Serum cytokine/chemokine profiles in acute exacerbation of chronic hepatitis B: Clinical and mechanistic implications
Journal
Journal of Gastroenterology and Hepatology (Australia)
Journal Volume
29
Journal Issue
8
Pages
1629-1636
Date Issued
2014
Author(s)
Wu H.-L.
Chen T.-C
Wu W.-H
Abstract
Background and Aims: 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. ? 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
SDGs
Other Subjects
alanine aminotransferase; chemokine; CXCL9 chemokine; cytokine; gamma interferon; gamma interferon inducible protein 10; hepatitis B(e) antigen; interleukin 10; interleukin 2; interleukin 4; interleukin 6; interleukin 8; monocyte chemotactic protein 1; RANTES; tumor necrosis factor alpha; virus DNA; alanine aminotransferase; biological marker; chemokine; cytokine; gamma interferon inducible protein 10; interleukin 10; interleukin 4; interleukin 6; virus DNA; acute exacerbation; adult; alanine aminotransferase blood level; article; chronic hepatitis; clinical feature; disease association; disease course; disease exacerbation; female; hepatitis B; Hepatitis B virus genotype B; Hepatitis B virus genotype C; human; major clinical study; male; priority journal; prospective study; protein blood level; protein expression; receiver operating characteristic; virus load; virus replication; blood; follow up; genetics; hepatitis B; Hepatitis B virus; middle aged; virology; Adult; Alanine Transaminase; Biological Markers; Chemokine CXCL10; Chemokines; Cytokines; Disease Progression; DNA, Viral; Female; Follow-Up Studies; Hepatitis B virus; Hepatitis B, Chronic; Humans; Interleukin-10; Interleukin-4; Interleukin-6; Male; Middle Aged; Viral Load
Publisher
Blackwell Publishing
Type
journal article