title: Interleukin-6 as an early diagnostic marker for bacterial sepsis in patients with liver cirrhosis.
abstract: OBJECTIVE
  Liver cirrhosis is associated with frequent bacterial infections that increase the mortality rate. However, the early diagnosis and treatment of these infections are often difficult. In this retrospective-prospective observational study, the serum levels of interleukin-6 (IL-6) and procalcitonin (PCT) were measured in 233 cirrhotic patients to evaluate the early diagnostic and prognostic values of IL-6 and PCT for cirrhotic patients.
  
  
  METHODS
  Cirrhotic patients admitted to the Liver Research Center of the First Affiliated Hospital of Fujian Medical University between 1 October 2012 and 30 June 2014 were enrolled. They showed no evidence of infection on admission, and all had first onset of fever and met the systemic inflammatory response syndrome criteria 72 hours after admission. The serum IL-6 and PCT levels were determined on admission, at the onset of fever (0 hour) and 24 and 48 hours after fever onset.
  
  
  RESULTS
  A total of 233 cirrhotic patients, including 183 men and 50 women, with a median age of 56 (46-65) years were enrolled. A training group of 159 patients was retrospectively enrolled from 1 October 2012 to 31 December 2013, and a validation group of 74 patients was prospectively enrolled from 1 January 2014 to 30 June 2014. Among these patients, 134 were diagnosed with bacterial sepsis, 96 of whom were in the training group and 38 of whom were in the validation group; infections were ultimately ruled out in 99 patients: 63 training patients and 36 validation patients. At 0 hour, the IL-6 and PCT levels as well as the proportion of neutrophils were much higher in septic patients than in nonseptic ones. The IL-6 level and proportion of neutrophils peaked upon the onset of fever, 24 hours before the PCT levels and white blood cell count, and then sharply declined. The area under the receiver operating characteristic curve of IL-6 for diagnosing sepsis was largest at the onset of fever (area under the receiver operating characteristic curve, 0.983; 95% confidence interval, 0.967-0.999). The threshold of IL-6 for diagnosis was 135 pg/mL, with a sensitivity of 94.8% and a specificity of 93.7%. These diagnostic values were also confirmed in the validation group, with a sensitivity of 97.4% and specificity of 80.6%. Eleven (11.5%) patients died, and 85 (88.5%) patients recovered in the sepsis group of training patients after a 4-week follow-up. The IL-6 level was significantly higher in the nonsurvival group than that in the survival group (1813.00 vs 472.10 pg/mL, P = .004) at the onset of sepsis. The cutoff value for predicting prognosis was 1105 pg/mL, with a sensitivity of 81.8% and a specificity of 76.5%.
  
  
  CONCLUSIONS
  The serum IL-6 levels increased earlier than the PCT in septic cirrhotic patients. The direct measurement of the serum IL-6 level can help to rapidly detect bacterial infection, thus allowing for early therapeutic decisions and prognostic predictions.
authors.affiliation: Liver Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China.
authors.forename: Su
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, The First Hospital of Putian City, The training hospital of Fujian Medical University, Putian, Fujian, 351100, China.
authors.forename: Zhongtao
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Liver Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China.
authors.forename: Mingfang
authors.initials: M
authors.lastname: Wang
authors.affiliation: Cardiology of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Weng
authors.affiliation: Liver Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China.
authors.forename: Dawu
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Department of Infectious Diseases, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China.
authors.forename: Yanliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Liver Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China. Electronic address: ezhu066@sina.com.
authors.forename: Yueyong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Liver Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China.
authors.forename: Jiaji
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D016470:Bacteremia / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D015415:Biomarkers / Q000097:blood*; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D042241:Early Diagnosis; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D015850:Interleukin-6; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide
keywords: Bacterial sepsis; Cirrhosis; Interleukin-6; Procalcitonin