Topic Highlights
Copyright ©2009 The WJG Press and Baishideng.
World J Gastroenterol. May 14, 2009; 15(18): 2190-2203
Published online May 14, 2009. doi: 10.3748/wjg.15.2190
Table 1 METAVIR and Ishak staging systems for liver fibrosis
DescriptionMETAVIR (F)Ishak (S)
No fibrosis00
Portal fibrosis without septa11-2
Portal fibrosis with few septa23
Septal fibrosis without cirrhosis34
Table 2 Pros and Cons of liver biopsy in staging of hepatic fibrosis
Staging of liver fibrosisInvasiveness (pain, bleeding)
Grade of necroinflammationCost (hospitalization)
Steatosis (common in hepatitis C)Sampling errors
Iron overload (common in hepatitis C)Possibly refused by patient, concern of physician
Comorbidities (autoimmunity stigmates)Static data, no information on fibrogenesis
Table 3 Features of an adequate liver biopsy sample
Length (mm)Portal tracts (n°)Ref.
Bigger is betterNA[32]
Table 4 Features of the ideal non-invasive method for liver fibrosis
Reliable (high diagnostic accuracy)
Widely available (simple, least expensive)
Providing information on both fibrosis stage and fibrogenesis activity
Validated by large-scale studies
Validated by independent studies (different authors from the proposing study)
Validated in various etiologies of CLDs (HCV, HBV, ALD, NAFLD)
Identifying clinically important fibrosis stages (significant fibrosis and cirrhosis)
Table 5 Single serum non-invasive markers for liver fibrosis
Direct markersIndirect markers
Hyaluronic acidPlatelet count
LamininAST, ALT
Procollagen IIIγGT
Type IV Collagenγ-globulins
Inhibitors of metalloproteinasesProthrombin time
Table 6 Combinations of serum parameters for non-invasive diagnosis of liver fibrosis
MarkerDescriptionSettings in which validation existsRef.
AST/ALTAST to ALT ratioHCV, HBV[6364657172]
APRIAST to platelets ratio indexHCV, HBV, HIV/HCV[64727580]
Forns’ indexAge, BMI, γGT, cholesterolHCV, HBV, HIV/HCV[67697275]
FibrotestAge, gender, α-2-macroglobulin, γGT, haptoglobin, apolipoprotein A1, total bilirubinHCV, HBV, ALD, NAFLD, HIV/HCV[6567727680]
ELFAge, hyaluronic acid, type III procollagen, TIMP1HCV, ALD, NAFLD[6062]
HepascoreBilirubin, γGT, hyaluronic acid, α-2-macroglobulin, age, sexHCV[5859]
Lok indexAST, ALT, platelets, INRHCV[68]
FibroindexAST, platelets, g-globulinsHCV[7172]
FibrometerAge, AST, platelets, hyaluronan, INR, α-2-macroglobulin, ureaHCV[5556]
Fibrospectα-2-macroglobulin, hyaluronan, TIMP1HCV[57]
Fib-4Age, AST, ALT, plateletsHCV, HBV, HIV/HCV[7375]
Table 7 Performance of several serum non-invasive markers for liver fibrosis (single or combination) as expressed as AUROC
Serum markerSignificant fibrosisCirrhosisRef.
Hyaluronic acid0.73-0.920.85-0.97[4047]
Type IV collagen0.83NA[5153]
Forns’ index0.75-0.86NA[67687072]
Table 8 Accuracy of fibroscan for the diagnosis of significant fibrosis and cirrhosis
Ref.EtiologyAccuracy forF2Accuracy for F4
[84] HCV 79 95
[86] HCV 80 96
[87] HCV NA 95
[88] HBV 87 88
[89] HBV 90 94
Table 9 Limitations of fibroscan in clinical practice
Difficult to perform in obese patients (5% rate failure)
Inter-observer and intra-observer variability influenced by liver steatosis
Influence of ALT flares (HBV reactivation)
Lower performance for diagnosis of significant fibrosis
Table 10 Main features of SAFE biopsy[6794] for significant fibrosis and cirrhosis in 2035 HCV cases
Significant fibrosisCirrhosis
Sensitivity (%) 100 92.7
Specificity (%) 77 90.4
Accuracy (%) 90 93
AUROC 0.9 0.92
Saved biopsies (%) 47 82
Table 11 Comparison of the performance of SAFE biopsy[6794], Fibropaca algorithm[96] and Leroy algorithm[97]. Results are expressed as percentages
SAFE biopsy for diagnosis of
Fibropaca algorithm for diagnosis of
Leroy algorithm for diagnosis ofF2
APRI needed100100100100100
Forns needed0010000
Fibrotest needed41.757.6100100100
Saved biopsies43.879.151.776.229.2
Table 12 Comparison of the performance of Bordeaux algorithm[98] and SAFE biopsy[6794]. Values are expressed as percentages
Bordeaux algorithm
SAFE biopsy
APRI needed 0 0 100 100
Fibrotest needed 100 100 43.7 61.9
Fibroscan needed 100 100 0 0
Accuracy 91 93 94 87
Biopsies saved 71.9 78.8 48.3 74.8