Genetic variation of IL-28B is associated with treatment response of patients with chronic hepatitis C / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the effect of IL-28B variation on the response of patients with chronic hepatitis C virus (HCV) infection to therapy.</p><p><b>METHODS</b>A total of 220 patients with chronic hepatitis C (CHC) were prospectively treated with pegilated interferon (peg-IFN) in combination with ribavirin (RBV) for 48 weeks. After completing the therapy, the patients were followed-up for 24 weeks and the therapeutic effectiveness was evaluated. The rs8099917 was identified from each cohort. The IL28B genotype was compared in hepatitis C patients to assess the effect of single nucleotide polymorphism (SNP) on different treatment response.</p><p><b>RESULT</b>The proportion of the rs8099917 TT, TG, and GG genotypes was 71.4%, 25.0%, and 3.6% in sustained viral response (SVR) group; 15.8%, 60.5%, 23.7% in null response (NR) group; 38.1%, 52.3%, 9.6% in relapse (RP) group. There was a statistically significant difference in the genotype among SVR, NR and RP groups (P < 0.001, Chi-square test). NR vs. SVR (TG vs. TT: OR = 7.67, 95% CI: 2.91-20.56, P < 0.001). RP vs. SVR (TG vs. TT: OR = 3.10, 95% CI: 1.14-6.36, P < 0.01).</p><p><b>CONCLUSIONS</b>The genotypes of IL-28 B (rs8099917) is closely related to the effectiveness of peg-IFN-alpha/RBV therapy, and it is an important predictive factor before treatment in patients with chronic hepatitis C.</p>

Genetic polymorphisms of IL-28B are associated with sustained virologic response in patients with chronic hepatitis C / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the relationship between polymorphism in the interleukin (IL)-28B gene and sustained virologic response (SVR) in chronic hepatitis C (CHC) patients.</p><p><b>METHODS</b>A total of 220 patients with CHC were prospectively treated with pegylated-interferon (peg-IFN) in combination with ribavirin (RBV) for 48 weeks, and followed-up for an additional 24 weeks. All patients were genotyped for the rs8099917 polymorphism and correlations with antiviral efficacy were determined by statistical analysis.</p><p><b>RESULTS</b>One-hundred-and-eighty-two (82.7%) of the patients achieved end-of-treatment virological response (ETVR). Significantly more patients in the ETVR group carried the rs8099917 genotypes of TT (93.5%) and GT+GG (68.8%), compared to the patients who did not achieve ETVR (X2=23.287, P less than 0.01). In addition, the patients who achieved SVR also represented significantly higher rates of both genotypes (TT: 86.2% and GT+GG: 60.6%; X2=15.531, P less than 0.01). In the SVR group: TT vs. GT+GG: odds ratio (OR)=4.063, 95% confidence interval (CI): 1.972-8.369; X2=15.531, P less than 0.01. In the RP group: TT vs. GT+GG: OR=0.246, 95% CI: 0.119-0.507; X2=15.531, P less than 0.01).</p><p><b>CONCLUSION</b>The IL-28B rs8099917 genotype is closely related to antiviral response of patients with chronic hepatitis C. Compared to carriers of the GT and GG genotypes, carriers of the TT genotype have higher SVR rates and lower RP rates. The TT genotype may be an important predictor of antiviral efficacy.</p>

Relationship between the genetic variation in interleukin 28B and response to antiviral therapy in patients with chronic hepatitis C / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Genetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. The aim of this research was to evaluate the role of IL-28B single nucleotide polymorphism (SNP) variations in Chinese patients undergoing pegylated interferon-α plus ribavirin (PEG-IFN-α/RBV) treatment.</p><p><b>METHODS</b>To determine the effect of IL-28B variation on the response to HCV therapy, these variants were genotyped in a cohort of 220 patients who were chronically infected with HCV and received combined PEG-IFN-α/RBV therapy.</p><p><b>RESULTS</b>The proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6% respectively, in the sustained virological response (SVR) group; 15.8%, 60.5%, and 23.7% respectively, in the null virological response (NVR) group; and 38.1%, 52.4%, and 9.5% respectively, in the relapse (Rel) group (P < 0.05). Logistic regression analysis showed that, compared to those having the CC genotype, CT heterozygotes had an increased risk of NVR and Rel (OR = 10.95, 95%CI = 4.12-29.11, P = 1.5×10(-7) and OR = 3.93, 95%CI = 1.86-8.32, P = 2.1×10(-4) respectively). The RNA quantification assay showed that patients with genotype CC exhibited much higher levels of IL-28 expression than those with genotype CT or TT (P < 0.001).</p><p><b>CONCLUSIONS</b>The IL-28B SNP rs12979860 genotype was related to the effectiveness of HCV therapy: patients with the CC rs12979860 genotype had higher rates of SVR than those with the CT or TT genotype, and the CC genotype revealed a significantly higher level of IL-28 mRNA expression.</p>

Safety evaluation and quality control of MSCs from hepatitis B patient in vitro / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To get mesenchymal stem cells (MSCs) from hepatitis B patient and to valuate the safety and quality after long-term culture in vitro.</p><p><b>METHODS</b>The cells obtained directly from bone marrow and cultured in Mesen Pro medium supplemented with FGF, and the morphology of MSCs was observed. Surface antigens of the MSCs were analyzed by flow-cytometry. The bacteria, virus, endotoxin and residual serum of cell suspension were detected. The MSCs and perpheral blood T lymphocytes were co-cultured in 48 well plates for 72 h and the T lymphocyte proliferation was measured by using MTT reduction method and the effect of MSCs on T lymphocyte transformation stimulated by PHA was also observed. The oncogenicity of MSCs was verified by the tumorigenesis test in sofo agar. The genetic stability of MSCs was examined by karyotype analysis.</p><p><b>RESULT</b>The MSCs from hepatitis B patient could be passaged to many generations and had strong abilities of proliferation. They expressed stem cell-surface antigens and maintained normal karyotype, prevented the pollution of bacteria and viruses, inhibited the immune response of allogenic T lymphocytes and no oncogenicity found.</p><p><b>CONCLUSION</b>The MSCs have proliferative potentials, can be passaged in long-term cultures in Mesen Pro medium without oncogenicity, can maintain normal karyotype, can inhibit the immune response of T lymphocytes and can alleviate the grafe-versus diseases. The MSCs can be served as a new type of cells in cell and gene therapy.</p>

Study on HBV antigens and IL-12 affecting T cell-mediated immunity in HBsAg carriers / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of HBV antigens and pathological mechanism of chronic HBV infection by analyzing the cellular immune function of peripheral blood mononuclear cells (PBMCs) from HBsAg carriers.</p><p><b>METHODS</b>PBMCs were prepared from individuals with chronic asymptomatic HBV infection and cultured in the presence of different antigens and/ or cytokines. The levels of cytokines in culture supernatants were detected by ELISA method. The phenotype of the cells was detected by FACS.</p><p><b>RESULTS</b>The levels of IFN y secreted by PBMCs from HBsAg carriers were (48.3+/-19.8) pg/ml, significantly lower than that from healthy controls (t = 3.023, P less than 0.05); The IFN y produced by PBMCs from HBeAg positive patients due to HBsAg and HBcAg stimulation were (50.4+/-51.6) pg/ml and (63.2+/-36.9) pg/ml, significantly lower than that of HBeAg negative patients (t = 2.468 and 3.184, P less than 0.05, respectively). The IL-12p70 secreted by PBMCs from HBeAg positive patients was also significantly lower than that of HBeAg negative patients (P less than 0.05); Exogenous IL-12 promoted significantly PBMCs to secrete IFN y (P less than 0.01) and IL-12 combined with HBV antigens activated CD8+CD45RA+CCR7+ and CD8+CD45RA-CD62L+ cells. IL-12 secreted by PBMCs decreased in HBeAg positive patients, which may be the crucial reason of viral persistence in chronic HBV carriers. Exogenous IL-12 combined with specific HBV antigen could promote the central memory CD8+ T cells to produce IFN y.</p>