht Woodchuck Hepatitis Virus cart}St animals were injected. Delta infection occurred constantly in each animal up to the I0 serum dilution. Delta hepatitis was ~ndistinEuishable from the acute and chronic disease observed either in humans and chimpanzess. H D V l ~ A was detected by molecular l~ybridisation 4 to 6 weeks after inoculation with I0 to i0 serum dilution and persisted in circulation throughout the entire follow-up of 3 to i0 months post-inoculation. All available liver biopsy samples resulted HDAg-positive durinE both acute and chronic phase of infection. HistoloEy demonstrated early development of chronic active hepatitis with features identical to those observed in human Delta patients. Delta hepatitis in woodchucks is therefore an ideal model for the therapeutic approach to this eludent pathogen.
275
LACTITOL Vs. LACTULOSE IN THE TREATMENTOF CHRONIC RECURRENTPORTALSYSTEMIC ENCEPHALOPATHY (PSE) D. Heredia, J. Ter~s, N. Orteu, J. Rod,s. Liver Unlt, Hospital Clinic i Provincial, Medical School. Barcelona. Spain.
Previous data suggested that l a c t i t o l (beta-galactoside-sorbitol), a new synthetic non absorbable dissacharide, has beneficial effects on chronic and acute PSE. To compare the efficacy and patient acceptability of l a c t i t o l vs. lactulose in chronic recurrent PSE, 25 cirrhotic patients with history of repeated episodes of PSE who required chronic administration of lactulose, were included in a controlled cross-over c l i n i c a l t r i a l in which patients received at random l a c t i t o l (at an i n i t i a l dosage of lOg./6h.) or lactulose (15 ml/6h) during a three months period and then crossed-over to the alternative treatment for the following three months. Doseswere adjusted to obtain two bowel movementsper day.During the study period the daily protein intake was 40-60 g. Clinical and analytical data ( i n cluding amonia levels) as well as EEG, numberconnection test and PSE index, were collected before treatment and monthly until the end of the treatment. During treatment patients f i l l e d a questionnaire with daily dosage, stool frequency and consistency, acceptability (very poor, p o o r , mild, very good) and other incidences. Five patients had to be excluded to the analysis because of early death or lack of follow-up. No significant differences were found between l a c t i t o l and lactulose on the neurological and biological parameters, suggesting that the two treatments could be considered as equally effective. Lactitol was significantly better accepted t h a n lactulose (p=.02) the taste of which being assessed too sweet and provoking nausea. In conclusion, l a c t i t o l is a good alternative to lactulose in patients with chronic recurrent PSE, spetially in those who intolerate the excessive sweetness of lactulose.
S143