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.
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 观察阿德福韦酯联合拉米夫定治疗阿德福韦酯治疗48周后应答不佳，HBeAg阳性慢性乙型肝炎的疗效和安全性。 方法 选择2006年1月-2010年12月间阿德福韦酯治疗48周后乙型肝炎病毒 DNAgt;104 copies/mL的26例慢性乙型肝炎患者，给与拉米夫定（100 mg，1次/d）联合治疗。观察治疗12周，24周时的应答情况。 结果 所有纳入26例患者在联合拉米夫定优化治疗24周后，无论是病毒学应答还是血清学应答都获得显著的改善，无一例患者观察到有耐药以及药物不良反应发生。 结论 联合拉米夫定是对阿德福韦酯应答不佳慢性乙型肝炎患者安全有效的干预策略之一。【Abstract】 Objective To observe the effect and safety of adefovir dipivoxil (ADV) combined with lamnivudine (LAM) in treating HBeAg-positive chronic hepatitis B (CHB) patients with poor response to ADV monotherapy for 48 weeks. Methods Twenty-six HBeAg-positive CHB patients received initial treatment of ADV from January 2006 to December 2010, and their serum HBV-DNA still maintained over or equal to 1.0×104 copies/mL after 48 weeks. These patients received the optimized treatment of ADV (10 mg, one time per day) combined with LAM (100 mg, one time per day). Patients′ responses to the treatment at the 12th and 24th week were observed. Results Compared with baseline, ADV plus LAM had an improved response rate of virological response, biochemical response and HBeAg/HBeAb seroconversion. No LAM-resistant or ADV-resistant mutations were detected. In all the 26 patients, no adverse reactions were observed. Conclusion Optimized therapy combining LAM and ADV can be a good choice for patients with hepatitis B who have a poor response to ADV monotherapy.
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.
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.
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。
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。
ObjectiveTo systematically review the efficacy of lamivudine (LAM) plus adefovir (ADV) versus entecavir (ETV) monotherapy for LAM-resistant chronic hepatitis B patients. MethodsWe electronically searched databases including PubMed, The Cochrane Library (Issue 12, 2013), CBM, CNKI, VIP, WanFang Data from their inception to December 2013, to collect randomized controlled trials (RCTs) or cohort studies of LAM+ADV versus ETV for LAM-resistant chronic hepatitis B. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.2 software. ResultsA total of 13 RCTs and 5 cohort studies involving 1 336 patients were included. The results of meta-analyses of RCTs showed that:there were no significant differences between the LAM+ADV group and the ETV group in the negative rates of serum HBV-DNA (RR=1.00, 95%CI 0.91 to 1.10, P=0.94), HBeAg (RR=0.90, 95%CI 0.70 to 1.17, P=0.43), serum ALT recovery rate (RR=0.97, 95%CI 0.90 to 1.05, P=0.45) and serum HBeAg conversion rate (RR=0.71, 95%CI 0.40 to 1.24, P=0.22) at the 48th week. The results of meta-analyses of cohort studies showed that:there were no significant differences between the two groups in the negative rates of serum HBV-DNA (RR=1.37, 95% CI 0.91 to 2.06, P=0.13) and serum ALT recovery rate (RR=0.99, 95%CI 0.87 to 1.12, P=0.87), but the ETV group had higher serum HBeAg conversion rate (RR=0.24, 95% CI 0.07 to 0.79, P=0.02). ConclusionCurrent evidence shows that the efficacy of LAM+ADV is similar to ETV at the 48th week for LAM-resistant chronic hepatitis B patients. Due to 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.