title: Serum cytokine/chemokine profiles in acute exacerbation of chronic hepatitis B: clinical and mechanistic implications.
abstract: OBJECTIVE
  Acute exacerbation (AE) of chronic hepatitis B virus (HBV) infection is common and negatively impacts the clinical outcome. Although upsurge of viral load always precedes or coincides with AE, the underlying immunological mechanisms remain unclear and were investigated.
  
  
  METHODS
  We prospectively followed the serum cytokine/chemokine profiles, viral load, and alanine aminotransferase (ALT) levels in 250 patients and identified 44 consecutive patients (male: 72.7%; age: 40.4 ± 9.7 years; hepatitis B e antigen [HBeAg] positivity: 63.6%; genotype B/C: 75%/25%) who developed AE during the follow-up in a medical center. The impact of clinical characteristics (age, gender, HBeAg, ALT, HBV genotype), cytokines (tumor necrosis factor-alpha, interferon gamma, interleukin [IL]-2, IL-4, IL-6, and IL-10), and chemokines (CXCL10/interferon gamma-induced protein [IP]-10, CCL2/MCP-1, CXCL9/MIG, CCL5/RANTES, and CXCL8/IL-8) on the serum HBV DNA dynamics at different time points (baseline, peak of serum HBV DNA level, peak of serum ALT level, and after AE) were analyzed.
  
  
  RESULTS
  Of 44 patients, serum HBV DNA level surged before the peak of serum ALT level in 23 (52.3%), and coincided with the peak of ALT in 21 (47.7%). The upsurge of serum viral load significantly correlated with the increase of IL-10 (P = 0.0037) and CXCL10/IP-10 (P = 0.0044). Upsurge of serum viral load was preceded by an increase in serum IL-4 (P < 0.05), IL-6 (P < 0.05), and IL-10 (P < 0.05). Combination of HBV genotype, IL-6 level at baseline, and ALT level at the peak of serum HBV DNA reliably predicted subsequent AE pattern (P = 0.0116).
  
  
  CONCLUSIONS
  Enhanced Th2 activity is likely involved in the surge of HBV DNA level before hepatitis exacerbation.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Wu
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.forename: Ting-Chih
authors.initials: TC
authors.lastname: Chen
authors.forename: Wen-Hsuan
authors.initials: WH
authors.lastname: Wu
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Liu
authors.forename: Tung-Hung
authors.initials: TH
authors.lastname: Su
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Yang
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood; D018925:Chemokines / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000821:virology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; D018925:Chemokines; D016207:Cytokines; D004279:DNA, Viral; D015850:Interleukin-6; D016753:Interleukin-10; D015847:Interleukin-4; D000410:Alanine Transaminase
keywords: acute exacerbation; chemokine; cytokine; hepatitis B