Autotaxin is a valuable biomarker for the prediction of liver fibrosis in patients with non‐alcoholic fatty liver disease

Abstract

Aim We investigated the characteristics of serum autotaxin (ATX) and its diagnostic performance for liver fibrosis in a large cohort of patients with non‐alcoholic fatty liver disease (NAFLD). Methods We compared the usefulness of ATX and other fibrosis markers in 307 biopsy‐confirmed NAFLD patients. In addition, in 145 participants with NAFLD, we compared the diagnostic performance of ATX with that of non‐invasive imaging methods (vibration‐controlled transient elastography and magnetic resonance elastography [MRE]). Results Serum ATX concentration was significantly correlated with fibrosis stage in male and female NAFLD patients. In male patients, the area under the receiver operating characteristic (AUROC) curve values of ATX for the diagnosis of ≥stage 1, ≥stage 2, ≥stage 3, and ≥stage 4 fibrosis were 0.65, 0.75, 0.81, and 0.95, respectively. In female NAFLD participants, the AUROC values were all >0.81. The sensitivity of ATX was highest for the diagnosis of ≥stage 2 and ≥stage 3 fibrosis in both men and women with NAFLD. In the comparison between ATX and non‐invasive imaging methods, the AUROC for MRE was the highest at every stage of fibrosis. Conclusions Serum ATX concentration is significantly correlated with fibrosis stage in NAFLD patients. The diagnostic accuracy of ATX for liver fibrosis is lower than that of MRE, but the sensitivities of ATX for the diagnosis of ≥stage 2 and ≥stage 3 were highest. We conclude that ATX is useful for the selection of patients requiring further evaluation for liver fibrosis.

Deregulated Lysophosphatidic Acid Metabolism and Signaling in Liver Cancer

“…Free fatty acids levels, high levels of glucose and the increased number of adipocytes are probably responsible for the increased ATX and LPA circulatory levels observed in NAFLD coexisting with T2DM and obesity. In line with this, blood ATX and LPA levels are also independently associated with liver steatosis and insulin resistance [187,188] as well as liver fibrosis severity [148]. Furthermore, in older or obese people, serum ATX correlates with multiple measures of adiposity and glucose homeostasis / insulin action [188].…”

“…Liver cirrhosis develops upon chronic liver damage of different etiologies (viral, autoimmune, metabolic, alcohol, cholestatic). ATX levels positively correlated with liver fibrosis stage and serve as a predictor of liver disease severity and overall survival regardless of the liver disease etiology [145,146,147,148,149], whereas serum LPA levels correlated with ATX levels [147]. Moreover, HCC specimens with underlying cirrhosis display higher ATX expression levels compared to non-cirrhotic HCC specimens [150].…”

“…Accordingly, alterations in either glucose or free fatty acid levels in the context of T2DM, obesity and NAFLD may alter the metabolic activity of Heps possibly favoring their malignant transformation. Such a metabolic alteration appears to be the deregulated phospholipid metabolism that leads to an increased amount of LPA as evidenced by the observed increased ATX and LPA levels in the circulation of obese, T2DM and NAFLD patients [27,148,186,187,188,189]. Free fatty acids levels, high levels of glucose and the increased number of adipocytes are probably responsible for the increased ATX and LPA circulatory levels observed in NAFLD coexisting with T2DM and obesity.…”

Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein as a Screening Tool for Significant Liver Fibrosis in Health Checkup

“…An investigation of the prevalence of significant fibrosis in subjects with low serum fibrosis markers would provide clinically and epidemiologically essential information for further understanding CLD, and further studies in this regard are important. Furthermore, the utility of other liver fibrosis markers, such as the N-terminal propeptide of type 3 procollagen or autotaxin [51,52], has been reported recently, and it will be necessary to compare the diagnostic ability and cost-effectiveness between these fibrosis markers, ultrasound-based elastography, and WFA + -M2BP in the general population in the future.…”

FIB-4 First in Diagnostic Algorithm of MAFLD at the Era of “Global Metabodemic “

“…FIB-4 first strategy would decrease costs and decrease unnecessary referrals as well as increase access to screening in non-specialized facilities. It remains unknown which parameters are the most appropriate as 2 nd step among a variety of NITs, including ELF test [15], Mac-2 binding protein glycated isomer (M2BPGi) [95][96][97], type IV collagen 7S [88,96], ProC3 [98], and autotaxin [99,100].…”