| Objective:To discuss the influential factors of sustained virological response(SVR) rates in the treatment of chronic hepatitis C with the combination of peginterferonα-2a and ribavirin.To study the relationship among HCV genotypes,rapid/early response and SVR.To analyze the influence of individual treatment on the anti-viral effect of chronic hepatitis C.Methods:92 CHC patients enrolled from September 2006,in digestive department of China and Japan Union Hospital were collected.All patients conformed to the Diagnosis standards in Chronic Hepatitis C prevention and treatment guidelines,which was established in 2004 by the Chinese Medical Association and the Chinese Hepatitis Prevention Foundation.60 male,32 female,the proportion of male to female is 1.875:1.Average age of patients is 40.52±8.39. Three Patients comfected with hepatitis B virus,whose HBVDNA are higher than1×10~3copies/mL.Quantity of HCV RNA of all patients were mensured at 4 weeks and 12 weeks. Period of treatments were decided,according to the reaponse status at 12 weeks.All patients were used PEG-interferonα-2a(40KD)180μg weekly subcutaneous injection plus ribavirin(RBV) 800-1000mg/pd.Treatment were followed up after the end of 24 weeks.Serum marker of HCV was detected by ELISA.Biochemical indicators were detected with Beckman automatic biochemical analyzer.Serum HCV RATA level were detected with real-time fluorescence quantitative polymerase chain reaction(FQ-PCR) method.HCV RNA genotypes were analyzed by polymerase chain reaction-micro-nucleic acid hybridization-ELISA method.Results:Gender,age,ribavirin dose and the baseline viral load have a significant effect on SVR rates,P＜0.05.Level of white blood cells,hemoglobin and platelet have no significant effect on SVR.SVR of genotype 2 and those patients whose genotype didn't identified is 79.6%,which is significantly higher than genotype 1(53.5%),P＜0.05.and the RVR and cEVR rate of non-1 genotype is significantly higher than genotype 1 patients.SVR of patients with RVR is 100%, is significantly higher than patients with no RVR,P＜0.05.At the same time,the recurrence rate decreased significantly.The treatment of patients with no cEVR is extended to 72 weeks, and SVR is 70%,which is significantly higher than SVR of 48 weeks treatment,P＜0.05;the recurrence rate of 72 weeks treatment is 25%,which is significantly higher than the recurrence rate of 48 weeks treatment,P＜0.05.Patients with no cEVR was given thymosinαfor 12 weeks,the virus unpredictable rate in 24 weeks of who is 75%(6/8),which is significantly higher than those without using thymosinα,P＜0.05;and the ETVR and SVR rates of patients using thymosinαrespectively are 75%(6/8),63%(5/8),which is significantly higher than those without using thymosinαpatients,P＜0.05.Three HCV/HBV-coinfected individuals were treated with PEG-IFNα-2a ribavirin combined treatment.There are two cases whose HCV RNA and HBV DNA were not detected in 12 weeks,but one case whose HBV DNA still was positive in the end of the treatment.The HBV DNA and HCV RNA quantitative analysis in liver tissues showed that three cases of liver tissue HCV RNA were negative,but the level of HBV DNA in liver tissue is still positive.The adverse reactions of PEG-IFNα-2a combined ribavirin antiviral therapy are mainly fever,influenza-like syndrome,decreased peripheral blood neutrophil and platelet counts decreased,anemia,weight loss and hair loss,etc;some patients with thyroid disease(hyperthyroidism).Conclusions:Gender,age,ribavirin dose and the baseline viral load have a significant effect on SVR rates in the treatment of chronic hepatitis C with the combination of peginterferonα-2a and ribavirin.Level of white blood cells,hemoglobin and platelet have no significant effect on SVR.HCV genotype has important clinical significance.The pathogenicity and the response to antiviral treatment of different genotypes have a lot of difference.The response treatment of genotype 1 is poor.The SVR of genotype 2 patients is significantly higher than genotype 1 patients.A large number of clinical data showed that:the duration of HCV RNA load＜3 log10copies/ml is associated with the rate of SVR and relapse rate.The SVR of patients with RVR at 4 weeks,which is significantly higher than the SVR rate of patients with no RVR.At the same time,the recurrence rate decreased significantly.Clinical practice has proved that:48 weeks of treatment in all patients can not achieve satisfactory result.No early virologic response strongly predict poor sustained virologic response,especially genotype 1 patients. The duration of treatment in patients without cEVR is extended to 72 weeks in our study,and the SVR rate is significantly higher than the SVR rate of 48 weeks treatment.Therefore,the refractory patients should be given extended treatment to enhance the efficacy of anti-virus therapy.Thymosinαhave an effect on human immune system.In the patients with poor response to interferon therapy,thymosinαcan be combined with interferon treatment.To achieve better result,patients without cEVR was given thymosinαfor 12 weeks in our study. SVR of patients using thymosinαrespectively are significantly higher than those patients not using thymosinαpatients.Three HCV/HBV-coinfected individuals were treated with PEG-IFNα-2a ribavirin combined treatment,there are two cases whose Unpredictable rate and HBV DNA were not detected at 12 weeks,but one case whose HBV DNA still was positive.At the end of the treatment,the HBV DNA and HCV RNA quantitative analysis of liver tissues showed that three cases in liver tissue HCV RNA were negative,but two cases of liver tissue HBV DNA is still positive.In HCV/HBV-coinfected individuals,unpredictable rate of HCV RNA in serum was significantly higher than that of HBV DNA.Unpredictable rate of HCV RNA in liver tissue was significantly higher than that of HBV DNA.The adverse reactions of PEG-IFNα-2a combined ribavirin antiviral therapy are mainly fever,influenza-like syndrome, decreased peripheral blood neutrophil and platelet counts decreased,anemia,weight loss and hair loss,etc;some patients with thyroid disease(hyperthyroidism).In short,pegylated interferonα-2a combined ribavirin is the cornerstone treatment of chronic hepatitis C.To improve the efficacy of antiviral therapy in chronic hepatitis C and reduce the recurrence rate, according to different genotypes,HCVRNA quantitative and virologic response,the severity of disease,serious adverse reactions,response and co-exist the possibility of individual diseases, "individualized" treatment should be planned,it is the treatment direction in the future. |
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