Abstract
Frailty, a clinical phenotype of decreased physiologic reserve, is a strong determinant of adverse health outcomes in patients with cirrhosis. The only cirrhosis-specific frailty metric is the Liver Frailty Index (LFI) which must be administered in person and may not be feasible for every clinical scenario. We sought to discover candidate serum/plasma protein biomarkers that could differentiate frail from robust patients with cirrhosis. Included were 140 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with LFI assessments and available serum/plasma samples. We selected 70 pairs of patients on opposite ends of the frailty spectrum (LFI> 4.4 for frail and LFI<3.2 for robust) who were matched by age, sex, etiology, HCC, and MELDNa. Twenty-five biomarkers with biologically plausible associations with frailty were analyzed by ELISA by a single laboratory. Conditional logistic regression was used to examine their association with frailty. Of the 25 biomarkers analyzed, we identified 7 proteins that were differentially expressed between frail and robust. We observed differences in 6 of the 7 proteins in the expected direction: a) higher median values in frail versus robust with growth-differentiation factor-15 (3682 vs. 2249pg/mL), interleukin-6 (17.4 vs. 6.4pg/mL), tumor necrosis factor-alpha receptor 1 (2062 vs. 1627pg/mL), leucine-rich alpha-2 glycoprotein (44.0 vs. 38.6ug/mL), and myostatin (4066 vs. 6006ng/mL), and b) lower median values in frail versus robust with alpha-2-Heremans-Schmid glycoprotein (0.11 vs. 0.13mg/mL) and free total testosterone (1.2 vs. 2.4ng/mL). These biomarkers represent inflammatory, musculoskeletal, and endocrine/metabolic systems, reflecting the multiple physiologic derangements observed in frailty. These data lay the foundation for confirmatory work and development of a laboratory frailty index for patients with cirrhosis to improve diagnosis and prognostication.
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Schedule a callMore From: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
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