Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infections

Background: Bacterial infections are common cause of morbidity and mortality in patients with cirrhosis. The early diagnosis of these infections is rather difficult. Aims: To assess the accuracy of acute phase proteins in the identification of bacterial infections. Methods: Concentration of C-reactive protein (CRP), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP), sCD14 and antimicrobial antibodies were measured in serum of 368 well-characterized patients with cirrhosis of whom 139 had documented infection. Clinical data was gathered by reviewing the patients' medical charts. Results: Serum levels of CRP, PCT and LBP were significantly higher in patients with clinically overt infections. Among the markers, CRP -using a 10 mg/L cut-off value-proved to be the most accurate in identifying patients with infection (AUC: 0.93). The accuracy of CRP, however, decreased in advanced stage of the disease, most probably because of the significantly elevated CRP levels in non-infected patients. Combination of CRP and PCT increased the sensitivity and negative predictive value, compared with CRP on its own, by 10 and 5% respectively. During a 3-month followup period in patients without overt infections, Kaplan-Meier and proportional Cox-regression analyses showed that a CRP value of > 10 mg/L (P = 0.035) was independently associated with a shorter duration to progress to clinically significant bacterial infections. There was no correlation between acute phase protein levels and antimicrobial seroreactivity. Conclusions: C-reactive protein on its own is a sensitive screening test for the presence of bacterial infections in cirrhosis and is also a useful marker to predict the likelihood of clinically significant bacterial infections in patients without overt infections.