聚乙二醇干扰素α-2a与拉米夫定治疗HBeAg阳性慢性乙型肝炎的经济学评价

目的评估聚乙二醇干扰素α-2a与拉米夫定治疗HBeAg阳性慢性乙型肝炎的成本效果。方法运用相关文献资料和Delphi专家咨询数据，采用Markov模型对聚乙二醇干扰素α-2a与拉米夫定治疗慢性乙型肝炎疗效进行经济学评价。结果与使用拉米夫定1～4年比较，使用聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎患者1年，人均延长寿命0．52～0．79年，每延长1年寿命所需增加的医疗费用为16563～18954元。结论使用聚乙二醇干扰素α-2a1年相比于使用拉米夫定1～4年治疗HBeAg阳性慢性乙型肝炎具有更好的成本效果。     

核苷(酸)类药物与聚乙二醇干扰素α-2a治疗HBeAg阴性慢性乙型肝炎的药物经济学评价

目的 对核苷(酸)类药物与聚乙二醇干扰素α-2a治疗HBeAg阴性慢性乙型肝炎进行药物经济学评价. 方法 根据慢性乙型肝炎进展的规律,构建含多个健康状态的Markov模型,使用模型估计不同方案治疗HBeAg阴性慢性乙型肝炎患者的长期效果和医疗费用,并进行增量分析.结果 与非抗病毒治疗相比,抗病毒治疗均能使患者生存年限延长,其中使用恩替卡韦(耐药后加阿德福韦酯)2年治疗效果最好,可以延长1.12个质量调整生命年;而使用拉米夫定2年(耐药后加阿德福韦酯)最具成本效果,可以延长0.95个质量调整生命年,增加的总医疗费用为15 459 元,每延长1个质量调整生命年多需的医疗费用为16 273元.结论 目前国内对HBeAg阴性慢性乙型肝炎的抗病毒治疗方案中,使用恩替卡韦(耐药后加用阿德福韦酯)可以达到最好的治疗效果,而使用拉米夫定(耐药后加阿德福韦酯)较之其他方案则更具有成本效果.     

聚乙二醇化干扰素α-2a治疗拉米夫定失效的慢性乙型肝炎临床分析

拉米夫定治疗慢性乙型肝炎可有效抑制乙型肝炎病毒（HBV）DNA复制,但耐药发生率随着治疗时间延长而增加,且未发生HBeAg血清学转换者停药后易反弹。因此,探索治疗拉米夫定失效的慢性乙型肝炎的新策略十分重要。我们尝试采用聚乙二醇化干扰素α-2a（PEGIFNα-2a,罗氏制药有限公司生产）治疗拉米夫定失效的慢性乙型肝炎患者,并长期观察HBVDNA水平、HBsAg和HBeAg的转换率,同时评估该方法的疗效和安全性。     

拉米夫定耐药e抗原阳性乙型肝炎应用恩替卡韦或阿德福韦酯联合聚乙二醇干扰素α-2a的疗效评价

目的评价拉米夫定耐药e抗原阳性乙型肝炎分别应用恩替卡韦或阿德福韦酯联合聚乙二醇干扰素α-2a的疗效。方法随机选取2013年3月至2016年3月我院收治拉米夫定耐药HBeAg阳性慢性乙型肝炎患者80例,依据治疗方法将患者分为两组,即恩替卡韦联合聚乙二醇干扰素α-2a为A组(n=40例),阿德福韦酯联合聚乙二醇干扰素α-2a为B组(n=40例),然后A组根据4周时HBV DNA下降再分为2组,下降2 log10为A1组,下降2 log10为A2组,A2组加用阿德福韦酯继续治疗,24周、48周时对4组患者的HBsAg、HBV DNA血清阴转,HBsAg、HBeAg血清转换,ALT复常情况及不良反应发生情况进行统计分析。结果A组和B组患者不良反应发生率分别为7.5%(3/40),8.0%(4/40),差异无统计学意义(P0.05);A组患者24周、48周时的HBeAg血清转换率均显著高于B组(P0.05);A1组患者24周、48周时的HBeAg血清转换率均显著高于A2组(P0.05)结论恩替卡韦降低HBV DNA载量后再联合聚乙二醇干扰素α-2a治疗拉米夫定耐药e抗原阳性乙型肝炎的疗效较阿德福韦酯联合聚乙二醇干扰素α-2a好,其疗效受到HBV DNA载量下降水平、继续治疗方法的影响。     

替比夫定和拉米夫定治疗e抗原阳性和阴性慢性乙型肝炎的药物经济学评价

目的 对替比夫定和拉米夫定治疗e抗原阳性和阴性慢性乙型肝炎进行药物经济学评价.方法 基于医疗保险角度开展药物经济学评价研究.依据慢性乙型肝炎的疾病进展规律,构建Markov模型,以GLOBE 2年临床试验结果为主要资料来源.另收集不同乙型肝炎相关疾病状态下的年医疗费用和生活质量评分情况.以增量成本效果比作为评价指标,并对分析结果进行灵敏度分析.结果 与拉米夫定相比,替比夫定治疗HBeAg阳性慢性乙型肝炎患者每延长1个质量调整生命年(QALY)多需的医疗费用在北京和广州分别为5403元、4916元.治疗HBeAg阴性慢性乙型肝炎患者的增量成本效果比在两地分别为28 239元/QALY和29 618元/QALY.根据文献报道的全国乙型肝炎相关疾病经济负担,与拉米夫定相比,替比夫定治疗HBeAg阳性和阴性慢性乙型肝炎患者每延长1个质量调整生命年多需的医疗费用分别为1282元和31 565元.结论 按世界卫生组织建议标准,替比夫定较拉米夫定治疗HBeAg阳性和阴性慢性乙型肝炎更具成本效果.     

慢性乙型肝炎恩替卡韦经治后联合长效干扰素的疗效预测分析

目的 分析我院恩替卡韦经治的慢性乙型肝炎患者联合聚乙二醇干扰素α-2a治疗的疗效及探讨预测疗效的相关指标.方法 选取恩替卡韦治疗至少1年且HBV DNA阴性的慢性乙型肝炎患者,予恩替卡韦联合聚乙二醇干扰素α-2a治疗48周或延长至72周,观察至96周.结果 共纳入35例患者,分为两组,基线HBeAg阳性组(18例)、H...     

聚乙二醇干扰素α-2a治疗阿德福韦酯经治的e抗原阳性慢性乙型肝炎临床观察

目的：观察聚乙二醇干扰素治疗阿德福韦酯经治的e抗原阳性的慢性乙型肝炎患者,对其HBVDNA、e抗原阴转率、e抗原-抗体转换率、S抗原阴转率、S抗原-抗体转换率的影响,寻找实现核苷经治患者早日、安全停药的办法。方法将服用阿德福韦酯二年以上e抗原阳性的慢性乙型肝炎患者中未能达到中国2010年版《慢性乙型肝炎防治指南》规定的停药标准的30例,随机分为两组,一组（派罗欣组）停用阿德福韦酯,换用聚乙二醇干扰素α-2a（派罗欣）治疗。二组（阿德福韦酯组）继续用阿德福韦酯治疗。结果治疗48周时,第一组有44％的患者达到了理想的停药标准,明显高于第二组（25％的患者达到理想的停药标准）（P＜0．01）。结论聚乙二醇干扰素α-2a（派罗欣）治疗阿德福韦酯经治慢性乙型肝炎患者,可增加患者e抗原、s抗原阴转率,e抗原-抗体、s抗原-抗体的血清学转换率,达到理想的停药标准,实现患者早日、安全停药。     

拉米夫定治疗慢性乙型肝炎的经济学评价

目的 评估拉米夫定治疗慢性乙型肝炎的经济学价值。方法 运用临床试验和相关文献资料，采用Markov模型对拉米夫定治疗慢性乙型肝炎进行经济学评价。结果 与安慰剂相比，拉米夫定每延长1年寿命，所需医疗费用在25000元以下，疗程较长者的拉米夫定治疗与疗程较短者相比，每延长1年寿命所需的医疗费用在38500元以下。结论 拉米夫定具有成本效果，疗程越长，成本效果越好。     

聚乙二醇干扰素α-2a治疗HBeAg阴性的乙型肝炎临床疗效观察

目的评价聚乙二醇化干扰素α-2a(PEG-IFNα-2a)治疗HBeAg阴性的慢性乙型肝炎的临床疗效和安全性。方法68例HBeAg阴性的慢性乙型肝炎患者随机分配到PEG-IFNα-2a治疗组和普通干扰素对照组。结果治疗组的ALT复常率、HBV DNA阴转率分别显著高于对照组(P<0.05);随访48周时,治疗组ALT阳性及HBV DNA阳性复发率分别显著低于对照组(P<0.05);两组不良反应的发生率无显著性差异(P>0.05)。结论PEG-IFNα-2a治疗HBeAg阴性的慢性乙型肝炎优于普通干扰素,具有较持久的病毒学和血清学应答率,每周1次给药方式,可使患者具有更好的依从性。     

聚乙二醇干扰素α-2a与干扰素α-2b治疗慢性乙型肝炎的临床疗效对比分析

本组应用聚乙二醇干扰素α-2a(PEG-IFN-α2a)治疗慢性乙型肝炎20例,与单用普通干扰素α2b例进行疗效对比,现将结果报道如下:1资料和方法1·1病例选择:诊断符合2000年修订的《病毒性肝炎防治方案》选择慢性乙型肝炎40例,分为二组:聚乙二醇干扰素α-2a 20例,其平均年龄为41·5±1     

Pegylated interferons in chronic HBV: Alone or as combination therapy

Pegylated interferons have been investigated recently in the treatment of chronic hepatitis B in both hepatitis B e antigen (HBeAg)-positive, as well as HBeAg-negative, Asian and white patients. Pegylated interferon alfa-2a monotherapy has been compared in randomized studies with standard interferon, lamivudine, and with a combination of pegylated interferon and lamivudine. The results indicate the superiority of pegylated interferon alfa-2a over standard interferon and lamivudine and failure of combination therapy to further enhance antiviral efficacy. A trial with pegylated interferon alfa-2b in HBeAg-negative disease showed no benefit of combination therapy compared with pegylated interferon monotherapy, but there was no lamivudine monotherapy arm in the study. Pending final trial results and regulatory approval, pegylated interferons are likely to be recommended as the first-line therapy for chronic hepatitis B.     

Treatment of chronic hepatitis B with the sequential administration of interferon and lamivudine

BACKGROUND/AIMS: Interferon monotherapy has been shown to induce a sustained viral response in 30-40% of patients with HbeAg-positive chronic hepatitis B infection. Similarly, lamivudine monotherapy causes HBeAg seroconversion in less than 20% of patients treated for one year. This study aims to assess the efficacy and safety of the sequential administration of interferon alfa-2a plus lamivudine to patients with chronic hepatitis B in comparison to lamivudine monotherapy. METHODOLOGY: Sixty-one patients with HbeAg-positive chronic hepatitis B infection and raised ALT were randomized to receive either interferon Alfa-2a, 4.5 million units daily for 16 weeks plus lamivudine 100 mg daily starting from week 5 and continuing for 48 weeks (Group A, n = 32) or lamivudine monotherapy for 48 weeks (Group B; n = 29). Patients were followed for 48 weeks after completion of therapy. RESULTS: HBeAg seroconversion to anti-HB +ve was observed in 2 (6.2%) patients in Group A. Both patients remained HBeAg negative and HBV-DNA negative throughout the follow-up phase. None of the group B patients seroconverted at the end of therapy or during follow-up (P = NS). All group A patients experienced at least one side effect and as a result, one dropped out. All group B patients completed the study without side effects. CONCLUSIONS: The sequential administration of interferon plus lamivudine was not superior to lamivudine monotherapy for the treatment of chronic hepatitis B and was associated with more side effects.     

阿德福韦酯治疗慢性乙型肝炎65例观察

目的探讨阿德福韦酯单独或联合拉米夫定治疗慢性乙型肝炎的疗效。方法 12例HBeAg阳性患者给予阿德福韦酯,39例HBeAg阳性患者给予拉米夫定和阿德福韦酯,14例HBeAg阴性患者接受阿德福韦酯治疗。各组均观察24个月。结果联合治疗HBeAg阳性和阿德福韦酯治疗HBeAg阴性患者在治疗3个月、6个月、12个月和24个月时,血清HBV DNA水平均明显低于阿德福韦酯治疗HBeAg阳性患者;三组ALT复常率无显著性相差。结论阿德福韦酯联合拉米夫定初始治疗HBeAg阳性或阿德福韦酯治疗HBeAg阴性慢性乙型肝炎患者均能取得较好的疗效。     

Cost-effectiveness of telbivudine versus lamivudine for chronic hepatitis B

Background and aimChronic hepatitis B is a highly prevalent disease worldwide, leading to serious consequences if not properly treated. Six treatment options for chronic hepatitis B are currently provided by the Brazilian public health system. Telbivudine is a nucleoside analogue that is neither included in the Brazilian clinical protocol nor in the therapeutic guidelines for chronic hepatitis B.ObjectiveThe aim of this study was to evaluate the cost-effectiveness of telbivudine for the viewpoint of the Brazilian public system, comparing it to lamivudine.MethodsA Markov model was used to project lifetime complications and costs of treatment with lamivudine or telbivudine for chronic hepatitis B in both HBeAg-positive and HBeAg-negative patients. To evaluate disease progression, probabilities and utilities of virologic response, virologic resistance, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, treatment, interruption of treatment, death and seroconversion were collected in systematic reviews. Costs were collected in DATASUS, ABC da Saúde and scientific literature.ResultsHigher rate of virologic response and seroconversion was obtained with telbivudine, and also higher values of quality adjusted life years. However lamivudine is associated with lower costs and also lower cost-effectiveness values. The incremental cost-effectiveness ratios for telbivudine, when compared with lamivudine, were US$ 30,575 and US$ 40,457, respectively for HBeAg-positive and HBeAg-negative patients.ConclusionsIn chronic hepatitis B lamivudine is a more cost-effective or even cost-saving strategy when compared with telbivudine     

Optimal duration of additional therapy after biochemical and virological responses to lamivudine in patients with HBeAg-negative chronic hepatitis B: a randomized trial

Aim:  The endpoint of treatment with nucleoside analogs remains unclear for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We report the results of a randomized trial to determine the optimal duration of additional therapy after response to lamivudine in HBeAg-negative patients.
Methods:  Twenty-two patients with HBeAg-negative chronic hepatitis B who exhibited biochemical and virological responses to lamivudine were enrolled. When patients responded to treatment, they were randomly assigned to receive 12 more months of therapy (Group A, 11 patients) or 24 more months of therapy (Group B, 11 patients).
Results:  The baseline characteristics of the patients were similar in the two groups. Biochemical and virological responses were obtained in all patients within 6 months. Drug resistance developed in one patient in Group A during month 7 of additional therapy, and in five patients in Group B from months 13–23 of additional therapy. Ten patients in Group A and six in Group B completed the protocol and were included in analysis. Eight of the 10 patients in Group A experienced relapse between months 2 and 14 after the discontinuation of therapy, while three of the six patients in Group B experienced relapse between months 2 and 24. There was no difference in cumulative relapse rate between the groups ( P  = 0.275).
Conclusion:  Additional therapy with lamivudine for longer than 12 months after biochemical and virological responses in patients with HBeAg-negative chronic hepatitis B could increase the risk of drug resistance, but did not reduce the rate of relapse.     

End-of-treatment virologic response does not predict relapse after lamivudine treatment for chronic hepatitis B

AIM: Attaining hepatitis B e antigen (HBeAg) seroconversion during lamivudine treatment is associated with fewer relapses in HBeAg-positive patients. In HBeAg-negative patients, predictors for post-treatment relapse remain largely unknown. We therefore studied whether end-of-treatment virologic response correlated with relapse after lamivudine treatment. METHODS: We prospectively analyzed 12 HBeAg-negative patients and 14 HBeAg-positive patients with chronic hepatitis B, who received at least 9 mo of lamivudine treatment and were followed up for 12 mo post-treatment. Relapse of hepatitis B activity was defined by an elevation of serum ALT level above twice the upper limit of normal as well as reappearance of serum HBV DNA by the branched DNA assay or HBeAg during the follow-up period. The serum viral loads during and at the end of treatment were further determined by a quantitative real-time polymerase chain reaction assay. RESULTS: Relapse occurred in 6 (50.0%) HBeAg-negative patients within 12 mo post-treatment. Two relapsers had end-of-treatment serum viral load <1 000 copies/mL, the proportion was not significantly different from that in the 6 non-relapsers (33.3% vs 16.7%; P = 1.00). Hepatitis B virus (HBV) DNA levels did not correlate with post-treatment relapse in HBeAg-positive patients either. However, genotype C patients tended to have a lower relapse rate than genotype B patients (14.3% vs 57.9%, P = 0.08). CONCLUSION: Our results suggest that end-of-treatment virologic response cannot predict post-treatment relapse in patients with HBeAg-negative or -positive chronic hepatitis B. The impact of HBV genotype on the response to lamivudine treatment awaits further studies.     

Clinical experience with lamivudine

Lamivudine, an oral nucleoside analogue, has demonstrated efficacy against the hepatitis B virus (HBV) in both HBeAg-positive and HBeAg-negative patients with chronic hepatitis B. Treatment with lamivudine is safe and well tolerated and induces a virological and biochemical response in most patients within a short time. Significant histological improvement was seen in clinical trials after 52 weeks of lamivudine treatment. However, durable posttreatment remission of chronic hepatitis B has not been shown to occur in a significant number of lamivudine-treated patients. To maintain the response to treatment, therefore, long-term therapy is required. Prolongation of therapy, however, is associated with the emergence of HBV resistance to lamivudine in most patients. This is accompanied by virological rebound and reversal of the initial therapeutic response, and sometimes by exacerbation of hepatitis. The need remains for effective, safe, and tolerable oral agents with durable activity against HBV.     

Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen-negative patients receiving lamivudine therapy

Lamivudine has been shown to be effective in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, but its long-term efficacy and the rate of resistant mutations in patients with HBeAg-negative chronic hepatitis B is less clear. Twenty-nine patients with HBeAg-negative chronic hepatitis B, who have received lamivudine for at least 1 year were studied to determine the antiviral response, the rate and pattern of lamivudine-resistant mutations, and the effect of lamivudine-resistant mutations on HBeAg status. The mean duration of treatment was 21 +/- 7 months. Before treatment, core promoter variant was detected in 16 (55%) patients and precore stop codon variant in 18 (62%) patients. Serum hepatitis B virus (HBV) DNA was detected by solution hybridization assay in 62%, 4%, and 24% and by polymerase chain reaction (PCR) assay in 100%, 31%, and 40% at months 0, 6, and 24, respectively. The cumulative rates of detection of lamivudine-resistant mutations after 1 and 2 years of treatment were 10% and 56%, respectively. In addition to the duration of treatment, core promoter mutation was associated with the selection of lamivudine-resistant mutants. Three patients with lamivudine-resistant mutations had reversion of the precore stop codon mutation; in 2 patients this was accompanied by the reappearance of HBeAg. We found that lamivudine-resistant mutants were detected at similar rates in patients with HBeAg-negative as in patients with HBeAg-positive chronic hepatitis B. Additional changes in other parts of the HBV genome may restore the replication fitness of lamivudine-resistant mutants.     

Reversion from precore/core promoter mutants to wild-type hepatitis B virus during the course of lamivudine therapy

The effect of lamivudine administration on the evolution of precore/core promoter mutation is unknown. The aim of this study was to determine the changes of precore/core promoter sequences in chronic type B hepatitis patients treated with lamivudine. Serial sera were obtained from 11 patients before, at the beginning of, and during therapy. Serum samples were polymerase chain reaction-amplified, and nucleotide sequences of hepatitis B virus (HBV) were analyzed. At baseline, precore and core promoter mutations were found in 6 and 4 of 11 patients, respectively. A precore stop codon mutant was replaced by a wild-type virus in all 6 patients infected with precore mutant at a median treatment of 12 months (vs. before therapy; P =.011). Mutations in the core promoter appeared in only 1 of 10 patients (vs. before therapy; P =.021). However, precore and core promoter mutations appeared in 5 and 7 of 10 patients at a median treatment of 21 months, respectively. Acute exacerbation occurred after lamivudine withdrawal in 2 patients who had hepatitis B e antigen (HBeAg) loss or seroconversion. The serum remained HBeAg-negative throughout the study period, and each of 2 patients had precore wild-type virus during acute exacerbation. HBV mutants with core gene deletions are not eliminated completely during prolonged therapy in 2 patients in whom the HBV genomes had core gene deletions at baseline. In conclusion, lamivudine therapy resulted in reversion from precore/core promoter mutants to wild-type. However, mutations in the precore and core promoter region reappeared during prolonged therapy. HBeAg-negative wild-type precore hepatitis B virus could be selected after lamivudine withdrawal in patients who had HBeAg loss or seroconversion.     

Lamivudine/pegylated interferon alfa-2b sequential combination therapy compared with lamivudine monotherapy in HBeAg-negative chronic hepatitis B

BACKGROUND AND AIM: Monotherapy has been proven insufficient in achieving sustained control of chronic hepatitis B. We aimed to assess the efficacy of combined sequential administration of lamivudine and pegylated interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-negative chronic hepatitis B. METHODS: Eighteen patients were given sequential combination treatment starting with 3 months of lamivudine monotherapy followed by 9 months of pegylated interferon alfa-2b (after a 3-month period of concomitant administration of the two drugs) and 24 patients received lamivudine monotherapy. RESULTS: At the end of treatment, 88.9% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy had hepatitis B virus (HBV) DNA levels below 400 copies/mL (P = not significant). At the end of treatment, 72.2% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy achieved alanine aminotransferase normalization (P = not significant). After 12 months of follow up, 33.3% of the patients who received sequential combination treatment and 16.7% of those who received lamivudine monotherapy had HBV-DNA levels below 400 copies/mL (P = 0.4). After 12 months of follow up, 72.2% of the patients who received sequential combination treatment and 25.0% of those who received lamivudine monotherapy had normal alanine aminotransferase levels (P < 0.01). Twenty-five percent of the patients in the lamivudine monotherapy group had virological breakthrough compared to none in the sequential combination treatment group (P = 0.06). CONCLUSIONS: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.