Significance of T-Cell Subsets for Clinical Response to Peginterferon Alfa-2a Therapy in HBeAg-Positive Chronic Hepatitis B Patients

Li Zhu,1– 3,&ast; Jin Li,4,5,&ast; Junchi Xu,4,5 Fan Chen,2,3 Xunxun Wu,2,3 Chuanwu Zhu1– 3 1Department of Infectious Diseases, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Hepatology, the Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Hepatology, the Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, People’s Republic of China; 4Central Laboratory, the Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 5Central Laboratory, the Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanwu Zhu, Department of Infectious Diseases, the Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China, Email zhuchw@126.comIntroduction: The adaptive immune response may reflect the immunomodulatory efficacy during peginterferon alfa-2a (PEG-IFN α-2a) treatment in chronic hepatitis B (CHB) patients. We evaluated the predictive efficiency of T-cell subsets on patient’s response to PEG-IFN α-2a treatment.Methods: The proportions of CD8+PD-1+, CD8+Tim-3+ and CD4+CD25high T-cells were measured at baseline and week 52 in CHB patients who underwent PEG-IFN α-2a treatment. The proportions of T-cell subsets were compared among different responders and non-responders (determined by biochemical, serological, and virological responses).Results: The baseline proportions of the three T-cell subsets were significantly higher in CHB patients (65 cases) than in healthy controls (28 cases), while the proportions declined significantly after 52 weeks of PEG-IFN treatment. Responders (ALT < 40 IU/L, 89.2% [58/65]; HBV DNA < 2.7 log10 IU/ml, 66.2% [43/65]; and HBeAg seroconversion [SR], 53.9% [35/65]) experienced more pronounced declines in the proportion of T-cell subsets compared to non-responders. In particular, the baseline proportions of CD4+CD25high T-cells displayed significant difference between SR and non-SR groups. The stepwise logistic regression analysis identified that CD4+CD25high T-cells combined with baseline HBV DNA and ALT can predict SR and CR (ALT < 40 IU/L, HBV DNA < 2.7 log10 IU/mL and HBeAg seroconversion) after 52 weeks of PEG-IFN treatment with high accuracy.Conclusion: PEG-IFN therapy induces significant declines in the proportion of some key T-cell subsets in HBeAg-positive patients. The model constructed with CD4+CD25high T-cells combined with ATL and HBV DNA may help to predict the efficacy of PEG-IFN α-2a therapy.Keywords: PEG-IFN α-2a, chronic hepatitis B, clinical response, HBeAg seroconversion, T-cell subsets