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Serum cytokine/chemokine profiles in acute exacerbation of chronic hepatitis B : Clinical and mechanistic implications
Author(s) -
Wu HuiLin,
Kao JiaHorng,
Chen TingChih,
Wu WenHsuan,
Liu ChenHua,
Su TungHung,
Yang HungChih,
Chen DingShinn,
Chen PeiJer,
Liu ChunJen
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12606
Subject(s) - medicine , exacerbation , immunology , viral load , chemokine , hbeag , hepatitis b , hepatitis b virus , cytokine , immune system , hbsag , virus
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 ( CXCL 10/interferon gamma‐induced protein [ IP ]‐10, CCL 2/ MCP ‐1, CXCL 9/ MIG , CCL 5/ RANTES , and CXCL 8/ 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 CXCL 10/ 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 T h2 activity is likely involved in the surge of HBV DNA level before hepatitis exacerbation.