Plasma GlycA, a Glycoprotein Marker of Chronic Inflammation, and All-Cause Mortality in Cirrhotic Patients and Liver Transplant Recipients

Abstract

Low-grade chronic inflammation may impact liver disease. We investigated the extent to which circulating GlycA, a glycoprotein biomarker of low-grade inflammation, and high-sensitivity C-reactive protein (hs-CRP) are altered in patients with cirrhosis and liver transplant recipients (LTRs) and examined their associations with all-cause mortality. Plasma GlycA (nuclear magnetic resonance spectroscopy) and hs-CRP (nephelometry) were assessed in 129 patients with cirrhosis on the waiting list for liver transplantation and 367 LTRs (TransplantLines cohort study; NCT03272841) and compared with 4837 participants from the population-based PREVEND cohort. GlycA levels were lower, while hs-CRP levels were higher in patients with cirrhosis compared to PREVEND participants (p < 0.001). Notably, GlycA increased, but hs-CRP decreased after transplantation. In LTRs, both GlycA and hs-CRP levels were higher than in PREVEND participants (p < 0.001). Survival was impaired in patients with cirrhosis and LTRs with the highest GlycA and the highest hs-CRP tertiles. In Cox regression analysis, GlycA remained associated with mortality in cirrhotic patients after adjusting for potential confounders and for hs-CRP (HR per 1-SD increment: 2.34 [95% CI 1.07-5.13]), while the association with hs-CRP after adjusting was lost. In LTRs, both GlycA and hs-CRP were also associated with mortality (adjusted HR: 1.60 [95% CI: 1.2-2.14] and 1.64 [95% CI: 1.08-2.51], respectively) but not independent of each other. GlycA increases while hs-CRP decreases after liver transplantation. Both inflammatory markers may be associated with all-cause mortality in cirrhotic patients and LTRs, while the association for GlycA seems at least as strong as that for hs-CRP.

Keywords: GlycA; chronic inflammation; hs-CRP; liver cirrhosis; liver transplantation; mortality.

Figure 1

Changes in plasma GlycA and high-sensitivity C-reactive protein (hs-CRP) levels in cirrhotic patients and liver transplant recipients (LTRs). (A) Comparison of plasma GlycA levels between cirrhotic patients and LTRs (unpaired). (B) Comparison of hs-CRP levels between cirrhotic patients and LTRs (unpaired), (C) Paired analysis of GlycA levels in a subset of 30 patients studied twice, that is, before and after liver transplantation. (D) Paired analysis of hs-CRP levels in a subset of 23 patients studied twice, that is, before and after liver transplantation. GlycA levels significantly increase after LT, while hs-CRP levels show a significant decrease. p < 0.001 (***), p < 0.01 (**).

Figure 2

The scatter plot illustrates the positive correlation between plasma GlycA levels and high-sensitivity C-reactive protein (hs-CRP; ln-transformed) across three distinct populations: patients with cirrhosis, liver transplant recipients (LTRs), and PREVEND study participants. The colored lines represent the linear fit for each group, with shaded areas indicating the 95% confidence intervals. Cirrhotic patients (blue line) show a moderate correlation between GlycA and hs-CRP (R = 0.459, p < 0.001). LTRs (orange line) and PREVEND participants (green line) exhibit a stronger correlation (R = 0.679 and R = 0.669, respectively; both p < 0.001).

Figure 3

Kaplan–Meier survival curves for GlycA and hs-CRP levels in relation to all-cause mortality. (A) Survival probability for cirrhotic patients on the waiting list for liver transplantation according to GlycA tertiles (T1: <276 μmol/L; T2: 276–360 μmol/L; and T3: >360 μmol/L) (log-rank test T3 vs. T1, p = 0.033). (B) Survival probability on the waiting list for cirrhotic patients according to hs-CRP tertiles (T1: <5 mg/L; T2: 5–18 mg/L; and T3: >18 mg/L) (log-rank test T3 vs. T1, p = 0.003). (C) Post-liver transplant survival probability for liver transplant recipients (LTRs) according to GlycA tertiles (T1: <339 μmol/L; T2: 339–414 μmol/L; and T3: >414 μmol/L) (log-rank test T3 vs. T1, p = 0.005). (D) Post-liver transplant survival probability for LTRs according to hs-CRP tertiles (T1: <1.2 mg/L; T2: 1.2–3.5 mg/L; and T3: >3.5 mg/L) (log-rank test T3 vs. T1, p = 0.024). LTR: liver transplant recipient; hs-CRP: high-sensitivity C-reactive protein.