肝移植病人服用替比夫定后并发肌病和周围神经病3例分析

目的 探讨肝移植病人服用替比夫定后并发肌病（myopathy,MP）和周围神经病（peripheral neuropathy,PNP）的诊治方法。 方法 回顾分析2008年6月至2009年6月中山大学附属第三医院3例肝移植病人服用替比夫定后并发MP和PNP的临床特点及诊治过程。 结果 应用替比夫定的肝移植病人MP和PNP发生率为11.5%（3/26）,出现症状时间平均为用药后11.7个月,诊断时间平均为出现症状后10.7个月,治疗后平均3个月临床症状基本消失。 结论 肝移植病人同时服用替比夫定和他克莫司时MP和PNP的发生率较高,应注意观察其相关症状,监测血肌酸磷酸激酶和肌红蛋白,以便早期诊断和治疗MP和PNP。     

Telbivudine in the treatment of chronic hepatitis B

Introduction  The treatment of chronic hepatitis B virus (HBV) infection has been revolutionized in the past decade by the increased availability of effective antiviral agents. Telbivudine is an L-nucleoside that is structurally related to lamivudine and has recently been approved for use in patients with chronic HBV infection. Telbivudine is highly selective for HBV DNA and inhibits viral DNA synthesis with no effect on human DNA or other viruses. This article reviews the pharmacology, pharmacokinetics, therapeutic efficacy and safety of telbivudine, and discusses its place in the current armamentarium against HBV. Methods  Relevant publications were identified from searches of Medline and PubMed between 2000 and 2008, using the search terms “hepatitis B/HBV,” “telbivudine/LdT,” “β-L-thymidine,” “pharmacokinetics,” “safety,” “adverse events,” and “resistance.” The reference lists of retrieved articles were searched for relevant studies. Results  Phase 3 clinical studies demonstrate that telbivudine is superior to lamivudine over a 2-year period in hepatitis B e-antigen (HBeAg)-positive and HBeAg-negative patients. Telbivudine was associated with a statistically signficantly greater reduction in HBV DNA, greater proportion of alanine aminotransferase normalization, and greater histological response than lamivudine. Furthermore, telbivudine use resulted in fewer cases of treatment failure and less virological resistance than lamivudine. However, after 2 years of therapy, telbivudine resistance was appreciable (25%) and considerably higher than that seen with other new antivirals such as tenofovir and entecavir. Overall, telbivudine was found to be safe, although grade 3 or 4 adverse events, including elevations in creatine kinase, were more commonly found in patients receiving telbivudine than lamivudine. Telbivudine is not active against lamivudine-resistant HBV. Conclusions  Telbivudine is a new antiviral agent joining the armamentarium against HBV. It is superior to lamivudine in terms of therapeutic response and resistance profile. However, concerns about resistance with long-term use, along with inferior cost-effective analyses, have relegated telbivudine to a second-line agent in the management of chronic HBV infection.     

慢性乙型肝炎合并脂肪肝对替比夫定疗效的影响

目的了解慢性乙型肝炎合并脂肪肝病人对替比夫定抗乙型肝炎病毒疗效的影响。方法回顾分析128例使用替比夫定抗乙型肝炎病毒治疗慢性乙型肝炎病人的肝组织病理检查,分为慢性乙型肝炎合并脂肪肝组43例,男性32例,女性11例,年龄(36±s 16)岁;单纯慢性乙肝组85例,男性62例,女性23例,年龄(37±11)岁。结果替比夫定抗病毒治疗1年丙氨酸转移酶(ALT)复常率2组分别为60%和84%(χ~2=5.892,P<0.01),乙肝病毒脱氧核糖核酸(HBV DNA)转阴率分别为70%和86%(χ~2=5.135,P<0.01)。肝穿病理结果存在肝细胞脂肪变性的慢性乙型肝炎病人对于替比夫定抗乙型肝炎病毒的ALT复常率和HBV DNA转阴率下降。结论肝细胞脂肪变性是影响替比夫定抗病毒疗效的重要因素之一。     

替比夫定单用及与阿德福韦或干扰素联用出现肌病的初步观察

目的：观察替比夫定单用及与阿德福韦或干扰素联用出现的肌病并分析其相关因素。方法：对2007年1月至2008年1月我院用替比夫定单药治疗及与阿德福韦或干扰素联合治疗出现肌病的5例患者进行调查，并对药物的用法用量，肌病的临床表现以及实验室检测结果进行分析。结果：5例患者均为男性，年龄25～45岁。1例服用替比夫定600mg，1次／d，治疗1个月。1例服用替比夫定600mg，2次／d，治疗2个月，后改为600mg，1次／d，并加用阿德福韦10mg，1次／d，治疗5个月。3例分别服用替比夫定600mg，1次／d，隔日肌内注射干扰素300万U，治疗3～9个月。5例患者均出现肌肉酸痛，全身乏力，其中1例伴有心肌受累，3例有神经症状、5例中有4例CK水平升高（311～900U／L）。结论：替比夫定单用或与阿德福韦或干扰素联用可能引起肌病，肌病严重程度可能与替比夫定的剂量有一定关联。     

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.     

替比夫定初治慢性乙型肝炎患者疗效与安全性观察

目的分析HBeAg阳性、阴性慢性乙型肝炎(CHB)患者初次使用替比夫定的疗效及安全性。方法 73例CHB患者(HBeAg阳性50例,阴性23例),接受替比夫定治疗至少1年,于治疗基线、病毒学应答前每个月、病毒学应答后每3个月检测HBV DNA、ALT、HBV血清标志物,观察治疗期间累计病毒学应答率、血清学转换率和耐药率;分析12、24周HBeAg下降幅度对预测血清学转换的价值;根据患者的情况不定期检测肌酸激酶(CK)。结果 (1)HBeAg阳性、阴性累计病毒学应答率1年分别为96%、100%,2年分别为96%、100%,其中90%HBeAg阳性、95%阴性患者在24周获得病毒学应答;(2)HBeAg阳性者1、2年累计血清学转换率分别为48%、61%;(3)HBeAg阳性、阴性累计耐药率1年分别为2%、4%,2年分别为24%、11%;(4)12、24周HBeAg下降幅度预测血清学转换的cut-off值分别为0.2557、0.3844log PEIU/ml,12周HBeAg下降幅度≥0.2557log PEIU/ml、24周≥0.3844log PEIU/ml的患者较低于该值者2年累计血清学转换率高,χ2值分别为28.996、15.036,P均=0.000(log-rank);(5)186人次查CK,78.8%数值超过参考范围(>140 IU/L),其中95.6%升高值在2级内,3级以上仅占4.4%。CK升高者无明显肌痛、肌炎,3～6个月内能自行下降至正常,无因CK升高而停药者。结论替比夫定对初治HBeAg阳性、阴性CHB患者疗效佳、安全性好。12、24周HBeAg下降幅度可作为2年血清学转换预测指标。     

替比夫定联合阿德福韦酯对 HBeAg 阳性慢性乙型肝炎的疗效观察

目的：探讨替比夫定联合阿德福韦酯对HBeAg阳性慢性乙型肝炎患者的疗效。方法将76例慢性乙型肝炎患者分为干扰素组和替比夫定组,干扰素组应用聚乙二醇干扰素α-2a联合阿德福韦酯,替比夫定组给予替比夫定联合阿德福韦酯,治疗48周,观察血清谷氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的含量和正常化率及血清HBsAg、HBeAg和乙肝病毒（HBV） DNA的含量及HBeAg阴转率和血清转换率及HBV DNA低于检测下限值率变化。结果2组治疗后24周和48周ALT和AST的含量及血清HBsAg、 HBeAg和HBV DNA的含量均明显降低（ P ＜0．01）,而替比夫定组治疗后降低量更显著;ALT和AST正常化率,HBeAg阴转率和血清转换率及HBV DNA低于检测下限值率显著增加（ P ＜0．01）,而替比夫定组治疗后的增加量更显著。结论替比夫定联合阿德福韦酯的治疗效果比干扰素联合阿德福韦酯的治疗更加显著。