Evidence Table 5: Key Question 4A. Diagnostic Accuracy

Evidence Table 5: Key Question 4a. Diagnostic Accuracy

Study, Year / Test / Method of data collection / Derivation study / Country / N / Proportion with fibrosis or cirrhosis / Definition of a positive test / Cutoffs predefined / Biopsy Overall Quality / Population characteristics / Proportion unexaminable by screening test or reference standard / Reported predictive values consistent with calculated values based on reported prevalence, sensitivity, and specificity /
Adams, 20057 / Hepascore (bilirubin, g-glutamyltransferase, hyaluronic acid, a-2 macroglobulin, age, and sex)
Fibrotest / Prospective / Derivation and validation samples reported separately / Australia / 117 (derivation sample)
104 (validation sample) / Fibrosis (METAVIR F2-F4): 44% (derivation sample) and 57% (validation sample)
Cirrhosis (METAVIR F4): 6% and 16% / Hepascore: Cutoff ≥0.5 (range 0.0-1.0) for fibrosis; ≥0.84 for cirrhosis / No for derivation sample, yes for validation sample / All ≥5 portal tracts; median 9 portal tracts and 13 mm / Derivation vs. validation sample
Age: 40 vs. 41 years
Female: 32% vs. 27%
Genotype 1: 61% vs. 48%
All treatment-naïve / Not stated / Predictive values not reported
Ahmad, 20118 / Fibrosis-cirrhosis index (alkaline phosphatase, bilirubin, albumin, platelet count)
AST/ALT ratio
APRI
FIB-4
Fibrosis Index
Alkaline phosphatase
Bilirubin
Albumin
Platelet count / Retrospective / Yes (for fibrosis-cirrhosis index) / Pakistan / 157 / Fibrosis (METAVIR F2-F4): 57%
Cirrhosis (METAVIR F4): 13% / Fibrosis-cirrhosis index >0.130 or >1.25
AST/ALT ratio >1
APRI >0.5 or >1.5
FIB-4 >1.45 or >3.25
Fibrosis Index >2.1 or >3.3
Alkaline phosphatase >120 or >240 IU/l
Bilirubin >0.95 or >1.5 mg/dl
Albumin <3.85 or <4.1 g/dl
Platelet count <100,000 or <150,000 / No for fibrosis-cirrhosis index, otherwise yes / Not stated / Age: 38 years
Female: 27%
Genotype 1: 14%
All treatment-naïve / Not stated / Yes
Alsatie, 20079 / 5-item predictive index (DM, platelet count, INR, bilirubin, AST) / Retrospective / Derivation and validation samples reported separately / USA / 190 (derivation sample)
94 (validation sample) / Fibrosis (METAVIR F2-F4): 41%
Cirrhosis (METAVIR F4): 17%) / 5-item predictive index: Cutoffs ranged from 0 to 4 / No for derivation sample, yes for validation sample / All ≥15 mm / Reported for derivation and validation samples together
Age: 45 years
Female: 40%
Genotype 1: 50%
All treatment-naïve / Not stated / Yes
Adler, 200810 / Fibrotest
FIB-4
Forns' Index
APRI
Fibroindex / Unclear / No / Belgium / 152 / Fibrosis (METAVIR F2-F4): 73%
Cirrhosis (METAVIR F4): 12% / Only AUROC reported / Only AUROC reported / Not stated / Not reported / Not stated / Only AUROC reported
Anderson, 200011 / AST/ALT ratio / Retrospective / No / Canada / 133 / Fibrosis or cirrhosis (method unclear): 82%
Cirrhosis (method unclear): 46% / AST/ALT ratio ≥1 / Yes / Not reported / Age: 46 years
Female: 30%
Genotype 1: Not reported
All had elevated ALT
18% on treatment / 6/139 excluded for unavailable liver biopsy / Yes
Becker, 200912 / HepascoreAPRIFIB-4 / Unclear / No / USA / 391 / Fibrosis (METAVIR F2-F4): 50%Cirrhosis (METAVIR F4): 19% / Hepascore >0.2, >0.55, or ≥0.8APRI >0.5 or >1.5FIB-4 ≥1.45 or >3.2.5 / Yes for APRI and FIB-4, no for Hepascore / All ≥10 mm or ≥8 portal tracts; median 16 mm, 11% <10 mm / Age: 50 years
Female: 30%
Genotype 1: 75%
None treated at time of biopsy / Not stated / Yes
Bejarano, 200913 / Sabadell NIHCED index / Prospective / No / Spain / 321 / Severe fibrosis (Knodell 3-4): 59% (no patients had Knodell 2)
Cirrhosis (Knodell 4): 20% / Sabadell NIHCED index >6 / No / Mean 11.6 mm and 12.2 portal tracts / Age: 48 years
Female: 44%
Genotype 1: Not reported / Not stated / Yes
Berg, 200414 / APRI / Retrospective / No / Germany / 484 / Fibrosis (Scheuer F2-F4): 52%
Cirrhosis (Scheuer F4): 13% / APRI: Cutoffs ranged from >0.50 to >2.0 / Yes / Not reported / Age: 46 years
Female: 44%
Genotype 1: Not reported
All treatment-naïve / Not stated / Yes
Ben Jazia, 200915 / AST/ALT ratio
APRI
Platelet count / Retrospective / No / Tunisia / 35 / Fibrosis (METAVIR F2-F4): 77%
Cirrhosis (METAVIR F4): Not reported / APRI >0.72
AST/ALT ratio and platelet count: Cutoffs not reported / No / Not reported / Age: 49 years
Female: 69%
Genotype 1: 46%
All treatment-naïve / Not reported / No
Boeker, 200216 / TIMP-1MMP-2Hyaluronic acidASTALTAlkaline phosphataseGGTAlbumin / Unclear / No / Germany / 78 / Fibrosis (Ishak, grades not reported): 46% (27/59, excluding patient with cirrhosis)Cirrhosis (Ishak, grades not reported): 24% (19/78) / TIMP-1 (Biotrak) >950 mcg/lTIMP-1 (Quantikine) >85 mcg/lMMP-2 (Biotrak) >1500 mcg/lMMP-2 (Quantikine) >320 mcg/lHyaluronic acid >30 mcg/lAST >18 U/lALT >22 U/lAlkaline phosphatase >190 U/lGGT >28 U/lAlbumin <37 g/l / Unclear / Not reported / Age: Not reportedFemale: Not reportedGenotype 1: Not reported / Not stated / Predictive values not reported
Bonacini, 199717 / Cirrhosis discriminant score (platelet count, AST/ALT ratio, prothrombin index, ascites, spider angiomata)AST/ALT ratio / Retrospective / Yes / USA / 79 / Fibrosis: Not reportedSevere fibrosis (Knodell F3-F4): 35%Cirrhosis: Not reported / Cirrhosis discriminant score ≥7 or ≥8AST/ALT ratio / No (for cirrhosis discriminant score) / Not reported / Age: Not reportedFemale: Not reportedGenotype 1: Not reportedNo histologic evidence of alcoholic liver disease / Not stated / Predictive values not reported
Borroni, 200618 / AST/ALT ratio
Cirrhosis Discriminant Score
APRI
Pohl's Index
Age-platelet index / Retrospective / No / Italy / 228 / Severe fibrosis (Knodell F3-F4): 49%
Cirrhosis (Knodell F4): 13%) / AST/ALT ratio ≥1
Cirrhosis Discriminant Score >2 or >7
APRI ≥2
Pohl's Index positive
Age-platelet index ≥6
Combinations of APRI and age-platelet index: cutoffs not reported / No / All ≥6 portal fields / Age: 42 years
Female: 27%
Genotype 1: 47%
All elevated transaminases
All treatment-naïve / 4 with <6 portal tracts excluded from analysis / Yes
Bota, 201119 / King's score
Forn's Index
APRI / Retrospective / No / Romania / 212 / Fibrosis (METAVIR F2-F4): 91%
Severe fibrosis (METAVIR F3-F4): 45%
Cirrhosis (METAVIR F4) / Only AUROC reported / Only AUROC reported / All >=8 portal tracts; mean 34 mm / Age: 50 years
Female: 67%
Genotype 1: Not reported / Not stated / Only AUROC reported
Bourliere, 200820 / HepascoreFibrotest / Prospective / No / France / 467 / Fibrosis (METAVIR F2-F4): 49%Cirrhosis (METAVIR F4): 7.5% / Hepascore ≥0.5 and ≥0.84 or not reportedFibrotest: Not reported / Unclear / Mean 20 mm and median 9 portal tracts; 59% ≥15 mm and ≥5 portal tracts / Age: 47 yearsFemale: 41%Genotype 1: Not reported / Not stated / Yes
Bourliere, 200621 / Fibrotest
APRI
Forn's Index / Unclear / No / France / 235 / Fibrosis (METAVIR F2-F4): 42%
Cirrhosis (METAVIR F4): 6.8% / Fibrotest >0.1 or ≥0.6
APRI >0.5 to >2
Forn's Index: ≥4.21 or >6.9 / Yes / Mean 20 mm and median 9 portal tracts; 59% ≥15 mm and ≥5 portal tracts / Age: 46 years
Female: 45%
Genotype 1: Not reported / Not stated / Yes
Boursier, 201222 / SAFE algorithm (based on APRI and Fibrotest) / Retrospective / No / France / 1785 / Fibrosis (METAVIR F2-F4): 55%
Cirrhosis (METAVIR F4): 13% / SAFE fibrosis algorithm positive
SAFE cirrhosis algorithm positive / Yes / >=15 mm in 79% / Mean age: 48 years
Female: 40%
Genotype 1: Not reported
Excluded for alcohol >30 g/day (men) or >20 g/day (women) / Not stated / Yes
Boursier, 201123 / FibroMeter / Unclear / No / France / 349 (derivation sample)
380 (validation sample) / Derivation vs. validation sample
Fibrosis (METAVIR F2-F4): 68% vs. 49%
Cirrhosis (METAVIR F4): 12% vs. 18% / Not reported / No / 94% ≥15 mm and ≥8 portal tracts / Derivation vs. validation sample
Age: 52 vs. 51 years
Female: 40% vs. 38%
Genotype 1: Not reported / Not stated / Predictive values not reported
Boursier, 200924 / FibroMeterFibrotestHepascoreAPRIModified Fibrotest / Retrospective / No, except for modified Fibrotest / France / 1056 / Fibrosis (METAVIR F2-F4): 52%Cirrhosis (METAVIR F4): 11% / FibroMeter >0.628, >0.830, or >0.979
Fibrotest >0.448, >0.631, >0.660, or >0.862
Hepascore >0.497, >0.801, >0.904, or >0.999
APRI >0.581, >0.652, >1.159, or >2.532
Modified Fibrometer >0.089 or >0.442 / No / Not reported / Mean age: 46 years
Female: 40%
Genotype 1: Not reported / Not stated / Yes
Burton, 201125 / APRI / Retrospective / No / USA / 268 (142 black, 117 white) / Fibrosis (Batt-Ludwig 2-4): 49%Cirrhosis (Batt-Ludwig 4): 16% / APRI: Cutoffs ranged from >0.50 to >1.0 / No / Not reported / Age: 52 years
Female: 4.5%
Genotype 1: 81%
All treatment-naïve / Not stated / Yes
Cales, 201026 / FibroMeter
FibroMeter 3G (hyaluronic acid replaced with GGT)
FibroTest
Hepascore / Retrospective / Yes (for FibroMeter 3G) / France / 1056 (derivation sample)
458 (validation sample) / Fibrosis (METAVIR F2-F4): 52% and 48%
Cirrhosis (METAVIR F4): 11% and 15% / FibroMeter >0.419
FibroMeter 3G >0.440 / Unclear / Not reported / Only reported for derivation sample
Mean age: 46 years
Female: 40%
Genotype 1: Not reported
No antiviral treatment in last 6 months / Not stated / Only AUROC reported
Cales, 200827 / FibroMeter
Fibrotest
Hepascore
APRI
FIB-4 / Retrospective / No / France / 1056 / Fibrosis (METAVIR F2-F4): 52%
Cirrhosis (METAVIR F4): 11% / FibroMeter >0.419
Fibrotest >0.435
Hepascore >0.465
APRI >0.548
FIB-4 >1.116 / No / Not reported / Mean age: 46 years
Female: 40%
Genotype 1: Not reported
No antiviral treatment in last 6 months / Not stated / Yes
Castera, 201028 / SAFE algorithm (based on APRI and Fibrotest) / Prospective / No (for SAFE algorithm) / France / 302 / Fibrosis (METAVIR F2-F4): 76%
Cirrhosis (METAVIR F4): 25% / APRI: Algorithm based on scores ≤0.5, 0.5-1.5, or >1.5
Fibrotest (for patients with APRI 0.5-1.5): >0.48 / Yes / All ≥10 mm and ≥6 portal tracts; mean 20 mm and 15 portal tracts / Age: 52 years
Female: 43%
Genotype 1: Not reported
All elevated ALT / 12 insufficient liver tissue / Yes
Castera, 200929 / AST/ALT ratioAPRI Prothrombin indexPlatelet countFibrotestLok Index / Prospective / No / France / 298 / Fibrosis (METAVIR F2-F4): 74%Cirrhosis (METAVIR F4): 23% / Platelet count: <150
Fibrotest: ≥0.75
Prothrombin index: ≤85%
AST/ALT ratio: ≥1
APRI: ≥1.0 or 2.0
Lok Index: ≥0.2 or ≥0.5 / Yes / All ≥10 mm and ≥6 portal tracts; mean 20 mm and 15 portal tracts / Age: 52 yearsFemale: 43%Genotype 1: Not reported / Not reported / Yes
Castera, 200530 / APRI
Fibrotest / Prospective / No / France / 193 / Fibrosis (METAVIR F2-F4): 74%
Cirrhosis (METAVIR F4): 25% / Only AUROC reported / Only AUROC reported / Median 17 mm, median 2 fragments / Age: 51 years
Female: 43%
Genotype 1: Not reported / Not reported / Unable to construct 2 x 2 table
Cheong, 201131 / Significant Fibrosis Index (haptoglobin, a2MG, TIMP1, MMP2, GGT)
Zeng Index
APRI
Forn's Index
FIB-4
ELF index / Prospective / Yes (for Significant Fibrosis Index) / Korea / HCV infected: 79 (derivation sample) and 27 (validation sample) / Derivation and validation samples, respectively (includes persons with HCV and HBV infection)
Fibrosis (METAVIR F2-F4): 79% and 77%
Cirrhosis (METAVIR F4): 13% and 28% / Significant Fibrosis Index >2.2 or >3.3 / No (for Significant Fibrosis Index) / Mean 12.6 mm and mean 13.2 portal tracts; 71% had ≥11 portal tracts / Derivation vs. validation samples (includes persons with HCV and HBV infection)
Age: 42 vs. 42 years
Female: 31% vs. 35%
Genotype 1: Not reported
No antiviral treatment in last 6 months / Not reported / Sensitivity, specificity, and predictive values not reported for HCV subgroup
Cheung, 201132 / Fibrosis-protein Index (a-2 macroglobulin and hemopexin)APRI / Unclear / Yes (for Fibrosis-protein Index) / Belgium / 62 (derivation sample)
73 (validation sample) / Derivation and validation samples, respectivelyFibrosis (METAVIR F2-F4): 50% and 71%Cirrhosis (METAVIR F4): 26% and 14% / Fibrosis-protein Index: >3.53 and >4.78APRI: >0.5 or >1.0 / No (for Fibrosis-protein Index), yes for APRI / Median 1.6-2.0 cm and >8 portal tracts / Derivation vs. validation samples
Age: 50 vs. 50 years
Female: 48% vs/ 53%
Genotype 1 or 4: 69% vs. 71%
All treatment-naïve / Not reported / Yes for Fibrosis-protein Index, not reported for APRI
Cheung, 200833 / Platelet count
Normalized AST/ALT ratio
Pohl score
APRI
Lok Index / Prospective / No / USA / 490 / Fibrosis (Batt-Ludwig 2-4): 66%
Cirrhosis (Batt-Ludwig 4): 14% / Platelet count: <100 or <150
Normalized AST/ALT ratio: ≥1
Pohl score: Positive (platelet count <150 and AST/ALT ratio ≥1)
APRI: ≥0.5, ≥1.0, ≥1.5, or ≥2.0
Lok Index: >0.2 or >0.5 / Yes / Not reported / Age: 49 years
Female: 2%
Genotype 1: Not reported / Not reported / Yes, except for AST/ALT ratio for severe fibrosis
Chrysanthos, 200634 / APRI / Unclear / No / Greece / 284 / Fibrosis (Ishak score ≥3): 51%Cirrhosis (Ishak score 5 or 6): 20% / APRI: >0.50 or >1.50 for fibrosis, >1.00 or >2.00 for cirrhosis / Yes / All >1.5 cm / Age: 49 years
Female: 49%
Genotype 1: Not reported
No antiviral treatment last 6 months / 14 patients out of entire (HCV + HCV) sample of 489 patients had inadequate biopsy specimen / Yes