Relationship between liver dysfunction, lipoprotein concentration and mortality during sepsis

Abstract

Background: High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU).

Methods: A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin≥ 2N or aspartate aminotransferase/alanine aminotransferase concentrations ≥ 2N. Short-term and one-year prognostic outcomes were prospectively assessed.

Results: A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers.

Conclusion: Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis.

Fig 1. Kaplan–Meier estimates of survival in the 28 days after the onset of sepsis for patients according to hepatic dysfunction status.

Fig 2. Comparison between total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and triglyceride concentrations at admission, according to hepatic dysfunction status.

TC: total cholesterol, HDL-C: high-density lipoprotein-cholesterol, LDL: low-density lipoprotein-cholesterol, TG: triglycerides. HD: hepatic dysfunction.

Fig 3. Kaplan–Meier estimates of survival in the 28 days after the onset of sepsis for patients with different initial levels of lipoproteins.

TC: total cholesterol, HDL-C: high-density lipoprotein-cholesterol, LDL: low-density lipoprotein-cholesterol, TG: triglycerides.

Fig 4. Kaplan–Meier estimates of survival in the 28 days after the onset of sepsis for patients with different initial levels of lipoproteins, according to hepatic dysfunction status.

TC: total cholesterol, HDL-C: high-density lipoprotein-cholesterol, LDL: low-density lipoprotein-cholesterol, TG: triglycerides.

Fig 5. Correlation between lipoprotein, triglycerides, total cholesterol and hepatic markers.

TC: total cholesterol, HDL-C: high-density lipoprotein-cholesterol, LDL: low-density lipoprotein-cholesterol, TG: triglycerides, TB: total bilirubin, ASAT: aspartate aminotransferase, ALAT: alanine aminotransferase.