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Objective@#To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied.@*Methods@#Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded.@*Results@#The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild.@*Conclusions@#The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.
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Objective@#To investigate the differences in frequency and function of natural killer cells (NK) between chronic hepatitis B (CHB) and acute hepatitis B (AHB).@*Methods@#Patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of NK, CD56dimNK, CD56brightNK and the expression of functional molecules IFNAR2 and NKp46 on the surface of NK cells were detected respectively among patients with CHB in IA phase, patients with AHB, and those recovered from AHB. At the same time, their correlations with ALT, HBV DNA and HBV markers were analyzed.@*Results@#Between IA and AHB, the frequencies of NK cells and NKp46dim NK cells in AHB cases were significantly lower than those in IA cases, but the frequency of NKp46high NK cells in AHB was higher than that in IA. For patients who recovered from AHB, the frequency of NK cells and NKp46dim NK cells increased; the varied ranges of frequencies of CD56dimNK, IFNAR2+ NK and NKp46+ NK cells were on the rise, while the frequency of NKp46high NK cells decreased after the recovery from AHB, and the varied ranges of CD56brightNK and IFNAR2MFI, NKp46MFI decreased. In AHB, HBVDNA loads were positively correlated with ALT levels. Before and after the recovery of AHB: ΔHBV DNA and ΔALT, Δ NK/LY (%) were positively correlated; ΔALT and ΔNKp46highNK/NK(%), ΔNKp46MFI, ΔIFNAR2MFI were positively correlated.@*Conclusions@#In CHB immune active phase, the activity of peripheral blood NK cells was too weak to remove the virus, but NK cells play an important role in eliminating the viruses and mediating liver tissue inflammation in AHB.
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Objective@#To investigate the differences in function of plasmacytoid dendritic cells (pDC) and CD4+ T helper cells (CD4+ Th cells) between acute hepatitis B (AHB) and chronic hepatitis B (CHB).@*Methods@#In this study, patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of pDC, CD86+ pDC, CD4+ T cells and their subsets, surface functional molecules were detected respectively among patients with chronic HBV infection in IA phase, patients with AHB, those recovered from AHB. Meanwhile, their correlations with ALT, HBV DNA and HBV markers were analyzed.@*Results@#The ALT level in AHB was significantly higher than that in IA, and inflammation was more obvious in AHB. Between IA and AHB, CD86+ pDC frequency and the mean fluorescence intensity of functional molecule CD86 (CD86MFI) were higher in IA than those in AHB, but the frequency of CD4+ T cells in AHB was higher than that in IA. For patients who got over AHB, the frequency of CD86+ pDC increased; Th1 were on the rise, while the frequencies of CD4+ T and Th2 decreased after the recovery of AHB, and Th2 / Th1 ratio decreased..In AHB, HBVDNA loads were positively correlated with ALT levels and Th2 frequencies.@*Conclusions@#In CHB immune active phase, CD86+ pDC with stimulating function played an important role, but the cellular immune response of CD4+ T cells decreased. In AHB inflammatory stage, CD4+ T cells played a strong cellular immune response, which result ed in viral clearance. Th2 cells regulation of CD4+ T cells played a dominant role, which was involved in the inflammatory response, and the cytotoxic role of Th1 cells during the recovery period was dominant, playing a strong cellular immune response, then the virus were completely eliminated.
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Aim:to detect how Rb-deficiency will affect responses to TGF-? induced cell cycle arrest of hepatocyte.Methods:primary hepatocytes were isolated and cultured,and Rb-specific adenovirus siRNA was transformed into cells.Then TGF-? was added daily and cell growth and cell cycles variations.Western blot and FQ-RT-PCR were adopted to detect pRb,E2F,c-MYC and p16 expression changes.Results:Primary hepatocytes were isolated and infected with Rb-specific siRNA adenovirus.In control cells,treatment with TGF-? prevented cells to enter S phase via decreased cMYC activity,activation of P16INK4A activity.In Rb-null hepatocytes,E2F and cMYC activity decreased slightly but P16INK4A was not activated and the great majority of cells continued cycling.Rb is therefore central to TGF?-induced cell cycle arrest in hepatocytes.Conclusion:The present results show that otherwise genetically normal hepatocytes with disabled Rb genes respond less well to the antiproliferative effects of TGF-?.