title: Association between serum soluble CD14 and IL-8 levels and clinical outcome in primary biliary cholangitis.
abstract: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by portal inflammation and immune-mediated destruction of intrahepatic bile ducts that often leads to liver decompensation and liver failure. Although the biochemical response to ursodeoxycholic acid (UDCA) can predict disease outcome in PBC, few biomarkers have been identified as prognostic tools applicable prior to UDCA treatment. We therefore sought to identify such indicators of long-term outcome in PBC in the Japanese population.
  
  
  
  The prebiopsy serum samples and subsequent clinical data of 136 patients with PBC treated with UDCA were analysed over a median follow-up period of 8.8 years. Serum levels of biomarkers related to microbial translocation (sCD14, EndoCAb and I-FABP) were measured along with those of 33 cytokines and chemokines and additional auto-antibodies. Associations between the tested parameters and the clinical outcomes of liver decompensation and liver-related death/liver transplantation were evaluated using the Cox proportional hazards model with stepwise methods and Kaplan-Meier analysis.
  
  
  
  Elevated levels of serum IL-8, and sCD14 before UDCA therapy were significantly associated with both liver decompensation and liver-related death/liver transplantation. In multivariate analyses, IL-8≥46.5 pg/mL or sCD14≥2.0 μg/mL at enrolment demonstrated the same results. Kaplan-Meier analysis also revealed IL-8 and sCD14 to be significantly associated with a poor outcome. sCD14 was significantly correlated with IL-8. EndoCAb and I-FABP were not related to disease outcome.
  
  
  
  Serum IL-8 and sCD14 levels before UDCA therapy represent noninvasive surrogate markers of prognosis in patients with PBC.
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Takeji
authors.identifier: 0000-0001-7985-919X
authors.initials: T
authors.lastname: Umemura
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sekiguchi
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Joshita
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Fujimori
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ichikawa
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Michiharu
authors.initials: M
authors.lastname: Komatsu
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Inova Diagnostics, San Diego, CA, USA.
authors.forename: Zakera
authors.initials: Z
authors.lastname: Shums
authors.affiliation: Inova Diagnostics, San Diego, CA, USA.
authors.forename: Gary L
authors.identifier: 0000-0001-8992-1866
authors.initials: GL
authors.lastname: Norman
authors.affiliation: Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
mesh_terms: D015415:Biomarkers / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D007564:Japan; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000628:therapy*; D017093:Liver Failure / Q000401:mortality*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D002756:Cholagogues and Choleretics; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D014580:Ursodeoxycholic Acid
keywords: decompensation; liver-related death; microbial translocation; primary biliary cholangitis; transplantation