Evaluation of liver fibrosis JeanClaude TRINCHET

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Evaluation of liver fibrosis Jean-Claude
TRINCHET
Hôpital Jean Verdier - 93140 Bondy AP-HP -
Université Paris 13
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Evaluation of liver fibrosis
Liver biopsy or non invasive methods?
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Why to assess liver fibrosis ?
causative agent

• Fibrosis
• Morphological disturb.
• Hemodynamic disturb.
• Portal hypertension
• Functional disturb.
• Carcinogenesis

chronic liver disease
Clinical objectives
cirrhosis
decompensation 4 yr.
HCC 3 yr.
death 4 yr.
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Why to assess liver fibrosis ?

• Clinical objectives
• Assessment of lesions in a patient with CLD
• Metavir fibrosis F2 gt antiviral treatment
• Cirrhosis gt EVR prevention, HCC screening
• Surveillance
• Regression of lesions after treatment
• Cirrhosis occurrence (EV, HCC)
• Screening for fibrosing CLD in general population

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Evaluation of liver fibrosis
LB gold standard method
Semiquantitative scores (viral hepatitis) Knodell,
Ishak, Métavir, Scheuer, etc.

• Morbidity
• Low acceptability
• High cost
• Sampling error
• LB 1 / 50 000

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Evaluation of liver fibrosis

• Non invasive methods
• Blood tests
• Liver stiffness measurement
• Imaging
• (Endoscopy)

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Evaluation of liver fibrosis
Non invasive methods
Endoscopy
Imaging
Cirrhosis dysmorph., portal hypertension high
Sp, low Se
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Blood tests

• PIIINP, collagen type IV, laminin
• hyaluronic acid, MMP, TIMP
• AST, ALT, gamma-GT
• bilirubin, prothrombin act., platelets
• gamma-globulins, transferrin, ferritin
• alpha 2-macroglob. , haptoglobin, apo A1
• cholesterol, HOMA
• etc.

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Fibrosis scores

• Poynard, 1991 PT, GGT, ApoA1 PGA
• Bonacini, 1997 AST/ALT, platelets, PT
• Imbert-Bismut, 2001 bili, GGT, hapto., a2MG,
  apoA1 Fibrotest
• Luo, 2002 glob/alb, platelets or AST/ALT
• Forns, 2002 age, GGT, cholesterol, platelets
• Kaul, 2002 sex, spider naevi, AST, platelets
• Wai, 2003 AST/ platelets APRI
• Sud, 2004 age, AST, cholesterol, HOMA, alcohol
• Lainé, 2004 hyaluronic ac., transferrin
• Rosenberg, 2004 age, hyalur., coll. IV, coll. VI,
  lamin., PIIINP, TIMP-1 ELF
• Patel, 2004 TIMP-1, a2MG, hyaluronic
  ac. Fibrospect
• Leroy, 2004 PIIINP, MMP1
• Hui, 2005 BMI, platelets, albumin, bilirubin
• Lok, 2005 AST/ALT, platelets, INR
• Adams, 2005 bili, GGT, hyaluronic ac., a2MG, age,
  sex Hepascore
• Cales, 2005 AST, platelets, PT, a2MG, hyalur.,
  urea, age Fibrometre

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Fibrosis scores
Fibrotest
HCV (n 339)
Imbert-Bismut et al. Lancet 20013572069-75
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Fibrosis scores
Fibrotest
HCV (n339) Metavir F2 AUC 0,827 Index lt
0,10 NPV 100 Index gt 0,60 PPV gt 90 LB
- 46
Imbert-Bismut et al. Lancet 20013572069-75
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Fibrosis scores
HCV - Criterion F0-1 vs F2-3-4
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Fibrosis scores
HCV - Criterion F0-1-2-3 vs F4 (cirrhosis)
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Liver stiffness measurement (Fibroscan)
LB x 100
Probe
Sandrin et al. Ultrasound Med Biol 2003291-8
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Liver stiffness measurement (Fibroscan)
HCV (n 327)
AUC 0.79 0.91 0.97
Ziol et al. Hepatology 2005128343-50
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Evaluation of liver fibrosis
LB
Fibroscan
Fibrotest
ROC
PPV
Hepascore
NPV
Fibrometre
?
Sp
Se
Forns
LR-
LR
Fibrospect
AUC
Leroy
ELF
APRI
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Evaluation of liver fibrosis

• Methodology
• Prospective studies
• Intention-to-diagnose
• Diagnostic indices Se Sp PPV NPV LHR
  ROC
• Simultaneous comparison of methods
• Independent studies
• Independent populations
• Various etiologies of liver diseases
• Limits and causes of FP and FN

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Evaluation of liver fibrosis

• Fibrotest
• Validation for main etiologies VHC, VHB, VIH,
  NASH, MAF
• False positives and false negatives
• Influence of physiological parameters fasting
• Interlaboratories reproducibility
• Follow-up with or without treatment (HCV, HBV)
• Comparison to other methods
• Independent medical teams and patient populations

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Evaluation of liver fibrosis
Comparison between methods
HCV (n 183)
Castéra et al. Gastroenterology 2005128343-50
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Evaluation of liver fibrosis
Etiologies of CLD
No cirrhosis(n842)
Cirrhosis(n165)
Liver stiffness (kPa)
Fibroscan
Ganne-Carrié et al., AFEF et AASLD 2005
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Limitations of non invasive methods
Evaluation of liver fibrosis
Fibrotest Fibroscan Technical pb. - obesity
(5-10) False positive hemolysis extensive fib.
Gilbert dis. perisinusoidal fib.
infection False negative inflammation macronodul
ar cirrh. inactive cirrh.

• Poynard et al. Clin Chem 2004 - Ganne-Carrié et
  al. , Castéra et al. AASLD 2005

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Follow-up
Fibrotest HCV (n 165)
n 17
Poynard et al. J Viral Hepat 20029128-33
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Screening of cirrhosis

• Drinkers
• n 380

Fibroscan n 380
Failure n 50 (13)
LSM gt 13 kPa n 44 (13)
Refusal or CI n 5
LB n 39
cirrhosis n 38
F3 n 1

• Plat. gt 120 000
• PT gt 80
• n 15
• LSM lt 28 kPa

Melin et al. AASLD 2005
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Evaluation of liver fibrosis
What is the gold standard method ?
?
LB
whole liver
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Non invasive methods ?
Clinical data
Usual blood tests
US-doppler
Diagnostic accuracy
LB
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Non invasive methods ?
Clinical data
Usual blood tests
US-doppler
Diagnostic accuracy
Blood tests ?
Liver stiffness ?
LB
Additional value of the new method ?
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Conclusion

• Non invasive methods will have a major role in
  clinical management of patients with CLD in the
  (very) near future.
• To determine what tests have the best additional
  value is not yet possible.
• Combining two or several tests seems very
  promising blood test(s) Fibroscan ?
• The main objective for clinicians is improvement
  in patient clinical management (not decreasing LB
  number).