814 Xibing G et al. response did not increase in the 49 patients before their disease deteriorated (P > 0.05). The nonspecific and HBV-specific cellular immunity parameters, determined on an average of 10 days after admission—i.e. after the disease in 49 cases progressed to severe liver disease—are listed in Table 5. The mean CD4+, CD4+/CD8+, and NK cell levels in Group A were significant- ly lower than in Group B (P < 0.01), and the mean CD8+ and nonspecific CTL values in Group A were significantly higher than in Group B (P < 0.01). However, the HBV-spe- cific CTL count was higher in Group A than in Group B (0.33 vs. 0.30) (P < 0.01). 4.4. Comparison of T Cell Subgroups, HBV Specific CTLs, Nonspecific CTLs, and NK Cells in Group A before and after Disease Progression to Severe Liver Disease The T cell subgroup, HBV-specific CTL, nonspecific CTL, and NK cell levels in Group A before and after progres- sion to chronic severe hepatitis B and Group B at base- line and 10 days after admission are listed in Table 6. After deterioration of the disease, the mean values of CD4+, CD4+/CD8+, and NK cell levels decreased significantly (P < 0.01), the change in CD3+ T cells was not significant (P > 0.05), and the mean values of CD8+ and nonspecific CTL increased significantly (P < 0.01), whereas the HBV-specif- ic CTL response did not show any significant change (P > 0.05). All 7 parameters of cellular immunity in Group B did not show any significant changes between baseline and 10 days after admission (P > 0.05), except for a de- crease in HBV-specific CTL responses (Table 6). 5. Discussion The results of the present study show that there were significant increases in peripheral blood CD8+ cells and nonspecific CTLs in patients with chronic severe hepa- titis B (early stage), suggesting that the immunological pathogenesis of chronic severe hepatitis B is related to significant increases in CD8+ and nonspecific CTL levels and these increases can predict that CHB will progress to severe hepatitis. In China, most cases of severe chronic hepatitis result from HBV infection. Chronic severe hepa- titis B progresses rapidly and is difficult to manage. The mortality rate of severe chronic hepatitis is over 50% (4, 5), and 36.9% of cases with chronic severe hepatitis occurred on the basis of CHB (6). Preventing or halting the deterioration can obviously improve the prognosis of CHB patients. To do so, it is necessary to determine or predict in which CHB patients the disease will progress to severe hepatitis so that corresponding measures can be taken. It is commonly believed that the pathogenesis of hepatitis B is the consequence of cellular immune re- sponses that cause damage to the liver, although they are aimed primarily at removing HBV from the liver tissue (1). The exacerbation of chronic hepatitis is mainly due to the action of CD8+ CTLs, which kill liver cells directly through double identification of major histocompatibil- Cellular Immunity after Chronic Hepatitis B ity complex (MHC) antigen and hepatitis B antigen (7). In an animal model of severe hepatitis, Ando et al. dem- onstrated that CD8+ cells cause the necrosis of many liver cells through cellular immunity (8). However, recent studies suggest that cellular immune mechanisms for eliminating HBV can be divided into specific and non- specific responses (3). Specific cellular immune respons- es of the body that are induced by the virus may be an important factor in eliminating the virus (9). There are two routes for virus-specific CTLs to remove HBV: cyto- toxic and noncytolytic (10). In the noncytotoxic route, specific T lymphocytes only clear the virus from target cells, without injuring the target cell itself. In the process of clearing the virus by specific T cells, the noncytolytic route may play a more important role (11). Nonspecific cellular immunity is relatively weak in clearing HBV, but it may cause liver cell injuries in the process (12-14). Thus, we studied the changes in HBV-specific and nonspecific cellular immune responses before and after CHB pro- gressed to chronic severe hepatitis B to provide evidence for the rational treatment, control, and prevention of de- terioration of CHB. In this study, CD3+, CD4+, CD4+:CD8+ ratio, and NK cell levels in 255 CHB patients were lower than in healthy controls (P < 0.01). CD8+ and nonspecific CTL levels were higher than in healthy controls (P < 0.01), which clearly indicates that cellular immunity in CHB patients is dys- functional. The levels of CD4+ and NK cells of Group A (i.e., patients whose disease progressed to severe hepatitis) were lower than in the same patients on Day 2 (baseline) of admission (P < 0.01), which were lower than Group B baseline levels (P < 0.01), and the latter was lower than in the healthy control group (P < 0.01). These levels in Group A after progression to severe hepatitis were lower than in Group B 10 days after admission (P < 0.01). The levels of CD8+ and nonspecific CTLs in Group A after progression to severe hepatitis were higher than in the same group at baseline (P < 0.01), which were higher than the baseline levels in Group B (P < 0.01), and the latter was higher than in the healthy control group (P < 0.01). These parameters in Group A after deterioration to severe hepatitis were higher than in Group B 10 days after admission (P < 0.01). In patients with chronic severe hepatitis B, CD4+ levels decrease and CD8+ levels increase (15). The CD8+ T cells that increase in patients with viral hepatitis are mainly CTL (15). Our study also demonstrates this phenomenon. HBV-specific CTL levels were not associated with dete- rioration of the disease, since there was no significant difference in specific CTL levels between Groups A and B at baseline (P > 0.05) or in Group A before and after the disease progressed to severe hepatitis (P > 0.05). On the other hand, in patients with severe chronic hepatitis, NK cells may migrate to the target cells via chemotaxis and exert antiviral actions or kill liver cells directly, which can reduce NK cell numbers (16). This study shows that peripheral blood CD8+ and nonspecific CTLs in patients with chronic severe hepatitis B (early stage) increased significantly compared with CHB patients whose disease Hepat Mon. 2011;11(10):810-815