Serum autotaxin levels are correlated with hepatic fibrosis and ballooning in patients with non-alcoholic fatty liver disease

Table 1 Clinicopathological features of 186 patients with non-alcoholic fatty liver disease

	All (n = 186)	Male (n = 80)	Female (n = 106)
	Median (IQR)/n	Median (IQR)/n	Median (IQR)/n	P value1
Age (yr)	56 (46-65)	50 (38-59)	61 (54-66)	< 0.001
BMI (kg/m2)	26.2 (23.8-29.6)	26.1 (24.3-29.4)	26.5 (23.6-29.7)	NS
Laboratory data
Albumin (g/dL)	4.5 (4.3-4.7)	4.6 (4.4-4.8)	4.4 (4.2-4.7)	< 0.001
T-bil (mg/dL)	0.87 (0.69-1.17)	0.94 (0.74-1.26)	0.81 (0.67-1.07)	< 0.05
AST (IU/L)	41 (30-65)	39 (30-62)	42 (30-69)	NS
ALT (IU/L)	63 (38-97)	68 (43-103)	53 (33-89)	NS
γ-GT (IU/L)	54 (35-92)	64 (43-99)	50 (32-81)	< 0.05
TG (mg/dL)	122 (92-159)	122 (91-159)	121 (95-159)	NS
LDL-C (mg/dL)	130 (107-151)	132 (105-154)	130 (109-149)	NS
HDL-C (mg/dL)	51 (44-60)	48 (44-56)	55 (47-63)
Plt (× 104/μL)	23.1 (18.5-26.8)	23.0 (19.6-26.7)	23.3 (17.6-26.9)	NS
HbA1c (%)	5.9 (5.7-6.6)	5.9 (5.6-6.5)	5.9 (5.7-6.6)	NS
FBG (mg/dL)	108 (98-121)	108 (98-121)	108 (97-121)	NS
IRI (mU/L)	11.2 (7.2-16.7)	10.5 (6.8-16.3)	11.5 (7.4-17.2)	NS
HOMA-IR	3.0 (1.9-4.6)	2.9 (1.8-4.5)	3.2 (2.0-4.7)	NS
Fe (μg/dL)	111 (90-137)	120 (92-146)	104 (88-129)	< 0.05
Ferritin (ng/mL)	146 (79-274)	172 (126-293)	113 (58-236)	< 0.001
AFP (ng/mL)	3.2 (2.2-4.8)	2.8 (2.1-4.0)	3.4 (2.6-5.2)	< 0.01
Fibrosis markers
HA (ng/mL)	51 (28-91)	41 (25-62)	63 (34-118)	< 0.001
4C7S (ng/mL)	4.6 (3.8-5.7)	4.5 (3.8-5.5)	4.7 (3.8-6.6)	NS
FIB-4	1.35 (0.94-2.18)	1.12 (0.77-1.88)	1.53 (1.13-2.51)	< 0.001
APRI	0.69 (0.46-1.13)	0.66 (0.44-1.03)	0.71 (0.46-1.25)	NS
Histological findings
Steatosis (1/2/3)	57/90/39	24/41/15	33/49/24	NS
Lobular inflammation (0/1/2/3)	9/101/69/7	6/48/23/3	3/53/46/4	< 0.05
Ballooning (0/1/2)	43/98/45	22/44/14	21/54/31	NS
Fibrosis (0/1/2/3/4)	35/89/19/34/9	16/43/8/13/0	19/46/11/21/9	NS

¹Comparison between male and female subjects. IQR: Interquartile range; BMI: Body mass index; T-bil: Total bilirubin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γ-GT: Gamma-glutamyltransferase; TG: Triglyceride; LDL-C: Low density lipoprotein cholesterol; HDL-C: High density lipoprotein cholesterol; Plt: Platelet; FBG: Fasting blood glucose; IRI: Immunoreactive insulin; HOMA-IR: Homeostasis model assessment of insulin resistance; AFP: Alpha-fetoprotein; HA: Hyaluronic acid; 4C7S: Type 4 collagen•7S; FIB-4: Fibrosis-4 index; APRI: AST to platelet ratio; NS: Not significant.

Table 2 Correlation between autotaxin and clinicopathological findings

	All (n = 186)		Male (n = 80)		Female (n = 106)
	r	P value	r	P value	r	P value
Age (yr)	0.48	< 0.001	0.45	< 0.001	0.28	< 0.01
BMI (kg/m2)	0.18	< 0.05	0.06	NS	0.31	< 0.01
Platelet (× 104/μL)	-0.32	< 0.001	-0.28	< 0.05	-0.43	< 0.001
Albumin (g/dL)	-0.32	< 0.001	-0.10	NS	-0.31	< 0.01
AST (IU/L)	0.31	< 0.001	0.34	< 0.01	0.40	< 0.001
ALT (IU/L)	0.06	NS	0.14	NS	0.24	< 0.05
TG (mg/dL)	-0.09	NS	-0.14	NS	-0.08	NS
LDL-C (mg/dL)	-0.04	NS	-0.01	NS	-0.06	NS
HDL-C (mg/dL)	0.13	NS	-0.04	NS	-0.04	< 0.001
FBG (mg/dL)	0.22	< 0.01	0.36	0.001	0.21	< 0.05
IRI (mU/L)	0.20	< 0.01	0.15	NS	0.31	0.002
HOMA-IR	0.22	< 0.01	0.22	< 0.05	0.31	0.001
Fe (μg/dL)	0.09	NS	0.12	NS	0.35	< 0.001
Ferritin (ng/mL)	0.04	NS	0.22	NS	0.31	0.002
HA (ng/mL)	0.49	< 0.001	0.47	< 0.001	0.46	< 0.001
4C7S (ng/mL)	0.40	< 0.001	0.30	< 0.01	0.50	< 0.001
FIB-4	0.58	< 0.001	0.51	< 0.001	0.60	< 0.001
APRI	0.43	< 0.001	0.45	< 0.001	0.55	< 0.001
Histological findings
Steatosis score	0.02	NS	0.12	NS	-0.03	NS
Lobular inflammation score	0.22	< 0.01	0.06	NS	0.25	< 0.01
Ballooning score	0.36	< 0.001	0.34	< 0.01	0.38	< 0.001
NAS	0.27	< 0.001	0.27	< 0.05	0.26	< 0.01
Fibrosis stage	0.45	< 0.001	0.44	< 0.001	0.53	< 0.001

Correlations were calculated using Spearman’s test. ATX: Autotaxin; BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; TG: Triglyceride; LDL-C: Low density lipoprotein cholesterol; HDL-C: High density lipoprotein cholesterol; FBG: Fasting blood glucose; IRI: Immunoreactive insulin; HOMA-IR: Homeostasis model assessment of insulin resistance; HA: Hyaluronic acid; 4C7S: Type 4 collagen•7S; FIB-4: Fibrosis-4 index; APRI: AST to platelet ratio; NAS: NAFLD activity score; NS: Not significant.

Table 3 Diagnostic performance of autotaxin for predicting liver fibrosis stage in patients with non-alcoholic fatty liver disease

	Cut off	AUC	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)
All patients
≥ F1	0.73	0.71	77	57	89	36	73
≥ F2	1.19	0.75	45	94	80	77	78
≥ F3	1.19	0.75	51	91	63	86	82
F4	1.20	0.87	78	85	21	99	84
Male
≥ F1	0.70	0.73	58	94	97	36	65
≥ F2	0.71	0.75	81	68	47	91	71
F3	0.82	0.74	62	82	40	92	79
Female
≥ F1	1.03	0.76	53	95	98	31	60
≥ F2	1.19	0.80	66	91	82	81	81
≥ F3	1.19	0.78	73	86	67	89	82
F4	1.20	0.78	78	74	22	97	75

ATX: Autotaxin; AUC: Area under the receiver operating characteristic curve; PPV: Positive predictive value; NPV: Negative predictive value.

Table 4 Diagnostic performance of autotaxin and conventional fibrosis indicators for predicting severe fibrosis (≥ F3) in patients with non-alcoholic fatty liver disease

	AUC	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)
All patients
ATX	0.75	51	91	63	86	82
HA	0.82	93	63	44	96	70
4C7S	0.87	75	88	64	92	85
APRI	0.82	60	89	62	88	82
FIB-4	0.85	79	74	48	92	75
Male
ATX	0.74	62	82	40	92	79
HA	0.76	85	72	41	95	75
4C7S	0.81	69	89	56	94	86
APRI	0.74	77	64	29	93	66
FIB-4	0.81	92	75	41	98	78
Female
ATX	0.78	73	86	67	89	82
HA	0.86	78	86	68	91	83
4C7S	0.89	78	90	75	92	87
APRI	0.86	63	95	83	87	86
FIB-4	0.85	80	75	56	90	76

AUC: Area under the receiver operating characteristic curve; PPV: Positive predictive value; NPV: Negative predictive value; ATX: Autotaxin; HA: Hyaluronic acid; 4C7S: Type 4 collagen•7S; APRI: AST to platelet ratio; FIB-4: Fibrosis-4 index.