Abstract
Autotaxin (ATX) is a secreted enzyme metabolized by liver sinusoidal endothelial cells that has been associated with liver fibrosis. We evaluated serum ATX values in 128 treatment-naïve, histologically assessed primary biliary cholangitis (PBC) patients and 80 healthy controls for comparisons of clinical parameters in a case-control study. The median ATX concentrations in controls and PBC patients of Nakanuma’s stage I, II, III, and IV were 0.70, 0.80, 0.87, 1.03, and 1.70 mg/L, respectively, which increased significantly with disease stage (r = 0.53, P < 0.0001) as confirmed by Scheuer’s classification (r = 0.43, P < 0.0001). ATX correlated with Wisteria floribunda agglutinin-positive Mac-2 binding protein (M2BPGi) (r = 0.51, P < 0.0001) and fibrosis index based on four factors (FIB-4) index (r = 0.51, P < 0.0001). While ALP and M2BPGi levels had decreased significantly (both P < 0.001) by 12 months of ursodeoxycholic acid treatment, ATX had not (0.95 to 0.96 mg/L) (P = 0.07). We observed in a longitudinal study that ATX increased significantly (P < 0.00001) over 18 years in an independent group of 29 patients. Patients succumbing to disease-related death showed a significantly higher ATX increase rate (0.05 mg/L/year) than did survivors (0.02 mg/L/year) (P < 0.01). ATX therefore appears useful for assessing disease stage and prognosis in PBC.
Highlights
As recommended by most guidelines[13,14,15], ursodeoxycholic acid (UDCA) is currently the most effective treatment for primary biliary cholangitis (PBC) and has remarkably improved disease prognosis
Nakagawa et al described that lysophosphatidic acid (LPA) and ATX were pathophysiologically involved in liver fibrosis based on the evidence that LPA stimulated proliferation and contractility in hepatic stellate cells[32]
This study demonstrated a clear association of ATX with disease progression in patients with PBC
Summary
As recommended by most guidelines[13,14,15], ursodeoxycholic acid (UDCA) is currently the most effective treatment for PBC and has remarkably improved disease prognosis. Nakagawa et al described that lysophosphatidic acid (LPA) and ATX were pathophysiologically involved in liver fibrosis based on the evidence that LPA stimulated proliferation and contractility in hepatic stellate cells[32]. Thereafter, serum ATX has been reported as a novel marker candidate to assess liver fibrosis, histological activity grade, and disease outcome[32,33,34,35,36,37,38,39]. The molecular mechanisms involved in the pathogenesis of cholestatic pruritus remain unknown, the ATX-LPA signaling axis is suspected to play an important role based on evidence of increased ATX activity in affected patients[40,41]. The present study evaluated the performance of serum ATX in predicting histological disease stage in PBC in comparison with currently established indices. We examined the clinical characteristics of ATX over time in patients with PBC in a longitudinal study
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