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Copyright ©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Oct 21, 2014; 20(39): 14156-14171
Published online Oct 21, 2014. doi: 10.3748/wjg.v20.i39.14156
Table 1 Immunologic characteristics of the stages of chronic hepatitis B
Stage of CHBMarkers of stageT cell subsets
Th1Th2Th17TregCTL
Immune tolerance stageHBsAg+ HBeAg+ HBeAb- HBV DNA + ALT normal Liver histology: normal or mild inflammation[56]Inactive HBe/HBc-specific Th1[53]Predominance of HBeAg-specific Th2 cells. Predominance of anti-inflammatory cytokines - IL-4, IL-5, IL-10[53,56]Significant accumulation of CD4+CD25+ FoxP3+ Treg cells in the liver. CD8+ CTLA-4+ FoxP3+ Treg cells present[117]
Immune clearance stageHBsAg+ HBeAg+ HBeAb- HBV DNA + ALT ↑ Liver histology: active inflammation[56]Intrahepatic CD4+ T cells are mostly Th1 cells. Predominance of IL-2, IFNγ, TNFα cytokines[141]Inactive HBe-specific Th2 clones with low avidity[141]High content of Th17 in the liver[126] and in the blood[127]Treg cells elevate in the beginning and then fall in the liver and elevate in the blood[123,128,132]HBcAg-specific CD8+ CTLs increase in the liver[34] but not in the blood[56,142]
Inactive HBsAg carrier stageHBsAg+ HBeAg- HBeAb+ HBV DNA+ ALT normal/↑Predominance of inflammatory Th1 cells[56]HBV-specific central memory CD8+ T cell response[143]
Liver histology: mild inflammation or inactive cirrhosis[56]Low HBV-specific immune responses[84]
Reactivation stageHBsAg+ HBeAg- HBeAb+ HBV DNA +/- ALT normal/↑ Liver histology: from normal to cirrhosis and hepatocellular carcinoma[56]Predominance of inflammatory Th1 cells[56]HBeAg-specific Th2 cells fall down[56]CD8+ CTLs fall down[144]
Anergy of HBc/HBeAg and HBeAg specific T-cells in the liver[117] Serum cytokine levels (interferon IFNγ, TNFα, IL-1β, IL-4, IL-12, IL-10, IL-2, IL-5, IL-8) are evaluated[145]
CHB: Chronic hepatitis B; Th: T helper; Tregs: Regulatory T cells; CTL: Cytotoxic T cells; IL: Interleukin; ALT: Alanine transaminase; INF: Interferon; TNF: Tumor necrosis factor; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; HBcAb: Hepatitis B virus core antibody; HBV: Hepatitis B virus.