Efficacy of switching to telbivudine in chronic hepatitis B patients treated previously with lamivudine

Background: Telbivudine showed greater antiviral suppression than lamivudine in phase II and III clinical trials. Aims: The present phase IIIb, randomized, double‐blind, multicentre global trial assessed the antiviral efficacy and safety of telbivudine switch in chronic hepatitis B (CHB) patients who exhibited persistent viraemia under lamivudine therapy. Methods: HBeAg‐positive and HBeAg‐negative adult patients (N=246) with persistent viraemia [hepatitis B virus (HBV) DNA>3 log₁₀ copies/ml] under lamivudine treatment for 12–52 weeks were randomized (1:1) to continue lamivudine 100 mg/day or switch to telbivudine 600 mg/day for 1 year. Primary endpoint was the reduction in serum HBV DNA levels from baseline at Week 24. Results: The mean reduction in serum HBV DNA levels from baseline with telbivudine was significantly higher than lamivudine at Week 24 (?1.9 ± 0.18 vs. ?0.9 ± 0.27 log₁₀ copies/ml; P<0.001) and maintained through 1 year. The rate of treatment failure was significantly lower (P<0.001) for patients who switched to telbivudine (5%) compared with those who continued lamivudine (20%) after 52 weeks of treatment. In the telbivudine group, treatment failure occurred in only five patients with >24 weeks of prior lamivudine treatment, all associated with pre‐existent lamivudine‐resistant mutations. Genotypic resistance rates were higher in patients continuing lamivudine compared with those who switched to telbivudine with <24 weeks of lamivudine exposure. Both treatments were well tolerated with similar safety profiles. Conclusions: Early (≤24 weeks) switch to telbivudine improves virological outcomes in CHB patients with persistent viral replication under lamivudine treatment.     

替比夫定治疗乙型肝炎肝硬化的疗效观察

目的 观察替比夫定治疗乙型肝炎肝硬化患者48周时的疗效.方法 80例乙型肝炎肝硬化患者分为两组,每组40例,分别给予口服替比夫定600 mg/d或拉米夫定100 mg/d,持续治疗48周.观察治疗不同时间点患者的病毒学、生物化学指标、凝血酶原活动度(PTA)、Child-Pugh积分及病毒耐药等变化情况.结果 替比夫定组患者血清HBV DNA在治疗前为(6.52±1.33)log10拷贝/ml,在接受替比夫定治疗后2、4、8,12、24、48周时的下降值分别为(2.09±1.30)log10拷贝/ml、(2.83±1.22)log,o拷贝/ml、(3.23±1.27)log10拷贝/ml、(3.42±1.32)log10拷贝/ml、(3.65±1.30)log10拷贝/ml及(3.67±1.43)log10拷贝/ml.在24、48周时均有92.5%(37/40)的患者HBV DNA阴转.在治疗24、48周时,分别有30.0%(6/20)及35.0%(7/20)的患者出现了HBeAg血清学转换.在治疗48周时ALT、AST明显下降,白蛋白、总胆红素、PTA及Child Pugh积分等指标均有所改善(P<0.05),治疗48周时替比夫定组YMDD变异率为5.0%.治疗后24、48周HBV DNA水平下降值、HBV DNA阴转率替比夫定组高于拉米夫定组(P<0.05).结论 替比夫定能快速有效抑制乙型肝炎肝硬化患者的病毒复制,使HBV DNA水平下降,同时可以改善肝功能,且具有较低耐药率.     

Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: Results at 1 year of a randomized, double-blind trial

Chronic hepatitis B and its life-threatening sequelae are highly prevalent in China. There is a need for effective new therapies to suppress hepatitis B virus (HBV) replication and ameliorate liver disease. In this study, we compared the efficacy of telbivudine, a nucleoside analogue, with lamivudine in Chinese patients. In this phase III, double-blind, multicenter trial conducted in China, 332 patients with compensated hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B were randomly assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine daily for 104 weeks. The primary efficacy endpoint was reduction in serum HBV DNA levels at week 52 of treatment. Secondary endpoints included clearance of HBV DNA to undetectable levels, HBeAg loss and seroconversion, therapeutic response, and alanine aminotransferase (ALT) normalization. Viral resistance and safety were assessed. At week 52, among 290 HBeAg-positive patients, mean reductions of serum HBV DNA were significantly greater in telbivudine recipients than lamivudine recipients (6.3 log(10) versus 5.5 log(10), P < 0.001), and HBV DNA was polymerase chain reaction-negative in significantly more telbivudine recipients than lamivudine recipients (67% versus 38%, P < 0.001). ALT normalization (87% versus 75%, P = 0.007), therapeutic response (85% versus 62%, P = 0.001), and HBeAg loss (31% versus 20%, P = 0.047) were also significantly more common in the telbivudine group. Treatment effects showed similar patterns in the smaller HBeAg-negative group (n = 42). Viral resistance in telbivudine recipients was approximately half that observed with lamivudine; however, this difference was not statistically significant. Clinical adverse events were similar in the two treatment groups. CONCLUSION: In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance.     

Combined lamivudine and famciclovir therapy for patients with chronic hepatitis B

OBJECTIVE: No single antiviral drug is able to eradicate hepatitis B virus (HBV) infection. It has been shown in vitro that lamivudine and panciclovir (the active metabolite of famciclovir) act synergistically to inhibit HBV replication. To study the therapeutic efficacy of combined lamivudine and famciclovir therapy in patients with chronic hepatitis B. METHODS: Twenty‐one patients with chronic hepatitis B, who had been given lamivudine monotherapy for more than 6 months without improve­ment, had increased serum alanine aminotransferase (ALT) and HBV‐DNA levels, and were positive for hepatitis B surface antigen (HBsAg); 17 were positive for HBeAg. The diagnosis was verified by histology in 12 HBeAg‐positive cases. All patients were given combined therapy with lami­vudine (100 mg q.d.) and famciclovir (500 mg t.i.d.) orally for 4 months, and then with lamivudine alone for 5?10 months. RESULTS: Serum HBV‐DNA levels were initially 1 × 10^{8.19 ± 1.18} copies/mL, then decreased to 1 × 10^{5.25 ± 1.18} copies/mL at the end of the combined treatment and 1 × 10^{5.25 ± 1.82} copies/mL in the follow‐up period (P < 0.01). Serum ALT decreased from 225 ± 110 U/L before the trial to 79 ± 50 U/L at the end of the combined treatment and 81 ± 48 U/L in the follow‐up period (P < 0.01). In 17 HBeAg‐positive patients, eight (47.1%) had HBeAg/anti‐hepatitis B e antigen (HBeAg) seroconversion with a significant decrease of HBV‐DNA (<1 × 10⁴ copies/mL) and normal ALT (P < 0.01). Of four HBeAg‐negative patients, three had decreased levels of HBV‐DNA, to below 1 × 10⁴ copies/mL, which was associated with a significant decrease in ALT. Two patients had recurrent flare‐ups in the follow‐up period, but both HBV‐DNA and ALT were lower than the pretreatment levels. In 10 patients who underwent a second liver biopsy, improvements in inflammatory activity and fibrosis were seen in eight (80%) and four (40%) cases, respectively (P < 0.05). CONCLUSIONS: The combination treatment of lamivudine and famciclovir has synergistic or additive anti‐HBV effects, and may be an alternative therapy for patients with active chronic hepatitis B.     

替比夫定或拉米夫定抗乙型肝炎病毒的疗效预测探讨

目的观察替比夫定、拉米夫定治疗24周时对HBV的抑制程度,与治疗1年疗效的相关性,探讨临床实用的疗效预测指标。方法Ⅲ期临床研究,采用随机、对照、双盲、双模拟、多中心设计。共入组慢性乙型肝炎患者332例,其中替比夫定组167例,拉米夫定组165例。根据治疗24周时血清HBV DNA的水平,将患者分为4组：PCR低于检测下限（QL）组（〈300拷贝／ml）、QL-〈10^3拷贝／ml组、10^3-〈10^4拷贝／ml组和≥104拷贝／ml组。结果治疗52周时,替比夫定组血清HBV DNA自基线下降6．2log10,拉米夫定组下降5．4log10,t=3．6,P〈0．01,差异有统计学意义。HBV DNA低于检测下限的比例分别为69．6％和43．4％,χ^2=6．5,P〈0．01,差异有统计学意义。不论替比夫定组还是拉米夫定组治疗24周时HBV DNA水平越低,在52周HBV DNA达到PCR检测不到的水平、HBeAg血清转换和ALT复常的比率越高,48周病毒耐药的发生率越低。24周时替比夫定组HBV DNA低于检测下限的患者在52周时达到HBeAg血清转换的比率为43．3％,≥300拷贝／ml患者为8．8％,χ^2=21．6,P〈0．01,差异有统计学意义。结论替比夫定或拉米夫定治疗24周时,PCR检测不到HBV DNA,提示在52周可达到较佳疗效;24周时病毒水平下降不理想提示发生耐药的可能性增加。24周对HBV DNA的抑制程度可作为1年疗效的预测指标。     

替比夫定治疗HBeAg阳性慢性乙型肝炎48周疗效观察

目的观察比较替比夫定与拉米夫定治疗HBeAg阳性慢性乙型肝炎48周的疗效。方法73例患者按就诊顺序分别纳入治疗组（30例）和对照组（43例）。治疗组每天口服替比夫定600mg,对照组每天口服拉米夫定100mg,疗程均为48周。治疗前和治疗4、12、24、48周分别检测血清HBVDNA定量、血清HBV标志物、ALT水平。比较2组48周时HBVDNA水平、HBVDNA阴转率、HBeAg血清转换率、ALT复常率。结果2组HBVDNA水平随治疗时间延长均有所下降,治疗4周时下降最明显,治疗48周时治疗组平均下降水平大于对照组（P=0．001）。治疗组HBVDNA的阴转率为93．3％,高于对照组（69．3％）,P〈0．05,差异有统计学意义。48周时治疗组HBeAg血清转换率为33.3％,对照组为25．5％（P=0．472）,2组之间差异无统计学意义。2组间ALT复常率差异无统计学意义。结论替比夫定治疗HBeAg阳性慢性乙型肝炎48周的疗效优于拉米夫定。     

Interferon for treatment of breakthrough infection with hepatitis B virus mutants developing during long-term lamivudine therapy

Background: We aimed to treat patients with chronic hepatitis B on long-term treatment with lamivudine who developed lamivudine-resistant hepatitis B virus (HBV) mutants along with clinical relapses. Methods: Of 217 patients with chronic hepatitis B who had been treated with lamivudine for 1–6 years, 23 (11%) developed lamivudine-resistant hepatitis B virus (HBV) mutants. Seven of them, including 1 whose case was previously reported, received interferon (IFN) daily for 4 weeks and then two or three times a week thereafter to cope with exacerbation of hepatitis. We investigated the efficacy of this IFN therapy in 6 patients, excluding the 1 previously reported. Results: In 4 patients, HBV DNA decreased to below the detectable limit of the branched DNA assay (<0.7 MEq/ml) accompanied by normalization of transaminase levels. During IFN therapy, 2 patients seroconverted to antibody to hepatitis B e antigen (HBeAg) and showed normalized transaminase levels. Interferon was required in 7 of the 111 (6%) patients with chronic hepatitis B who were positive for HBeAg, but in none of the 106 who were positive for antibody to HBeAg (P = 0.014). Conclusions: The efficacy of IFN in controlling virological breakthroughs and exacerbation of hepatitis by infection with lamivudine-resistant HBV mutants in patients with HBeAg-positive chronic hepatitis B could enhance the versatility of lamivudine, which may have to be given to them indefinitely. Received: December 11, 2001 / Accepted: May 17, 2002 Reprint requests to: F. Suzuki Editorial on page 988     

比较替比夫定与拉米夫定治疗慢性乙型肝炎疗效的Meta分析

目的评价替比夫定与拉米夫定对比治疗慢性乙型肝炎（CHB）的疗效。方法检索2007年4月至2010年8月万方数据、维普资讯、中国生物医学文献数据库,根据纳入标准、排除标准,对入选的6篇随机对照试验（RCT）的研究结果,采用RevMan5.0.2软件进行分析。结果与对照组相比,替比夫定能更显著地提高HBV DNA转阴率、HBeAg转阴率、HBeAg血清转换率和ALT复常率：相对危险度（RR）分别为1.39[95%CI（1.26～1.54）,Z=6.45,P〈0.00001]、1.46[95%CI（1.16～1.84）,Z=3.24,P=0.001]、1.47[95%CI（1.12～1.92）,Z=2.77,P=0.006]和1.15[95%CI（1.09～1.22）,Z=4.88,P〈0.00001];且降低耐药率：优势比（OR）为0.31[95%CI（0.20～0.48）,Z=5.15,P〈0.00001];而两组不良事件发生率的差异无统计学意义[OR=1.36,95%CI（0.84～2.20）,Z=1.27,P=0.20]。结论采用替比夫定与拉米夫定对比治疗CHB患者,能更显著地降低HBV DNA,提高HBeAg血清转阴率、转换率和ALT复常率,降低耐药率,且不增加药物不良反应。     

扶正祛邪饮与替比夫定联合治疗对慢性乙型肝炎HBeAg血清转换作用的非随机对照研究临床观察

目的:探讨扶正祛邪饮与替比夫定联合治疗慢性乙型肝炎的疗效,重点观察HBeAg血清转换指标。方法:96例患者按意愿分为联合组50例和对照组46例,联合组患者口服替比夫定片,1次/d,600mg/次,疗程12个月。另加服扶正祛邪饮,2次/d,150ml/次,疗程6个月;对照组患者单用替比夫定,用法和疗程与联合组相同。观察两组患者治疗前后的临床症状改善、肝功能好转、HBV DNA下降、HBeAg转阴及HBeAg/抗-HBe血清转换的效果。结果:两组患者治疗后的ALT、AST、TBil、HBeAg转阴率、HBeAg/抗-HBe血清转换率、HBV DNA转阴率,与治疗前比较差异有显著性意义(P<0.01或P<0.05);两组患者治疗后的比较,联合组在ALT水平、HBeAg转阴率、HBeAg/抗-HBe血清转换率等早期应答方面优于对照组(P<0.05),联合组HBeAg转阴率、HBeAg/抗-HBe血清转换率在治疗12月时高于对照组,但差异无统计学意义(P>0.05)。结论:扶正祛邪饮联合替比夫定片治疗慢性乙型肝炎早期疗效明显,肝功能恢复较快,且能促进HBeAg转阴和HBeAg/抗-HBe血清转换提前应答,可作为慢性乙型肝炎治疗的辅助药物。     

Telbivudine in the treatment of chronic hepatitis B

Treatment of chronic hepatitis B with oral nucleos(t)ide analogs is evolving rapidly with newer compounds gaining approval. Recently, the US FDA and European Medicines Agency (EMEA) have approved telbivudine, a potent anti-hepatitis B virus (HBV)-specific agent with a hitherto excellent safety profile. This review focuses on the efficacy of this agent in chronic hepatitis B compared with lamivudine, evaluated clinically in Phase II and a large Phase III study. Monitoring of the virologic response under treatment with sensitive HBV-DNA assays has been applied, aiming at increasing efficacy and reducing HBV resistance. The results are critically presented and the evolving concept of effective long-term telbivudine and other nucleos(t)ide analog therapy, predicted by the extent of suppression of HBV replication at week 24, are analyzed and discussed.     

Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B

BACKGROUND AND AIMS: Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV). METHODS: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase (ALT) level > or =1.2 times the upper limit of normal, and serum HBV DNA level > or =6 log(10) copies/mL despite ongoing treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary end point was the time-weighted average change from baseline in serum HBV DNA level (DAVG) up to week 16. RESULTS: Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG(16) was -0.07 in the lamivudine group compared with -2.45 and -2.46 log(10) copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log(10) copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53%) and 9 of 18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19 (5%) recipients of lamivudine. Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative. CONCLUSIONS: These data, limited to patients with compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV.     

Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation

BACKGROUND AND AIMS: High-dose intravenous hepatitis B immunoglobulin (HBIG) may prevent recurrent hepatitis B virus (HBV) infection, but the cost has limited its widespread use in countries with endemic HBV infection. We report on long-term safety and efficacy of an alternative strategy of very low doses (400-800 IU/month) of intramuscular (IM) HBIG plus lamivudine. METHODS: Australian and New Zealand patients who received low-dose HBIG plus lamivudine following liver transplantation for HBV-related end-stage liver disease were studied. Prior to transplantation, patients with detectable serum HBV DNA received lamivudine 100 mg daily. Posttransplantation, all patients received lamivudine 100 mg daily plus IM HBIG 400 or 800 IU daily for 1 week then monthly thereafter. Serum HBV DNA levels were measured prior to lamivudine, at transplantation, and at 12 months posttransplantation. Serum titers of antibody to HBV surface antigen were measured at 1, 3, and 12 months posttransplantation. RESULTS: Between February 1996 and October 2004, 147 patients received low-dose HBIG plus lamivudine. Thirty-one percent were hepatitis B e antigen positive, and 85% were HBV DNA+ prior to transplantation. The median duration of pretransplantation lamivudine was 92 days (range, 1-1775). Median follow-up posttransplantation was 1860 days. Kaplan-Meier patient survival was 92% at 1 year and 88% at 5 years. The actuarial risk of HBV recurrence was 1% at 1 year and 4% at 5 years. Baseline HBV DNA titer was associated with HBV recurrence. CONCLUSION: Low-dose IM HBIG plus lamivudine provides safe and effective long-term prophylaxis against recurrent HBV at <10% the cost of the high-dose regimen.     

Improving clinical outcomes of chronic hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection is a global health problem, leading to cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths. Universal hepatitis B vaccination is the most cost–effective way to eradicate HBV infection with the remarkable reduction of chronic carriage, neonatal fulminant hepatitis and childhood HCC. The introduction of highly effective antiviral agents, including lamivudine, adefovir dipivoxil, entecavir, telbivudine, tenofovir disoproxil fumarate and pegylated interferons further improve short-, medium- and long-term outcomes of chronic HBV infection, such as ALT normalization, HBV DNA suppression, HBeAg seroconversion, HBsAg seroclearance, fibrosis regression, reduction of cirrhosis, HCC, liver-related deaths and the need for liver transplantation. Above all, sustained and profound viral suppression is the key to improve the clinical outcomes of chronic hepatitis B.     

Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naïve patients with HBV-related decompensated cirrhosis

Summary. Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double‐blind trial randomized 232 treatment‐naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once‐daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child‐Turcotte‐Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent‐to‐treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol‐defined composite endpoint in intent‐to‐treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.     

定量检测慢性乙型肝炎患者肝组织乙型肝炎病毒DNA的临床价值

目的探讨慢性乙型肝炎(CHB)患者肝内乙型肝炎病毒(HBV)DNA载量与血清HBV DNA、乙型肝炎病毒e抗原(HBeAg)水平的相关性及其在抗病毒治疗中的意义.方法41例HBeAg阳性CHB患者,在干扰素α和拉米夫定联合治疗前进行肝穿刺,取肝组织分别进行HBV DNA检测及组织学检查,据肝组织HBVDNA载量小于等于或大于104fg/cm3将其分为两组,治疗前及治疗期间监测其肝功能、血清HBeAg及HBV DNA情况.结果(1)肝组织HBV DNA载量高于血清HBV DNA载量(对数值4.081±1.127与3.163±1.010,t=2.218,P＜0.05),二者高度相关(r=0.840,t=4.322,P＜0.001);肝组织HBV DNA载量与血清HBeAg亦呈正相关(r=0.459,t=3.056,P＜0.005).(2)肝组织HBV DNA载量与肝组织炎症活动度呈反向关系(x2=3.874,P＜0.05).(3)治疗期间两组患者血清HBV DNA水平均明显下降,治疗前肝组织HBV DNA水平低者效果较好;治疗1年时HBeAg、抗-HBe血清转化率以肝组织HBV DNA水平低者为高(HBeAg转阴率68.4%与36.4%,x2=4.194,P＜0.05;抗-HBe阳转率73.7%与40.9%,x2=4.447,P＜0.05).结论肝组织HBV DNA水平较血清HBV DNA、HBeAg水平更能准确反映肝组织HBV DNA复制情况,且能间接反映机体的免疫状态,可作为抗病毒治疗适应证选择及疗效预测因子.     

替比夫定治疗活动性乙型肝炎肝硬化疗效观察

目的观察和比较替比夫定与拉米夫定治疗活动性乙型肝炎肝硬化的疗效和安全性。方法 65例活动性乙型肝炎肝硬化患者被随机分为治疗组（30例）和对照组（35例）。在常规综合治疗的基础上,治疗组给予替比夫定600mg/d口服,对照组给予拉米夫定100mg/d口服,观察72周。结果两组随治疗时间延长,患者血清HBVDNA水平下降,肝功能改善,Child-Pugh计分降低;替比夫定组治疗24周、48周和72周时,患者血清HBV DNA水平及治疗72周时ALT和Child-Pugh计分下降均优于拉米夫定组（P〈0.05或P〈0.01）;两组ALT复常、HBV DNA阴转和HBeAg阴转率无统计学差异（P〉0.05）。结论替比夫定和拉米夫定均可有效地抑制乙型肝炎肝硬化患者体内的HBV复制,改善肝功能。     

国产阿德福韦酯片治疗拉米夫定失效HBeAg阳性慢性乙型肝炎患者的临床研究

目的评价国产阿德福韦酯片（ADV）10mg／d治疗拉米夫定（LAM）失效的HBeAg阳性慢性乙型肝炎患者的疗效和安全性。方法随机、有限的（12周）双盲、安慰剂对照、多中心临床研究。筛选合格的慢性乙型肝炎患者按照2：1的随机比例,分为ADV＋LAM→ADV组：ADV10mg／d联合LAM100mg／d,治疗12周后改为单用ADV10mg／d治疗36周,共41例;安慰剂＋LAM→ADV组：安慰剂10mg／d联合LAM100mg／d,治疗12周后,改为单用ADV10mg／d,治疗36周,共18例。结果12周双盲治疗结束时,ADV＋LAM→ADV组患者血清中HBV DNA水平与基线相比的平均下降量（2．69lg拷贝／ml）、HBV DNA〈5lg拷贝／ml的患者比例（92．7％）、与基线相比下降≥2lg拷贝／ml的患者比例（78．1％）明显高于安慰剂＋LAM→ADV组（1．06lg拷贝／ml、33．3％、27．8％）,P=0．00。两组患者继续治疗,病毒学、血清学和生化学应答均有进一步改善。两组的不良事件发生率及其种类差异无统计学意义。治疗48周内未发现rtN236T和rtA181V突变。结论ADV10mg／d具有明显抗LAM失效的HBV株复制作用,且随着治疗时间延长作用增强,其安全性与安慰剂相似。     

Efficacy of lamivudine on hepatitis B viral status and liver function in patients with hepatitis B virus‐related hepatocellular carcinoma

Background/Aims: Treatment of patients with hepatocellular carcinoma (HCC) depends on the tumour extent and underlying liver function. Antiviral therapy with nucleoside/nucleotide analogues has been shown to be effective in improving the liver function of chronic hepatitis B (CHB) patients. We assessed whether lamivudine could induce biochemical and virological improvements in patients with hepatitis B virus‐related HCC. Patients/Methods: Of 148 CHB patients treated with 100 mg/day lamivudine for at least 6 months, 80 had HCC (CHB/HCC group) and 68 did not (CHB group). Biochemical and virological parameters were serially monitored. Results: Compared with the CHB group, the CHB/HCC group was older, had higher male predominance, bilirubin levels and liver cirrhosis rate, and lower albumin and hepatitis B virus (HBV) DNA levels and hepatitis B e antigen (HBeAg) positivity (P<0.05 each). The two groups showed similar cumulative rates of alanine aminotransferase normalization, HBV DNA seroconversion, HBeAg loss and viral breakthrough during 12 months of lamivudine treatment. After 12 months, the CHB/HCC group showed, relative to baseline, increased albumin levels (3.51±0.5 vs. 3.72±0.5 mg/ml) and decreased ascites scores (1.63±0.7 vs. 1.45±0.6) and Child–Pugh scores (6.92±1.9 vs. 6.02±1.38) (P<0.05 each). Conclusion: Lamivudine had comparable antiviral effects both in patients with CHB and CHB/HCC, and improved underlying liver function in the latter group. Treatment of HBV may increase the chance of curative treatments in patients with HBV‐related HCC.     

Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B

BACKGROUND & AIMS: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. METHODS: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). RESULTS: Histologic improvement occurred in 55% (68/124) of entecavir-treated vs 28% (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55% (77/141) vs 4% (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log(10) copies/mL for entecavir-treated patients and -0.48 log(10) copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. CONCLUSIONS: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile.     

Treatment of hepatitis B with lamivudine and tenofovir in HIV/HBV-coinfected patients: factors associated with response

As therapy for human immunodeficiency virus (HIV) infection evolves, optimizing hepatitis B virus (HBV) treatment and identifying factors that impact its response in the HIV/HBV-coinfected population is critical. We identified retrospectively 45 HBV/HIV-coinfected patients with detectable HBV DNA by the Bayer VERSANT HBV 3.0 bDNA assay (limit of quantification 2000 copies/mL) at baseline and/or year 1 of therapy. Patients were divided into three groups based on the active HBV agent in their antiretroviral regimen: group 1 (n = 15) received lamivudine; group 2 (n = 10), lamivudine plus tenofovir and group 3 (n = 20), lamivudine followed by lamivudine plus tenofovir. HBV genotypes and resistance profiles were determined by the Bayer Trugene HBV 1.0 assay. More patients in group 2 achieved HBV DNA suppression below 2000 copies/mL (80%), loss of HBe antigen (HBeAg) (40%) and loss of HBeAg and gain of anti-HBe (20%) than did patients in group 1 or 3. More patients with HBV genotype A, achieved HBV DNA suppression <2000 copies/mL than did patients with non-A genotypes [74% (26/35) vs 20% (2/10)], respectively (P = 0.003). Risk for virological nonresponse was significant in those with non-A genotypes [odds ratio (OR) 11.1; 95% CI: 2.0-50], previous HIV therapy (OR 6.5; 95% CI: 1.2-35) and <90% compliance (OR 3.7; 95% CI: 0.99-14.3). Simultaneous therapy with lamivudine/tenofovir suppresses HBV DNA more effectively than lamivudine or tenofovir added to lamivudine. More patients infected with HBV genotype A responded than the non-A patients, regardless of therapeutic regimen, compliance or prior HIV therapy.