| Objective: to analyze antiviral effects of entecavir in patients with Hepatitis B virus-related cirrhosis and its association with the Knodell HAI score.Method:104 patients of hepatitis B virus-related cirrhosis with no prior history of antiviral therapy were enrolled to receive treatment with entecavir 0.5mg once daily.37 patients were taken hepatic histologic examination before and after-treatment.Results: The load of HBV DNA have decreased obviously at week 4, and at week 96,mean reductions of serum HBV DNA was 5.1log10 from baseline, HBV DNA became undetectable in 98.1%patients , and ALT became normal in 80.7%. HBeAg seroconversion occurred in 13.9%of 72 HBeAg positive patients. 61.54 % of these patients were classified as genotype C, 26.92% were genotype B. Similar proportions of different genotype patients achieved HBV DNA<1000copies/ml, ALT normalization and achieved HBeAg seroconversion. Patients with different Child-pugh score who were treated with entecavir had different progression of disease , In those patients who achieved progression, the proportion of Child-Pugh C grade patient was the highest, then was the Child-Pugh B grade patient, and the Child-Pugh A grade patient was the lowest. The higher of the HBV DNA load, the higher of the Knodell HAI score, after 96 weeks, the descended level of HBV DNA load and the descended level of the Knodell HAI score submitted positive correlation. The improvement rate of hepatic tissue is the highest in Child-Pugh A grade patient, furthermore, there was no aggravation in those patients, then was the Child-Pugh B grade patient, and the Child-Pugh C grade patient was the lowest.Conclusion: After entecavir treatment patients with Hepatitis B virus-related cirrhosis could get highly serum HBV DNA undetectable rate, ALT normalization and HBeAg seroconversion, progression of disease could be delayed. The hepatic histological damage could be improved. PartⅡClinical antiviral effects of adefovir dipivoxil in patients with Hepatitis B virus-related cirrhosis and its association with Knodell HAI scoreObjective:to analyze antiviral effects of adefovir dipivoxil in patients with Hepatitis B virus-related cirrhosis and its association with the Knodell HAI score.Method:114 patients of hepatitis B virus-related cirrhosis were enrolled to receive treatment with adefovir dipivoxil 10mg once daily(65 patients with no prior history of antiviral therapy,49 patients who was failure of lamivudine treatment).17 patients were taken hepatic histologic examination before and after-treatment.Results: HBV DNA became undetectable in 88.6% patients , and HBeAg seroconversion occurred in 18.1%of 72 HBeAg positive patients at week 192.114 patients′Child-Pugh score were higher after adefovir dipivoxil treatment to 192 weeks, the proportion of patients with Child-Pugh class A disease was significantly increased at Week 192 and Child-Pugh class C disease was significantly decreased at Week 192. Patients with different Child-pugh score who were treated with adefovir dipivoxil had different progression of disease , In those patients who achieved progression, the proportion of Child-Pugh C grade patient was the highest, then was the Child-Pugh B grade patient, and the Child-Pugh A grade patient was the lowest. 49 patients who was failure of lamivudine treatment plus with adefovir dipivoxil has a good effect. After 192 weeks, the descended level of HBV DNA load and the descended level of the Knodell HAI score submitted positive correlation.Conclusion: After adefovir dipivoxil treatment patients with Hepatitis B virus-related cirrhosis could get significant effect,and to the patients in failure of lamivudine in has a good effect. Sustainable suppress the level of HBV DNA and to improve the Child-Pugh score, as well as liver function statusis ,and be able to improve liver histology and delay the progression of disease. PartⅢStudy on clinical efficacy of telbivudine therapy and comparison with other Nucleos(t)ide Analogs in the patients with chronic hepatitis BObjective: The aim of this study was to investigate the clinical efficacy of antiviral therapy with telbivudine for chronic hepatitis B patients and compare the efficacy among LdT with other nucleos(t)ide analogs treatment.Methods: Nucleos(t)ide analogs na?ve patients with chronic hepatitis B who met the diagnostic and treatment criteria were randomly assigned into three groups to receive telbivudine (600mg once daily) or entecavir (0.5mg once daily) or adefovir dipivoxil (10mg once daily) for 108 weeks. The responses of antiviral therapy were evaluated respectively.Results: At week 4, the rates of achieving undetectable HBV DNA and ALT normalization were 38.5% and 32.6%, respectively, which increased to 88.5% and 96.9% at week 108 in the telbivudine group. In 61 HBeAg-positive patients, HBeAg loss and HBeAg seroconversion at week 108 were achieved by 39.3% and 23.0% patients respectively. The higher rates of undetectable HBV DNA and HBeAg seroconversion and lower antiviral resistance rate at week 108 in the patients with HBV DNA <3log10 copies/mL at week 12 and 24 were significant than in those with HBV DNA≥3log10 copies/mL at week 12 and 24 (P<0.05, respectively). The effectiveness analysis for three different antiviral therapy groups showed that the telbivudine group and the entecavir group had similar rates of undetectable HBV DNA and ALT normalization at week 12 and 24, which were higher than those in the adefovir dipivoxil group (P<0.05, respectively), the rates of undetectable HBV DNA and ALT normalization were similar in three groups at week 108. However, the highest rates of HBeAg loss and HBeAg seroconversion in the telbivudine group after continuous treatment for 108 weeks were 39.3% and 23.0% respectively, which were significantly higher than those of the entecavir and the adefovir dipivoxil group. The 108-week antiviral therapy with different nucleos(t)ide analogs could significantly improve Child-Pugh score in patients with liver cirrhosis.Conclusions: Telbivudine showed rapid and potent HBV DNA suppression and high HBeAg seroconversion, the Child-Pugh score in the patients with liver cirrhosis could be improved by long-term therapy with telbivudine, and the patients with early virologic response achieve a low incidence of drug-resistance.PartⅣClinical antiviral effects of Peg-IFNα-2a in patients with chronic hepatitis B and its association with Knodell HAI scoreObjective:to analyze antiviral effects of Peg-IFNα-2a in patients with chronic hepatitis B and its association with the Knodell HAI score.Method: 92 patients of chronic hepatitis B with no prior history of antiviral therapy were enrolled to receive treatment with Peg-IFNα-2a 180μg subcutaneous injection once weekly. Based on antiviral response at week 12 Individualized treatment, the patients who did not get early response divided into extend the treatment to 72-week group, the combined nucleoside (acid) analogue treatment group and 48 weeks of conventional treatment group. Among them, 24 patients were taken hepatic histologic examination before and after-treatment.Results: To extend the treatment group′SVR (78.3%) was significantly higher than the conventional therapy group (38.1%), P <0.05, the HBeAg seroconversion rate and the HBsAg disappearance rate was significantly higher than the conventional therapy group, follow-up 24 weeks the average decline in the level of HBsAg was higher than the conventional treatment group. The average decrease of HBV DNA in the combined entecavir and adefovir dipivoxil group was 3.9 log10 and 3.7 log10 respectively, significantly higher than the conventional therapy group, the two groups′SVR were 83.3% and 85.7%, also significantly higher than conventional therapy group (38.1%), P <0.05, At week 48 and follow-up24 weeks after treatment the average decline in the level of HBsAg were significantly higher than the conventional treatment group. Follow-up 24 weeks after treatment liver histological improvement rate was 50%, including combined treatment group was 62.5%, to extend the treatment group was 55.6%, the two groups were significantly higher than conventional treatment group. C genotype in non-early virological response group was 73.7%, significantly higher than that in the early virological response group, P<0.05. Non-early virological response patients who HBV DNA≥7log10copies/ml were as high as 44.7%, while the low (3～5log10copies/ml) were significantly less than the early virologic response group, P <0.05. The average decline in the level of HBsAg in non-early virological response group was significantly lower than the average decline in early virological response group, P <0.05.Conclusion: Peg-IFNα-2a treatment the patients with poor early antiviral response can be extended to 72 weeks or combined entecavir, adefovir dipivoxil and other nucleotides analogues, and markedly increase SVR and reduce HBeAg , HBsAg levels, even achieve the conversion. The long-term effective antiviral therapy in patients with chronic hepatitis B can also decrease Knodell HAI score and improve liver histology, delay and prevent disease progression. |
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