Muharrem KESKİN,
Saliha UYSAL,
Ramazan DERTLİ,
Nurcan UNVER,
Ramazan YOLAÇAN,
Ali DEMİR,
Mehmet ASİL,
Hakki POLAT,
Murat BİYİK,
Huseyin ATASEVEN,
Yusuf KAYAR
4210
Serum soluble TWEAK levels in non-alcoholic fatty liver disease
Serum soluble TWEAK levels in non-alcoholic fatty liver disease
Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The exact pathogenesis of NAFLD hasnot been fully elucidated. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of TNF superfamily and it hasbeen implicated in the pathogenesis of several diseases including liver inflammation and fibrosis. Current study was conducted toevaluate serum sTWEAK levels in patients with NAFLD.Material and Methods: Seventeen patients with biopsy proven non-alcoholic steatohepatitis (NASH), 22 patients with simplehepatosteatosis and 30 healthy controls were included in the study and serum sTWEAK concentrations were measured usingcommercial ELISA kits.Results: Mean serum sTWEAK concentration was significantly lower in the NASH group when compared to the simple hepatosteatosisgroup and healthy controls (199.6±101.2 pg/mL, 246.1±65.7 pg/mL and 277.6±117.6 pg/mL respectively, p=0.029). ROC analysesfor sTWEAK to differentiate NASH patients from healthy controls and from simple hepatosteatosis revealed that AUC for sTWEAKwas 0.712 (%95 CI, 0.543-0.880). For the specified cut off value, 171.1 pg/mL positive and negative predictive values calculated were64.3% and 85.5% respectively.Conclusion: Serum sTWEAK concentration is decreasedin patients with NASH when compared to patients with simple hepatosteatosisand healthy controls.
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- 1. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev
Gastroenterol Hepatol 2013;10:686-90.
- 2. Harmon RC, Tiniakos DG, Argo CK. Inflammation in
nonalcoholic steatohepatitis. Expert Rev Gastroenterol
Hepatol 2011;5:189-200.
- 3. Masarone M, Rosato V, Dallio M, at al. role of oxidative stress
in pathophysiology of nonalcoholic fatty liver disease. Oxid
Med Cell Longev 2018:11;2018:9547613.
- 4. Asil M, Dertli R., Biyik, et al. Dynamic thiol-disulfide
homeostasis is disturbed in patients with non-alcoholic
fatty liver disease. Laboratoriums Medizin 2017;42:31-38.
- 5. Meli R, Mattace RG, Calignano A. Role of innate immune
response in non-alcoholic fatty liver disease: metabolic
complications and therapeutic tools. Front Immunol
2014:23;5:177.
- 6. Burkly LC, Michaelson JS, Hahm K, et al. TWEAKing tissue
remodeling by a multifunctional cytokine: role of TWEAK/
Fn14 pathway in health and disease.Cytokine. 2007;40:1-
16.
- 7. Wiley SR, Cassiano L, Lofton T, et al. A novel TNF receptor
family member binds TWEAK and is implicated in
angiogenesis.Immunity. 2001;15:837-46.
- 8. Novoyatleva T, Sajjad A, Engel FB. TWEAK-Fn14 cytokinereceptor
axis: a new player of myocardial remodeling and
cardiac failure. Front Immunol. 2014;11:5-50.
- 9. Turkmen K, Tonbul HZ, Erdur FM, et al. Soluble TWEAK
independently predicts atherosclerosis in renal transplant
patients. BMC Nephrol. 2013;14:144.
- 10. Choe JY, Kim SK. Serum TWEAK as a biomarker for disease
activity of systemic lupus erythematosus. Inflamm Res.
2016;65:479-88.
- 11. Kawashima R, Kawamura YI, Oshio T, et al. Interleukin-13
damages intestinal mucosa via TWEAK and Fn14 in mice-a
pathway associated with ulcerative colitis. Gastroenterology
2011;141:2119-29.
- 12. Wilhelm A, Shepherd EL, Amatucci A, et al. Interaction
of TWEAK with Fn14 leads to the progression of fibrotic
liver disease by directly modulating hepatic stellate cell
proliferation. J Pathol. 2016;239:109-21.
- 13. Affò S, Dominguez M, Lozano JJ, et al. Transcriptome
analysis identifies TNF superfamily receptors as potential
therapeutic targets in alcoholic hepatitis. Gut. 2013;62:452-
60.
- 14. Asil M, Dertli R. Serum soluble TWEAK levels are decreased
in treatment naive noncirrhotic chronic hepatitis B patients.
Medicine (Baltimore). 2016;95:e4763.
- 15. Eryılmaz MA, Baktık S, Ay S, et al. Incidence of pathologies
detected by abdominal ultrasonography screening. Selçuk
Tıp Derg 2014;30: 19-22.
- 16. Feng SLY, Guo Y, Factor VM, et al. The Fn14 immediate-early
response gene is induced during liver regeneration and
highly expressed in both human and murine hepatocellular
carcinomas. Am J Pathol 2000;156:1253–61.
- 17. Jakubowski A, Ambrose C, Parr M, et al. TWEAK induces liver
progenitor cell proliferation. J Clin Invest 2005;115:2330-40.
- 18. Lozano-Bartolomé J, Llauradó G, Rodriguez MM, et al.
Reduced circulating levels of sTWEAK are associated with
NAFLD and may affect hepatocyte triglyceride accumulation.
Int J Obes (Lond). 2016;40:1337-45.
- 19. Karaca G, Swiderska-Syn M, Xie G, et al. TWEAK/Fn14
signaling is required for liver regeneration after partial
hepatectomy in mice. PLoS One 2014;9:e83987.
- 20. Wilhelm A, Shepherd EL, Amatucci A, et al. Interaction
of TWEAK with Fn14 leads to the progression of fibrotic
liver disease by directly modulating hepatic stellate cell
proliferation. J Pathol 2016;239:109-21.
- 21. Jelić-Ivanović Z, Bujisić N, Spasić S, et al.Circulating
sTWEAK improves the prediction of coronary artery disease.
Clin Biochem 2009;42:1381-6.
- 22. Moreno JA, Dejouvencel T, Labreuche J, et al. Peripheral
artery disease is associated with a high CD163/TWEAK
plasma ratio. Arterioscler Thromb Vasc Biol 2010;30:1253-
62.
- 23. Kralisch S, Ziegelmeier M, Bachmann A, et al. Serum levels of
the atherosclerosis biomarker sTWEAKare decreased in type
2 diabetes and end-stage renal disease. Atherosclerosis
2008;199:440-4.
- 24. Carrero JJ1, Ortiz A, Qureshi AR, et al. Additive effects
of soluble TWEAK and inflammation on mortality in
hemodialysis patients. Clin J Am Soc Nephrol 2009;4:110-8.