Routine blood tests to predict liver fibrosis in chronic hepatitis C

doi:10.3748/wjg.v18.i8.746

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Feb 28, 2012 (publication date) through May 8, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Feb 28, 2012; 18(8): 746-753
Published online Feb 28, 2012. doi: 10.3748/wjg.v18.i8.746

Table 1 Fibrosis tests composed of laboratory parameters

Fibrosis test	Calculation
AAR	AST/ALT
APRI	[(AST/ULN)/platelet count (10⁹/L)] × 100
FibroQ	(10 × age × AST × PT INR)/(PLT × ALT)
CDS	Platelet count (10⁹/L): > 340 = 0; 280-339 = 1; 220-279 = 2; 160-219 = 3; 100-159 = 4; 40-99 = 5; < 40 = 6
CDS	ALT/AST ratio: > 1.7 = 0; 1.2-1.7 = 1; 0.6-1.19 = 2; < 0.6 = 3
API	INR: < 1.1 = 0; 1.1-1.4 = 1; > 1.4 = 2 CDS is the sum of the above (possible value, 0-11)
	Age (yr): < 30 = 0; 30-39 = 1; 40-49 = 2; 50-59= 3; 60-69 = 4; > 70 = 5
	Platelet count (10⁹/L): ≥ 225 = 0; 200-224 = 1; 175-199 = 2; 150-174 = 3; 125-149 = 4; ≤ 125 = 5
	API is the sum of the above (possible value, 0-10)
Pohl score	Positive: AAR ≥ 1 and platelet count < 150 × 10⁹/L
FIB-4 index	[Age (yr) × AST (U/L)]/[platelet count (10⁹/L) × ALT (U/L) 1/2]
Lok’s model	Log odds (predicting cirrhosis) = -5.56 to 0.0089 × platelet (× 10³/mm³) + 1.26 × AST/ALT ratio + 5.27 × PT INR Predicted probability = exp (log odds)/[1 + exp (log odds)]

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; AAR: AST/ALT ratio; APRI: AST-to-platelet ratio index; API: Age-platelet index; CDS: Cirrhosis discriminant score; ULN: Upper limit of normal; PLT: Posterolateral thoracotomy; PT-INR: Prothrombin time international normalized ratio.

Table 2 Clinical characteristics of 237 patients with chronic hepatitis C

Male/female	135/102
Age (yr)	54.3 ± 11.6 (19-76)
AST (U/L)	101.2 ± 56.0 (21-348)
ALT (U/L)	156.3 ± 92.5 (24-637)
PT INR	1.049 ± 0.080 (0.88-1.34)
PLT (× 10³/μL)	170.9 ± 55.1 (60-373)
Hemoglobin (g/L)	14.4 ± 1.37 (9.0-18.0)
WBC count (x 10⁹/L)	5.85 ± 1.73 (2.8-16.7)
Creatinine (mg/dL)	0.94 ± 0.23 (1.0-2.0)
FT4 (μg/dL)	1.12 ± 0.19 (1.0-2.0)
TSH (mU/mL)	2.06 ± 2.13 (0.1-23.0)

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; PLT: Posterolateral thoracotomy; PT-INR: Prothrombin time international normalized ratio; WBC: White blood cell; FT4: Free thyroxine; TSH: Thyroid stimulating hormone.

Table 3 Correlation of histological fibrosis severity with the variables

	Bivariate Spearman’s rank correlation coefficient (95% CI)	P value
Age (yr)	0.232 (0.108-0.349)	< 0.001
AST (U/L)	0.188 (0.062-0.308)	0.004
ALT (U/L)	-0.028 (-0.155 to 0.100)	0.666
PT INR	0.337 (0.219-0.445)	< 0.001
PLT (× 10³/μL)	-0.326 (-0.435 to -0.207)	< 0.001
Hb	-0.176 (-0.297 to -0.050)	0.005
WBC	-0.053 (-0.179 to 0.075)	0.404
Cr	-0.152 (-0.274 to -0.025)	0.02
FT4	-0.167 (-0.288 to -0.040)	0.014
TSH	0.065 (-0.063 to 0.191)	0.341
Bil(T)	0.135 (0.008-0.258)	0.04
AAR	0.341 (0.223-0.449)	< 0.001
APRI	0.322 (0.203-0.431)	< 0.001
FibroQ	0.444 (0.336-0.541)	< 0.001
FIB-4	0.429 (0.319-0.528)	< 0.001
CDS	0.185 (0.059-0.305)	0.004
API	0.360 (0.244-0.466)	< 0.001
Lok’s model	0.430 (0.320-0.528)	< 0.001
Pohl score	0.144 (0.017-0.267)	0.027

We used Fisher’s Z-transform to compute asymmetric confidence limits for the Spearman's rank correlation coefficients. Hb: Hemoglobin; Bil(T): Total bilirubin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; PLT: Posterolateral thoracotomy; PT-INR: Prothrombin time international normalized ratio; WBC: White blood cell; FT4: Free thyroxine; TSH: Thyroid stimulating hormone; AAR: AST/ALT ratio; APRI: AST-to-platelet ratio index; API: Age-platelet index; CDS: Cirrhosis discriminant score.

Table 4 Correlation between fibrosis score and aspartate aminotransferase-to-platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, and FibroQ, FIB-4, cirrhosis discriminant score, age-platelet index, Lok’s model, Pohl score

Metavir fibrosis score	F1	F2	F3	F4
Patient number (%)	41 (17.3)	85 (35.9)	98 (41.4)	13 (5.5)
AAR	0.566 ± 0.162^c^e	0.673 ± 0.250	0.749 ± 0.222	0.776 ± 0.175
APRI	1.433 ± 1.040^a	1.919 ± 1.904	2.320 ± 1.390	2.508 ± 1.102
FibroQ	1.485 ± 0.855^gⁱ	2.532 ± 1.660^m	3.563 ± 2.056	3.581 ± 1.812
FIB-4	1.79 ± 1.13^gⁱ^m	2.79 ± 2.03	3.75 ± 1.97	3.82 ± 1.57
CDS	5.61 ± 1.16	5.69 ± 1.19	6.14 ± 1.12	6.15 ± 1.41
API	3.95 ± 2.06^gⁱ^m	5.25 ± 2.24	6.40 ± 2.29	6.15 ± 1.63
Lok’s model	0.22 ± 0.12^k^m^o	0.32 ± 0.18	0.43 ± 0.19	0.46 ± 0.18
Pohl score	0	0.01 ± 0.11	0.08 ± 0.28	0.04 ± 0.19

^aP < 0.05, F1 vs F3;

^cP < 0.01, F1 vs F3;

^eP < 0.05, F1 vs F4;

^gP < 0.05, F1 vs F2;

ⁱP < 0.01, F1 vs F3 and F4;

^kP < 0.01, F1 vs F2, F3 and F4;

^mP < 0.01, F2 vs F3;

^oP < 0.05, F2 vs F4. AAR: AST/ALT ratio; APRI: AST-to-platelet ratio index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; API: Age-platelet index; CDS: Cirrhosis discriminant score.

Table 5 Performance of simple fibrosis prediction tests for significant fibrosis (F2, F3 and F4) and extensive fibrosis (F3 and F4)

Metavir fibrosis score vs	AUC (F2, F3, F4)(95% CI)	AUC (F3, F4)(95% CI)
AAR	0.709 (0.626-0.792)	0.675 (0.607-0.743)
APRI	0.651 (0.566-0.736)	0.681 (0.613-0.749)
FibroQ	0.789 (0.720-0.857)	0.728 (0.662-0.793)
FIB-4	0.785 (0.686-0.830)	0.725 (0.659-0.791)
CDS	0.580 (0.485-0.674)	0.609 (0.537-0.680)
API	0.739 (0.660-0.818)	0.696 (0.628-0.764)
Lok’s model	0.768 (0.695-0.840)	0.721 (0.656-0.786)
Pohl score	0.523 (0.429-0.617)	0.532 (0.458-0.606)

AAR: AST/ALT ratio; APRI: AST-to-platelet ratio index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; API: Age-platelet index; CDS: Cirrhosis discriminant score; AUC: Area under the receiver operating characteristic curve.

Table 6 Diagnostic accuracy of simple fibrosis prediction tests for significant and extensive fibrosis

Score	Cut-off value	(%)	Significant fibrosis (F2, F3 and F4)				Extensive fibrosis (F3 and F4)
Score	Cut-off value	(%)	Sen	Spe	PPV	NPV	Sen	Spe	PPV	NPV
FibroQ	> 0.6	94.9	96.4	12.2	84.0	41.7	97.3	7.14	48.0	75.0
	> 1.2	79.7	85.7	48.8	88.9	41.7	90.1	29.4	52.9	77.1
	> 1.4	74.3	80.1	53.7	89.2	36.1	86.5	36.5	54.5	75.4
	> 1.6	70.0	77.6	65.9	91.6	38.0	85.6	43.7	57.2	77.5
	> 1.8	66.2	74.0	70.7	92.4	36.3	83.8	49.2	59.2	77.5
	> 2.0	60.8	69.4	80.5	94.4	35.5	82.0	57.9	63.2	78.5
	> 2.6	44.3	51.0	87.8	95.2	27.3	64.9	73.8	68.6	70.5
AAR	> 0.4	97.0	95.4	12.2	83.9	35.7	96.4	7.1	47.8	69.2
	> 0.6	61.2	67.9	70.7	91.7	31.5	77.5	53.2	59.3	72.8
	> 0.8	28.7	31.6	85.4	91.2	20.7	36.9	78.6	60.3	58.6
	> 1.0	6.8	8.16	100	100	18.5	10.8	96.8	75.0	55.2
APRI	> 0.5	95.8	96.9	9.7	83.7	40.0	99.1	7.1	48.5	90.0
	> 1	72.6	75.5	41.5	86.0	26.2	87.4	40.5	56.4	78.5
	> 1.5	54.0	56.6	58.5	86.7	22.0	69.4	59.5	60.2	68.8
	> 2	39.7	45.4	87.8	94.7	25.2	55.0	73.8	64.9	65.0
CDS	> 5	88.6	88.8	12.2	82.9	18.5	92.8	15.1	49.0	70.4
	> 6	63.7	66.3	48.8	86.1	23.3	73.9	45.2	54.3	66.3
	> 7	29.1	30.6	78.0	87.0	19.0	34.2	75.4	55.1	56.5
	> 8	8.9	9.7	95.1	90.5	18.1	12.6	94.4	66.7	55.1
API	> 4	75.9	81.6	51.2	88.9	36.8	87.4	34.1	53.9	75.4
	> 5	67.1	73.5	63.4	90.6	33.3	82.0	46.0	57.2	74.4
	> 6	57.4	63.3	70.7	91.2	28.7	74.8	57.9	61.0	72.3
	> 7	39.7	46.4	92.7	96.8	26.6	56.8	75.4	67.0	66.4
Pohl score	Positive	3.8	4.59	100	100	18.0	7.2	99.2	88.9	54.8
FIB-4	> 1.45	75.5	81.6	53.7	89.4	37.9	87.4	34.9	54.2	75.9
	> 2	62.0	69.4	73.2	92.5	33.3	81.1	54.8	61.2	76.7
	> 2.5	53.6	61.2	82.9	94.5	30.9	74.8	65.1	65.4	74.5
	> 3	46.0	52.6	85.4	94.5	27.3	66.7	72.2	67.9	71.1
	> 3.25	40.9	47.4	90.2	95.9	26.4	61.3	77.0	70.1	69.3
Lok’s model	> 0.2	74.7	81.6	58.5	90.4	40.4	88.3	37.3	55.4	78.3
	> 0.4	35.0	40.8	92.7	96.4	24.7	51.4	79.4	68.7	64.9
	> 0.5	24.1	28.6	97.6	98.2	22.2	37.8	88.1	73.7	61.7

AAR: AST/ALT ratio; APRI: AST-to-platelet ratio index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; API: Age-platelet index; CDS: Cirrhosis discriminant score; Sen: Sensitivity; Spe: Specificity; PPV: Positive predictive value; NPV: Negative predictive value.

Citation: Hsieh YY, Tung SY, Lee K, Wu CS, Wei KL, Shen CH, Chang TS, Lin YH. Routine blood tests to predict liver fibrosis in chronic hepatitis C. World J Gastroenterol 2012; 18(8): 746-753
URL: https://www.wjgnet.com/1007-9327/full/v18/i8/746.htm
DOI: https://dx.doi.org/10.3748/wjg.v18.i8.746