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

Abstract

Aim: To examine the relationship between serum autotaxin (ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease (NAFLD) patients.

Methods: One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled. Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays. Sera obtained from 160 healthy, non-obese individuals were used as controls. Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman's test. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). Cut-off values were identified by the Youden index, and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.

Results: Serum ATX levels were significantly higher in NAFLD patients than in controls (0.86 mg/L vs 0.76 mg/L, P < 0.001) and correlated significantly with ballooning score and fibrosis stage (r = 0.36, P < 0.001 and r = 0.45, P < 0.001, respectively). Such tendencies were stronger in female patients. There were no remarkable relationships between ATX and serum alanine aminotransferase, lipid profiles, or steatosis scores. The AUC values of ATX for predicting the presence of fibrosis (≥ F1), significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4), were all more than 0.70 in respective analyses.

Conclusion: Serum ATX levels may at least partially reflect histological severity in NAFLD.

Keywords: Autotaxin; Ballooning; Fibrosis; Non-alcoholic fatty liver disease.

Figure 1

Comparison of autotaxin levels between controls and all patients with non-alcoholic fatty liver disease (A) and according to gender (B). The box plot shows the interquartile range, 95% confidence interval, and median. The difference between each group was tested with the Mann Whitney U test. ^eP < 0.001. ATX: Autotaxin; NAFLD: Non-alcoholic fatty liver disease.

Figure 2

Relationship between autotaxin and histological grade in non-alcoholic fatty liver disease patients for steatosis (A), lobular inflammation (B), ballooning (C), and fibrosis (D). Table 1 presents the number of subjects for each histological stage. The Kruskal-Wallis test was used for multi-group simultaneous comparisons. P values are displayed in the upper left of each graph. ATX: Autotaxin; NAFLD: Non-alcoholic fatty liver disease; NS: Not significant.

Figure 3

Relationship between autotaxin and histological grade in non-alcoholic fatty liver disease patients by gender for steatosis (A), lobular inflammation (B), ballooning (C), and fibrosis (D). Table 1 presents the number of subjects for each histological stage. The Kruskal-Wallis test was used for multi-group simultaneous comparisons. P values are displayed in the upper left of each graph. ATX: Autotaxin; NAFLD: Non-alcoholic fatty liver disease; NS: Not significant.

Figure 4

Receiver operating characteristic analysis of autotaxin for the estimation of the presence of fibrosis (≥ F1), significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) in all (A), male (B), and female (C) patients. The areas under the receiver operating characteristic curve are displayed in the lower right of each graph. AUC: Receiver operating characteristic curve; F: Fibrosis.