Serum Autotaxin Is a Useful Disease Progression Marker in Patients with Primary Biliary Cholangitis

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-naive, 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.ArticleSCIENTIFIC REPORTS.8:8159(2018)journal articl

Advances in pharmacotherapy for primary biliary cirrhosis

INTRODUCTION: Primary Biliary Cirrhosis (PBC) is a chronic autoimmune liver disease mostly seen in middle aged women characterized by progressive non-suppurative destruction of small bile ducts resulting in intrahepatic cholestasis, parenchymal injury, and ultimately end stage liver disease. Despite major breakthroughs in our understanding of PBC, there remains only one FDA-approved agent for treatment: ursodeoxycholic acid (UDCA) to which one third of patients are unresponsive. AREAS COVERED: Biochemical response to treatment with UDCA is associated with excellent survival rates in PBC patients. However, there is a need for alternative treatments for non-responders. Results from human epidemiological and genetic studies as well as preclinical studies in PBC animal models have provided a strong impetus for the development of new therapeutic agents. In this review, we discuss the recent advances in translational research in PBC focusing on promising therapeutic approaches, namely immune-based targeted therapies and agents targeting the synthesis and circulation of bile acids. EXPERT OPINION: We are in a new era for the development of novel therapies for PBC. Data on fibrates, budesonide, and obeticholic acid offer encouragement for non-responders to UDCA