BACKGROUNDThe Fc receptor associated pathway might improve the immune responses against hepatitis B virus (HBV) as previously described by us. In addition, the Flt3 ligand (FL) has been reported to potentiate antigen presenting cells in vivo and may act as a potential adjuvant to boost antigen-specific immune responses. In this study, the immune efficacies of a set of fusion proteins of HBsAg and Fc and/or FL were evaluated in HBsAg transgenic mice.

METHODSThe fusion proteins composed of HBsAg and the Fc domain of murine IgG1 (HBsAg-Fc) and/or the Flt3 ligand, and yeast-derived recombinant HBsAg were used as immunogen to immunize HBsAg transgenic mice, respectively. Serum and liver HBsAg levels, serum anti-HBsAg and cytokine profile, and the activities of alanine aminotransferase (ALT)/AST were investigated after immunization.

RESULTSAfter six injections, the most pronounced decrease in serum and liver HBsAg levels was observed in the HBsAg-Fc immunized group. In addition, serum Th1 cytokines and ALT/AST activities were highest in this group, indicating an effective induction of a favorable cellular immune response. Interestingly, the fusion protein containing HBsAg-Fc and the Flt3 ligand stimulated an alternative Th1-type immune response featured with high level productions of tumor necrosis factor α (TNF-α) and monocyte chemoabstractant protein 1 (MCP-1), causing a more severe cytotoxicity in hepatocytes while showed less effective in reducing serum HBsAg level.

CONCLUSIONHBsAg-Fc is effective in eliciting both the humoral and cellular immune responses against HBsAg in HBsAg transgenic mice, which makes it a potential immunogen for the immunotherapy of chronic hepatitis B.

Animals ; Chemokine CCL2 ; metabolism ; Cytokines ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepatitis B Surface Antigens ; genetics ; immunology ; metabolism ; Immunity, Cellular ; immunology ; Immunity, Humoral ; immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Receptors, Fc ; genetics ; immunology ; metabolism ; Recombinant Fusion Proteins ; genetics ; immunology ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the relationship between hepatitis C virus (HCV) genotype, serum viral load and ALT levels, and the factors associated with the viral relapse after IFN treatment in patients with chronic hepatitis C.

METHODSThe HCV RNA levels were determined with Cobas Amplicor Monitor Test, version 2.0, and HCV genotypes were examined by means of PCR products of 5' NTR digested with restriction endonucleases. The patients with chronic hepatitis C were treated with PEG-IFN alpha -2a and Roferon-A for 24 weeks. Those with a viral response after 24 week treatment were followed for an additional 24 weeks. The association of clinical characteristics, such as sex, age, the way of the HCV infection, IFN treatment history and platelet counts, and the HCV genotype, virus load and medicine used for the viral relapse after IFN treatment were analyzed.

RESULTSOf the 208 chronic hepatitis C patients, the ALT levels were not related to HCV RNA levels (r = 0.093, P > 0.05). No difference of ALT levels between HCV genotypes was found, and the HCV RNA load was also of no difference between HCV genotype 1 patients and non 1 patients. Of the 119 patients with viral response after 24 week treatment, 58 cases (48.7%) relapsed after another 24 week's follow-up. Relapse was not significantly related to the clinical characteristics, such as sex, age, mode of the infection, treatment history of IFN, AST/ALT ratio, platelet counts and the baseline viral load. Among patients with genotype 1 virus, the relapse rate was significantly higher than those patients with non-genotype 1 virus (54.5% vs 32.1%, P=0.039). The relapse rate after PEG-IFN alpha -2a treatment was lower than that of Roferon-A treatment (47.0% vs. 52.8%), but not significantly.

CONCLUSIONThe viral relapse of chronic hepatitis C patients after IFN treatment was significantly associated with the genotypes of the HCV.

Antiviral Agents ; therapeutic use ; Female ; Genotype ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; RNA, Viral ; blood ; Recombinant Proteins ; Recurrence ; Treatment Outcome ; Viral Load

OBJECTIVETo investigate the influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C.

METHODSThe genotypes of HCV virus were determined in the patients enrolled into the Randomized, opened and controlled trial of Peg-IFN alpha-2a (Pegasys) treatment, controlled with IFN-alpha-2a (Roferon-A), on chronic hepatitis C patients in China. The serum ALT levels and HCV RNA concentration of the patients were detected in the time of before treatment, the end of therapy and follow-up. The influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C was analyzed in intention to treat (ITT) population.

RESULTSThe HCV genotypes of 202 cases were determined. 158 (78.2%) cases infected with genotype 1 HCV and 44 (21.8%) cases with genotype non-1. For overall patients, the viral response at the end of treatment (ETVR) and sustained viral response (SVR) rates were 53.8% and 25.3% respectively in patients with genotype 1 HCV, but in genotype non-1 patients those was 61.4% and 43.2%, and the difference of SVR between genotype 1 and non-1 was significant (P=0.021). After grouped by the used drugs, in the patients given Pegasys treatment, the ETVR rates of patients with genotype 1 and non-1 HCV infection were 76.8% and 81.0%, the difference was not significant (P=0.686), but the difference of SVR rates, which were 35.4% and 66.7%, of the patients was significant (P=0.01). The viral relapse rate of genotype 1 was 55.6%; it was significant higher than that of genotype non-1 (23.5%) (P=0.02). In Roferon-A group, the ETVR and SVR rates of patients with genotype 1 HCV were 29.0% and 14.5%, which were lower, but not significant, than those of patients with genotype non-1 (43.5% and 21.7%). The viral relapse rate of genotype 1 was 72.7% and higher, but not significant, than that of genotype non-1 also (50.0%) (P=0.21).

CONCLUSIONHCV genotype could affects the efficacies, mainly the sustained responses, of IFN treatment of patients with chronic hepatitis C, and the effects of IFN were related to the kinds of drugs and therapeutic course.

Antiviral Agents ; therapeutic use ; Genotype ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; Recurrence

OBJECTIVETo evaluate the efficacy and investigate the influencing factors of the interferon (IFN) retreatment for patients with chronic hepatitis C relapsed after a previous IFN treatment.

METHODSA retrospective study was designed to analyze the retreatment with IFN of 60 relapsed chronic hepatitis C patients. All patients were from a randomized, opened and multi-center clinical trial about the efficacy and security of PEG-IFNalpha-2a compared to CIFNalpha-2a in the treatment of chronic hepatitis C in China. There were 35 patients treated with PEG-IFNalpha-2a and 25 with CIFNalpha-2a. The main parameter to evaluate the efficacy was sustained viral response (SVR) rate. The influence of viral concentration in serum, genotype and drug categories on the responses to IFN were analyzed.

RESULTSFor all the patients, the end of treatment virus response (ETVR) and SVR rates were 55.00% and 35.00% respectively. ETVR rate of PEG-IFNalpha-2a was significantly higher than that of CIFNalpha-2a (74.29% and 28.00% respectively, P < 0.01). SVR rate of PEG-IFNalpha-2a was also markedly higher than that of CIFNalpha-2a (45.71% and 20.00% respectively, P < 0.05). However, there was no significant difference between the high and low viral load groups. Among the patients with genotype 1, ETVR and SVR rates of PEG-IFNalpha-2a (75.00%, 45.83%) were significantly higher than those of CIFNalpha-2a (22.22%, 11.11%), (P < 0.01, P < 0.05 respectively), but in patients with genotype non-1, there were no such differences between the two groups.

CONCLUSIONSome relapsed patients were not responsive to the IFN retreatment. The efficacy of PEG-IFNalpha-2a was superior to CIFNalpha-2a. The conventional IFN was not suggested to be used in the relapsed cases with genotype 1. The viral load was not associated with the efficacy of IFN retreatment.

Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis C, Chronic ; therapy ; Humans ; Interferon-alpha ; therapeutic use ; Interferon-beta ; Interferons ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; Recurrence ; Retrospective Studies

OBJECTIVEThe aim of this paper was to investigate the factors associated with viral response and HBeAg seroconversion and the relationship between them at different stages of interferon treatment in HBeAg-positive chronic hepatitis B patients.

METHODSPEG-IFN alfa-2a was injected subcutaneously in doses of 180 microg once a week for 48 weeks to HBeAg-positive chronic hepatitis B patients, and the patients were followed for another 24 weeks after the treatment. The serum HBV DNA load was measured by real-time quantitative PCR assay. Microparticle enzyme immunoassay analysis (MEIA) was then carried out by an automatic enzyme immunoassay analysis instrument to measure HBeAg and anti-HBe. Virological response and HBeAg seroconversion rates, and the factors associated with them were analyzed.

RESULTSThe differences in ALT baselines between viral responding and non-responding groups were significant at treatment time and at the end of the follow-up period. These differences were also significant in patients with HBeAg seroconversion at 12 weeks and at the end of the follow-up period compared with the non-conversion group. No significant difference of HBV DNA baseline was observed between the HBeAg seroconversion and non-conversion group. At 12, 24 and 48 weeks, in patients with viral response during the treatment, their HBeAg seroconversion rates were 43.8%, 21.4% and 18.9% respectively; their respective HBeAg seroconversion rates remaining at 72 weeks were 42.9%, 33.3% and 27.6%. HBeAg seroconversion was related to HBV DNA negativity at 48 weeks treatment in the multivariate analysis (OR=2.15, 95.0% CI=1.744-2.664, P less than 0.01).

CONCLUSIONSViral response and early and sustained HBeAg seroconversion were associated with pretreatment ALT levels. HBeAg seroconversion was related to viral response during IFN treatment, but not to the baseline HBV DNA load.

Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; Young Adult

OBJECTIVETo investigate the predictors of IFN therapy in patients with chronic hepatitis C through making the multivariate logistic regression analysis.

METHODSThe patients in the opened, randomized and controlled trial were enrolled into two group, pegasys and Roferon-A group, and were given 24 weeks of pegasys (injection of 180 microg a week), and Roferon-A (injection three times of Roferon-A 3 MU a week) therapy, and followed 24 weeks. The HCV RNA content was determined at the time before, end of treatment and at the followed-up. The association of the response to the treatment with the clinical characteristics including age, gender, way of HCV infection, history of IFN treatment, planet count, AST/ALT ratio, HCV RNA level, HCV genotype and treatment drugs was made trough multivariate logistic regression analysis.

RESULTSThe PP population containing 197 cases was analyzed. After controlling for age, gender, way of HCV infection, history of IFN treatment, planet count, AST/ALT ratio, HCV RNA level and treatment, the HCV genotype was not predictor of the end of treatment viral response (ETVR) to IFN therapy (OR 0.604, 95% CI 0.271-1.349, P = 0.219), but was the independent predictor of sustained viral response (SVR) (OR 0.408, 95% CI 0.189-0.881, P = 0.023). After controlling for other characteristics, the treatment drug was the predictors of ETVR (OR 0.105, 95% CI 0.052-0.212, P < 0.001) and SVR (OR 0.255, 95% CI 0.123-0.529, P < 0.001).

CONCLUSIONThe pegasys using and HCV genotype were the independent predictors of the response to antiviral therapy in chronic hepatitis C.

Adolescent ; Adult ; Aged ; Antiviral Agents ; administration & dosage ; Female ; Follow-Up Studies ; Genotype ; Hepacivirus ; drug effects ; genetics ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; Logistic Models ; Male ; Middle Aged ; Polyethylene Glycols ; administration & dosage ; RNA, Viral ; blood ; Recombinant Proteins