Single nucleotide polymorphisms of the IL28B and sustained virologic response of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy: a meta-analysis

Hepatitis C is a global health problem and represents a major cause of liver disease and socioeconomic burden. Effective antiviral therapy may prevent these complications, but the current treatment for patients with chronic hepatitis C virus [HCV] infection does not produce sustained virologic response. Therefore, identification of the determinants of response to treatment is a high priority. A number of host and viral factors have been associated with treatment outcomes. To assess the associations of single nucleotide polymorphisms [SNP] of the IL28B and sustained virologic response [SVR] of patients with chronic hepatitis C to PEG-interferon/ ribavirin therapy. We searched PubMed, Medline and Cochrane Library, and found 7 eligible papers involved in this study. Then we performed a meta-analysis comparing the SVR rate of SNP of the IL28B in individuals with PEG-interferon/ribavirin therapy. Meanwhile, the SVR rate between different races and HCV genotypes was studied. The sustained virologic response rate was higher in patients with the rs12979860 CC and rs8099917 TT alleles in the IL28B SNP, comparing with the rs12979860 CT, or TT and rs8099917 TG or GG. Furthermore, a higher SVR was observed in the Caucasians than in Afro-Americans [OR =3.85, 95% CI:3.06-4.83]; the percentage of rs12979860 TT genotype was lower in Caucasians than that of Afro-Americans [OR=3.45, 95% CI=2.68-4.44]. Between different HCV genotypes, the SVR was much lower in those with HCV genotype 1 than those with genotype 2/3 [OR=0.16, 95%CI: 0.11-0.24]. IL28B is significantly associated with response of PEG-interferon/ ribavirin therapy of patients with chronic HCV infection. Both the rs12979860 and rs8099917 alleles could be used as independent predictors of the treatment response. The rs12979860 allele in particular, is more important from our study. The polymorphism even explains part the difference in response rate between different ethnic groups and HCV genotypes

Immune response to HSP70-HBcAg(18-27) complex in HBV transgenic mice / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To study the cellular immune response to HSP70-HBcAg(18-27) complex in HBV transgenic mice.</p><p><b>METHOD</b>HSP70-HBcAg(18-27) complex was reconstituted in vitro, then it was injected into HBV transgenic mice to observe the cellular immune response. At the same time, we investigated whether HSP70-HBcAg(18-27) complex could generate antigen specific cytotoxic T lymphocyte responses in spleen cells.</p><p><b>RESULTS</b>Our results demonstrated that HSP70-HBcAg(18-27) complex increased levels of CD4+ and CD8+ T cells in the spleens and peripheral blood of HBV transgenic mice, and the complex also activated dendritic and natural killer cells.</p><p><b>CONCLUSION</b>HSP70-HBcAg(18-27) complex has an immunological antigenicity in raising the immunoresponse to chronic HBV infection in HBV transgenic mice. HSP70-HBcAg(18-27) complex might be considered as a candidate for further studies on its role as a therapeutic vaccine against chronic HBV infection in humans.</p>

Effect of tumor antigen specific CTL induced by dendritic cells on a model of human hepatocellular carcinoma in nude mice (LCI-D20) / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the cure effect of tumor antigen specific CTL on a model of human hepatocellular carcinoma in nude mice LCI-D20.</p><p><b>METHODS</b>Dendritic cells (DCs) were induced from peripheral blood mononuclear cells of healthy people in vitro by using recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and interleukin-4 (rhIL-4) and were pulsed with tumor antigen from hepatocellular carcinoma cell line MHCC97H. Then tumor antigen specific cytotoxic T lymphocytes (CTLs) were induced. By intraperitoneal injection of tumour antigen specific CTLs into the LCI-D20, the preventive and therapeutic effects of these CTLs to HCC in the LCI-D20 model were assessed. Cytokine-induced killer (CIK) cells and phosphate buffer solution were used as controls at the same time.</p><p><b>RESULTS</b>The weights of tumors in the tumor antigen specific CTL group, in the CIK cell group and in the blank group were (1.11+/-0.63), (1.12+/-0.36) and (2.68+/-0.53) grams respectively (t = 5.18, t = 6.06, P < 0.01). The amount of blood alpha fetal protein in the tumor antigen specific CTL and CIK groups were (52.1+/-9.7) microg/L and (48.6+/-5.2) microg/L, and was (82.2+/-7.2) microg/L in the blank group (t = 17.26, t = 22.07, P < 0.01 respectively). The metastasis rates in livers were 16.7%, 16.7% and 58.3% in the tumor antigen specific CTL, CIK cell and blank control groups respectively (chi2= 4.44, P < 0.01). The survival time of the mice in the tumor antigen specific CTL group was (79.0+/-5.02) days, (73.3+/-7.0) days in the CIK group, and (52.3+/-5.2) days in the blank group (t = 14.56, t = 17.54, P < 0.01).</p><p><b>CONCLUSION</b>Tumor antigen specific CTLs may prevent metastasis in the LCI-D20 model and prolong the survival time.</p>

Experimental gene therapy mediated by fractalkine (FK) for murine liver cancer / 中华肝脏病杂志

<p><b>OBJECTIVES</b>Chemokines play an important role in the infiltration of immune cells into tumor tissues. Anti-tumor immune response has been elicited in many tumor models by chemokine gene transfection. The aim of this study was to evaluate the possibility of inducing anti-hepatocellular carcinoma active immune response by transfection of mouse hepatocellular carcinoma cells MM45T.Li with chemokine FK gene.</p><p><b>METHODS</b>Mouse FK gene was transduced into mouse hepatocellular carcinoma cells MM45T.Li using of liposome.G418-resistant clones were selected and the FK mRNA expression was detected by RT-PCR. In vivo experiments were performed to observe the tumorigenicity of wild type MM45T.Li and FK gene modified tumor cells. The immune cell infiltration in tumor tissues was detected histopathologically. The level of CD4+ and CD8+ T cells in peripheral blood were detected by FACS.</p><p><b>RESULTS</b>RT-PCR detection showed that FK was expressed in FK gene transfected G418-resistant clones (MM45T.Li-FK), but not in the wild type MM45T.Li. In vivo experiments the tumorigenicity of MM45T.Li-FK had decreased compared to the wild type MM45T.Li. In the tumor tissues from MM45T.Li-FK, many infiltrated immune cells were found, but few immune cells infiltrated into the tumor tissues from the controls. The level of CD4+ and CD8+ T cells had obviously increased in MM45T.Li-FK compared to the controls (P < 0.01).</p><p><b>CONCLUSION</b>Transfection with chemokine FK gene can induce anti-hepatocellular carcinoma active immune response.</p>