Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival in Patients with Cholestatic Liver Diseases

Overview

Journal Sci Rep

Specialty Science

Date 2016 Aug 11

PMID 27506882

Citations 30

Authors

Ewa Wunsch

Marcin Krawczyk

Malgorzata Milkiewicz

Jocelyn Trottier

Olivier Barbier

Markus F Neurath

Frank Lammert

Andreas E Kremer

Piotr Milkiewicz

Affiliations

Soon will be listed here.

Abstract

Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have recently been linked to cholestatic pruritus and liver injury. We aimed to investigate whether ATX is an indicator of cholestatic liver injury, health-related quality of life (HRQoL) and prognosis based on a group of 233 patients, 118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing cholangitis (PSC). Patients were followed for 1-60 months, cumulative survival rates were calculated. ATX activity was significantly higher in both groups than in the 103 controls, particularly in patients with cirrhosis and in patients with longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC exhibited increased ATX activity. ATX activity was correlated with liver biochemistry, MELD, Mayo Risk scores and was associated with worse disease-specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was a negative predictor of survival. Increased ATX levels were associated with a 4-fold higher risk of death/liver transplantation in patients with PBC and a 2.6-fold higher risk in patients with PSC. We conclude that in patients with cholestatic conditions, ATX is not only associated with pruritus but also indicates impairment of other HRQoL aspects, liver dysfunction, and can serve as a predictor of survival.

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References

Trottier J, Bialek A, Caron P, Straka R, Milkiewicz P, Barbier O . Profiling circulating and urinary bile acids in patients with biliary obstruction before and after biliary stenting. PLoS One. 2011; 6(7):e22094. PMC: 3132779. DOI: 10.1371/journal.pone.0022094. View

Masuda A, Nakamura K, Izutsu K, Igarashi K, Ohkawa R, Jona M . Serum autotaxin measurement in haematological malignancies: a promising marker for follicular lymphoma. Br J Haematol. 2008; 143(1):60-70. DOI: 10.1111/j.1365-2141.2008.07325.x. View

Jansen S, Andries M, Vekemans K, Vanbilloen H, Verbruggen A, Bollen M . Rapid clearance of the circulating metastatic factor autotaxin by the scavenger receptors of liver sinusoidal endothelial cells. Cancer Lett. 2009; 284(2):216-21. DOI: 10.1016/j.canlet.2009.04.029. View

Nakanaga K, Hama K, Aoki J . Autotaxin--an LPA producing enzyme with diverse functions. J Biochem. 2010; 148(1):13-24. DOI: 10.1093/jb/mvq052. View

Hirschfield G, Mason A, Luketic V, Lindor K, Gordon S, Mayo M . Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology. 2014; 148(4):751-61.e8. DOI: 10.1053/j.gastro.2014.12.005. View

Wunsch E, Trottier J, Milkiewicz M, Raszeja-Wyszomirska J, Hirschfield G, Barbier O . Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis. Hepatology. 2014; 60(3):931-40. DOI: 10.1002/hep.27074. View

Mells G, Pells G, Newton J, Bathgate A, Burroughs A, Heneghan M . Impact of primary biliary cirrhosis on perceived quality of life: the UK-PBC national study. Hepatology. 2013; 58(1):273-83. DOI: 10.1002/hep.26365. View

Montali L, Tanaka A, Riva P, Takahashi H, Cocchi C, Ueno Y . A short version of a HRQoL questionnaire for Italian and Japanese patients with Primary Biliary Cirrhosis. Dig Liver Dis. 2010; 42(10):718-23. DOI: 10.1016/j.dld.2010.01.004. View

Shimizu Y, Murao K, Tanaka T, Kubo Y, Tokumura A . Increased lysophospholipase D activity of autotaxin in sera of patients with atopic dermatitis. J Dermatol Sci. 2014; 74(2):162-5. DOI: 10.1016/j.jdermsci.2014.01.010. View

10.

Corpechot C, Abenavoli L, Rabahi N, Chretien Y, Andreani T, Johanet C . Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology. 2008; 48(3):871-7. DOI: 10.1002/hep.22428. View

11.

Nakagawa H, Ikeda H, Nakamura K, Ohkawa R, Masuzaki R, Tateishi R . Autotaxin as a novel serum marker of liver fibrosis. Clin Chim Acta. 2011; 412(13-14):1201-6. DOI: 10.1016/j.cca.2011.03.014. View

12.

. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009; 51(2):237-67. DOI: 10.1016/j.jhep.2009.04.009. View

13.

Trottier J, Bialek A, Caron P, Straka R, Heathcote J, Milkiewicz P . Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: a pilot study. Dig Liver Dis. 2011; 44(4):303-10. DOI: 10.1016/j.dld.2011.10.025. View

14.

Ware Jr J, Sherbourne C . The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992; 30(6):473-83. View

15.

Kremer A, van Dijk R, Leckie P, Schaap F, Kuiper E, Mettang T . Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions. Hepatology. 2012; 56(4):1391-400. DOI: 10.1002/hep.25748. View

16.

Jankowski M . Autotaxin: its role in biology of melanoma cells and as a pharmacological target. Enzyme Res. 2011; 2011:194857. PMC: 3057024. DOI: 10.4061/2011/194857. View

17.

Bolier R, Tolenaars D, Kremer A, Saris J, Pares A, Verheij J . Enteroendocrine cells are a potential source of serum autotaxin in men. Biochim Biophys Acta. 2016; 1862(4):696-704. DOI: 10.1016/j.bbadis.2016.01.012. View

18.

Kremer A, Oude Elferink R, Beuers U . Pathophysiology and current management of pruritus in liver disease. Clin Res Hepatol Gastroenterol. 2011; 35(2):89-97. DOI: 10.1016/j.clinre.2010.10.007. View

19.

Jacoby A, Rannard A, Buck D, Bhala N, Newton J, James O . Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis. Gut. 2005; 54(11):1622-9. PMC: 1774759. DOI: 10.1136/gut.2005.065862. View

20.

Kremer A, Bolier R, Dixon P, Geenes V, Chambers J, Tolenaars D . Autotaxin activity has a high accuracy to diagnose intrahepatic cholestasis of pregnancy. J Hepatol. 2014; 62(4):897-904. DOI: 10.1016/j.jhep.2014.10.041. View