The prognostic significance of HDL-associated apolipoproteins in ascitic fluid from patients with cirrhosis and spontaneous bacterial peritonitis

Abstract

Abstract Apolipoproteins (Apo) A-I and A-II are major components of high-density lipoproteins (HDL) with immunomodulatory functions. Low serum apoA-I levels indicate complications of cirrhosis. We hypothesized that HDL-associated apolipoproteins in ascitic fluid (AF) are differentially abundant during spontaneous bacterial peritonitis (SBP). Serum and non-infected AF samples from 18 patients with cirrhosis (cohort 1) were analyzed using LC–MS/MS to identify differentially regulated apolipoproteins. In cohort 2, samples from 59 patients with SBP and 59 without were analyzed for AF apoA-II and apoA-I concentrations using ELISA, and cumulative 90-day transplant-free survival was analyzed. Proteomic analysis indicated depletion of AF apoA-II in the absence of SBP. Lower AF apoA-II and apoA-I correlated with lower AF protein and albumin, higher serum bilirubin, and lower platelets. During SBP, AF apoA-II levels significantly increased, leading to higher apoA-II/apoA-I ratios. AF apoA-II, but not apoA-I, correlated with peritoneal IL-6 concentrations. AF apoA-II > 45 µg/ml during SBP indicated an increased risk of death or transplantation within 90 days and remained a predictor of transplant or death after adjustment for age and MELD (adjusted hazard ratio, 2.59; 95% CI, 1.08–5.91; P = 0.032). In summary, the composition of HDL-associated apolipoproteins in ascites is altered during SBP and correlates with disease course.