title: IL-6 significantly correlates with p-STAT3 expression and presents high variceal bleeding with mortality in cirrhotic patients: A cross-sectional study.
abstract: OBJECTIVE
  Effective mediators activate downstream transducers regulating inflammation and angiogenesis. Correlation among mediators IL-6, IL-27, TNF-α, and VEGF with STAT proteins at diverse clinical-pathologic stages of cirrhotic patients remains limited.
  
  
  METHODS
  Plasma mediators were assayed from 158 naïve liver cirrhosis (LC-total group) and 144 non-LC individuals. The LC-total group included 69 hepatitis B virus-infected (LC-HBV) patients, 40 hepatitis C virus-infected (LC-HCV) patients, and 49 patients without HBV-/HCV- infection (LC-NBNC). Another 144 non-LC individuals comprised 54 healthy persons (HG) and 90 chronic hepatitis patients (CH-total) as the control group. To correlate with plasma mediators, 52 paired liver tissues (CH: 41 and LC: 11 cases) served for p-STAT1 and p-STAT3 immunostaining.
  
  
  RESULTS
  Although IL-6, IL-27, TNF-α, and VEGF were expressed significantly in CH-total versus HG (p = 0.011, p < 0.001, p = 0.007, p = 0.004, respectively) and overall viral hepatitis patients versus HG (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively), only IL-6 presented the strongest correlation in cirrhotic patients than noncirrhotic patients (LC-HBV vs. HG, p < 0.001, vs. CH-HBV, p = 0.001; LC-HCV vs. HG, p = 0.001, vs. CH-HCV, p = 0.031; LC-NBNC vs. HG, p < 0.001). Over-expressed IL-6 linked with poorer liver function (albumin: r = -0.346, p < 0.001; bilirubin: r = 0.271, p = 0.001; INR: r = 0.308, p < 0.001; Child-Turcotte-Pugh Classification C vs. A or B, p = 0.001, p = 0.007, respectively), variceal severity (p = 0.045), and bleeding (p = 0.047), as well as patients' mortality (p = 0.005). Furthermore, plasma IL-6 significantly correlated with tissues p-STAT3 expression (r = 0.737, p = 0.010) (IL-27: r = 0.078, p = 0.820; TNF-α: r = -0.145, p = 0.670; VEGF: r = 0.142, p = 0.678) in cirrhotic patients than noncirrhotic patients.
  
  
  CONCLUSIONS
  Over-expression of IL-6 reflects hepatic dysfunction and varices bleeding with mortality, as well as correlates p-STAT3 expression in cirrhotic patients.
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Jung-Ta
authors.initials: JT
authors.lastname: Kao
authors.affiliation: Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Cheng-Ju
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Lung
authors.initials: CL
authors.lastname: Feng
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Tsai
authors.affiliation: School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Yao-Li
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan. Electronic address: yyw@mail.cmu.edu.tw.
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D004932:Esophageal and Gastric Varices / Q000150:complications*; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology* / Q000401:mortality*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D050796:STAT3 Transcription Factor / Q000097:blood*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Cirrhotic patients; HBV/HCV infection; IL-6; p-STAT3