Declining diagnostic accuracy of non-invasive fibrosis tests is associated with elevated alanine aminotransferase in chronic hepatitis B

doi:10.12998/wjcc.v6.i12.521

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World Journal of Clinical Cases

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

Retrospective Study

World J Clin Cases. Oct 26, 2018; 6(12): 521-530
Published online Oct 26, 2018. doi: 10.12998/wjcc.v6.i12.521

Table 1 Baseline characteristics of the subjects

Characteristics	Total group(n = 599)	ALT ≤ 40 group (n = 272)	40 < ALT ≤ 80group (n = 190)	ALT > 80 group(n = 137)	P-value
Age (yr)	37 (29, 44)	39 (31.25, 46)	37.5 (28, 43.25)	34 (28, 40.5)	< 0.001
Male (%)	349 (58.3)	131 (48.2)	130 (68.4)	88 (64.2)	< 0.001
ALT (U/L)	44 (28, 76)	26 (31, 33)	56 (48, 66)	127 (95, 218.5)	< 0.001
AST (U/L)	32 (24, 48)	24 (20, 28)	36 (31, 42)	70 (55, 115.5)	< 0.001
GGT (U/L)	25 (17, 41)	19 (14, 25)	30 (20, 41.25)	48 (30, 78)	< 0.001
Cholesterol (mmol/L)	4.31 (3.84, 4.96)	4.35 (3.86, 4.95)	4.24 (3.75, 4.95)	4.34 (3.84, 4.99)	0.732
PLT (10⁹/L)	182 (150, 217)	184 (155, 223)	177.5 (145.5, 212)	180 (149, 215)	0.215
INR	1 (1, 1.1)	1 (1, 1.1)	1 (0.99, 1.1)	1 (0.94, 1.1)	0.4
HBV DNA (log₁₀IU/mL)	7.03 (4.24, 8.23)	4.77 (3.32, 7.78)	7.64 (5.72, 8.23)	8.03 (6.81, 8.23)	< 0.001
S (%)
S0	264 (44.1)	128 (47.1)	80 (42.1)	56 (40.9)
S1	147 (24.5)	73 (26.8)	53 (27.9)	21 (15.3)
S2	96 (16)	35 (12.9)	29 (15.3)	32 (23.4)
S3	54 (9)	19 (7.0)	18 (9.5)	17 (12.4)
S4	38 (6.3)	17 (6.3)	10 (5.3)	11 (8.0)
Stage S0-1 fibrosis	411 (68.6)	201 (73.9)	133 (70)	77 (56.2)	0.001
Stage S2-4 fibrosis	188 (31.4)	71 (26.1)	57 (30)	60 (43.8)
APRI	0.53 (0.38,0.86)	0.38 (0.3, 0.49)	0.61 (0.44,0.8)	1.16 (0.88, 1.93)	< 0.001
FIB-4	1.02 (0.72,1.47)	1.02 (0.72,1.37)	0.96 (0.66,1.55)	1.22 (0.82, 1.79)	< 0.001
GPR	0.22 (0.15,0.38)	0.16 (0.11, 0.23)	0.24 (0.17,0.38)	0.42 (0.25, 0.68)	< 0.001
King’s score	6.77 (4.31,11.49)	4.89 (3.54,7.03)	7.18 (4.58,11.58)	13.04 (9.81, 27.15)	< 0.001
Forns index	6.48 (5.44,7.51)	6.33 (5.37,7.37)	6.57 (5.51,7.69)	6.65 (5.57, 7.57)	0.081

Data are expressed as the n (%) or median (interquartile range, IQR). ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; PLT: Platelet; S: Stage of fibrosis; GPR: Gamma-glutamyl transpeptidase (GGT)-to-platelet ratio; APRI: Aspartate aminotransferase (AST)-to-platelet (PLT) ratio index; FIB-4: Fibrosis index based on 4 factors; INR: International sensitivity index.

Table 2 Fibrosis scores of the non-invasive tests for liver fibrosis stages in the different alanine aminotransferase groups

Characteristics	APRI	FIB-4	GPR	King’s score	Forns index
S0 (n)
ALT ≤ 40 (128) 40 < ALT ≤ 80 (80) ALT > 80 (56) P-value	0.37 (0.26-0.44) 0.51 (0.39-0.68) 1.02 (0.85-1.5) < 0.001	0.88 (0.65-1.26) 0.77 (0.57-1.15) 0.97 (0.74-1.52) 0.019	0.15 (0.1-0.2) 0.22 (0.14-0.31) 0.29 (0.22-0.48) < 0.001	4.3 (3.09-5.89) 5.91 (4.1-8.08) 11.62 (7.99-18.36) < 0.001	6.06 (5.04-7.03) 6.16 (4.91-7.04) 6.27 (5.36-7.26) 0.5
S1 (n)
ALT ≤ 40 (73) 40 < ALT ≤ 80 (53) ALT > 80 (21) P-value	0.36 (0.3-0.44) 0.52 (0.42-0.72) 0.94 (0.65-1.68) < 0.001	0.92 (0.7-1.29) 0.82 (0.58-1.28) 1.1 (0.85-1.36) 0.177	0.13 (0.1-0.19) 0.23 (0.19-0.32) 0.55 (0.23-0.89) < 0.001	4.59 (3.54-6.42) 6.55 (4.11-9.67) 11.7 (8.58-21.25) < 0.001	5.9 (5.24-6.99) 6.04 (5.34-7.32) 6.95 (6.06-7.54) 0.098
S2 (n)
ALT ≤ 40 (35) 40 < ALT ≤ 80 (29) ALT > 80 (32) P-value	0.44 (0.37-0.58) 0.76 (0.66-0.93) 1.32 (0.87-2.15) < 0.001	1.2 (0.8-1.54) 1.34 (0.98-1.83) 1.24 (0.82-1.73) 0.472	0.2 (0.12-0.34) 0.32 (0.21-0.54) 0.45 (0.25-1.09) < 0.001	5.88 (4.26-9.25) 10.9 (7.6-13.85) 12.42 (9.95-28.94) < 0.001	6.79 (5.97-8.06) 7.55 (6.41-8.1) 6.5 (5.41-7.67) 0.111
S3 (n)
ALT ≤ 40 (19) 40 < ALT ≤ 80 (18) ALT > 80 (17) P-value	0.49 (0.38-0.74) 0.81 (0.73-0.98) 1.95 (1.35-5.32) < 0.001	1.2 (0.9-1.62) 1.57 (1.18-2.11) 2.23 (1.47-2.81) 0.023	0.34 (0.17-0.44) 0.46 (0.22-0.57) 0.89 (0.46-1.57) 0.001	7.28 (4.44-9.28) 11.8 (9.59-16.76) 28.37 (18.46-48.99) < 0.001	7.48 (6.4-8.01) 7.99 (7.01-8.79) 7.38 (6.32-9.15) 0.538
S4 (n)
ALT ≤ 40 (17) 40 < ALT ≤ 80 (10) ALT > 80 (11) P-value	0.57 (0.49-0.73) 0.67 (0.6-0.85) 1.95 (1.09-3.37) < 0.001	1.78 (1.24-2.49) 1.31 (1.09-1.45) 1.82 (0.92-3.3) 0.168	0.35 (0.18-0.58) 0.4 (0.29-0.5) 0.55 (0.46-0.94) 0.019	9.48 (6.15-14.1) 8.96 (8.26-11.96) 27.56 (12.86-45.31) 0.001	8.4 (6.35-9.3) 7.67 (6.71-8.15) 7.48 (5.77-9.11) 0.617

Data are expressed as the median (interquartile range, IQR); ALT: Alanine aminotransferase; S: Stage of fibrosis; GPR: Gamma-glutamyl transpeptidase (GGT)-to-platelet ratio; APRI: Aspartate aminotransferase (AST)-to-platelet (PLT) ratio index; FIB-4: Fibrosis index based on 4 factors.

Table 3 Areas under the receiver operating characteristics curves of the non-invasive tests for prediction of significant fibrosis, advanced fibrosis and cirrhosis in the different alanine aminotransferase groups

Tests	ALT ≤ 40			40 < ALT ≤ 80			ALT > 80
	≥ S2	≥ S3	S4	≥ S2	≥ S3	S4	≥ S2	≥ S3	S4
APRI
AUROC 95%CI P-value Diagnostic accuracy (optimized cut off)	0.746 0.676-0.815 < 0.001 75.74% (≤ 0.5) 73.90% (> 1.5)	0.795 0.716-0.873 < 0.001 -	0.833 0.744-0.922 < 0.001 93.01% (< 1.0) 93.75% (≥ 2.0)	0.79 0.727-0.854 < 0.001 62.63% (≤ 0.5) 72.63% (> 1.5)	0.751 0.678-0.824 < 0.001 -	0.626 0.519-0.732 0.182 83.68% (< 1.0) 94.21% (≥ 2.0)	0.701 0.612-0.789 < 0.001 45.99% (≤ 0.5) 66.42% (> 1.5)	0.778 0.688-0.868 < 0.001 -	0.71 0.568-0.851 0.021 42.34% (< 1.0) 77.37% (≥ 2.0)
FIB-4
AUROC 95%CI P-value Diagnostic accuracy (optimized cut off)	0.705 0.635-0.774 < 0.001 -	0.736 0.647-0.825 < 0.001 78.68% (< 1.45) 87.13% (> 3.25)	0.792 0.665-0.919 < 0.001 -	0.767 0.699-0.836 < 0.001 -	0.747 0.666-0.829 < 0.001 72.63% (< 1.45) 85.79% (> 3.25)	0.663 0.563-0.763 0.083 -	0.672 0.582-0.762 0.001 -	0.765 0.668-0.863 < 0.001 72.26% (< 1.45) 81.02% (> 3.25)	0.698 0.533-0.862 0.03 -
GPR
AUROC 95%CI P-value Diagnostic accuracy (optimized cut off)	0.755 0.684-0.826 < 0.001 81.62% (≥ 0.32)	0.814 0.737-0.892 < 0.001 87.13% (≥ 0.32)	0.799 0.69-0.907 < 0.001 93.01% (≥ 0.56)	0.726 0.648-0.803 < 0.001 71.05% (≥ 0.32)	0.732 0.633-0.83 < 0.001 70.53% (≥ 0.32)	0.723 0.607-0.839 0.018 84.74% (≥ 0.56)	0.696 0.607-00.785 < 0.001 61.31% (≥ 0.32)	0.748 0.654-0.841 < 0.001 52.55% (≥ 0.32)	0.693 0.58-0.807 0.034 65.69% (≥ 0.56)
King’s score
AUROC 95%CI P-value Diagnostic accuracy (optimized cut off)	0.75 0.685-0.816 < 0.001 77.21% (≥ 12.3)	0.773 0.689-0.857 < 0.001 -	0.831 0.733-0.929 < 0.001 94.44% (> 16.7)	0.781 0.715-0.847 < 0.001 72.11% (≥ 12.3)	0.751 0.672-0.83 < 0.001 -	0.659 0.56-0.759 0.09 87.37% (> 16.7)	0.69 0.601-0.779 0.001 43.80% (≥ 12.3)	0.784 0.694-0.874 < 0.001 -	0.719 0.577-0.862 0.016 61.31% (> 16.7)
Forns index
AUROC 95%CI P-value Diagnostic accuracy (optimized cut off)	0.731 0.661-0.8 < 0.001 33.09% (< 4.2) 68.75% (> 6.9)	0.758 0.668-0.849 < 0.001 -	0.79 0.665-0.915 < 0.001 -	0.752 0.677-0.827 < 0.001 35.79% (< 4.2) 66.84% (> 6.9)	0.754 0.66-0.848 < 0.001 -	0.708 0.587-0.829 0.027 -	0.604 0.508-0.7 0.038 46.72% (< 4.2) 58.39% (> 6.9)	0.7 0.588-0.81 0.001 -	0.662 0.485-0.838 0.076 -

ALT: Alanine aminotransferase; S: Stage of fibrosis; GPR: Gamma-glutamyl transpeptidase (GGT)-to-platelet ratio; APRI: Aspartate aminotransferase (AST)-to-platelet (PLT) ratio index; FIB-4: Fibrosis index based on 4 factors; AUROC: Areas under the receiver operating characteristics curve.

Table 4 The grading system based on the receiver operating characteristic curves of the non-invasive tests for predicting significant fibrosis, advanced fibrosis and cirrhosis in the different alanine aminotransferase groups

ALT groups	AUROC					Points	Grade
	≥ 0.8	0.750-0.800	0.700-0.750	0.650-0.70	< 0.65
ALT ≤ 40	GPR (≥ S3)	APRI (≥ S3)	APRI (≥ S2)	-	-	22	A
	APRI (S4)	FIB-4 (S4)	FIB-4 (≥ S2)
	King’s score (S4)	GPR (≥ S2)	FIB-4 (≥ S3)
		GPR (S4)	Forns index (≥ S2)
		King’s score (≥ S2)
		King’s score (≥ S3)
		Forns index (≥ S3)
		Forns index (S4)
40 < ALT ≤ 80	-	APRI (≥ S2)	FIB-4 (≥ S3)	FIB-4 (S4)	APRI (S4)	16.5	B
		APRI (≥ S3)	GPR (≥ S2)	King’s score (S4)
		FIB-4 (≥ S2)	GPR (≥ S3)
		King’s score (≥ S2)	GPR (S4)
		King’s score (≥ S3)	Forns index (S4)
		Forns index (≥ S2)
		Forns index (≥ S3)
ALT > 80	-	APRI (≥ S3)	APRI (≥ S2)	FIB-4 (≥ S2)	Forns index (≥ S2)	12.5	B
		King’s score (≥ S3)	APRI (S4)	FIB-4 (S4)
		FIB-4 (≥ S3)	GPR (≥ S3)	GPR (≥ S2)
			King’s score (S4)	GPR (S4)
			Forns index (≥ S3)	King’s score (≥ S2)
				Forns index (S4)

≥ 0.8: 2 points; 0.750-0.800: 1.5 points; 0.700-0.750: 1 point; 0.650-0.700: 0.5 points; < 0.65: 0 points; Grade A: 20-30 points; Grade B: 10-20 points; Grade C: 0-10 points. ALT: Alanine aminotransferase; S: Stage of fibrosis; GPR: Gamma-glutamyl transpeptidase (GGT)-to-platelet ratio; APRI: Aspartate aminotransferase (AST)-to-platelet (PLT) ratio index; FIB-4: Fibrosis index based on 4 factors; AUROC: Areas under the receiver operating characteristics curve.

Citation: Wang L, Fan YX, Dou XG. Declining diagnostic accuracy of non-invasive fibrosis tests is associated with elevated alanine aminotransferase in chronic hepatitis B. World J Clin Cases 2018; 6(12): 521-530
URL: https://www.wjgnet.com/2307-8960/full/v6/i12/521.htm
DOI: https://dx.doi.org/10.12998/wjcc.v6.i12.521