ObjectiveTo systematically review the efficacy of peginterferon alpha (PEG-IFNα) initially combined with lamivudine (LAM) or adefovir (ADV) in treatment of HBeAg-positive chronic hepatitis B (CHB) patients. MethodsWe electronically searched databases including The Cochrane Library (Issue 11, 2014), PubMed, CBM, CNKI, VIP, and WanFang Data from inception to December 2014, to collect randomized controlled trials (RCTs) about PEG-IFNα initially combined with LAM or ADV for HBeAg-positive CHB. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.2 software. ResultsA total of 11 RCTs involving 2031 patients were included. The results of meta-analysis showed that: After 48 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus ADV group was significantly higher than that of the PEG-IFNα monotherapy group (8.6% vs. 0%, OR=7.73, 95%CI 1.53 to 39.05, P=0.01) or the ADV monotherapy group (8.5% vs. 0%, OR=7.75, 95%CI 1.07 to 56.23, P=0.04); and the HBsAg seroclearance rate in the combination therapy group was significantly higher than that of the ADV monotherapy group (10.5% vs. 1.2%, OR=5.56, 95%CI to 2.14 to 14.47, P=0.0004). After 52 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus LAM group was significantly higher than that of the PEG-IFNα monotherapy group (11.6% vs. 5.6%, OR=2.21, 95%CI 1.04 to 4.72, P=0.04). After 26 weeks of follow-up, no significant differences were found between the combination therapy group and the PEG-IFNα monotherapy group in HBsAg seroclearance rate and HBsAg seroconversion rate (all P values >0.05). ConclusionCurrent evidence shows that, compared with PEG-IFNα, LAM, or ADV monotherapy, PEG-IFNα plus LAM or ADV could improve the HBsAg seroclearance or seroconversion rate after 48-52 weeks of treatment for HBeAg-positive CHB, but this effect is still limited. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveTo evaluate the clinical efficacy and safety of telbivudine (TEV) combined with adefovir dipivoxil (ADV) for chronic hepatitis B (CHB), so as to provide references for clinical practice and research. MethodsWe electronically searched databases including The Cochrane Library (Issue 7, 2013), PubMed, EMbase, Web of Science, CBM, CNKI, VIP, and WanFang Data from inception to August 21st, 2013, for the relevant randomized controlled trials (RCTs). Other sources were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the quality of included studies. Then, meta-analysis was performed using RevMan 5.1 software. ResultsA Total of 11 RCTs involving 1 010 patients were included. The trial group were given TEV combined with ADV, while the control group were given TEV alone or ADV alone. The results of metaanalysis showed that, the combined use was superior to TEV alone or ADV alone in improving HBV-DNA negative rates at 12-, 24-, 48-weeks, HBeAg negative rates at 12-, 24-, 48-weeks, and ALT recovery rates at 12-, 24-weeks (P < 0.05). The results of qualitative analysis showed that, the trial group had a lower drug resistance rate, and both were alike in the incidence of adverse reaction. ConclusionCompared with TEV alone or ADV alone, TEV combined with ADV could improve the clinical efficacy of treating CHB which is also fairly safe. Due to the limited quantity and quality of the included studies, the aforementioned conclusion still needs to be further verified by conducting more large-scale and high quality RCTs.
目的 评估替比夫定与阿德福韦酯联合治疗优化阿德福韦酯单药治疗应答不佳的阳性慢性乙型肝炎患者的疗效。 方法 选择2008年6月－2009年8月间共26例阿德福韦酯治疗至少12个月且病毒学应答不佳的乙型肝炎病毒e抗原（HBeAg），阳性的慢性乙型肝炎患者，在10 mg阿德福韦酯治疗的基础上，加用600 mg替比夫定。肝功能和乙型肝炎病毒（HBV） DNA每3个月评估1次，乙型肝炎两对半和腹部B型超声每半年评估1次。 结果 在第1年的治疗期间，所有患者血清HBV DNA水平均呈进行性下降，其中24例（92.3%）血清HBV DNA水平在联合治疗12个月时低于检测值下限，有25例（96.2%）患者丙氨酸转氨酶水平复常。治疗6个月时，分别有7例（26.9%）和2例（7.7%）患者发生HBeAg消失和血清学转换；治疗12个月时，分别有11例（42.3%）和8例（30.8%）患者发生HBeAg消失和血清学转换。整个治疗期间，26例患者均未出现病毒学突破。 结论 阿德福韦酯单药治疗应答不佳时，加用替比夫定可有效控制病毒，使患者获得较好的病毒学、生化学和免疫学应答。Objective To evaluate the curative efficacy of telbivudine combined with defovir dipivoxil on positive-HBeAg chronic hepatitis B patients with suboptimal response to adefovir dipivoxil. Methods A total of 26 HBeAg-positive patients with suboptimal response to adefovir dipivoxil (treated with adefovir dipivoxil for more than 12 months) were treated with adefovir dipivoxil 10 mg in addition to telbivudine 600 mg between June 2008 and August 2009. Liver function and serum hepatitis B virus (HBV) DNA tests were assessed at the baseline and 3-month intervals, whereas HBV serological markers and abdominal ultrasonography were carried out every 6 months. Results During the first year of treatment, all patients showed a progressive decline of serum HBV DNA levels; while undetectable serum HBV DNA and normalization of alanine aminotransferase was achieved in 24(92.3%) and 25 (96.2%) patients, respectively, at the end of the first year of treatment. The 6- and 12-month cumulative rates of HBeAg loss were 26.9% (7/26) and 42.3% (11/26), respectively; and corresponding cumulative rates of HBeAg/anti-HBe seroconversion were 7.7% (2/26) and 30.8 (8/26), respectively. During the observation period, no virological breakthrough was detected. Conclusion Telbivudine combined with defovir dipivoxil may be a good choice for patients with suboptimal response to adefovir dipivoxil, which could induce effective viral inhibition and help patients obtain more virological, biochemical and immunological responses.
摘要:目的: 观察拉米夫定联合阿德福韦酯治疗E抗原阴性的慢性乙型肝炎患者的疗效和安全性。 方法 :2006～2007年来我院就诊的慢性乙型肝炎患者,给予拉米夫定100 mg/d,阿德福韦酯 100 mg/d,观察治疗前及治疗后12、24 及48周谷丙转氨酶水平、HBV DNA水平、乙型肝炎病毒血清标志物的应答效果及肾功能变化。 结果 :治疗12周、24周和48周时,HBV DNA转阴率分别为17%、43%和87%,且各组间差异具有统计学意义(P lt;005);ALT复常率分别为13%,67%和100%,且各组间差异具有统计学意义(P lt;005);治疗48周时,所有患者均未发生表面抗原的消失;整个治疗过程中,患者的耐受性良好,未发生一例严重不良事件。 结论 :拉米夫定联合阿德福韦酯治疗E抗原阴性的慢性乙肝患者,可获得较好的临床疗效,该治疗策略为临床抗病毒治疗提供了新的选择。Abstract: Objective: To observe the curative efficacy and safety of lamivudine combined with adefovir dipivoxil on HBeAgnegative initial treated chronic hepatitis B (CHB) patients. Methods : Outatients from our hospital between June, 2006 and August, 2007, who received lamivudine 100 mg and adefovir dipivoxil 10 mg per day were screened. And the level of ALT, HBV DNA, and urea nitrogen, as well as the statue of HBsAg and antiHBs were detected at week 12, 24, and 48 Results : The undetectable rates of HBV DNA were 17%, 43%, and 87% at week 12, 24, and 48 respectively, and the difference in response rate were statistic significantly (Plt;005). The ALT normalization rate were 13%, 67%, and 100% at week 12, 24, and 48 respectively, and the difference in response rate were statistic significantly (Plt;005); During the course of antiviral therapy, the loss of HBsAg was not observed and all patients were well tolerated. Conclusion : The combination of lamivudine and adefovir dipivoxil were effective for HBeAgnegative CHB patients, and this treatment strategy provided us a new option in clinical antiviral practice.
ObjectiveTo explore the effectiveness of lamividine (LAM) combined with adefovir (ADV) versus entecavir (ETV) for lamivudine-resistant (LAM-R) hepatitis B in renal transplant recipients. MethodOutpatients and inpatients of lamivudine-resistant kidney graft recipients with chronic hepatitis B admitted to West China Hospital and the People's Hospital of Santai County during Jan 2007 to Mar 2012 were divided into A group (LAM+ADV) and B group (ETV). And the level of alanine aminotransferase (ALT), level of serum creatinine, HBV serological markers and HBV-DNA load were compared by SPSS 16.0 software. ResultsA total of 15 patients were included. The mean age was 36.7±6.6 years old, the majority of patients were male. After treatment for 4 weeks, 12 weeks, 24 weeks, 48 weeks, 96 weeks, no significant differences were found between two groups in liver function normalization rates, the HBV-DNA negative conversion rates and serum creatinine level. ConclusionsLAM add-on ADV combination therapy and ETV monotherapy were both safe and effective in LAM-R kidney transplants with CHB, but the load of HBV-DNA in some patients were still positive at the endpoint. Elevated serum creatinine level may occur in some patients who treated with ADV. Consequently, for HBsAg-positive kidney transplantation patients, those anti-HBV drugs that are more effective, safer and less resistant may be better in the beginning of treatment.
目的 比较拉米夫定+阿德福韦酯联合治疗与阿德福韦酯单药治疗对阿德福韦酯停药后出现病毒学反弹而无基因型耐药变异患者的疗效及安全性。 方法 回顾研究2007年1月－2012年1月在传染科门诊就诊的67例阿德福韦酯治疗获得病毒学应答但停药后出现病毒学反弹的e抗原阳性慢性乙型肝炎患者，分别给予拉米夫定+阿德福韦酯联合治疗（联合组，n=35）和阿德福韦酯单药治疗（单药组，n=32）。 结果 治疗1年后，联合组（32例，85.7%）较单药组（21例，65.6%）有更多的患者重新获得了丙氨酸转氨酶复常（P=0.009），联合组34例（97.1%）乙型肝炎病毒DNA阴转，单药组22例（68.8%）阴转，两组差异有统计学意义（P=0.002）；在血清学转换方面，联合组和单药组分别有4例（11.4%）和1例（3.1%）患者获得了e抗原的血清学转换。在治疗中所有患者均未发生任何严重不良反应。 结论 阿德福韦酯停药后出现病毒学反弹，选择拉米夫定与阿德福韦酯联合治疗可使患者重新获得较好的生化学和病毒学应答。
目的 采用干扰素和阿德福韦酯治疗慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异，比较两种治疗策略的临床疗效。 方法 选择2002年2月-年12月经100 mg拉米夫定治疗后出现YMDD变异的慢性乙型肝炎患者76例。其中，男52例，女24例；年龄18~55岁，平均年龄33岁。服用100 mg拉米夫定52～156周发生YMDD变异，HBV DNA低于治疗前水平，丙氨酸转移酶(alanine aminotransferase，ALT)lt;2×ULN/L患者分为A组(26例)，继续用100 mg拉米夫定治疗48周；服用100 mg拉米夫定52～156周发生YMDD变异，HBV DNA定量检测高于或等于治疗前水平，ALTgt;2×ULN/L，根据患者自愿分为B组(27例)和C组(23例)。B组用100 mg拉米夫定联合10 mg阿德福韦酯治疗48周；C组用干扰素治疗48周。分别观察3组ALT复常率及HBV DNA转阴率、HBeAg阳性患者血清学转换率。 结果 治疗48周时，B、C组患者ALT复常率分别是74.1%和78.3%，明显高于A组的34.6%，差异有统计学意义(Plt;0.05)；B、C组患者HBV DNA转阴率分别是77.7%和73.9%，明显高于A组的11.5%，差异有统计学意义(Plt;0.05)；3组HBeAg阳性患者血清学转换率比较，差异均无统计学意义(Pgt;0.05)。 结论 慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异，继续用拉米夫定治疗疗效不理想，改用干扰素或联合阿德福韦酯治疗更安全有效。
Objective To compare adefovir monotherapy with adefovir-thymosin alpha-1 combination therapy for chronic hepatitis B. Methods We searched The Cochrane Library, MEDLINE, PubMed, the Chinese Biomedical Database (CBM), CNKI, Wanfang, and VIP databases up to February 2010 to identify randomized controlled trials (RCTs) comparing adefovir plus thymosin alpha-1 versus adefovir alone for chronic hepatitis B. We also scanned references of all included studies and pertinent reviews. The methodological quality assessment and data extraction were conducted by two reviewers independently according to the Cochrane Reviewer’s Handbook 5.0.2 . Meta-analyses were performed using RevMan 5.0 software. Results Eleven trials involving 895 patients were included. The results of meta-analyses shoued: the HBeAg seroconversion rate of the combination therapy group was higher than that of the monotherapy group, both at the sixth month and the twelfth month (RR=1.77, 95%CI 1.38 to 2.27; RR=1.74, 95%CI 1.44 to 2.10); and there were also significant differences between the two groups for secondary outcomes including HBV-DNA negative, ALT normalization, etc.Conclusion Adefovir-thymosin alpha-1 combination therapy might be more effective than adefovir monotherapy for chronic hepatitis B. Significant differences are even observed at the sixth month. However, the results should be interpreted with caution because of the low quality of the included studies. High-quality, large-scale RCTs are needed to further prove the results.