不同抗病毒治疗方案与慢性乙肝疾病转归的关系及影响因素分析
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摘要
近年来慢性乙肝治疗领域的一大进展是人们已经认识到只有从根本上抑制乙肝病毒的复制才能够明显延缓疾病的进展,甚至还可使已经发生肝硬化的病理损伤逆转。因此慢性乙肝,包括乙型肝炎肝硬化的抗病毒治疗已逐渐引起人们的重视,并被认为是控制疾病进展的关键环节。干扰素及核苷(酸)类药物是目前规范化治疗慢性乙肝的两类药物,大量研究表明其可明显改善慢性乙肝患者的预后,但由于核苷(酸)类药物长期应用的耐药性以及抗病毒治疗适应症选择等诸多问题的影响,在乙肝治疗领域仍存在诸多问题需要进一步探讨。因此本研究主要从以下四方面分析了不同核苷(酸)类似物及干扰素抗病毒治疗的临床疗效及相关影响因素。
一、恩替卡韦抗病毒治疗104例乙型肝炎肝硬化患者96周临床疗效及其对肝组织学活动指数的影响。观察了恩替卡韦抗病毒治疗104例乙型肝炎肝硬化患者96周临床疗效及其对肝组织学活动指数的影响,结果表明恩替卡韦抗病毒治疗104例乙型肝炎肝硬化患者96周时HBV DNA不可测率、ALT复常率及HBeAg血清转换率分别达到98.1%、80.7%及13.9%。104例乙型肝炎肝硬化患者以C基因型为主,B、C基因型患者抗病毒疗效相似。抗病毒治疗96周可明显延缓乙型肝炎肝硬化患者的疾病进展。37例行肝组织学检查患者治疗96周时肝组织学明显改善,且抗病毒治疗96周后血清HBV DNA下降水平与Knodell HAI评分下降水平呈正相关。
二、阿德福韦酯抗病毒治疗乙型肝炎肝硬化患者4年临床疗效及对肝组织学的影响。观察了阿德福韦酯抗病毒治疗114例(阿德福韦酯初治患者65例,既往应用拉米夫定耐药的乙型肝炎肝硬化患者29例,应用拉米夫定应答不佳者20例)乙型肝炎肝硬化患者192周临床疗效及对肝组织学的影响,结果表明阿德福韦酯抗病毒治疗114例乙型肝炎肝硬化患者192周时HBV DNA不可测率及HBeAg血清转换率分别达到88.6%及18.1%。抗病毒治疗至192周Child-Pugh分级均有所提高,其中Child A级患者比例明显增加,并且Child A级患者未出现疾病进展。49例应用拉米夫定治疗失效的乙型肝炎肝硬化患者加用阿德福韦酯后也获得较好的疗效,且抗病毒治疗至192周Child-Pugh分级也均有所改善。17例行肝组织学检查患者治疗192周时肝组织学明显改善,且抗病毒治疗192周后血清HBV DNA下降水平与Knodell HAI评分下降水平呈正相关。
三、替比夫定抗病毒治疗慢性乙肝的临床疗效及其与其他核苷(酸)类似物的比较。观察了替比夫定抗病毒治疗96例慢性乙肝患者108周临床疗效及其与恩替卡韦及阿德福韦酯抗病毒治疗疗效的比较,结果表明替比夫定能够快速强效抑制病毒,替比夫定组及恩替卡韦组在治疗12周及24周时HBV DNA不可测率及ALT复常率相近,均高于阿德福韦酯组,108周时三组HBV DNA不可测率及ALT复常率相接近。替比夫定组抗病毒治疗至108周时的HBeAg消失率及转换率最高,明显高于恩替卡韦组和阿德福韦酯组。不同核苷(酸)类似物抗病毒治疗108周均可使肝硬化患者Child-Pugh分级明显改善。替比夫定抗病毒治疗至12周及24周时HBV DNA水平<3 log10拷贝/ml的患者,108周时的HBV DNA不可测率、HBeAg血清学转换率明显高于HBV DNA≥3 log10拷贝/ml的患者,耐药发生率低于HBV DNA≥3 log10拷贝/ml的患者。
四、聚乙二醇干扰素α-2a个体化治疗慢性乙肝患者的临床疗效及其与肝组织Knodell HAI评分的关系。对聚乙二醇干扰素α-2a个体化治疗未获得早期病毒学应答患者的临床疗效及其与肝组织Knodell HAI评分的关系进行分析,结果表明延长至72周疗程组及联合恩替卡韦及阿德福韦酯组的持久应答率均明显高于常规治疗组,且HBsAg平均下降水平也明显高于常规治疗组。停药后24周联合治疗组肝组织学改善率最高,其次为延长治疗组,两组均明显高于常规治疗组。C基因型在非早期病毒学应答组中占73.7%,明显高于其在早期病毒学应答组中所占比例。非早期病毒学应答组患者治疗前HBV DNA≥7log10copies/ml者较多,高达44.7%,而低水平(3～5log10copies/ml)者显著少于早期病毒学应答组。非早期病毒学应答组12周HBsAg平均下降水平明显低于早期病毒学应答组。
总之,本研究深入探讨了不同核苷(酸)类似物及干扰素抗病毒治疗慢性乙肝患者的临床疗效及相关影响因素,评价了抗病毒治疗对肝组织学的影响,为个体化抗病毒治疗提供进一步的研究依据。
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 score
Objective: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 B
Objective: 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 score
Objective: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.
一、恩替卡韦抗病毒治疗104例乙型肝炎肝硬化患者96周临床疗效及其对肝组织学活动指数的影响。观察了恩替卡韦抗病毒治疗104例乙型肝炎肝硬化患者96周临床疗效及其对肝组织学活动指数的影响,结果表明恩替卡韦抗病毒治疗104例乙型肝炎肝硬化患者96周时HBV DNA不可测率、ALT复常率及HBeAg血清转换率分别达到98.1%、80.7%及13.9%。104例乙型肝炎肝硬化患者以C基因型为主,B、C基因型患者抗病毒疗效相似。抗病毒治疗96周可明显延缓乙型肝炎肝硬化患者的疾病进展。37例行肝组织学检查患者治疗96周时肝组织学明显改善,且抗病毒治疗96周后血清HBV DNA下降水平与Knodell HAI评分下降水平呈正相关。
二、阿德福韦酯抗病毒治疗乙型肝炎肝硬化患者4年临床疗效及对肝组织学的影响。观察了阿德福韦酯抗病毒治疗114例(阿德福韦酯初治患者65例,既往应用拉米夫定耐药的乙型肝炎肝硬化患者29例,应用拉米夫定应答不佳者20例)乙型肝炎肝硬化患者192周临床疗效及对肝组织学的影响,结果表明阿德福韦酯抗病毒治疗114例乙型肝炎肝硬化患者192周时HBV DNA不可测率及HBeAg血清转换率分别达到88.6%及18.1%。抗病毒治疗至192周Child-Pugh分级均有所提高,其中Child A级患者比例明显增加,并且Child A级患者未出现疾病进展。49例应用拉米夫定治疗失效的乙型肝炎肝硬化患者加用阿德福韦酯后也获得较好的疗效,且抗病毒治疗至192周Child-Pugh分级也均有所改善。17例行肝组织学检查患者治疗192周时肝组织学明显改善,且抗病毒治疗192周后血清HBV DNA下降水平与Knodell HAI评分下降水平呈正相关。
三、替比夫定抗病毒治疗慢性乙肝的临床疗效及其与其他核苷(酸)类似物的比较。观察了替比夫定抗病毒治疗96例慢性乙肝患者108周临床疗效及其与恩替卡韦及阿德福韦酯抗病毒治疗疗效的比较,结果表明替比夫定能够快速强效抑制病毒,替比夫定组及恩替卡韦组在治疗12周及24周时HBV DNA不可测率及ALT复常率相近,均高于阿德福韦酯组,108周时三组HBV DNA不可测率及ALT复常率相接近。替比夫定组抗病毒治疗至108周时的HBeAg消失率及转换率最高,明显高于恩替卡韦组和阿德福韦酯组。不同核苷(酸)类似物抗病毒治疗108周均可使肝硬化患者Child-Pugh分级明显改善。替比夫定抗病毒治疗至12周及24周时HBV DNA水平<3 log10拷贝/ml的患者,108周时的HBV DNA不可测率、HBeAg血清学转换率明显高于HBV DNA≥3 log10拷贝/ml的患者,耐药发生率低于HBV DNA≥3 log10拷贝/ml的患者。
四、聚乙二醇干扰素α-2a个体化治疗慢性乙肝患者的临床疗效及其与肝组织Knodell HAI评分的关系。对聚乙二醇干扰素α-2a个体化治疗未获得早期病毒学应答患者的临床疗效及其与肝组织Knodell HAI评分的关系进行分析,结果表明延长至72周疗程组及联合恩替卡韦及阿德福韦酯组的持久应答率均明显高于常规治疗组,且HBsAg平均下降水平也明显高于常规治疗组。停药后24周联合治疗组肝组织学改善率最高,其次为延长治疗组,两组均明显高于常规治疗组。C基因型在非早期病毒学应答组中占73.7%,明显高于其在早期病毒学应答组中所占比例。非早期病毒学应答组患者治疗前HBV DNA≥7log10copies/ml者较多,高达44.7%,而低水平(3～5log10copies/ml)者显著少于早期病毒学应答组。非早期病毒学应答组12周HBsAg平均下降水平明显低于早期病毒学应答组。
总之,本研究深入探讨了不同核苷(酸)类似物及干扰素抗病毒治疗慢性乙肝患者的临床疗效及相关影响因素,评价了抗病毒治疗对肝组织学的影响,为个体化抗病毒治疗提供进一步的研究依据。
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 score
Objective: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 B
Objective: 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 score
Objective: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.
引文
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2. Marcellin P, Chan HLY, Lai CL et al. In hepatitis B patients treated with either adefovir or telbivudine, maximal early HBV suppression at 24 weeks predicts optimal one-year efficacy. J Hepatol 2007; 46(Suppl. 1): S193.
3. Lai CL, Leung N, Teo EK et al. A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology 2005; 129(2): 528–536.
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6. Livingston SE, Simonetti JP, Bulkow LR et al. Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D and F. Hepatology 2008; 47(5): 1788–1790.
7. Pan XC, Yang F, Chen M. The effect of telbivudine on peripheral blood CD4+CD25+ regulatory T cells and its significance in patients with chronic hepatitis B. Zhonghua GanZang Bing Za Zhi 2008; 16(12): 885–888.
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9. Keeffe EB, Zeuzem S, Koff RS et al. Report of an International Workshop: Roadmap for Management of Patients Receiving Oral Therapy for Chronic Hepatitis B. J Clin Gastroenterol Hepatol 2007; 5(8): 890–897.
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