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Re-treatment with interferon plus ribavirin of chronic hepatitis C nonresponders to interferon monotherapy: A meta-analysis of individual patient data
Liver
85 HYPERECHOIC HEPATGCELLULAR CARCINOMA @ICC) SMALLER THAN 3 CM OCCURRING IN LIVER CIRRHOSIS. PREVALENCE AND STATISTICAL CORRELATIONS IN 419 CONSECUTIVE PATIENTS. M Pompili, E Caturelli*, DA Siena*, ME Lippi, M Covmo, I. Grille, G Pignatam,F Pizmlante,A Andriulli*, G Gasbtini, GL Rapaccini lshtuto di Medicina Internae Geriatria, UCSC, Roma, e *Dwisione ti Gastmentemlogia.IRCCS CasaSollievo della Sofierema, San Giovanni Rotondo(FG), Italy Univ. Cattolica S.Cuore Most of HCCs smaller than 3 cm, arising in cirrhotic liver, show anhypoechoic ultrasound(US) pattern.Hperechoic HCC shows a prevalenceranging from 2% to 16% in easternseries, andhas beencorrelatedto well-differentiatedhistologic pattern. In this study we evaluatedtheprevalenceof hyperechoic HCC p&ton in a large seriesof cirrhotic patientswith small singletumor, correlating this patternto clinical, histologic, andUS parameters.We studied419 consecutive cirrhotic patients (medianage70 yn) with singleHCC smaller than 3 cm. Cirrhosis was HCV-related in 319 cases and dueto other causes in IO0 patients.On US all HCCs were classified as hypoechoic, isoechoic, hyperechcic, or nodule-in-nodule.HCC diagnosiswas achievedby oneor more of the following methods:tine needlebiopsy, spiral TC, MRI, angiogmphy,surgical resection, alphafetnpmtein higher than2M) nglml. In 241 caseshistological and/orcytological grading of the tumor was available(well differentiatedHCC in 150 cases, moderately differentiatedin 63 cases,andpoorly differentiatedin 28 cases). Fnrtbenncre, we comlated the hyperechoic patternto the following paameten: age,sex. cirrhosis etiology, US patternof liver pamnchyma,andgmdmg of HCC. Statisticalanalysiswas performed by meansof Pearsoncorrelation test. Small HCC was classtfied as hypoechoic in 321cases (77%), hypaechoic in 63 cases(IS%), isoechoic in 23 cases(5%) and nodule-in-nodulem I2 cases (3O%)/.). Prevalenceof hyperechoic HCC patternwas sigrdficantly higher in patientsyounger than 70 years (46/210,22%), comparedto older patients(171209,8%). p=O.O04. Noneof the remaining evalustedparameterswas correlated to hyperechoic pattern We found a very high prevalenceofhyperechoic pattern in our largeseries of single HCCs smallerthan 3 cm mcuning in cirrhotic patients.Prevalencewas IS% consideringthe whole population andas high as 22% in subjectsyounger than 70 years. The ccc-ce of well, moderatelyand poorly differentiatedtumor was similar in hyperechoic HCCs comparedto the hpechoic ones
;6 UPDATE ON HOME CARE FOR DECOMPENSATED CIRRHOSIS Rica-Rcsellini S:, Polifemo A.M.*#, Paolti MTP. , Milandri ML. , Montaletti I.‘, Sari C.*, P. Gremmtieti, D’Impaio N:. *IJ.O. di Gaswcndemlogia ed EndosccpiaDigestiva Osp. MorBagni Forli AssistenzaDomiciliam Integrata, #AFMF Associazione Forlivese pm le M&tie de1Fegato (no profit ONLUS), Forli Italy Relatme:Rima-Rosellini S. G. B. Morgagni Backgcmm~ Home care and hospitalat home schemeshave gmwn in importancein health services in both EuropeandNorth America and am seenas a possiblesubstitute for inpatient care in the National health service. Hospital at home schemesis alternativeto hospital to prevent admission into an acutehospital or to facilitate the early dischargeof patients from an acutehospital. Previously thesepatients fnsucntly were in hospital for prolongedperiods of time. Now patients dischargedearly from the hospitalshould be observedin the outpatientsetting andpatientswith dependaxe in personalactivity shouldbe mated in the home setting. Aim to evaluatehome c.we for decompmsatedcirrhosis. Material and methods:In the community of Fcrli imtovative home cue pmgmmmesprovide to facilitate the dischargefrom the acutehospital,treatment for advanced liver diseaseasuch as intmvencus treatmentandpamcentesiawtb salt-poor albumin infused intravenously in the sameperiod. The home care team consistedof one generalpractitioner, one gartmenterologist-hepatclogistandtwo-commtmi~ muses. Sixteenhospitalized,but medically stable,patients(X&F: 10/6,mean age67.3 yn, range43.90 yrs) with decompolsatedcirrhosis (ascites,ewephalcpathy gale I-II, 7 Child-Pughclass B, 9 Child-Pugh class C) and with dependencein personalactivity of daily living were early discharged andtreatedat home. Results: The mean follow-up at home was 6 months (range, l-21 months). The mean number ofhome visits, for eachpatient,was 15.3(range, 4-57). During home care pmgmmmespatientswas readmittedin the hospital,for different causes,one time in 3 patients,two times in 3 patientsand 3 times in 3 patients(meanvalue: I .I); actually the mottality rate is of 5O??(g/16). In OUTcommunity the daily ML of hospitalcare for cvrhotic patientswas f495.000 (255 Bum)andthe daily cost of home care was only f7O.OlM (31 Eum).Conclusions: Our prcliminq experienceindicatesthat some treatmentafor decompensatcdcirrhosis arefeasibleat home with patientsand family wegivers satisfaction. However, home care resulted in some cost shifdng to geneal practitioner, to patients and their families. Randomisedcontrolled trials areurgently neededto elucidatethe effects of the home care progmmmes for dewmpensatedcirrhosis. Funding: ‘FONDAZION’E DELLA CASSA DBI RISPARMI DI FORLF and “PROVINCIA DI FORLi-CBSBNA” provided funding for this study.
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87 PLASMA LEVELS OF MMP-Z,TIMP-I AND PIIIP AS MARKERS OF LIVER DISEASE IN HEPATITIS C RBCURRENT AFTER LIVER TRANSPLANTATION G. Tess& M. Gmdc, S Fagmoli, M. De Paoli, P. Bmn, G Leo, C. FeM. Chmmmante,R. Naccarato,M. Ruse Gasmxntemlogy Dpt, University of Padt@aly; PathologyDpt, ULSS 15 Veneto,Universtty of Padua,Italy; Labor&q Medicine Dpt, University Hospital of P&a, Italy: Gastmentemlogy University of L’Aquila, Italy A0 Padova Although liver biopsy II the gold standard,the needfor a non-invasive test for assessing tibmgenesisin cbmnio hepatitisC has long beennxogmiscd. No dataare available on serum markers of fibmgenesis in recurrent hepatitisC at701liver trsnsplxdation (RI-K). Aim of this study was to comparedplasmalevels of PIIIP, MMP-2, andTIMP-I with liver histology. Patientsand materials:Fitty consecutive caseswere studied(in which liver andblood sampleswere simulbmenuslyobtained)including 33 patientswith RHC and 17patientstransplantedfor non-HCV relatedend-stagediseaseswith no or minimal non specific histological liver damagepost-OLT (contmls).Plasmadetermiration was alsodone in 10blood donors (healthy contmls).PIIP WBS determinatedby RLA, TIMP-I and MMP-2 by ELISA. Histological activity (HAr) andfibrosis were assessedaccording to Ishak et al. Results: PIIIP values were significantly higher in the gmup with RHC comparedwith coni~~ls(~~0.02) and healthycontrols (pQ).OCO8).TTMF’-Iwas also highn in caseofRHC and the differencewith contmls wO.ooO) and he&by ~ntmls (jKO.000) was highly sign&ant. No difference was observed in plasma levels of MMP-2 betweenthe gmups. A significantdifference was found in the levels of TIMP-I betweenpatientswith mild (score c OT= 2) vs significant (score >Z)fihmsis @<0.000),whilethedifference was not statistically significant for PIIIP levels. As for HAI, m-1 (but not PIIIP) levels were fmmd significantly highs in casewith moderate-severeactivity (HAI X). Conclusions:TIMP-I andPW plasmalevels are significantly increased in RHC. TIMP-1 values strongly correlatewith the stageof fibmsis and the gradeof activity,suggestingthat its determinationmay be useful in the follow-up ofpatients with RHC
8‘8 R&TREATMENT WITH INTERFERON PLUS RIBAVIRIN OF CHRONIC HEPATITIS C NONRBSPONDERSTO INTERFERON MONOTHERAPY: A META-ANALYSIS OF INDIVIDUAL PATIENT DATA. CalogemCamm)l, SavinoBruno2, Filippo Schepis3,Anna Gramenzi 5. AlessandraM&a 6, MassimoPuoti 7, AIdo Spadam 8, Giorgio Samcco9, Filomcna Mmisca IO, Maria Gmzia Rmni 11 andAntomo Cmxi 4. IIShlEDA, CNR, Palermo.2Ist. Sci. Bio. S Paolo, Milano. 3Dip. Med. Spa., Catanzam.4Catt. Gast., Palermo.5Dip. Med. Int., Bologna.LDiv. Gastr., S. G. Rotondn. 7Clin Mal. I& Brcscia. 8Clin. Med. 1%Messina.90s~. Molinette, Torino. IODip. Sci. Al., Napoli l IOsp. Maggiore,Milana. materdomim Background & Atms: Retreatmentwith acombinationof a-interferon (IFN) plus ribavirin of patientswith &tonic hqtitis C who did not respad to lFN mowtherapy has not beenassessedin largecontrolled studies.Methods: To assessthe s&ctivmesa andtolerability of IFN/ribavirin reweatmentof ncmespondemto IFN and to identify predictors of complete(biochemicaland vimlogical) sustainedresponse,we performed a meta-analysisof individual data on 581 patients from IO centers Retreatmentwith various IFN schedules(mean total dose544 mcga units) anda flxed ribavirin dose(IOOC-I200 mudaily dependingon body weight) was given for 24 to 60 (mean 39.5) we&s. Results: Biochemicalet&of-&eabnent and sustainedresponseswere observed in 271,581(46.6%; 95% eonfidencx interval [CI] 42.6% - 50.7%) and in 109/581(18.7%; CI 15.6%22.0%) cases.Two hundredandsix out of 532 patients(38.7%; CI 34.6%- 42.9%) hadan end-oftreatmentcompletenspawe to l-ewatmen
85 HYPERECHOIC HEPATGCELLULAR CARCINOMA @ICC) SMALLER THAN 3 CM OCCURRING IN LIVER CIRRHOSIS. PREVALENCE AND STATISTICAL CORRELATIONS IN 419 CONSECUTIVE PATIENTS. M Pompili, E Caturelli*, DA Siena*, ME Lippi, M Covmo, I. Grille, G Pignatam,F Pizmlante,A Andriulli*, G Gasbtini, GL Rapaccini lshtuto di Medicina Internae Geriatria, UCSC, Roma, e *Dwisione ti Gastmentemlogia.IRCCS CasaSollievo della Sofierema, San Giovanni Rotondo(FG), Italy Univ. Cattolica S.Cuore Most of HCCs smaller than 3 cm, arising in cirrhotic liver, show anhypoechoic ultrasound(US) pattern.Hperechoic HCC shows a prevalenceranging from 2% to 16% in easternseries, andhas beencorrelatedto well-differentiatedhistologic pattern. In this study we evaluatedtheprevalenceof hyperechoic HCC p&ton in a large seriesof cirrhotic patientswith small singletumor, correlating this patternto clinical, histologic, andUS parameters.We studied419 consecutive cirrhotic patients (medianage70 yn) with singleHCC smaller than 3 cm. Cirrhosis was HCV-related in 319 cases and dueto other causes in IO0 patients.On US all HCCs were classified as hypoechoic, isoechoic, hyperechcic, or nodule-in-nodule.HCC diagnosiswas achievedby oneor more of the following methods:tine needlebiopsy, spiral TC, MRI, angiogmphy,surgical resection, alphafetnpmtein higher than2M) nglml. In 241 caseshistological and/orcytological grading of the tumor was available(well differentiatedHCC in 150 cases, moderately differentiatedin 63 cases,andpoorly differentiatedin 28 cases). Fnrtbenncre, we comlated the hyperechoic patternto the following paameten: age,sex. cirrhosis etiology, US patternof liver pamnchyma,andgmdmg of HCC. Statisticalanalysiswas performed by meansof Pearsoncorrelation test. Small HCC was classtfied as hypoechoic in 321cases (77%), hypaechoic in 63 cases(IS%), isoechoic in 23 cases(5%) and nodule-in-nodulem I2 cases (3O%)/.). Prevalenceof hyperechoic HCC patternwas sigrdficantly higher in patientsyounger than 70 years (46/210,22%), comparedto older patients(171209,8%). p=O.O04. Noneof the remaining evalustedparameterswas correlated to hyperechoic pattern We found a very high prevalenceofhyperechoic pattern in our largeseries of single HCCs smallerthan 3 cm mcuning in cirrhotic patients.Prevalencewas IS% consideringthe whole population andas high as 22% in subjectsyounger than 70 years. The ccc-ce of well, moderatelyand poorly differentiatedtumor was similar in hyperechoic HCCs comparedto the hpechoic ones
;6 UPDATE ON HOME CARE FOR DECOMPENSATED CIRRHOSIS Rica-Rcsellini S:, Polifemo A.M.*#, Paolti MTP. , Milandri ML. , Montaletti I.‘, Sari C.*, P. Gremmtieti, D’Impaio N:. *IJ.O. di Gaswcndemlogia ed EndosccpiaDigestiva Osp. MorBagni Forli AssistenzaDomiciliam Integrata, #AFMF Associazione Forlivese pm le M&tie de1Fegato (no profit ONLUS), Forli Italy Relatme:Rima-Rosellini S. G. B. Morgagni Backgcmm~ Home care and hospitalat home schemeshave gmwn in importancein health services in both EuropeandNorth America and am seenas a possiblesubstitute for inpatient care in the National health service. Hospital at home schemesis alternativeto hospital to prevent admission into an acutehospital or to facilitate the early dischargeof patients from an acutehospital. Previously thesepatients fnsucntly were in hospital for prolongedperiods of time. Now patients dischargedearly from the hospitalshould be observedin the outpatientsetting andpatientswith dependaxe in personalactivity shouldbe mated in the home setting. Aim to evaluatehome c.we for decompmsatedcirrhosis. Material and methods:In the community of Fcrli imtovative home cue pmgmmmesprovide to facilitate the dischargefrom the acutehospital,treatment for advanced liver diseaseasuch as intmvencus treatmentandpamcentesiawtb salt-poor albumin infused intravenously in the sameperiod. The home care team consistedof one generalpractitioner, one gartmenterologist-hepatclogistandtwo-commtmi~ muses. Sixteenhospitalized,but medically stable,patients(X&F: 10/6,mean age67.3 yn, range43.90 yrs) with decompolsatedcirrhosis (ascites,ewephalcpathy gale I-II, 7 Child-Pughclass B, 9 Child-Pugh class C) and with dependencein personalactivity of daily living were early discharged andtreatedat home. Results: The mean follow-up at home was 6 months (range, l-21 months). The mean number ofhome visits, for eachpatient,was 15.3(range, 4-57). During home care pmgmmmespatientswas readmittedin the hospital,for different causes,one time in 3 patients,two times in 3 patientsand 3 times in 3 patients(meanvalue: I .I); actually the mottality rate is of 5O??(g/16). In OUTcommunity the daily ML of hospitalcare for cvrhotic patientswas f495.000 (255 Bum)andthe daily cost of home care was only f7O.OlM (31 Eum).Conclusions: Our prcliminq experienceindicatesthat some treatmentafor decompensatcdcirrhosis arefeasibleat home with patientsand family wegivers satisfaction. However, home care resulted in some cost shifdng to geneal practitioner, to patients and their families. Randomisedcontrolled trials areurgently neededto elucidatethe effects of the home care progmmmes for dewmpensatedcirrhosis. Funding: ‘FONDAZION’E DELLA CASSA DBI RISPARMI DI FORLF and “PROVINCIA DI FORLi-CBSBNA” provided funding for this study.
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87 PLASMA LEVELS OF MMP-Z,TIMP-I AND PIIIP AS MARKERS OF LIVER DISEASE IN HEPATITIS C RBCURRENT AFTER LIVER TRANSPLANTATION G. Tess& M. Gmdc, S Fagmoli, M. De Paoli, P. Bmn, G Leo, C. FeM. Chmmmante,R. Naccarato,M. Ruse Gasmxntemlogy Dpt, University of Padt@aly; PathologyDpt, ULSS 15 Veneto,Universtty of Padua,Italy; Labor&q Medicine Dpt, University Hospital of P&a, Italy: Gastmentemlogy University of L’Aquila, Italy A0 Padova Although liver biopsy II the gold standard,the needfor a non-invasive test for assessing tibmgenesisin cbmnio hepatitisC has long beennxogmiscd. No dataare available on serum markers of fibmgenesis in recurrent hepatitisC at701liver trsnsplxdation (RI-K). Aim of this study was to comparedplasmalevels of PIIIP, MMP-2, andTIMP-I with liver histology. Patientsand materials:Fitty consecutive caseswere studied(in which liver andblood sampleswere simulbmenuslyobtained)including 33 patientswith RHC and 17patientstransplantedfor non-HCV relatedend-stagediseaseswith no or minimal non specific histological liver damagepost-OLT (contmls).Plasmadetermiration was alsodone in 10blood donors (healthy contmls).PIIP WBS determinatedby RLA, TIMP-I and MMP-2 by ELISA. Histological activity (HAr) andfibrosis were assessedaccording to Ishak et al. Results: PIIIP values were significantly higher in the gmup with RHC comparedwith coni~~ls(~~0.02) and healthycontrols (pQ).OCO8).TTMF’-Iwas also highn in caseofRHC and the differencewith contmls wO.ooO) and he&by ~ntmls (jKO.000) was highly sign&ant. No difference was observed in plasma levels of MMP-2 betweenthe gmups. A significantdifference was found in the levels of TIMP-I betweenpatientswith mild (score c OT= 2) vs significant (score >Z)fihmsis @<0.000),whilethedifference was not statistically significant for PIIIP levels. As for HAI, m-1 (but not PIIIP) levels were fmmd significantly highs in casewith moderate-severeactivity (HAI X). Conclusions:TIMP-I andPW plasmalevels are significantly increased in RHC. TIMP-1 values strongly correlatewith the stageof fibmsis and the gradeof activity,suggestingthat its determinationmay be useful in the follow-up ofpatients with RHC
8‘8 R&TREATMENT WITH INTERFERON PLUS RIBAVIRIN OF CHRONIC HEPATITIS C NONRBSPONDERSTO INTERFERON MONOTHERAPY: A META-ANALYSIS OF INDIVIDUAL PATIENT DATA. CalogemCamm)l, SavinoBruno2, Filippo Schepis3,Anna Gramenzi 5. AlessandraM&a 6, MassimoPuoti 7, AIdo Spadam 8, Giorgio Samcco9, Filomcna Mmisca IO, Maria Gmzia Rmni 11 andAntomo Cmxi 4. IIShlEDA, CNR, Palermo.2Ist. Sci. Bio. S Paolo, Milano. 3Dip. Med. Spa., Catanzam.4Catt. Gast., Palermo.5Dip. Med. Int., Bologna.LDiv. Gastr., S. G. Rotondn. 7Clin Mal. I& Brcscia. 8Clin. Med. 1%Messina.90s~. Molinette, Torino. IODip. Sci. Al., Napoli l IOsp. Maggiore,Milana. materdomim Background & Atms: Retreatmentwith acombinationof a-interferon (IFN) plus ribavirin of patientswith &tonic hqtitis C who did not respad to lFN mowtherapy has not beenassessedin largecontrolled studies.Methods: To assessthe s&ctivmesa andtolerability of IFN/ribavirin reweatmentof ncmespondemto IFN and to identify predictors of complete(biochemicaland vimlogical) sustainedresponse,we performed a meta-analysisof individual data on 581 patients from IO centers Retreatmentwith various IFN schedules(mean total dose544 mcga units) anda flxed ribavirin dose(IOOC-I200 mudaily dependingon body weight) was given for 24 to 60 (mean 39.5) we&s. Results: Biochemicalet&of-&eabnent and sustainedresponseswere observed in 271,581(46.6%; 95% eonfidencx interval [CI] 42.6% - 50.7%) and in 109/581(18.7%; CI 15.6%22.0%) cases.Two hundredandsix out of 532 patients(38.7%; CI 34.6%- 42.9%) hadan end-oftreatmentcompletenspawe to l-ewatmen