Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease

Table 1 Correlation between degree of liver fibrosis and clinical and laboratory data (n = 112).

Clinical/laboratory data	Degree of liver fibrosis
	Portal/Septal	Pericellular	Fibrosis stage
Age (yr)	0.265 (P = 0.005)	0.172 (P = 0.07)	0.302 (P = 0.001)
BMI	0.220 (P = 0.020)	0.236 (P = 0.012)	0.238 (P = 0.011)
Platelet	-0.331 (P<0.001)	-0.133 (P = 0.2)	-0.298 (P = 0.001)
Albumin	-0.295 (P = 0.002)	-0.078 (P = 0.4)	-0.291 (P = 0.002)
AST	0.306 (P = 0.001)	0.384 (P P<0.001)	0.340 (P<0.001)
AST/ALT	0.458 (P<0.001)	0.420 (P P<0.001)	0.438 (P<0.001)
IgG (n=100)	0.261 (P =0.009)	0.141 (P = 0.1)	0.208 (P = 0.038)
IgA (n=94)	0.281 (P<0.006)	0.285 (P = 0.005)	0.291 (P = 0.004)
IgM (n=100)	0.256 (P =0.010)	0.188 (P = 0.06)	0.266 (P = 0.008)
Type IV Ccollagen 7S	0.580 (P<0.001)	0.516 (P<0.001)	0.607 (P<0.001)
Hyaluronic acid	0.543 (P<0.001)	0.387 (P<0.001)	0.553 (P<0.001)
Ferritin (n = 98)	0.205 (P = 0.043)	0.120 (P = 0.2)	0.252 (P = 0.012)
HbA1c (n = 96)	0.309 (P = 0.002)	0.211 (P = 0.039)	0.315 (P = 0.002)
FFA (n = 80)	0.238 (P = 0.033)	0.271 (P = 0.015)	0.276 (P = 0.013)
HOMA-R (n = 82)	0.224 (P = 0.043)	0.164 (P = 0.1)	0.222 (P = 0.045)

Table 2 Comparison between patients with fatty liver and with NASH (mean±SD).

	Fatty liver alone	NASH	P value
Number	42	70
Age (yr)	45.2±13.6	53.8±14.4	0.002
Gender (female)	22 (52.4%)	54 (77.1%)	0.012
BMI	28.2±4.9	29.6±5.2	NS
Diabetes mellitus (%)	8 (19.0%)	26 (37.1%)	0.044
Platelet count (±104/mL)	23.8±4.8	21.1±6.8	0.036
Prothrombin time (%)	98.5±11.1	91.6±13.6	0.009
Albumin (g/dL)	4.4±0.3	4.3±0.4	0.01 7
AST (IU/L)	56.7±30.8	87.5±48.1	<0.001
ALT (IU/L)	110.1±68.2	117.1±65.1	NS
AST/ALT ratio	0.56±0.2	0.82±0.4	<0.001
GGT (IU/L)	124.9±96.6	106.2±129.3	NS
IgG (mg/dL)	1 377.1±366.7	1 526.9±423.3	NS
IgA (mg/dL)	313.1±191.3	356.9±134.1	NS
IgM (mg/dL)	124.2±47.9	162.8±82.4	0.004
Type IV collagen 7S (ng/mL)	4.1±0.9	6.0±2.0	<0.001
Hyaluronic acid (ng/mL)	29.0±20.0	103.4±116.8	<0.001
Fasting glucose (mg/dL)	107.8±34.4	120.2±51.8	NS
HbA1c (%)	5.4±1.0	6.2±1.7	0.005
Ferritin (ng/mL)	151.7±107.0	351.5±455.7	0.001
FFA (mEq/L)	0.6±0.2	0.7±0.3	0.022
HOMA-R	5.1±6.3	6.0±6.6	NS

Table 3 Comparison between NAFLD patients with stage 0-2 fibrosis and those with stage 3 and 4 fibrosis (mean±SD).

	Stages 0-2 fibrosis	Stages 3,4 fibrosis	P value
Number	64	48
Age (yr)	47.8±14.5	54.3±14.0	0.02
Gender (female)	38 (59.4%)	38 (79.2%)	0.04
BMI	28.3±4.8	30.1±5.4	NS
Diabetes mellitus (%)	15 (23.4%)	19 (39.6%)	NS
Platelet count (±104/mL)	23.8±5.1	20.3±7.1	0.004
Prothrombin time (%)	96.9±11.1	90.1±14.7	0.018
Albumin (g/dL)	4.4±0.3	4.3±0.4	0.03
AST (IU/L)	67.0±37.5	87.9±51.2	0.02
ALT (IU/L)	113.1±65.2	116.3±67.9	NS
AST/ALT ratio	0.66±0.4	0.82±0.3	0.015
GGT (IU/L)	133.5±141.6	85.7±66.6	0.019
IgG (mg/dL)	1 408.1±367.0	1 555.5±446.4	NS
IgA (mg/dL)	316.3±172.3	371.0±133.5	NS
IgM (mg/dL)	137.2±79.1	163.8±64.9	NS
Type IV collagen 7S (ng/mL)	4.6±1.5	6.3±2.0	<0.001
Hyaluronic acid (ng/mL)	50.4±74.3	108.8±118.7	0.004
Fasting glucose (mg/dL)	115.1±49.4	116.6±43.1	NS
HbA1c (%)	5.6±1.2	6.4±1.9	0.01
Ferritin (ng/mL)	253.8±52.6	320.1±373.0	NS
FFA (mEq/L)	0.6±0.3	0.8±0.3	0.007
HOMA-R	5.7±5.8	5.8±4.6	NS

Table 4 Diagnostic accuracy of the markers of liver fibrosis for NASH.

	ROC analysis		Cutoff value	Accuracy
	AUC (95% CI)	P value		Se (%)	Sp (%)	PPV (%)	NPV (%)
(a) Type IV collagen 7S	0.828 (0.754-0.902)	0.000	≥5.0 ng/mL	70.0	81.0	86.0	61.8
(b) Hyaluronic acid	0.797 (0.716-0.879)	0.000	≥43 ng/mL	65.7	90.5	92.0	61.3
Combination of Markers			a≥5.0 ng/mL	87.1	73.8	84.7	77.5
			or b≥43 ng/mL
			a≥5.0 ng/mL	48.6	97.6	97.1	53.2
			and b≥43 ng/mL

Abbreviations: ROC, receiver operating characteristic; AUC, area under the ROC curve; CI, confidence interval; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value.

Table 5 Diagnostic accuracy of the markers of liver fibrosis for severe fibrosis.

	ROC analysis		Cutoff value	Accuracy
	AUC (95% CI)	P value		Se (%)	Sp (%)	PPV (%)	NPV (%)
(a) Type IV collagen 7S	0.817 (0.736-0.897)	0.000	≥5.0 ng/mL	81.3	71.4	68.4	83.6
(b) Hyaluronic acid	0.797 (0.652-0.845)	0.000	≥50 ng/mL	68.8	82.8	75.0	77.9
Combination of Markers			a≥5.0 ng/mL	95.8	62.5	65.7	95.2
			or b≥50 ng/mL
			a≥5.0 ng/mL	54.2	92.2	83.9	72.8
			and b≥50 ng/mL

Abbreviations: ROC, receiver operating characteristic; AUC, area under the ROC curve; CI, confidence interval; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value.