Usefulness of autotaxin for the complications of liver cirrhosis

Table 1 Base clinical characteristics

Characteristics	Value
Number of patients, n	400
Age, yr	68.4 ± 11.4
Gender: Male, n (%)	240 (60.0)
Weight, kg	62.8 ± 13.3
Body mass index, kg/m2	24.0 ± 4.11
Aetiology: HCV/HBV/Alcohol/NASH/AIH/PBC/etc., n	130/50/108/60/18/9/25
HCV: SVR/non-SVR, n	84/46
Liver cancer, n (%)	84 (21)
Diabetes mellitus, n (%)	124 (31.0)
Hypertension, n (%)	120 (30.0)
Compensated/Decompensated, n	213/187
Hepatic ascites, n (%)	131 (32.8)
Hepatic encephalopathy, n (%)	103 (25.8)
Varicose vein rupture, n (%)	35 (8.8)
Child-Pugh score	6.62 ± 1.88
Child-Pugh class A/B/C, n	232/127/41
MELD-score	7.16 ± 4.48
ALBI score	-2.29 ± 0.68
White blood cells, /μL	4845 ± 3609
Hemoglobin, g/dL	12.5 ± 2.29
Platelets, × 104/μL	12.1 ± 6.53
Prothrombin time, %	75.9 ± 20.2
Serum albumin, g/dL	3.66 ± 0.72
Blood urea nitrogen, mg/dL	17.4 ± 9.9
Serum creatinine, mg/dL	0.97 ± 0.68
Aspartate aminotransferase, IU/L	39.4 ± 23.5
Alanine aminotransferase, IU/L	28.1 ± 18.7
Total bilirubin, mg/dL	1.25 ± 0.97
Serum sodium, mEq/L	139 ± 2.75
Hemoglobin A1c, %	5.94 ± 1.18
Total cholesterol, mg/dL	176 ± 40.8
Branched chain amino acid	4.97 ± 2.24
Ammonia, μg/dL	52.3 ± 40.9
Alpha-fetoprotein, ng/mL	54.4 ± 564

Data are expressed as mean, number (%), or mean ± SD. A total of 400 patients with liver cirrhosis were enrolled. The mean age was 68.4 ± 11.4 years, 240 patients (60.0%) were male, and 84 patients (21.0%) had liver cancer. The mean body weight was 62.8 ± 13.3 kg, and the mean body mass index was 24.0 ± 4.11. A total of 213 (53.3%) and 187 (46.8%) patients were compensated and decompensated, respectively. The numbers (and proportions) of decompensated liver cirrhosis in varix rupture, hepatic ascites, and hepatic encephalopathy were 35 (8.8%), 131 (32.8%), and 103 (25.8%), respectively. HBV: Hepatitis B virus; HCV: Hepatitis C virus; NASH: Non-alcoholic steatohepatitis; AIH: Autoimmune hepatitis; PBC: Primary biliary cholangitis; MELD: Model for end-stage liver disease; SVR: Sustained virologic response.

Table 2 Area under the receiver operator characteristic curves

Item	Parameter	Male	Female
		AUC (95%CI)	AUC (95%CI)
Hepatic encephalopathy	ATX	0.853 (0.795-0.911)	0.759 (0.658-0.860)
	MELD	0.644 (0.563-0.725)	0.727 (0.640-0.814)
	Fib 4 index	0.651 (0.568-0.734)	0.674 (0.538-0.789)
	APRI	0.670 (0.590-0.750)	0.640 (0.516-0.778)
	ALBI	0.825 (0.757-0.893)	0.815 (0.685-0.811)
Hepatic ascites	ATX	0.816 (0.756-0.877)	0.717 (0.616-0.819)
	MELD	0.640 (0.560-0.720)	0.744 (0.665-0.823)
	Fib 4 index	0.654 (0.569-0.738)	0.653 (0.540-0.765)
	APRI	0.663 (0.581-0.744)	0.633 (0.520-0.746)
	ALBI	0.863 (0.807-0.918)	0.787 (0.690-0.878)
Varix rupture	ATX	0.706 (0.558-0.855)	0.697 (0.512-0.882)
	MELD	0.514 (0.386-0.643)	0.612 (0.413-0.810)
	Fib 4 index	0.619 (0.462-0.775)	0.566 (0.299-0.833)
	APRI	0.653 (0.474-0.833)	0.579 (0.333-0.826)
	ALBI	0.608 (0.449-0.768)	0.614 (0.524-0.803)

The area under the receiver operating characteristic curves of autotaxin in men were higher than those in women and higher than those using other biomarkers for detecting encephalopathy and varix rupture. ATX: Autotaxin; Fib-4: Fibrosis-4; ALBI: Albumin-bilirubin index; MELD: Model for end-stage liver disease; APRI: Aspartate aminotransferase-to-platelet ratio index. AUC: Area under the receiver operating characteristic curve; CI: Confidence interval.

Table 3 Correlation between autotaxin and clinical characteristics

Characteristics	Male		Female
	r	P value	r	P value
Serum biomarker
MELD-score	0.293	0.001	0.211	0.040
Fibrosis 4 index	0.470	< 0.001	0.335	< 0.001
APRI	0.438	0.001	0.414	< 0.001
ALBI	0.614	< 0.001	0.452	< 0.001
Clinical laboratory data
White blood cells	-0.123	0.057	-0.130	0.102
Hemoglobin	-0.260	0.001	-0.268	0.001
Platelets	-0.289	0.001	-0.308	0.001
Prothrombin time	-0.443	< 0.001	-0.279	0.001
Serum albumin	-0.539	< 0.001	-0.451	< 0.001
Blood urea nitrogen	-0.093	0.152	-0.123	0.716
Serum creatinine	-0.036	0.580	-0.139	0.387
Aspartate aminotransferase	0.443	0.001	0.329	0.001
Alanine aminotransferase	0.225	0.022	0.249	0.001
Total bilirubin	0.538	< 0.001	0.300	0.001
Serum sodium	-0.282	0.001	-0.192	0.015
Hemoglobin A1c	-0.151	0.109	-0.094	0.282
Total cholesterol	-0.244	0.001	-0.231	0.001
BTR	-0.596	0.004	-0.298	0.003
Branched chain amino acid	-0.338	0.001	-0.260	0.374
Tyrosine	0.585	< 0.001	0.455	< 0.001
Ammonia	0.369	< 0.001	0.407	< 0.001
Alpha-fetoprotein	0.074	0.269	-0.051	0.549

The model for end-stage liver disease score, Fibrosis-4 index, aspartate aminotransferase-to-platelet ratio index, and albumin-bilirubin index (ALBI) score were correlated with the autotoxin level in both men and women. The correlation coefficient between ALBI and autotaxin in men was strong. Fib-4: Fibrosis-4; ALBI: Albumin-bilirubin index; MELD: Model for end-stage liver disease; APRI: Aspartate aminotransferase-to-platelet ratio index; BTR: Branched-chain amino acid and tyrosine ratio.