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A randomized controlled multicenter trial of interferon (IFN) induction followed by prolonged high dose IFN in combination with ribavirin (RBV) for relapser HCV patients
Abstracts
51 PARML PRESSURE OF AMMONIA; IS IT REALLY USEFUL :N THE EVALUAllON OF HEPATICENCEPHALOPATHY? tjjg&~F, Efreti C, Masini4 MerliM,Attfli AF and Riggio 0. II Gastmentembgk, Universti “La Saplenza” Roma Amrmnia is considered a oivokl factor in Ihe oathoaenesis of heoatic the This may be in pa-l abibuted to tie frequentuse of venous ansnonialevels, rather thafl arterial levels, to which the tin k direcOyexposed. h4oreover,only the unionized gaseous form of amvmia freely diffuses Uxough the Mood-brain barrier. Recendv a cormfar& betweentie ~ttdecendent odal uressure of ammonia (~NHJ) and the degree of HE has beenrip&d. Aim of the present study was lo led the usefulness of pN& in cirrWc pa6enk. For ‘his purpose we determinedarterialammzda andpNH in 35 cfrrholfc ptienk (age 63~1.3; sex 29M, SF; Child-Pughdasa 6 .J 13 8, 16 C; etiology 23 viral, 3 alcohc!) vith d&rent grades of HE (grade0 = 15pk, gradeI.11q 5 pk, prade ~ll-lV= ?5 pk). Wcreover, 18 p-dents xers svaluatedduringthe i:i episode and immediately a&r the resoluhonof Ihe aurdo@cN disorder.Patfenk were studied by clinical extintion (mfnf-msntd skte) and psw Wng (number corm&on test). Pa&al pressure of armonk was c&u&d from a-kdal Mood according to the Manning’s nomogramBoth alerial amnonia concentration (23893 vs 133519‘IS g6~fic(gldl; p=O.C#JIll)and pNH3(11.8~1.4 vs 5.7~0.6 vs 4,W:6 mmtig x lti p=O,CW!X) were higher in palienk with grade III-IV HE than in ihose with grade I.11or gad+ 0 HE. The corrda6on wi# the grade of HE was similarfor arterialan!mznia(F 0,77) and pNH3(r= 0.75). In Vie subgroup of 18 pa&nk reevaluated after the anelioiation of HE, pNHj was reduced irom 10.6fl.2 during HE to 5.6?0,7mmi!g x 1@5afkr HE (p= 0,007) while artei?al ammonia concen~ti la5 reduced horn 223,&21 to 141.3?17 ugldl IP=O.OO~I.However 61ecorrelationof oNH; with the arade of HE was Mt oe&r ian’fhat’of arktiai smmnfa (GO.57 is O,jg). Rnally.& in the patients wfth corrplete resdution d HE I.e. from grads III-IV HE to grade 0) pNHz was reduced in 6G% of pm and icueased M unchangedin Le remaining 40% lhe uxesponding figurefor arterialammoniawas 73% and 27% In condusiofl our data confvm Umfthe mnefalkn betweenaMnonia and HE k variable and show mat the dekminti of pNtb does not improve such relationship. Thus PNthis notmore usefulOwl adedd ammoniaconcentrationin the evralcaiion 2f
cIrrh& ptienk with hep& encephalqmhy.
TEE BURIED BUMPER SYNDROME (BBS). DIFFBRBNIIAL. TBBRAPEUTIC APPROACH AND PREVENTION PossIBumFs m, 0. Pinazi. %. Spaggiari. Module di Fzdoswpia digcstiva e Gartroenterologia - Y&one di Nuhizione. Artificiele. Azbnde -USL= di Pamu. BACKGROUND AND AIMS. Since its intmduction in 1980, the percntrmcous crdmxpy gmtmstcmy (PEG) pcoccdnre he.5 gained vdeqred pcpthity. PEG tubes can be inse#d safely. rapidly and with less cost than the swgicd tcdmiqne. An inusuel major complicadon of PEG introduction is migration of internal bumper (IB) fnto or tbmugb the. abdominalwallandiscalIcdBBS.ThctrtatmentconristinanmoMLof theembeddingOubcmdnpositioaofalrewPEG.Wenpoaour expericace with six pt who devdopcd BBS. PATIENTS AND METHODS. From January 1994 to May 2001 we performed 338 sPEG iawxdaw in our Inaition. A standard PEOpotocolwasutilizcd~rinsertionoftbefesdinghrbeOan eodoscopic visualization of lB was done. Afta 12-24 hours the insertion the extcmd bumper (EB) was slightly pi&d back to pnxnt excessive local presage and enteral nuhition (EN) w stmted. Six pt (1,7%) pl-cs&dwitbFToebnctj~ gestmtmy site diemftfort, or bakegc ~undcheinsatiOnsitc;ptcbancteristicsarC~inTable.ET couldnotberotDtodaad~~~intothe~hinallfascs.At
gaskic nwcosq totally migration of the IB repuired sutgexy because of major blecdiog daring endoswpy atternK Our data suggest that malignancies, low BMI at time of PEO placemeat rapid pt weight gain are adjunctiveriskfadortodevelopBBS;inthisptismandatoryatrinrmsivc clinical follow-up by nutritional home-care quip&.
50 INCIDENCE AND PROGRESSION OF PORTAL GASTROPAMYIN PAllENTSWH LWER CIRRHOSIS
HYPERTENSNE
.&Q&I&. Ang&ni S, Rfggio0, RfnaldiV, Attfli AF, and Merii ht. II Gastmenkrokgia, Universitl di Roma “La Sapien& Pwta hyperknsive gastzopathy(PHG) is a potential cause of gasfmintesfinai bkeding in p&nk !+#I liver cirrhosis, but ik clinical relevance is po&y d&ad. We eMed 234 ccmewhe cirrhotic pafknk (122 males and 84 fen&s, meanaga60212years, 16% post-dcohofk cfrrh&s) fw a mean fdow up d 37222monks. Noneof the pabents had past episodes of gastrdnksijnd bleeding,larpeesophapedvadces (EV) and none was assuming any keatmmt which muld affect6~ portalhemcdynamic. Upon enrofbnent 81% of patienoi wereChild ClassA Nonehada diagnosisof hepatocellular carcinoma. Pa6enk wers followedup as oupatienk: medical examination, ullrasonography and b&hen&@ were perfonnedat 6 months interval, while an endoscopy was performedevery 12 months.The end-points of Me study were: appearance IX pm&n of PHG,bleedingepisodesfrom this lesion and cumulative survival. Uponenro6menf40 pa6enk (19%) presented PHG. It was mild in 36 pafienk andsevere in 4 padenk. The overall prevalence of PHG was higher in pa&k
withCbfhWughdksa Band C ffian in patients with Chfld cfass A @
A RANDOMIZED CONTROLLED MULTICENTER TRIAL OF INTERFERON (IFN) INDUCTION FOLLOWED BY PROLONGED HIGH DOSE IFN IN COMBINATION WITH RIBAVIRIN (REV) FOR RELAPSER HCV PATIENTS
L,Za&, G Fomaciari, E Minola, P Fabris, S Boccia, M Giusti, G Abbati, M Felder, P Revere, A Rcdaelli, A Tono”, R Montanari, C Paternoster, E Buscarini, E Castagneni, G To&i, C Rizzo, S Suppressa, M Pantalena, F Fabris, L Lomonaco, A Tagger and G Fattovich. ’ Department of Gsstnxnlerology, University of Verona, Italy Alms: To evaluate the efficacy and tolerability of IFN a-2b induction therapy (TX) followed by prolonged time of combination TX with high dose of IFN a-2b and REV in relapser (RR) patients with chronic hepatitis C. Patients/methods:1 19 RR patients were randomly assigned to receive ao induction schedule with IFN a 5 MU daily (Group A: 59 patients) or IFN a 5 MU TIW (Group B: 60 patients) for 4 weeks followed by 5 MU TIW and RBV (1000/1200 &daily) for 44 w&s in both groups A and B. There were no statistical differences for sex, age, presence of cirrhosis or HCV genotypes between the two groups. Results: At present 99 patients have completed 48 weeks TX and 6 month follow-up is available in 87 and are the subjects of this interim intention to treat analysis. Percentages of patients with response to TX (normal ALT and negative serum HCV-RNA) were: 1 Endoftherapy 1 6 months after-y HCVtype 1 I /2!31AllI I IX3IAll n=37 “=62 II=99 n=34 n=53 n=87 Gmup A 1 56% 65% 1 62% So?? 64% 58% _ Growl3 1 47% 67% 1 60% 33% 61% 50% Five (12%) patients of Group A and 9 (19%) patients of Group B discontinued therapy for side effects. Conclusions: This interim analysis shows an overall sustained response (SR) in 47 (54%) out of 87 patients, a figure comparable to that obtained in relapser patients treated by lower IFN dose (3MU TIW) plus RBV for 24 weeks (1). However 1 month IFN induction followed by prolonged time of combination TX with high dose of IFN and REV tends to improve the SR among genotype 1 relapser patients as compared to standard combination therapy (1). 1. Davis GL et al, N Engl J Med 1998; 339: 1493-9.
A103
51 PARML PRESSURE OF AMMONIA; IS IT REALLY USEFUL :N THE EVALUAllON OF HEPATICENCEPHALOPATHY? tjjg&~F, Efreti C, Masini4 MerliM,Attfli AF and Riggio 0. II Gastmentembgk, Universti “La Saplenza” Roma Amrmnia is considered a oivokl factor in Ihe oathoaenesis of heoatic the This may be in pa-l abibuted to tie frequentuse of venous ansnonialevels, rather thafl arterial levels, to which the tin k direcOyexposed. h4oreover,only the unionized gaseous form of amvmia freely diffuses Uxough the Mood-brain barrier. Recendv a cormfar& betweentie ~ttdecendent odal uressure of ammonia (~NHJ) and the degree of HE has beenrip&d. Aim of the present study was lo led the usefulness of pN& in cirrWc pa6enk. For ‘his purpose we determinedarterialammzda andpNH in 35 cfrrholfc ptienk (age 63~1.3; sex 29M, SF; Child-Pughdasa 6 .J 13 8, 16 C; etiology 23 viral, 3 alcohc!) vith d&rent grades of HE (grade0 = 15pk, gradeI.11q 5 pk, prade ~ll-lV= ?5 pk). Wcreover, 18 p-dents xers svaluatedduringthe i:i episode and immediately a&r the resoluhonof Ihe aurdo@cN disorder.Patfenk were studied by clinical extintion (mfnf-msntd skte) and psw Wng (number corm&on test). Pa&al pressure of armonk was c&u&d from a-kdal Mood according to the Manning’s nomogramBoth alerial amnonia concentration (23893 vs 133519‘IS g6~fic(gldl; p=O.C#JIll)and pNH3(11.8~1.4 vs 5.7~0.6 vs 4,W:6 mmtig x lti p=O,CW!X) were higher in palienk with grade III-IV HE than in ihose with grade I.11or gad+ 0 HE. The corrda6on wi# the grade of HE was similarfor arterialan!mznia(F 0,77) and pNH3(r= 0.75). In Vie subgroup of 18 pa&nk reevaluated after the anelioiation of HE, pNHj was reduced irom 10.6fl.2 during HE to 5.6?0,7mmi!g x 1@5afkr HE (p= 0,007) while artei?al ammonia concen~ti la5 reduced horn 223,&21 to 141.3?17 ugldl IP=O.OO~I.However 61ecorrelationof oNH; with the arade of HE was Mt oe&r ian’fhat’of arktiai smmnfa (GO.57 is O,jg). Rnally.& in the patients wfth corrplete resdution d HE I.e. from grads III-IV HE to grade 0) pNHz was reduced in 6G% of pm and icueased M unchangedin Le remaining 40% lhe uxesponding figurefor arterialammoniawas 73% and 27% In condusiofl our data confvm Umfthe mnefalkn betweenaMnonia and HE k variable and show mat the dekminti of pNtb does not improve such relationship. Thus PNthis notmore usefulOwl adedd ammoniaconcentrationin the evralcaiion 2f
cIrrh& ptienk with hep& encephalqmhy.
TEE BURIED BUMPER SYNDROME (BBS). DIFFBRBNIIAL. TBBRAPEUTIC APPROACH AND PREVENTION PossIBumFs m, 0. Pinazi. %. Spaggiari. Module di Fzdoswpia digcstiva e Gartroenterologia - Y&one di Nuhizione. Artificiele. Azbnde -USL= di Pamu. BACKGROUND AND AIMS. Since its intmduction in 1980, the percntrmcous crdmxpy gmtmstcmy (PEG) pcoccdnre he.5 gained vdeqred pcpthity. PEG tubes can be inse#d safely. rapidly and with less cost than the swgicd tcdmiqne. An inusuel major complicadon of PEG introduction is migration of internal bumper (IB) fnto or tbmugb the. abdominalwallandiscalIcdBBS.ThctrtatmentconristinanmoMLof theembeddingOubcmdnpositioaofalrewPEG.Wenpoaour expericace with six pt who devdopcd BBS. PATIENTS AND METHODS. From January 1994 to May 2001 we performed 338 sPEG iawxdaw in our Inaition. A standard PEOpotocolwasutilizcd~rinsertionoftbefesdinghrbeOan eodoscopic visualization of lB was done. Afta 12-24 hours the insertion the extcmd bumper (EB) was slightly pi&d back to pnxnt excessive local presage and enteral nuhition (EN) w stmted. Six pt (1,7%) pl-cs&dwitbFToebnctj~ gestmtmy site diemftfort, or bakegc ~undcheinsatiOnsitc;ptcbancteristicsarC~inTable.ET couldnotberotDtodaad~~~intothe~hinallfascs.At
gaskic nwcosq totally migration of the IB repuired sutgexy because of major blecdiog daring endoswpy atternK Our data suggest that malignancies, low BMI at time of PEO placemeat rapid pt weight gain are adjunctiveriskfadortodevelopBBS;inthisptismandatoryatrinrmsivc clinical follow-up by nutritional home-care quip&.
50 INCIDENCE AND PROGRESSION OF PORTAL GASTROPAMYIN PAllENTSWH LWER CIRRHOSIS
HYPERTENSNE
.&Q&I&. Ang&ni S, Rfggio0, RfnaldiV, Attfli AF, and Merii ht. II Gastmenkrokgia, Universitl di Roma “La Sapien& Pwta hyperknsive gastzopathy(PHG) is a potential cause of gasfmintesfinai bkeding in p&nk !+#I liver cirrhosis, but ik clinical relevance is po&y d&ad. We eMed 234 ccmewhe cirrhotic pafknk (122 males and 84 fen&s, meanaga60212years, 16% post-dcohofk cfrrh&s) fw a mean fdow up d 37222monks. Noneof the pabents had past episodes of gastrdnksijnd bleeding,larpeesophapedvadces (EV) and none was assuming any keatmmt which muld affect6~ portalhemcdynamic. Upon enrofbnent 81% of patienoi wereChild ClassA Nonehada diagnosisof hepatocellular carcinoma. Pa6enk wers followedup as oupatienk: medical examination, ullrasonography and b&hen&@ were perfonnedat 6 months interval, while an endoscopy was performedevery 12 months.The end-points of Me study were: appearance IX pm&n of PHG,bleedingepisodesfrom this lesion and cumulative survival. Uponenro6menf40 pa6enk (19%) presented PHG. It was mild in 36 pafienk andsevere in 4 padenk. The overall prevalence of PHG was higher in pa&k
withCbfhWughdksa Band C ffian in patients with Chfld cfass A @
A RANDOMIZED CONTROLLED MULTICENTER TRIAL OF INTERFERON (IFN) INDUCTION FOLLOWED BY PROLONGED HIGH DOSE IFN IN COMBINATION WITH RIBAVIRIN (REV) FOR RELAPSER HCV PATIENTS
L,Za&, G Fomaciari, E Minola, P Fabris, S Boccia, M Giusti, G Abbati, M Felder, P Revere, A Rcdaelli, A Tono”, R Montanari, C Paternoster, E Buscarini, E Castagneni, G To&i, C Rizzo, S Suppressa, M Pantalena, F Fabris, L Lomonaco, A Tagger and G Fattovich. ’ Department of Gsstnxnlerology, University of Verona, Italy Alms: To evaluate the efficacy and tolerability of IFN a-2b induction therapy (TX) followed by prolonged time of combination TX with high dose of IFN a-2b and REV in relapser (RR) patients with chronic hepatitis C. Patients/methods:1 19 RR patients were randomly assigned to receive ao induction schedule with IFN a 5 MU daily (Group A: 59 patients) or IFN a 5 MU TIW (Group B: 60 patients) for 4 weeks followed by 5 MU TIW and RBV (1000/1200 &daily) for 44 w&s in both groups A and B. There were no statistical differences for sex, age, presence of cirrhosis or HCV genotypes between the two groups. Results: At present 99 patients have completed 48 weeks TX and 6 month follow-up is available in 87 and are the subjects of this interim intention to treat analysis. Percentages of patients with response to TX (normal ALT and negative serum HCV-RNA) were: 1 Endoftherapy 1 6 months after-y HCVtype 1 I /2!31AllI I IX3IAll n=37 “=62 II=99 n=34 n=53 n=87 Gmup A 1 56% 65% 1 62% So?? 64% 58% _ Growl3 1 47% 67% 1 60% 33% 61% 50% Five (12%) patients of Group A and 9 (19%) patients of Group B discontinued therapy for side effects. Conclusions: This interim analysis shows an overall sustained response (SR) in 47 (54%) out of 87 patients, a figure comparable to that obtained in relapser patients treated by lower IFN dose (3MU TIW) plus RBV for 24 weeks (1). However 1 month IFN induction followed by prolonged time of combination TX with high dose of IFN and REV tends to improve the SR among genotype 1 relapser patients as compared to standard combination therapy (1). 1. Davis GL et al, N Engl J Med 1998; 339: 1493-9.
A103