Mechanism of T cell hyporesponsiveness to HBcAg is associated with regulatory T cells in chronic hepatitis B

AIM： To study the mechanisms of hyporesponsiveness of HBV-specific CD4^＋ T cells by testing TH1 and TH2 commitment and regulatory T cells. METHODS： Nine patients with chronic hepatitis B were enrolled. Peripheral blood mononuclear cells were stimulated with HBcAg or HBsAg to evaluate their potential to commit to TH1 and TH2 differentiation. HBcAg-specific activity of regulatory T cells was evaluated by staining with antibodies to CD4, CD25, CTLA-4 and interleukin-10. The role of regulatory T cells was further assessed by treatment with anti-interleukin-10 antibody and depletion of CD4^＋CD25^＋ cells. RESULTS： Level of mRNAs for T-bet, IL-12R β2 and IL-4 was significantly lower in the patients than in healthy subjects with HBcAg stimulation. Although populations of CD4^＋CD25^highCTLA-4^＋ T cells were not different between the patients and healthy subjects, IL-10 secreting cells were found in CD4^＋ cells and CD4^＋CD25^＋ cells in the patients in response to HBcAg, and they were not found in cells which were stimulated with HBsAg. Addition of anti-IL-10 antibody recovered the amount of HBcAgspecific TH1 antibody compared with control antibody （P 〈 0.01, 0.34% ± 0.12% vs 0.15% ± 0.04%）. Deletion of CD4^＋CD25^＋ T cells increased the amount of HBcAgspecific TH1 antibody when compared with lymphoo/tes reconstituted using regulatory T cells （P 〈 0.01, 0.03% ± 0.02% vs 0.18% ± 0.05%）.CONCLUSION： The results indicate that the mechanism of T cell hyporesponsiveness to HBcAg includes activation of HBcAg-induced regulatory T cells in contrast to an increase in TH2-committed cells in response to HBsAg.

Pegylated interferon plus ribavirin for genotype Ib chronic hepatitis C in Japan

AIM:To evaluate the efficacy of pegylated interferon α-2b(peg-IFNα-2b) plus ribavirin(RBV) therapy in Japanese patients with chronic hepatitis C(CHC) genotype Ib and a high viral load.METHODS:One hundred and twenty CHC patients(58.3% male) who received peg-IFNα-2b plus RBV therapy for 48 wk were enrolled.Sustained virological response(SVR) and clinical parameters were evaluated.RESULTS:One hundred(83.3%) of 120 patients completed 48 wk of treatment.53 patients(44.3%) achieved SVR.Early virological response(EVR) and end of treatment response(ETR) rates were 50% and 73.3%,respectively.The clinical parameters(SVR vs non-SVR) associated with SVR,ALT(108.4 IU/L vs 74.5 IU/L,P = 0.063),EVR(76.4% vs 16.4%,P < 0.0001),adherence to peg-IFN(≥ 80% of planned dose) at week 12(48.1% vs 13.6%,P = 0.00036),adherence to peg-IFN at week 48(54.7% vs 16.2%,P < 0.0001) and adherence to RBV at week 48(56.1% vs 32.1%,P = 0.0102) were determined using univariate analysis,and EVR and adherence to peg-IFN at week 48 were determined using multivariate analysis.In the older patient group(> 56 years),SVR in females was significantly lower than that in males(17% vs 50%,P = 0.0262).EVR and adherence to Peg-IFN were demonstrated to be the main factors associated with SVR.CONCLUSION:Peg-IFNα-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients with CHC and resulted in a SVR rate of 44.3%.Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFNα-2b is important in improving the SVR rate.