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Serum Cell Death Biomarkers for Prediction of Liver Fibrosis and Poor Prognosis in Primary Biliary Cirrhosis

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Journal PLoS One
Date 2015 Jun 26
PMID 26110613
Citations 10
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Abstract

The development of simple, noninvasive markers of liver fibrosis is urgently needed for primary biliary cirrhosis (PBC). This study examined the ability of several serum biomarkers of cell death to estimate fibrosis and prognosis in PBC. A cohort of 130 patients with biopsy-proven PBC and 90 healthy subjects were enrolled. We assessed the utility of the M30 ELISA, which detects caspase-cleaved cytokeratin-18 (CK-18) fragments and is representative of apoptotic cell death, as well as the M65 and newly developed M65 Epideath (M65ED) ELISAs, which detect total CK-18 as indicators of overall cell death, in predicting clinically relevant fibrosis stage. All 3 cell death biomarkers were significantly higher in patients with PBC than in healthy controls and were significantly correlated with fibrosis stage. The areas under the receiver operating characteristic curve for the M65 and M65ED assays for differentiation among significant fibrosis, severe fibrosis, and cirrhosis were 0.66 and 0.76, 0.66 and 0.73, and 0.74 and 0.82, respectively. In multivariate analysis, high M65ED (hazard ratio 6.13; 95% confidence interval 1.18-31.69; P = 0.031) and severe fibrosis (hazard ratio 7.45; 95% confidence interval 1.82-30.51; P = 0.005) were independently associated with liver-related death, transplantation, or decompensation. High serum M65ED was also significantly associated with poor outcome in PBC (log-rank test; P = 0.001). Noninvasive cell death biomarkers appear to be clinically useful in predicting fibrosis in PBC. Moreover, the M65ED assay may represent a new surrogate marker of adverse disease outcome.

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References
1.
Feldstein A, Wieckowska A, Lopez A, Liu Y, Zein N, McCullough A . Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology. 2009; 50(4):1072-8. PMC: 2757511. DOI: 10.1002/hep.23050. View

2.
Denk G, Omary A, Reiter F, Hohenester S, Wimmer R, Holdenrieder S . Soluble intracellular adhesion molecule, M30 and M65 as serum markers of disease activity and prognosis in cholestatic liver diseases. Hepatol Res. 2014; 44(13):1286-98. DOI: 10.1111/hepr.12304. View

3.
Volkmann X, Anstaett M, Hadem J, Stiefel P, Bahr M, Lehner F . Caspase activation is associated with spontaneous recovery from acute liver failure. Hepatology. 2008; 47(5):1624-33. DOI: 10.1002/hep.22237. View

4.
Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G . Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol. 2010; 11(10):700-14. DOI: 10.1038/nrm2970. View

5.
Koehler E, Swain J, Sanderson S, Krishnan A, Watt K, Charlton M . Growth hormone, dehydroepiandrosterone and adiponectin levels in non-alcoholic steatohepatitis: an endocrine signature for advanced fibrosis in obese patients. Liver Int. 2011; 32(2):279-86. DOI: 10.1111/j.1478-3231.2011.02637.x. View