title: Serum levels of interleukin-22 and hepatitis B core-related antigen are associated with treatment response to entecavir therapy in chronic hepatitis B.
abstract: OBJECTIVE
  We sought to clarify the associations between serum cytokines and chemokines, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and hepatitis B virus (HBV) DNA and response to entecavir therapy in chronic hepatitis B.
  
  
  METHODS
  We analyzed six cytokines (interleukin [IL]-2, IL-6, IL-10, IL-12p70, IL-21 and IL-22) and five chemokines (CCL2, CCL3, CXCL9, CXCL10 and CXCL11) before and at 6, 12 and 24 months during entecavir therapy in 48 chronic hepatitis B patients. Quantitative measurement of HBsAg, HBcrAg and HBV DNA was performed. A virological response (VR) was defined as serum HBV DNA of less than 2.1 log copies/mL by treatment month 24.
  
  
  RESULTS
  Thirty-nine patients (81%) achieved a VR. Serum IL-6 (P = 0.031), CXCL-9 (P = 0.002), and CXCL-10 (P = 0.001) were high in chronic HBV and correlated positively with transaminases and bilirubin. Before treatment, elevated IL-22 (P = 0.031) and lower HBsAg (P = 0.001) and HBcrAg (P < 0.001), but not HBV DNA, were associated with a favorable treatment outcome. In multivariate analysis, high IL-22 (hazard ratio = 13.67, P = 0.046) and low HBcrAg (hazard ratio = 10.88, P = 0.048) were independently associated with a VR. The levels of IL-22 (P < 0.001), HBsAg (P < 0.001), and HBcrAg (P < 0.001) all decreased from baseline to 24 months of treatment in virological responders.
  
  
  CONCLUSIONS
  Serum IL-22 and HBcrAg are predictive markers of a VR to entecavir therapy in patients with chronic hepatitis B.
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Matsumoto, Japan.
authors.forename: Sadahisa
authors.initials: S
authors.lastname: Okuhara
authors.forename: Takeji
authors.initials: T
authors.lastname: Umemura
authors.forename: Satoru
authors.initials: S
authors.lastname: Joshita
authors.forename: Soichiro
authors.initials: S
authors.lastname: Shibata
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kimura
authors.forename: Susumu
authors.initials: S
authors.lastname: Morita
authors.forename: Michiharu
authors.initials: M
authors.lastname: Komatsu
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Kaname
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
keywords: entecavir; hepatitis B core-related antigen; hepatitis B surface antigen; hepatitis B virus; interleukin-22