Abstract
Autotaxin has been associated with liver disease severity and transplant-free survival. This study aimed to validate autotaxin as a biomarker in two cohorts of Norwegian large-duct PSC patients, one discovery panel (n = 165) and one validation panel (n = 87). Serum activity of autotaxin was measured in diluted sera by a fluorometric enzymatic assay. Patients reaching an end-point, liver transplantation or death, (discovery panel: n = 118 [71.5%]; validation panel: n = 35 [40.2%]), showed higher autotaxin activity compared with the other patients, P < 0.001 and P = 0.004, respectively. Kaplan-Meier survival analyses showed a strong association between increasing autotaxin activity and shorter liver transplant-free survival (discovery panel: P < 0.001, validation panel: P = 0.001). There was no relationship between autotaxin activity and the presence of inflammatory bowel disease or occurrence of hepatobiliary malignancy. In a multivariable analysis, high autotaxin activity was associated with an increased risk of liver transplantation or death (hazard ratio 2.03 (95% confidence interval 1.21–3.40), P < 0.01), independent from Mayo risk score, an in-house enhanced liver fibrosis score and interleukin-8 in serum. In conclusion, increased serum autotaxin activity is associated with reduced liver transplant-free survival independent from Mayo risk score and markers of inflammation and fibrosis.
Highlights
Primary sclerosing cholangitis (PSC) is a progressive inflammatory disease of the intra- and extrahepatic bile ducts, leading to strictures, cholestasis, cirrhosis and liver failure
High autotaxin activity is associated with poor prognosis in PSC patients
Adding disease panel as covariate, or doing analyses on liver-related deaths only, did not influence the results. In this cross-sectional study of autotaxin activity in two independent cohorts of PSC patients, we found a strong correlation between increasing autotaxin and shorter liver transplantation free survival
Summary
Primary sclerosing cholangitis (PSC) is a progressive inflammatory disease of the intra- and extrahepatic bile ducts, leading to strictures, cholestasis, cirrhosis and liver failure. Autotaxin is an enzyme that hydrolyzes lysophospholipids into lysophosphatidic acid (LPA), which has been identified as a potential mediator of cholestasis-associated pruritus[4]. The disease activity in PSC patients shows large variations over the disease course, and there are few tools available to predict prognosis and measure response to treatment for the individual patient. Autotaxin activity was described as a marker of severity of liver injury and survival in a study of a single cohort of patients with primary biliary cholangitis (PBC) and PSC14. P two independent Norwegian PSC panels, and explore the role of autotaxin as a potential biomarker for cancer development as well as associations with other novel biomarkers
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