| Objective:To investigate the change of the proportion of CD4+CD25+ regulatory T lymphocytes(Treg) in peripheral blood,sera level of TNF-α,IFN-γ,IL-10,IL-18 and their significance in patients with chronic severe hepatitis B treated by nucleotide analog. Methods:30 chronic severe hepatitis B patients and 30 chronic hepatitis B(CHB) as control group were recruited. Flow cytometry was used to detect the proportion of Treg before they were treated by nucleotide analog(week 0), at week 2, week 3 and week 4. Flow cytometry was used to detect the amount of peripheral blood CD4+ T lymphocyte and CD8+ T lymphocyte at week 0. 20 patients with chronic severe hepatitis B and 27 patients with CHB was detected their sera level of TNF-α,IFN-γ,IL-10 and IL-18 with ELISA. Results:The results showed that the proportion of Treg(1.4%) in patients with chronic severe hepatitis B was higher than that(0.4%) in CHB(t′=2.68, P=0.011). Comparing the proportion of peripheral blood Treg(1.5±2.0)% in dead patients with that(1.4±2.0)% in survival patients before therapy had no statistic difference(t=-0.18, P=0.858). We found that the Treg declined markedly in survival patients with chronic severe hepatitis B after nucleotide analog therapy. Proportion of Treg detected subsequently at week 2 had no statistic difference in patients who was dead(t=-0.45, P=0.66). Proportion of Treg detected subsequently at week 4 had statistic difference in survival patients(t=3.233, P=0.014). The results showed that the serum level of TNF-α(20.691±13.689) pg/mL in patients with chronic severe hepatitis B was lower than that(48.977±49.257) pg/mL in CHB(t=-2.839, P=0.008). The serum level of IFN-γ(51.294±40.927) pg/mL in patients with chronic severe hepatitis B was lower than that(227.295±283.417) pg/mL in CHB(t=-3.182, P=0.004). The serum level of IL-10(107.133±52.708) pg/mL in patients with chronic severe hepatitis B was lower than that(141.89±84.466) pg/mL in CHB(t=-1.731, P=0.09). The serum level of IL-18(343.846±200.828) pg/mL in patients with chronic severe hepatitis B was higher than that(208.662±116.062) pg/mL in CHB(t=2.909, P=0.006). Comparing the sera level of TNF-α,IFN-γand IL-10 in dead patients with that in survival patients had no statistic difference before therapy. IL-18 level detected subsequently at week 4 had statistic difference in survival patients(t=4.351, P=0.002). The amount of peripheral blood CD4+ T lymphocyte(389±249)/μL in patients with chronic severe hepatitis B was lower than that(525±204)/μL in CHB(t=-2.303, P=0.025). Comparing the amount of peripheral blood CD8+ T lymphocyte(222±206)/μL in patients with chronic severe hepatitis B with that(292±208)/μL in CHB patients had no statistic difference(t=-1.309, P=0.196). Conclusion:The proportion of Treg in patients with chronic severe hepatitis B decline by nucleotide analog therapy. Treg,TNF-α,IFN-γand IL-18 participate in the immune regulating in patients with chronic severe hepatitis B. And they maybe play an important role in the development of the disease. Treg and IL-18 may be regarded as one of the marks in judging the prognosis of chronic severe hepatitis B following treatment of nucleotide analog. |
