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 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

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

0.05),the difference of ALT,AST level and AST/ALT ratio between high viral load (serum HCV RNA≥8.5?10~5 IU/ml) group and low viral load (serum HCV RNA

Objective To investigate the diversity and antimicrobial susceptibility of cultivable commesal bacteria from 18 to 22 year-old healthy people′s nose and skin. Methods From June to August 2017,18 to 22 year-old healthy people (n=210) were swabbed on skin and nose and cultured with blood plates at Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Species determination was performed using matrix assisted laser desorption Lonization-time of flight-mass spectrometry(MALDI-TOF-MS);Susceptibility testing was performed on the major species by the disc diffusion method; Genomic characteristics of methicillin resistant Staphylococcus epidermidis(MRSE) were determined by pulsed field gel electrophoresis (PFGE) method;SCCmec typing was tested by polymerase chain reaction(PCR);Statistical analysis was performed using SPSS software and association statistics were tested using Chi-Square tests. Results In total, 25 genera were identified of cultivable bacteria from 210 healthy people′s nose (1497 isolates) and skin (941 isolates).Staphylococcus isolates from nose and skin accounted for 82.03% and 80.23% respectively.Eleven species were identified of all Staphylococcus isolates and coagulase-negative Staphylococci(CoNS)from nose and skin accounted for 90.72% and 99.21% respectively.Furthermore, a variety of other species and differences between men and women were observed. Susceptibility testing was done on 631 Staphylococcus isolates, which were sensitive to most antibiotics but show high prevalence of resistance towards penicillin (76.55%), erythromycin (41.20%), clindamycin (10.77%) and trimethoprim/sulfamethoxazole(10.14%). Methicillin Resistant Staphylococcus (MRS) (45 isolates) showed higher prevalence of resistance towards penicillin (χ2=12.17,P<0.001), erythromycin (χ2=10.80,P=0.001), levofloxacin (χ2=20.24, P<0.001) and trimethoprim/sulfamethoxazole (χ2=58.57,P<0.001) compared to methicillin sensitive Staphylococcus (MSS)(586 isolates). Moreover, multidrug resistance (MDR) was observed in 42.16% of 631 isolates and MRS showed a significantly higher proportion than MSS(100.00% vs 37.71%,χ2=66.49,P<0.001).PFGE generated 23 groups out of 33 MRSE isolates. SCCmec genotyping of MRSE showed the most prevalent type was SCCmecⅣ (66.67%). Conclusions Obvious genus and species diversity and genetic diversity were observed on cultivable bacteria from 18 to 22 year-old healthy people′s nose and skin,and CoNS was in the majority. Staphylococcus isolates from healthy people′s nose and skin were sensitive to most antibiotics,but show high prevalence of resistance towards penicillin, erythromycin, clindamycin and trimethoprim/sulfamethoxazole. In addition, MDR was serious especially in MRS. Commensal bacteria may act as reservoir for resistance genes facilitating bacteria infection.

Objective To compare the clinical outcomes of low-dose rabbit antithymocyte globulin (rATG ) vs basiliximab as induction therapy in recipients of ABO-incompatible kidney transplantation (ABOi-KT) .Methods Retrospective analysis was conducted for e the clinical data of 40 ABOi-KT recipients between March 2017 and March 2019 .17 recipients of them received induction therapy with basiliximab (basiliximab group) while another 23 recipients received low-dose rATG (rATG group ,rATG 25 mg/d × 3 d) .During a median follow-up period of 282 days , the data of serum creatinine and eGFR at 1 week and 1 month ,graft survival rate and complication rate of two groups were compared .Results No significant difference existed in age ,gender ,dialytic modality/ duration , blood groups of recipients , HLA mis-match , blood group antibody titers , dose of rituximab ,blood groups of donors or donor age ( P > 0 .05 ) . The times of double filtration plasmapheresis in Basiliximab group were more (P< 0 .05) .No significant difference existed in serum creatinine and eGFR at 1 week or 1 month ( P > 0 .05 ) . No significant difference existed in graft survival rate . No significant difference existed in rate of acute rejection ,parvovirus B19 infection , urinary tract infection or hematoma .Conclusions Low-dose of rATG is as effective as basiliximab for ABOi-KT recipients .And rATG does not increase the rate of infection .