MASSIMO PINZANI, M.D., Ph.D.MASSIMO PINZANI, M.D., Ph.D.DIPARTIMENTO DI MEDICINA INTERNA DIPARTIMENTO DI MEDICINA INTERNA CENTER FOR RESEARCH, HIGH EDUCATION AND CENTER FOR RESEARCH, HIGH EDUCATION AND TRANSFER TRANSFER ““DENOTheDENOThe””UNIVERSITAUNIVERSITA’’ DI FIRENZE, FIRENZE, ITALYDI FIRENZE, FIRENZE, ITALY
THE CLINICAL EVALUATION OF DISEASE THE CLINICAL EVALUATION OF DISEASE PROGRESSION IN CLD: TOWARDS AN PROGRESSION IN CLD: TOWARDS AN INTEGRATED SYSTEM?INTEGRATED SYSTEM?
I DO NOT HAVE ANY CONFLICT OF INTEREST IN THE I DO NOT HAVE ANY CONFLICT OF INTEREST IN THE COMMERCIAL DEVELOPMENT OF PRODUCTS OR DEVICES COMMERCIAL DEVELOPMENT OF PRODUCTS OR DEVICES
MENTIONED IN THIS PRESENTATIONMENTIONED IN THIS PRESENTATION
1.1.-- DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?
4.4.-- NONNON--INVASIVE METHODS: GOOD FOR ANY STAGE OF INVASIVE METHODS: GOOD FOR ANY STAGE OF FIBROTIC EVOLUTION?FIBROTIC EVOLUTION?
2.2.-- BIOCHEMICAL MARKERS: THE WAY TO GO ?BIOCHEMICAL MARKERS: THE WAY TO GO ?
3.3.-- TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC FLEXIBILITY?FLEXIBILITY?
THE CLINICAL EVALUATION OF DISEASE PROGRESSION THE CLINICAL EVALUATION OF DISEASE PROGRESSION IN CLD: TOWARDS AN INTEGRATED SYSTEM?IN CLD: TOWARDS AN INTEGRATED SYSTEM?
5.5.-- WHAT SHOULD WE DO NOW?WHAT SHOULD WE DO NOW?
6.6.-- WHAT SHOULD WE EXPECT WITHIN TEN YEARS?WHAT SHOULD WE EXPECT WITHIN TEN YEARS?
1.1.-- DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?
4.4.-- NONNON--INVASIVE METHODS: GOOD FOR ANY STAGE OF INVASIVE METHODS: GOOD FOR ANY STAGE OF FIBROTIC EVOLUTION?FIBROTIC EVOLUTION?
2.2.-- BIOCHEMICAL MARKERS: THE WAY TO GO ?BIOCHEMICAL MARKERS: THE WAY TO GO ?
3.3.-- TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC FLEXIBILITY?FLEXIBILITY?
THE CLINICAL EVALUATION OF DISEASE PROGRESSION THE CLINICAL EVALUATION OF DISEASE PROGRESSION IN CLD: TOWARDS AN INTEGRATED SYSTEM?IN CLD: TOWARDS AN INTEGRATED SYSTEM?
5.5.-- WHAT SHOULD WE DO NOW?WHAT SHOULD WE DO NOW?
6.6.-- WHAT SHOULD WE EXPECT WITHIN TEN YEARS?WHAT SHOULD WE EXPECT WITHIN TEN YEARS?
DDIAGNOSTICIAGNOSTIC AACCURACYCCURACY
ROC and AUROC curvesROC and AUROC curves: show the trade off between : show the trade off between sensitivity sensitivity and and specificityspecificity (any increase in sensitivity will be accompanied by a decrease (any increase in sensitivity will be accompanied by a decrease in in specificity).specificity).
SENSITIVITYSENSITIVITY:: the proportion of truly diseased persons, as measured the proportion of truly diseased persons, as measured by the by the gold standardgold standard, who are identified as diseased by the test under , who are identified as diseased by the test under study.study.
SPECIFICITYSPECIFICITY: the proportion of truly non diseased persons, as : the proportion of truly non diseased persons, as measured by the measured by the gold standardgold standard, who are so identified by the diagnostic test , who are so identified by the diagnostic test under study.under study.
NEGATIVE/POSITIVE PREDICTIVE VALUESNEGATIVE/POSITIVE PREDICTIVE VALUES: the probability : the probability that a person with a positive test is a true positive, or that athat a person with a positive test is a true positive, or that a person with person with a negative test truly does not have the disease. They are determa negative test truly does not have the disease. They are determined by ined by the the sensitivitysensitivity and and specificityspecificity of the test, and by the prevalence of the of the test, and by the prevalence of the condition for which the test is used.condition for which the test is used.
GOLD STANDARD ?GOLD STANDARD ?
NONNON--INVASIVE TESTINVASIVE TEST
1.1.-- DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?
4.4.-- NONNON--INVASIVE METHODS: GOOD FOR ANY STAGE OF INVASIVE METHODS: GOOD FOR ANY STAGE OF FIBROTIC EVOLUTION?FIBROTIC EVOLUTION?
2.2.-- BIOCHEMICAL MARKERS: THE WAY TO GO ?BIOCHEMICAL MARKERS: THE WAY TO GO ?
3.3.-- TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC FLEXIBILITY?FLEXIBILITY?
THE CLINICAL EVALUATION OF DISEASE PROGRESSION THE CLINICAL EVALUATION OF DISEASE PROGRESSION IN CLD: TOWARDS AN INTEGRATED SYSTEM?IN CLD: TOWARDS AN INTEGRATED SYSTEM?
5.5.-- WHAT SHOULD WE DO NOW?WHAT SHOULD WE DO NOW?
6.6.-- WHAT SHOULD WE EXPECT WITHIN TEN YEARS?WHAT SHOULD WE EXPECT WITHIN TEN YEARS?
Established and Candidate Biomarkers of Established and Candidate Biomarkers of FibrosisFibrosis
•• ““IndirectIndirect””: : Not related to Fibrogenesis Not related to Fibrogenesis –– AST, ALT, AST, ALT, γγGT, Apolipoprotein A1, bilirubin, GT, Apolipoprotein A1, bilirubin,
αα22--macroglobulin, haptoglobin, cholesterolmacroglobulin, haptoglobin, cholesterol–– HOMAHOMA--IR, HOGISIR, HOGIS–– Platelets, INR/PTPlatelets, INR/PT
•• ““DirectDirect””: : ECM components and enzymesECM components and enzymes–– HA, PIIINP, Collagen IV, Collagen VI, TIMPHA, PIIINP, Collagen IV, Collagen VI, TIMP--1, 1,
LamininLaminin, YKL, YKL--40, 40, TenascinTenascin, , UndulinUndulin, MMP, MMP--1, MMP1, MMP--22
COMPLICATIONS OF COMPLICATIONS OF PORTAL PORTAL
HYPERTENSIONHYPERTENSION
HEPATOCELLULAR HEPATOCELLULAR FAILUREFAILURE
FIBROGENESISFIBROGENESISINFLAMMATION AND INFLAMMATION AND ECM DEGRADATIONECM DEGRADATION
HEPATOCELLULAR HEPATOCELLULAR AND BILIARY AND BILIARY
DAMAGEDAMAGE
HAHATYPE IV COLLTYPE IV COLL
MMP2MMP2alpha2alpha2--MGMG
γγ--GLOBULINGLOBULINFERRITINFERRITIN
ALTALTASTASTGGTGGT
PIII NPPIII NPMMP1MMP1TIMP1TIMP1
CHOLESTEROLCHOLESTEROLHAPTOGLOBINHAPTOGLOBIN
APOAPO--A1A1BILIRUBINBILIRUBIN
INR/PIINR/PIALBUMINALBUMIN
PLATELET PLATELET COUNTCOUNT
TTHEHE OORIGINRIGIN OFOF BBIOCHEMICALIOCHEMICAL MMARKERSARKERS
AGE & GENDERAGE & GENDERINSULIN RESISTANCEINSULIN RESISTANCEBMI & VISCERAL OBESITYBMI & VISCERAL OBESITY
BBIOCHEMICAL IOCHEMICAL MMARKERS: ARKERS: OOVERALL VERALL PPERFORMANCEERFORMANCE
1.1.-- MILD/NO FIBROSIS vs. SIGNIFICANT FIBROSIS: MILD/NO FIBROSIS vs. SIGNIFICANT FIBROSIS: MEDIAN AUC = MEDIAN AUC = 0.770.77
2.2.-- CIRRHOSIS vs. NON CIRRHOSIS: MEDIAN CIRRHOSIS vs. NON CIRRHOSIS: MEDIAN AUC = AUC = 0.870.87
COMPLICATIONS OF COMPLICATIONS OF PORTAL PORTAL
HYPERTENSIONHYPERTENSION
HEPATOCELLULAR HEPATOCELLULAR FAILUREFAILURE
FIBROGENESISFIBROGENESISINFLAMMATION AND INFLAMMATION AND ECM DEGRADATIONECM DEGRADATION
HEPATOCELLULAR HEPATOCELLULAR AND BILIARY AND BILIARY
DAMAGEDAMAGE
PIII NPPIII NPMMP1MMP1TIMP1TIMP1
HAHATYPE IV COLLTYPE IV COLL
MMP2MMP2alpha2alpha2--MGMG
PLATELET PLATELET COUNTCOUNT
CHOLESTEROLCHOLESTEROLHAPTOGLOBINHAPTOGLOBIN
APOAPO--A1A1BILIRUBINBILIRUBIN
INR/PIINR/PIALBUMINALBUMIN
γγ--GLOBULINGLOBULINFERRITINFERRITIN
ALTALTASTASTγγGTGT
F0 F1 F2 F3 F4
GRAY AREAGRAY AREA
FIBROTESTFIBROTESTFORNS, APRI, FIBROINDEX, BONACINI, POHLFORNS, APRI, FIBROINDEX, BONACINI, POHL
ELFELF
MP3MP3
FIBROMETERFIBROMETER
IIMPLEMENTATION OF MPLEMENTATION OF BBIOCHEMICAL IOCHEMICAL MMARKERSARKERS
1.1.-- IMPROVE THE QUALITYIMPROVE THE QUALITY OF OF ““GOLDGOLD--STANDARDSSTANDARDS””
2.2.-- TEST THE DIAGNOSTIC ACCURACY IN TEST THE DIAGNOSTIC ACCURACY IN LONGITUDINAL AND LONGITUDINAL AND PROGNOSTICPROGNOSTIC STUDIESSTUDIES
3.3.-- WORK ON AN OPTIMAL WORK ON AN OPTIMAL ““RERE--SHUFFLESHUFFLE”” OF OF THE AVAILABLE MARKERS THE AVAILABLE MARKERS
4.4.-- EVALUATE THE EVALUATE THE CUMULATIVE POTENTIALCUMULATIVE POTENTIALOF DIFFERENT NON INVASIVE METHODSOF DIFFERENT NON INVASIVE METHODS
1.1.-- DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?
4.4.-- NONNON--INVASIVE METHODS: GOOD FOR ANY STAGE OF INVASIVE METHODS: GOOD FOR ANY STAGE OF FIBROTIC EVOLUTION?FIBROTIC EVOLUTION?
2.2.-- BIOCHEMICAL MARKERS: THE WAY TO GO ?BIOCHEMICAL MARKERS: THE WAY TO GO ?
3.3.-- TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC FLEXIBILITY?FLEXIBILITY?
THE CLINICAL EVALUATION OF DISEASE PROGRESSION THE CLINICAL EVALUATION OF DISEASE PROGRESSION IN CLD: TOWARDS AN INTEGRATED SYSTEM?IN CLD: TOWARDS AN INTEGRATED SYSTEM?
5.5.-- WHAT SHOULD WE DO NOW?WHAT SHOULD WE DO NOW?
6.6.-- WHAT SHOULD WE EXPECT WITHIN TEN YEARS?WHAT SHOULD WE EXPECT WITHIN TEN YEARS?
AUC
GRAY AREAGRAY AREA
TTRANSIENT RANSIENT EELASTOGRAPHY LASTOGRAPHY (LSM)(LSM): : PPROBLEMS & ROBLEMS & LLIMITATIONSIMITATIONS
1.1.-- LSM WORKS WELL ONLY WHEN THE AMOUNT OF LSM WORKS WELL ONLY WHEN THE AMOUNT OF FIBROSIS BECOMES SIGNIFICANT: I.E. FIBROSIS BECOMES SIGNIFICANT: I.E. >> F2. F2.
2.2.-- THE HIGH CUTTHE HIGH CUT--OFF VARIABILITY FOR OFF VARIABILITY FOR >> F4F4 IS LIKELY IS LIKELY DUE TO AN DUE TO AN INSUFFICIENT DEFINITIONINSUFFICIENT DEFINITION OF THE OF THE CIRRHOTIC STAGECIRRHOTIC STAGE
3.3.-- INTERINTER-- AND INTRAAND INTRA--OBSERVER AGREEMENTS ARE OBSERVER AGREEMENTS ARE EXCELLENT BUT SIGNIFICANTLY INFLUENCED BY BMI EXCELLENT BUT SIGNIFICANTLY INFLUENCED BY BMI AND DEGREE OF STEATOSIS AND DEGREE OF STEATOSIS 4.4.--THE THE ““NORMAL RANGENORMAL RANGE”” OF LSM VALUES STILL RELIES OF LSM VALUES STILL RELIES ON VALUES OF PTS CLASSIFIED AS ON VALUES OF PTS CLASSIFIED AS ““F0F0””
5.5.-- INCIDENCE AND RELEVANCE OF CONFOUNDING INCIDENCE AND RELEVANCE OF CONFOUNDING FACTORS, I.E. INFLAMMATION AND TISSUE EDEMAFACTORS, I.E. INFLAMMATION AND TISSUE EDEMA
TTRANSIENT RANSIENT EELASTOGRAPHY LASTOGRAPHY (LSM)(LSM): : PPROBLEMS & ROBLEMS & LLIMITATIONSIMITATIONS
1.1.-- LSM WORKS WELL ONLY WHEN THE AMOUNT OF LSM WORKS WELL ONLY WHEN THE AMOUNT OF FIBROSIS BECOMES SIGNIFICANT: I.E. FIBROSIS BECOMES SIGNIFICANT: I.E. >> F2. F2.
2.2.-- THE HIGH CUTTHE HIGH CUT--OFF VARIABILITY FOR OFF VARIABILITY FOR >> F4F4 IS LIKELY IS LIKELY DUE TO AN INSUFFICIENT DEFINITION OF THE DUE TO AN INSUFFICIENT DEFINITION OF THE CIRRHOTIC STAGECIRRHOTIC STAGE
3.3.-- INTERINTER-- AND INTRAAND INTRA--OBSERVER AGREEMENTS ARE OBSERVER AGREEMENTS ARE EXCELLENT BUT SIGNIFICANTLY INFLUENCED BY BMI EXCELLENT BUT SIGNIFICANTLY INFLUENCED BY BMI AND DEGREE OF STEATOSIS AND DEGREE OF STEATOSIS 4.4.--THE THE ““NORMAL RANGENORMAL RANGE”” OF LSM VALUES STILL RELIES OF LSM VALUES STILL RELIES ON VALUES OF PTS CLASSIFIED AS ON VALUES OF PTS CLASSIFIED AS ““F0F0””
5.5.-- INCIDENCE AND RELEVANCE OF CONFOUNDING INCIDENCE AND RELEVANCE OF CONFOUNDING FACTORS, FACTORS, I.E. INFLAMMATION AND TISSUE EDEMAI.E. INFLAMMATION AND TISSUE EDEMA
TTRANSIENT RANSIENT EELASTOGRAPHY LASTOGRAPHY (LSM)(LSM): : PPROBLEMS & ROBLEMS & LLIMITATIONSIMITATIONS
DOES LSM REFLECT ONLY THE FIBROTIC DOES LSM REFLECT ONLY THE FIBROTIC TRANSFORMATION OF LIVER TISSUE?TRANSFORMATION OF LIVER TISSUE?
00
500500
10001000
15001500
20002000
25002500
30003000
35003500
40004000
ALT (
U/
L)
ALT (
U/
L)
00
22
44
66
88
1010
1212
1414
1616
LS
M (
kP
a)
LS
M (
kP
a)
00
500500
10001000
15001500
20002000
25002500
30003000
AS
T (
U/
L)
AS
T (
U/
L)
00
22
44
66
88
1010
1212
1414
1616
LS
M (
LS
M (
kP
akP
a))
I II III I II III HEPATOLOGY 2007; 46:IN PRESSHEPATOLOGY 2007; 46:IN PRESS
1.1.-- DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?
4.4.-- NONNON--INVASIVE METHODS: GOOD FOR ANY STAGE OF INVASIVE METHODS: GOOD FOR ANY STAGE OF FIBROTIC EVOLUTION?FIBROTIC EVOLUTION?
2.2.-- BIOCHEMICAL MARKERS: THE WAY TO GO ?BIOCHEMICAL MARKERS: THE WAY TO GO ?
3.3.-- TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC FLEXIBILITY?FLEXIBILITY?
THE CLINICAL EVALUATION OF DISEASE PROGRESSION THE CLINICAL EVALUATION OF DISEASE PROGRESSION IN CLD: TOWARDS AN INTEGRATED SYSTEM?IN CLD: TOWARDS AN INTEGRATED SYSTEM?
5.5.-- WHAT SHOULD WE DO NOW?WHAT SHOULD WE DO NOW?
6.6.-- WHAT SHOULD WE EXPECT WITHIN TEN YEARS?WHAT SHOULD WE EXPECT WITHIN TEN YEARS?
Beyond Beyond ““F4F4””: A Clinical Limbo: A Clinical Limbo
F0/F1F0/F1 F4F4
HVPG > 5HVPG > 5 HVPG > 10HVPG > 10
Clinical Signs of Clinical Signs of DecompensatedDecompensatedCirrhosis/HCC Cirrhosis/HCC
HVPG > 12HVPG > 12
Significant Risk of Significant Risk of VaricealVariceal Bleeding Bleeding
PROGRESSION OF PROGRESSION OF CIRRHOSIS CIRRHOSIS (F4 A(F4 A--BB--C ???)C ???)
Patient FOLLOWPatient FOLLOW--UP: routine UP: routine lab test, US, AFPlab test, US, AFP
Liver Stiffness Value (Liver Stiffness Value (KPaKPa))
27.527.5 49.149.1 53.753.737.537.5 62.762.7
No Esophageal No Esophageal VaricesVaricesStage 2 or 3Stage 2 or 3
No ChildNo Child--Pugh B or CPugh B or C
No past history of No past history of ascitesascites
No Hepatocellular Carcinoma
No past history of variceal bleeding
HV
PG
(mm
Hg)
TransientTransient ElastographyElastography forfor DiagnosisDiagnosis of of AdvancedAdvanced FibrosisFibrosisand and PortalPortal HypertensionHypertension in in PatientsPatients WithWith HepatitisHepatitis C C
RecurrenceRecurrence After After LiverLiver TransplantationTransplantationCarrionCarrion etet al.al. LiverLiver TrasplantationTrasplantation 20062006
PearsonPearson’’s s correlationcorrelation 0.84; 0.84; P P < 0.001< 0.001
Hepatic Stiffness as a Predictor of HVPGHepatic Stiffness as a Predictor of HVPG
VIZZUTTI F. et AL, HEPATOLOGY 2007; 45:1290VIZZUTTI F. et AL, HEPATOLOGY 2007; 45:1290--12971297
●13.6 kPa
Hepatic Stiffness as a Predictor of HVPGHepatic Stiffness as a Predictor of HVPG
●
17.6 kPa
VIZZUTTI F. et AL, HEPATOLOGY 2007; 45:1290VIZZUTTI F. et AL, HEPATOLOGY 2007; 45:1290--12971297
Varices
Hepatic Stiffness is a Poor Predictor of Hepatic Stiffness is a Poor Predictor of Upper GI Upper GI VaricesVarices
●
17.6 kPa
VIZZUTTI F. et AL, HEPATOLOGY 2007; 45:1290VIZZUTTI F. et AL, HEPATOLOGY 2007; 45:1290--12971297
1.1.-- DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?
4.4.-- NONNON--INVASIVE METHODS: GOOD FOR ANY STAGE OF INVASIVE METHODS: GOOD FOR ANY STAGE OF FIBROTIC EVOLUTION?FIBROTIC EVOLUTION?
2.2.-- BIOCHEMICAL MARKERS: THE WAY TO GO ?BIOCHEMICAL MARKERS: THE WAY TO GO ?
3.3.-- TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC FLEXIBILITY?FLEXIBILITY?
THE CLINICAL EVALUATION OF DISEASE PROGRESSION THE CLINICAL EVALUATION OF DISEASE PROGRESSION IN CLD: TOWARDS AN INTEGRATED SYSTEM?IN CLD: TOWARDS AN INTEGRATED SYSTEM?
5.5.-- WHAT SHOULD WE DO NOW?WHAT SHOULD WE DO NOW?
6.6.-- WHAT SHOULD WE EXPECT WITHIN TEN YEARS?WHAT SHOULD WE EXPECT WITHIN TEN YEARS?
““A LITTLE KITCHEN MAKES A A LITTLE KITCHEN MAKES A LARGE HOUSELARGE HOUSE””
NNoo ssiiggnniiffiiccaanntt ffiibbrroossiiss
((ii..ee.. FF00--FF11))
NNoo bbiiooppssyy
CCiirrrrhhoossiiss ((ii..ee.. FF44))
FFoollllooww oorr ttrreeaatt
GGrraayy aarreeaa ((ii..ee.. FF22--FF33))
NNoo bbiiooppssyy
HHCCCC aanndd vvaarriicceess ssccrreeeenniinngg
BBiiooppssyy iiff rreessuullttss iinnfflluueennccee
mmaannaaggeemmeenntt
BBiiooppssyy iiff rreessuullttss iinnfflluueennccee
mmaannaaggeemmeenntt
SSuussppeecctteedd CChhrroonniicc LLiivveerr DDiisseeaassee
AAppppllyy ttwwoo uunnrreellaatteedd NNIITTss
CCoonnccoorrddaanntt NNIITTssDDiissccoorrddaanntt NNIITTss
A PA POSSIBLEOSSIBLE FFLOWLOW--CCHARTHART
1.1.-- DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?DIAGNOSTIC ACCURACY: ARE THERE GOLD STANDARDS ?
4.4.-- NONNON--INVASIVE METHODS: GOOD FOR ANY STAGE OF INVASIVE METHODS: GOOD FOR ANY STAGE OF FIBROTIC EVOLUTION?FIBROTIC EVOLUTION?
2.2.-- BIOCHEMICAL MARKERS: THE WAY TO GO ?BIOCHEMICAL MARKERS: THE WAY TO GO ?
3.3.-- TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC TRANSIENT ELASTOGRAPHY: MORE DIAGNOSTIC FLEXIBILITY?FLEXIBILITY?
THE CLINICAL EVALUATION OF DISEASE PROGRESSION THE CLINICAL EVALUATION OF DISEASE PROGRESSION IN CLD: TOWARDS AN INTEGRATED SYSTEM?IN CLD: TOWARDS AN INTEGRATED SYSTEM?
5.5.-- WHAT SHOULD WE DO NOW?WHAT SHOULD WE DO NOW?
6.6.-- WHAT SHOULD WE EXPECT WITHIN TEN YEARS?WHAT SHOULD WE EXPECT WITHIN TEN YEARS?
RRELATIVE ELATIVE PPORTAL ORTAL HHYPOPERFUSION OF YPOPERFUSION OF FFIBROTIC IBROTIC DDISTAL ISTAL PPARENCHYMAL WITH ARENCHYMAL WITH AARTERIAL RTERIAL
CCOMPENSATION AT OMPENSATION AT TCTC
METAVIR F4METAVIR F4
BIOLOGICAL EQUIVALENTBIOLOGICAL EQUIVALENT: PARENCHYMAL ARTERIALIZATION AND : PARENCHYMAL ARTERIALIZATION AND NEOANGIOGENESISNEOANGIOGENESIS
FFUTURE AND UTURE AND HHOPESOPES
1.1.-- TECHNOLOGICAL IMPROVEMENT OF TECHNOLOGICAL IMPROVEMENT OF STANDARD IMAGING METHODS (STANDARD IMAGING METHODS (CTCT--MRMR) WITH ) WITH DEDICATION TO THE STUDY OF DIFFUSE DEDICATION TO THE STUDY OF DIFFUSE (RATHER THAN FOCAL) TISSUE ALTERATIONS (RATHER THAN FOCAL) TISSUE ALTERATIONS (INCLUDING (INCLUDING ANGIOGENESISANGIOGENESIS))
2.2.-- DEVELOPMENT OF IMAGING METHODS DEVELOPMENT OF IMAGING METHODS EMPLOYING EMPLOYING BIOMARKERSBIOMARKERS: I.E. A MOLECULES : I.E. A MOLECULES THAT ASSOCIATED WITH A FLUOROCHROME THAT ASSOCIATED WITH A FLUOROCHROME ARE ABLE TO IDENTIFY RECEPTORS OR TO ARE ABLE TO IDENTIFY RECEPTORS OR TO DYNAMICALLY INTERACT WITH OTHER DYNAMICALLY INTERACT WITH OTHER MOLECULS ACTIVELY INVOLVED IN THE MOLECULS ACTIVELY INVOLVED IN THE PATHOGENIC PROCESSPATHOGENIC PROCESS ((PET SCANPET SCAN))
THE CLINICAL EVALUATION OF DISEASE PROGRESSION THE CLINICAL EVALUATION OF DISEASE PROGRESSION IN CLD: TOWARDS AN INTEGRATED SYSTEM?IN CLD: TOWARDS AN INTEGRATED SYSTEM?
F0F0 F4F4
HVPG HVPG > > 5 mmHg5 mmHgHVPG HVPG < < 10 mmHg10 mmHg
TOD
AY
TOD
AY
TOM
OR
RO
WTO
MO
RR
OW
LSM + BIOCHEMICAL LSM + BIOCHEMICAL MARKER(S) MARKER(S) w/wow/wo LIVER LIVER BIOPSYBIOPSY
LSMLSMHVPG HVPG w/wow/wo TJLB (+CM)TJLB (+CM)BIOCHEMICAL MARKERS ?BIOCHEMICAL MARKERS ?
ororF1F1 F2F2 F3F3
PET + BMKPET + BMK
CT, MRCT, MR
DOPPLER US WITH CMDOPPLER US WITH CM
AKNOWLEDGMENTSAKNOWLEDGMENTS
FRANCESCO VIZZUTTIFRANCESCO VIZZUTTI
UMBERTO ARENAUMBERTO ARENA
FABIO MARRAFABIO MARRA
ANTONIO PETRARCAANTONIO PETRARCA
STEFANO COLAGRANDESTEFANO COLAGRANDE
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