Study on the relationship between the serum levels of Th1/Th2 cytokines and the clinical manifestations of chronic hepatitis C and the outcome of interferon therapy / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigated the relationship between the serum levels of Th1/Th2 cytokines and the progress of viral hepatitis C and the outcome of interferon therapy.</p><p><b>METHODS</b>Serum cytokine detection used the method of ELISA. HCV genotype were classified by direct sequencing. HCV RNA loads were determined by fluorescence quantitative PCR.</p><p><b>RESULTS</b>The levels of IL-2 and TGF-beta in serum of patients with chronic hepatitis C were lower hut IL-5 was higher than those of normal control. The level of IL-6 was positively related to the sera level of ALT and was negatively related to sera HCV RNA load. Patients of HCV genotype 1 had higher sera quantities of IL-6 than those of genotype 2 and patients of genotype 2a had lower sera quantities of IL-2 than those of 2b. The levels of IL-2 had the tendency to decrease whereas IL-6 had the tendency to increase when time went on. The level of TGF-beta increased at early phase but decrease later. There were no difference of all cytokines detected between the groups of response and nonresponse before interferon therapy, hut the quantity of serum IFN-gamma were increased after interferon therapy in the response group.</p><p><b>CONCLUSION</b>The tested cytokines co-participate in the pathogenesis of chronic hepatitis C and have the relationship with the clinical manifestations of the patients. There were no correlation between the levels of Th1/Th2 cytokines in the serum before IFN treatment and the result of IFN therapy. Increasing IFN-gamma in the serum induced by IFN treatment is associated with sustained virological response.</p>

Mechanism of hepatitis B virus infection of trophoblast cells and hepatitis B virus intrauterine infection / 中华传染病杂志

1.0?10~7 copies/mL. The HBsAg IHC staining positive cells could be observed in 6 placental tissues and 3 fetus' liver tissues,and HBcAg was also positive in 1 case of fetus' liver tissue.After co-incubating the tropho- blastic cells and HBV DNA positive serum in vitro,HBsAg expression and HBV DNA could be detected.Apoptosis of HBV-infected trophoblastic cells increased,which was demonstrated by in vivo and in vitro experiments and the apoptosis of placental cells was correlated with the cord blood HBV DNA level.The results of in vitro experiments showed that the apoptosis of trophoblastic cells increased with the elongation of infection time.After 6 months,1 of 12 newborns was positive for HBsAg,HBeAg and anti-HBc,6 was positive for anti-HBs.Conclusions The mechanism of HBV intra-uterine infection may be that HBV breaches the placental barrier and infects the fetus.The localization and replication of HBV in fetal tissues and organs are probably the important factors of chronic HBV infections in neonates.The apoptosis of trophoblastic cells may be the protective mecha- nism for the placental barrier to block the HBV intra-uterine transmission.

The factors associated with viral relapse after interferon treatment in chronic hepatitis C patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>Of 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.</p><p><b>CONCLUSION</b>The viral relapse of chronic hepatitis C patients after IFN treatment was significantly associated with the genotypes of the HCV.</p>

Retreatment with interferon of relapsed chronic hepatitis C patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>For 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.</p><p><b>CONCLUSION</b>Some 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.</p>

The pegasys using and HCV genotype were the independent predictors of the response to antiviral therapy in chronic hepatitis C / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the predictors of IFN therapy in patients with chronic hepatitis C through making the multivariate logistic regression analysis.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>The pegasys using and HCV genotype were the independent predictors of the response to antiviral therapy in chronic hepatitis C.</p>

The influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>HCV 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.</p>

Non-relationship between HCV genotype,serum viral load,and ALT,AST levels in chronic hepatitis C patients / 中华检验医学杂志

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