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Impairment of cytochrome P-450 dependent liver metabolic activity in cirrhotic patients with Helicobacter pylori (H pylori) infection
Liuer-Clinical
59
57 A NATIONAL SURVEY ON LIVER BIOPSY IN CHRONIC HEPATITIS IN ITALY THE NEED FOR CLINICAL GUIDELINES A.I.G.O. CommIttee on the use of liver biopsy ln chronic hepabtis C Background and aims. Percutaneous lover biopsy (PLB) IS sbll the major tool for hepatologists to make a wnfldent diagnosis in patients with suspected liver disease. The execution of the procedure IS almost safe but major complications (including intraabdominal bleedinq and death) have been reported. Despite its wdelv use rn many ltallan centres, no definite guidelines’have been proposed to be followed by~cllnlclans to &hteve the optimal results from its use. We performed a natlonwlde survey between centres that routinely perform PLB m patients wth chrome liver damage to collect data on procedures, data pmcessmg and analysis dewed from hepatic histology. Methods. We sent a questionnaire to 90 ltallan Centres chosen for their specific Interest in the diagnosis and treatment of chronic liver disease. The questIons of wr survey were related to the procedure of hospltaksabon of patients, the laboratory tests performed before lhver bloosv. the clinical monitorina after the execubon. and the use of anv scorinq system to ev&& liver histology. I Results. Fifty five Italian centres (27 from north, 10 from centre, 16 from south) replied to our quesbonnare. The experience of these centres on lwer btopsy is well established since only 11 started to routinely perform PLB less than ten years ago Thirty centres (54.6%) reported performing more than 50 PLB a year but only 36 (69 1%) maintain a registry with all the informabon related to the patients. PLB is very occasionally performed as an outpatient procedure (4 out of 55) and the other cases are equally distributed as day-hospitals or regular admissions. All centres execute a complete blood count and coagulation tests but only 20 requires Mood group: only a very small proporhon need a radlcgraph of the chest or an electrocardiography About two thrd of Italian centres utlllze Menghln needle wth a diameter ranging from 1 2 to 1 6 mm, the remalnlng admit the use of Tru-cut. PLB is performed under ultrasound guide only in 21 centres (38.2%) while the majority Identify the site of lwer collection by previous ultrasound exammatlon. Laparoscopy is performed only in two centres. Fmally vital parameters ate regularly checked in the majority of pattents undergone to PLB in Italian liver centres (78 2%). The use of a scorinq svstem to analvse hepabc hlstoloqv 1swldelv used (51 out of 54) but no method used toqu.wtify grading.and s&g emergeas a favdurite Conclusions. Our survey indicate a wide variability on the procedures to execute PLB m patients wth suspected chronic liver disease. We belleve that standardizabon of a guidelme IS mandatory to help physicians to avold malor compllcatlons and optimlse mdlcatlons for the diagnosis and treatment
_
PROPRANOLOL TREATMENT NORMALIZES GASTRIC PERMEABILITY IN PORTAL HYPERTENSIVE GASTROPATHY M.R Gmfr.6.M. Lo Presti. 1.Hemell. W. Fries Dioartimento di Medicina In&ma e TeraoiaMedica, Universitidi Messina ’ Pohchnico Messina The pathophysiologyof gastmpatby dueto portal hypertension(PHG) is poorly understood.We havepreviously shown that PHG is associatedwith an increasedpermeability to sucrose andthat thedense of suear oenneationcorrelateswtb endoswuic severitv of ezstric damage(Eur 1 Gast&nteml H;p&l2000;12:529). Aim ofthe p&t study WA to &ass the effectof pmpranololon gastric permeability.Methods: we studied 8 patients(6 males; 6 with viral hepatopatby,2 with noncirrhotic portal fibrosis) with endosqikllly proven cesophagealvances andPHG. Gastmmtestinal permeabilitywas assessedI week atIer endoscopy(baseline) and7 days after tbempy with pmpnnoiol(20 to 60 mglday) by oral administrationof sucrose (40 g), la&dose (10 g) and manitol(5 g), Sugarrecoveries in 6h urine specimenswere measured swctmohotometxicallv. Pared t-test for comwisons betweenme- andpost-pmpranolol emups: mean&es +/- SEM: Results: the heart ratewas significantly~slowed6y pr&&lc4 (baseline:74 +/- 3, propmnolol: 59 +/- 2, pcO.05) indicatingan effective treatmentof portal hypertension. Urinary sucrose excrehon @¢ageof oral dose) droppedfrom pathnldgic v&s at baselineto normal oneweek affer pmpranolo1(0.171 +/- 0.041, 0.074 +/- 0.029, respectively; p
58 Impairmentof cytochmme P-450 dependentliver metabolicactivity in cirrhotic patients with Helicobacterpylori (H pylori) infection. Edoado Giannini, Federica Botta, Bmno Chiarbonello,Albnto Faso& Fe&+x Malfatti, Simone Polegato,Paola Romagnoli, EmanuelaTesta,Elena Pod&?, Roberto Tarta Gastrwntemlogy Unit and PostgmduateSchoolof Gastroentemlogy, Depaxtmentof Internal Medicine, University of Genoa,Italy. Dipatimento di Medic& Interna Backgwun~ Various digestive and extra-digestive diseaseshave beenassociatedwith H pylon gastic infection. l-he syskmic influcncc of gastric H pylori infection seenwto be mediatedby the releaseof various cytokiws. Bacterial inf&ions often determineimpairmentof liver metabolic function in patientswith liver diwse. Aims: To evaluate: I) the intlww of H pylmi infection on liver function as aascsxd by meansof monocthylglycinexylidide (MEGX) test, which depends upon liver blood flow andcytochmme P-450activity, and by 13C galactosebreath test (GBT), which dependson cytosolic enzymatic activity andis correlatedto hepatic functional mass. 2) tuner nonosis factor alpha m-alpha) semm levels. PatientsandMetimQ: Thirty-five patients WitI, liver cimhwis of variws aetiology who underwentMEGX andGBT were retrospectively evaluatedfor H pylori infection by meansof anti-H pylmi IgG. Main clinical, biochemical, and fkctiond chsractcristica of the patientswere analyscd on the basis of H pylori infection. Results: Twenty-me patienti (60%) were H pylori positive, and 11were negative (31.4%). No clinical or biochemical diffemnc~ were observed betweenH pylori positive or negative patients.H pylori infection showed110different ditibution wxrding to Child-Pugh’s classes (A, 55%. B andC, 67%). MFGX resulted signiticpntly lower at eachsamplingtime in II pylori positive (vs negatives) patients-X15 24.4+26.8vs 46a28.8&ml, p=O.O27.MEGX30.29.4a22.2 VI 51.3&26.4. p==O.O14. MEGX60,36.5*23.7 VI 59.5%24,p=o.~liS),while GBT sh&ed no s&a&ant diffe&es, both considering ?&tosc cum120 (2.511.7 vs 2.ti1.4, NS) andQloseih30 (l.l*l vs 1.2to.5, NS). Mediae TNF-alpha semm levels were no different betweenH pylori positive (16.1 pg/ml, 8.7-28.7, 95%Cl) and H pylori negativepatients(12.3 p&n!, 8.7-23.4,95%CI). Conclusions: H pylori infection seemsto electively atTcct cytahmme P-450liver aciivtty in cirrhotic pattents,while it does not seemto interfezewith hepatic functional mass.TNF-a dew not seemto be the mediatorof this impairment.Future studies are neededm evaluatethe impact of H pylori eradicationon citochmme P-450 dependentmetabolicliver function in cirrhotic patients.
EARLY CLINICAL EXPERIENCE WITH A CELL-BASED ARTIFICIAL LIVER IN FIJLMINANTLIVERFAILURE P.Paui, A.C.Puviani, M.Bmgli, P.Gorini,L.Vahti,A.Pinna,A.Pasetto, A.Cavallari,G.Martinelli, G.Azzenq EMorsiani Departmentsof Gastmentemlogy, Surgery,Anesthesiology andBiology, S.Anna Hospital and University ofFerr;na, and Departmentsof Surgery and Anesthesiology,University of Modena and Bologna,Italy S.ha Grthotopic liver txansplamation(OLT) has beenpmvcd to be the wly effective therapy for tidminat liver failure (FLFj, but the scarcity of organs leadsto an urgent ncces?.iQ’of liver support system development.Hepatocyte-basedbio-artificial liver (BAL) is under investigation, mainly 86bridging treatmentuntil a liver becomeavailable for OLT, or to pmmote spanteneousliver regeneration.We developeda novel radial-flow biweactm (RFB) for tbxedimemional, high-density hepatocyte culture. In preclintcal smdics, ie&ted porcine hepatocytcawere loadedinto laboratory-gradeRFB andcultured up to 2 weeks in recirculating scnun-iice tiawc culture. in which NH4CI andlidcaine were repate& added.Ammonia remax& urea syntbeeia,monoethylglycinexylide (&O?GX) production, oxygen uptake rate,glucose USC,andalbumin secretion were measuredtbereatler During the whole duration of the study, ammoniadecreasewas pamIleledby ureaprcduction, and MEGX level constantly incressed, indicatig that par&e hepatocytm rauined diffemntiatedand metabolicallyactive. An inte@atedBAL apparatuswas thendevelopedfor clinical use.At& plasmaphemsis,thepatient’splasmais timtly recirculated into a reservoir andthen through an oxygenatorbefore reachingtbe hqatocyte-filled RFB. Plasmais thenpumped through a specialized module for bilirubin and bile acid adscqtion, andtinally it ia filtered before recombinationwith blood andreturns to the patient.The RFB ia loadedwith m&viable, freshly isolatedporcine hewtowtes, ran&u from 80 to 250 ur. acoxdin~ to tbe uatientbody mass. This BAL w&m alioww.ior the s.i&&mw plasma&pan&n &t indep&ient pe&ion of all modules;by enablingat any time the sel&ive modification, sub#itution and/or exc1usionof a single MInpone”t of the cicuit, with atargetedtreatmentminimal duration of 12 hours. Aklcr experimentaltestingof the system in large laboratory animals,the BAL WBBncently unedto suppart 4 FLF patients(gmde IV coma), waiting for OLT. BAL treatmum lasted7-22 bourn.All patientstoleratedthe ~mcedures well, by showing-auimpmvement in the level of encephnlopathy,decreasein blood am&da, bilimbin, AST. ALT, andlactate,with full neurologicalrecovery tier OLT. Our initial clinical experiencecwfmts the safety oftbis BAL contiguration and suggestsits clinical efficacy BSa temporay liver support system in FLF patients.
59
57 A NATIONAL SURVEY ON LIVER BIOPSY IN CHRONIC HEPATITIS IN ITALY THE NEED FOR CLINICAL GUIDELINES A.I.G.O. CommIttee on the use of liver biopsy ln chronic hepabtis C Background and aims. Percutaneous lover biopsy (PLB) IS sbll the major tool for hepatologists to make a wnfldent diagnosis in patients with suspected liver disease. The execution of the procedure IS almost safe but major complications (including intraabdominal bleedinq and death) have been reported. Despite its wdelv use rn many ltallan centres, no definite guidelines’have been proposed to be followed by~cllnlclans to &hteve the optimal results from its use. We performed a natlonwlde survey between centres that routinely perform PLB m patients wth chrome liver damage to collect data on procedures, data pmcessmg and analysis dewed from hepatic histology. Methods. We sent a questionnaire to 90 ltallan Centres chosen for their specific Interest in the diagnosis and treatment of chronic liver disease. The questIons of wr survey were related to the procedure of hospltaksabon of patients, the laboratory tests performed before lhver bloosv. the clinical monitorina after the execubon. and the use of anv scorinq system to ev&& liver histology. I Results. Fifty five Italian centres (27 from north, 10 from centre, 16 from south) replied to our quesbonnare. The experience of these centres on lwer btopsy is well established since only 11 started to routinely perform PLB less than ten years ago Thirty centres (54.6%) reported performing more than 50 PLB a year but only 36 (69 1%) maintain a registry with all the informabon related to the patients. PLB is very occasionally performed as an outpatient procedure (4 out of 55) and the other cases are equally distributed as day-hospitals or regular admissions. All centres execute a complete blood count and coagulation tests but only 20 requires Mood group: only a very small proporhon need a radlcgraph of the chest or an electrocardiography About two thrd of Italian centres utlllze Menghln needle wth a diameter ranging from 1 2 to 1 6 mm, the remalnlng admit the use of Tru-cut. PLB is performed under ultrasound guide only in 21 centres (38.2%) while the majority Identify the site of lwer collection by previous ultrasound exammatlon. Laparoscopy is performed only in two centres. Fmally vital parameters ate regularly checked in the majority of pattents undergone to PLB in Italian liver centres (78 2%). The use of a scorinq svstem to analvse hepabc hlstoloqv 1swldelv used (51 out of 54) but no method used toqu.wtify grading.and s&g emergeas a favdurite Conclusions. Our survey indicate a wide variability on the procedures to execute PLB m patients wth suspected chronic liver disease. We belleve that standardizabon of a guidelme IS mandatory to help physicians to avold malor compllcatlons and optimlse mdlcatlons for the diagnosis and treatment
_
PROPRANOLOL TREATMENT NORMALIZES GASTRIC PERMEABILITY IN PORTAL HYPERTENSIVE GASTROPATHY M.R Gmfr.6.M. Lo Presti. 1.Hemell. W. Fries Dioartimento di Medicina In&ma e TeraoiaMedica, Universitidi Messina ’ Pohchnico Messina The pathophysiologyof gastmpatby dueto portal hypertension(PHG) is poorly understood.We havepreviously shown that PHG is associatedwith an increasedpermeability to sucrose andthat thedense of suear oenneationcorrelateswtb endoswuic severitv of ezstric damage(Eur 1 Gast&nteml H;p&l2000;12:529). Aim ofthe p&t study WA to &ass the effectof pmpranololon gastric permeability.Methods: we studied 8 patients(6 males; 6 with viral hepatopatby,2 with noncirrhotic portal fibrosis) with endosqikllly proven cesophagealvances andPHG. Gastmmtestinal permeabilitywas assessedI week atIer endoscopy(baseline) and7 days after tbempy with pmpnnoiol(20 to 60 mglday) by oral administrationof sucrose (40 g), la&dose (10 g) and manitol(5 g), Sugarrecoveries in 6h urine specimenswere measured swctmohotometxicallv. Pared t-test for comwisons betweenme- andpost-pmpranolol emups: mean&es +/- SEM: Results: the heart ratewas significantly~slowed6y pr&&lc4 (baseline:74 +/- 3, propmnolol: 59 +/- 2, pcO.05) indicatingan effective treatmentof portal hypertension. Urinary sucrose excrehon @¢ageof oral dose) droppedfrom pathnldgic v&s at baselineto normal oneweek affer pmpranolo1(0.171 +/- 0.041, 0.074 +/- 0.029, respectively; p
58 Impairmentof cytochmme P-450 dependentliver metabolicactivity in cirrhotic patients with Helicobacterpylori (H pylori) infection. Edoado Giannini, Federica Botta, Bmno Chiarbonello,Albnto Faso& Fe&+x Malfatti, Simone Polegato,Paola Romagnoli, EmanuelaTesta,Elena Pod&?, Roberto Tarta Gastrwntemlogy Unit and PostgmduateSchoolof Gastroentemlogy, Depaxtmentof Internal Medicine, University of Genoa,Italy. Dipatimento di Medic& Interna Backgwun~ Various digestive and extra-digestive diseaseshave beenassociatedwith H pylon gastic infection. l-he syskmic influcncc of gastric H pylori infection seenwto be mediatedby the releaseof various cytokiws. Bacterial inf&ions often determineimpairmentof liver metabolic function in patientswith liver diwse. Aims: To evaluate: I) the intlww of H pylmi infection on liver function as aascsxd by meansof monocthylglycinexylidide (MEGX) test, which depends upon liver blood flow andcytochmme P-450activity, and by 13C galactosebreath test (GBT), which dependson cytosolic enzymatic activity andis correlatedto hepatic functional mass. 2) tuner nonosis factor alpha m-alpha) semm levels. PatientsandMetimQ: Thirty-five patients WitI, liver cimhwis of variws aetiology who underwentMEGX andGBT were retrospectively evaluatedfor H pylori infection by meansof anti-H pylmi IgG. Main clinical, biochemical, and fkctiond chsractcristica of the patientswere analyscd on the basis of H pylori infection. Results: Twenty-me patienti (60%) were H pylori positive, and 11were negative (31.4%). No clinical or biochemical diffemnc~ were observed betweenH pylori positive or negative patients.H pylori infection showed110different ditibution wxrding to Child-Pugh’s classes (A, 55%. B andC, 67%). MFGX resulted signiticpntly lower at eachsamplingtime in II pylori positive (vs negatives) patients-X15 24.4+26.8vs 46a28.8&ml, p=O.O27.MEGX30.29.4a22.2 VI 51.3&26.4. p==O.O14. MEGX60,36.5*23.7 VI 59.5%24,p=o.~liS),while GBT sh&ed no s&a&ant diffe&es, both considering ?&tosc cum120 (2.511.7 vs 2.ti1.4, NS) andQloseih30 (l.l*l vs 1.2to.5, NS). Mediae TNF-alpha semm levels were no different betweenH pylori positive (16.1 pg/ml, 8.7-28.7, 95%Cl) and H pylori negativepatients(12.3 p&n!, 8.7-23.4,95%CI). Conclusions: H pylori infection seemsto electively atTcct cytahmme P-450liver aciivtty in cirrhotic pattents,while it does not seemto interfezewith hepatic functional mass.TNF-a dew not seemto be the mediatorof this impairment.Future studies are neededm evaluatethe impact of H pylori eradicationon citochmme P-450 dependentmetabolicliver function in cirrhotic patients.
EARLY CLINICAL EXPERIENCE WITH A CELL-BASED ARTIFICIAL LIVER IN FIJLMINANTLIVERFAILURE P.Paui, A.C.Puviani, M.Bmgli, P.Gorini,L.Vahti,A.Pinna,A.Pasetto, A.Cavallari,G.Martinelli, G.Azzenq EMorsiani Departmentsof Gastmentemlogy, Surgery,Anesthesiology andBiology, S.Anna Hospital and University ofFerr;na, and Departmentsof Surgery and Anesthesiology,University of Modena and Bologna,Italy S.ha Grthotopic liver txansplamation(OLT) has beenpmvcd to be the wly effective therapy for tidminat liver failure (FLFj, but the scarcity of organs leadsto an urgent ncces?.iQ’of liver support system development.Hepatocyte-basedbio-artificial liver (BAL) is under investigation, mainly 86bridging treatmentuntil a liver becomeavailable for OLT, or to pmmote spanteneousliver regeneration.We developeda novel radial-flow biweactm (RFB) for tbxedimemional, high-density hepatocyte culture. In preclintcal smdics, ie&ted porcine hepatocytcawere loadedinto laboratory-gradeRFB andcultured up to 2 weeks in recirculating scnun-iice tiawc culture. in which NH4CI andlidcaine were repate& added.Ammonia remax& urea syntbeeia,monoethylglycinexylide (&O?GX) production, oxygen uptake rate,glucose USC,andalbumin secretion were measuredtbereatler During the whole duration of the study, ammoniadecreasewas pamIleledby ureaprcduction, and MEGX level constantly incressed, indicatig that par&e hepatocytm rauined diffemntiatedand metabolicallyactive. An inte@atedBAL apparatuswas thendevelopedfor clinical use.At& plasmaphemsis,thepatient’splasmais timtly recirculated into a reservoir andthen through an oxygenatorbefore reachingtbe hqatocyte-filled RFB. Plasmais thenpumped through a specialized module for bilirubin and bile acid adscqtion, andtinally it ia filtered before recombinationwith blood andreturns to the patient.The RFB ia loadedwith m&viable, freshly isolatedporcine hewtowtes, ran&u from 80 to 250 ur. acoxdin~ to tbe uatientbody mass. This BAL w&m alioww.ior the s.i&&mw plasma&pan&n &t indep&ient pe&ion of all modules;by enablingat any time the sel&ive modification, sub#itution and/or exc1usionof a single MInpone”t of the cicuit, with atargetedtreatmentminimal duration of 12 hours. Aklcr experimentaltestingof the system in large laboratory animals,the BAL WBBncently unedto suppart 4 FLF patients(gmde IV coma), waiting for OLT. BAL treatmum lasted7-22 bourn.All patientstoleratedthe ~mcedures well, by showing-auimpmvement in the level of encephnlopathy,decreasein blood am&da, bilimbin, AST. ALT, andlactate,with full neurologicalrecovery tier OLT. Our initial clinical experiencecwfmts the safety oftbis BAL contiguration and suggestsits clinical efficacy BSa temporay liver support system in FLF patients.