Serum Autotaxin Concentrations Reflect Changes in Liver Stiffness and Fibrosis After Antiviral Therapy in Patients with Chronic Hepatitis C

Abstract

The purpose of this study was to determine whether serum autotaxin concentrations reflect liver stiffness in patients with chronic hepatitis C virus (HCV) treated with direct‐acting antiviral agents. Adult patients with chronic HCV were enrolled from January 2016 to August 2017. Autotaxin concentrations in these patients were compared with those of a control group consisting of healthy individuals. Liver stiffness was determined by transient elastography. The relationship between fibrosis markers and fibrosis scores was evaluated before and after treatment. Data from 155 HCV patients and 56 control subjects were analyzed. Autotaxin concentrations were significantly higher in HCV patients with liver stiffness scores less than or equal to 7.4 kPa versus controls. Autotaxin concentrations at the end of treatment and beyond were significantly lower than those prior to treatment. Pretreatment and posttreatment autotaxin concentrations in male and female patients with liver stiffness scores greater than 14.9 kPa changed significantly (P < 0.01 and P < 0.01, respectively). From the start of treatment to 6 months following treatment, the fibrosis marker/liver stiffness score ratios changed as follows: autotaxin: 0.189 (95% confidence interval [CI]: 0.169‐0.209) to 0.191 (95% CI: 0.166‐0.216; P= 0.88); Wisteria floribundaagglutinin‐positive Mac‐2‐binding protein: 0.294 (95% CI: 0.256‐0.332) to 0.223 (95% CI: 0.191‐0.255; P< 0.001); hyaluronic acid: 19.05 (95% CI: 14.29‐23.81) to 13.92 (95% CI: 11.16‐16.70; P = 0.044); and type IV collagen 7S: 0.560 (95% CI: 0.515‐0.604) to 0.546 (95% CI: 0.497‐0.895; P = 0.052). Conclusion: Autotaxin concentrations reflect liver stiffness before and after antiviral treatment in patients with chronic HCV infection.

The impact of achieving a sustained virological response with direct-acting antivirals on serum autotaxin levels in chronic hepatitis C patients

“…We detected that serum ATX concentrations were significantly decreased in CHC patients after achieving SVR12. This is supported by the findings of other studies [16,[26][27][28]. This significant difference was reproduced when classifying the patients according to gender, as previously proposed [16,17,27,33].…”

“…However, the extent of hepatic fibrosis regression should be assessed to decide which individuals remain at a high risk of HCC. Therefore, simple and reliable non-invasive methods are required to achieve this goal [16]; however, the value of serum biomarkers for the evaluation of liver fibrosis following DAA therapy has not been well evaluated [27]. We detected that serum ATX concentrations were significantly decreased in CHC patients after achieving SVR12.…”

“…Several reports suggested that the achievement of SVR with DAA therapy improves hepatic fibrosis in CHC patients [23,25]; however, the changes of serum ATX levels have been investigated in scarce studies in this context [16,[26][27][28] and its ability to reflect the regression of hepatic fibrosis remains uncertain. Therefore, we aimed to investigate the impact of achieving SVR with DAA therapy on serum ATX levels and whether these levels can reflect the regression of hepatic fibrosis in CHC patients.…”

The Autotaxin - Lysophosphatidic Acid Axis as a Novel Therapeutic Target for Liver Fibrosis

“…Furthermore, elevated serum levels of LPA and especially ATX have been detected in vivo in liver fibrosis models in diverse recent studies [61,62]. Hereby, specific studies were focused on different liver fibrosis origins including NAFLD [11] and chronic hepatitis B and C [12][13][14], demonstrating that elevated ATX levels are independent of disease etiology. A possible explanation on the serum ATX increase can be found in either or both of two aspects: an increase in ATX production as a result of fibrosis or a decrease in ATX clearance.…”

“…Novel therapeutics have been focused on inhibition of liver fibrosis specific pathways [7][8][9]. One pathway gaining interest as an important factor in liver fibrosis is the lysophosphatidic acid (LPA)autotaxin (ATX) signaling pathway, since elevated levels of LPA and ATX are found in fibrosis [10][11][12][13][14].…”