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The production of high-sensitivity C-reactive protein (hs-CRP) may be affected by hepatic function, and the clinical importance of hs-CRP in patients with liver cirrhosis is still not clear. The aim of this study was to evaluate the clinical implications of hs-CRP in cirrhotic patients with spontaneous bacterial peritonitis (SBP).We retrospectively investigated 336 consecutive patients treated for SBP from 2007 to 2012. The relationship between serum hs-CRP and the result of the treatment was assessed.A response to antibiotics was observed in 182 patients (54.2%), and 126 patients (37.5%) died of SBP. The initial hs-CRP (odds ratio=1.061, P=0.016), coexistent hepatocellular carcinoma, and Child-Pugh (CP) score were independent prognostic factors for high in-hospital mortality. Serum hs-CRP level was also an independent predictor of lower antibiotic response rate (odds ratio=0.916, P<0.001). However, hs-CRP was negatively correlated with the CP score (r=−0.199, P<0.001) and Model for End-Stage Liver Disease score (r=−0.182, P=0.001).This study found that serum hs-CRP level is related to a lower response rate to antibiotics, a higher mortality rate in patients with SBP. The hs-CRP level was negatively correlated with the CP and Model for End-Stage Liver Disease scores, which suggests that the prognostic function of hs-CRP was not a surrogate for hepatic dysfunction.