联合方案治疗拉米夫定耐药HBeAg阳性慢性乙型肝炎患者的临床观察

[目的]观察拉米夫定（LAM）联合阿德福韦酯（ADV）与恩替卡韦（ETV）联合ADV治疗LAM耐药HBeAg阳性慢性乙型肝炎（CHB）的临床疗效.[方法]选择LAM耐药的HBeAg阳性CHB患者50例,随机分为LAM联合ADV组（A组）,ETV联合ADV组（B组）,每组各25例,观察两组在治疗前及治疗12、24、48周时HBV DNA载量、谷丙转氨酶（ALT）水平、HBV血清标志物变化.[结果]两组在治疗12、24、48周HBV DNA均较治疗前下降（P＜0.05）;治疗48周时A组与B组的HBV DNA阴转率和ALT复常率率分别为76.0％与88.0％、80.0％与92.0％,两组间差异无统计学意义（P＞0.05）;治疗24周HBV DNA阴转率B组高于A组（分别为84.0％,52.0％）,差异有统计学意义（P＜0.05）;治疗24周ALT复常率B组高于A组（分别为80.0％,52.0％）,差异有统计学意义（P＜0.05）;治疗过程中两组HBeAg阴转率比较差异无统计学意义（P＞0.05）;未出现严重不良反应及病毒学突破.[结论]LAM联合ADV与ETV联合ADV治疗LAM耐药HBeAg阳性CHB患者均能获得良好的临床疗效且安全性良好;ETV联合ADV能快速抑制HBV DNA及降低ALT,早期HBV DNA阴转率及ALT复常率高于LAM联合ADV.     

乙型肝炎病毒基因分型与耐药突变基因位点的检测分析

目的分析乙型肝炎病毒(HBV)基因型及耐药突变基因位点,为指导临床抗病毒治疗合理用药提供依据。方法回顾分析2014年3月～2016年10月安徽中医药大学第一附属医院114例乙型肝炎患者HBV基因分型和拉米夫定(LAM)、替比夫定(LdT)、阿德福韦酯(ADV)和恩替卡韦(ETV)四种核苷类药物(NAs)耐药及耐药突变位点分布情况、HBV核酸(HBVDNA)定量、HBVE抗原(HBeAg)定量、丙氨酸氨基转移酶(ALT)的浓度、血小板(PLT)的含量。结果 114例乙型肝炎患者中检测出HBV基因C型61例,B型45例,D型3例,B+C混合型1例,B+D混合型1例,其他基因型5例。其中C型多于B型(P 0.05)。检出39例NAs耐药,耐药率为34.21%;C型与B型耐药无显著差异。C型患者HBeAg定量高于B型患者(P 0.05),PLT计数低于B型患者(P 0.05)。耐药突变位点最多见于rt204I;C型多位点突变高于B型(P 0.05)。LAM和LdT联合耐药最多见,两种及两种以上多重耐药高于单一耐药(P 0.01)。结论本研究中乙型肝炎患者HBV基因型多为C型,其次为B型。C型患者容易发生肝纤维化,更易发生多位点突变。NAs耐药以LAM和LdT联合耐药为主,多为两种以上联合耐药。检测HBV基因型和耐药突变基因位点对评价乙型肝炎临床治疗效果和指导临床抗病毒治疗合理用药具有十分重要的意义。     

阿德福韦酯治疗YMDD变异的慢性乙型肝炎的临床研究

目的：阿德福韦酯（ADV）治疗LAM耐药慢性乙型肝炎（CHB）患者的疗效。方法：选择LAM治疗后出现YMDD变异的HBeAg阳性CHB患者89例,其中随机分为（A组）43例接受ADV和LAM联合治疗3个月后,单用ADV治疗1年,B组45例给予ADV联合LAM治疗1年。结果：A、B两组治疗12月后,患者ALT复常率分别是60．5％、88．9％;HBVDNA阴转率分别为41．9％、82．2％,HBeAg阴转率分别是10．3％、29．7％。结论：ADV联合LAM治疗LAM耐药CHB患者有效,长期联合LAM能提高HBVDNA阴转率,有显著的抗病毒效果。     

乙型肝炎病毒逆转录酶基因突变的临床意义

目的 分析服用核苷酸类似物的乙肝患者逆转录酶(RT)基因突变模式及其与生化指标的相关性,探讨该基因突变的临床意义。方法 采用半巢式PCR对634例来自武汉地区的乙肝病毒感染者血浆HBV进行扩增后,Sanger测序法进行基因序列分析; 将RT基因突变组与野生组和各表型突变组中患者的谷氨酸氨基转移酶(ALT)、乙肝病毒e抗原(HBeAg)和HBV DNA阳性率作比较。结果 在测序成功的622例患者中,144例(23.15%)发生RT基因突变。他们在11个位点(rtM204,rtL180,rtA181,rtN236,rtV173,rtL80,rtM250,rtS202,rtV207,rtV214和rtV84)出现碱基突变。在突变组中,患者的ALT,HBeAg和HBV DNA阳性率显著高于非突变组(P<0.05)。表型分析显示:拉米夫定(LAM)耐药最常检测到,占52.78%,其次为阿德福伟(ADV)耐药占27.78%和恩替卡韦(ETV)耐药占6.94%,多重耐药LAM+ADV于18例患者中检出12.5%。多重耐药组患者ALT,HBeAg和HBV DNA阳性率高于其他耐药组(P<0.05); ADV耐药组患者ALT,HBeAg和HBV DNA阳性率高于LAM,ETV耐药组。结论 HBV RT区域的突变形式与血清学指标ALT,HBeAg和HBV DNA阳性状态有显著关联,该基因的突变形式可用作患者临床表现的指示指标。     

深圳地区慢性乙型肝炎病毒感染者天然耐药现状及其与基因型的关系

目的 了解深圳地区慢性乙型肝炎病毒(HBV)感染者的天然耐药现状,并对其基因分型和天然耐药基因进行分析。方法 收集2017年3月～2018年2月来深圳市龙华区人民医院就诊并确诊为HBV感染且未使用核苷(酸)类似物抗病毒治疗的患者503例。采用PCR-反向点杂交基因芯片法对患者标本的HBV基因型及其与HBV耐药相关基因突变进行分析。结果 503例HBV感染者中检出64例对拉米夫定(LMV)和/或阿德福韦酯(ADV)天然耐药,耐药率为12.72%,其中对LMV天然耐药率为73.44%,明显高于对ADV天然耐药率的23.44%和对LMV和ADV同时耐药的3.13%,差异有统计学意义(P0.01～0.05)。503例HBV感染者B基因型检出率68.59%,明显高于C基因型的23.06%、D基因型的2.59%及B+C混合基因型的5.77%,差异有统计学意义(P0.05～0.01)。对LMV和ADV天然耐药基因突变中,耐药基因型均以B型为主,其中对LMV天然耐药基因突变类型以rtM204V为主,突变率为36.17%,明显高于其他突变类型,差异有统计学意义(P0.01～0.05),对ADV天然耐药基因突变类型以rt236T为主,突变率为46.67%,明显高于其他突变类型,差异有统计学意义(P0.01～0.05),而2例对LMV和ADV同时耐药基因型以B型为主,基因突变类型均为rtM204V+rtN236T。结论 深圳地区慢性HBV感染者对LMV和/或ADV有一定的天然耐药率,基因突变主要见于B基因型,基因突变类型以rtM204V和rtN236T为主。因此,HBV感染者治疗前进行天然耐药、基因分型及突变类型检测,对提高HBV治疗效果和降低耐药率具有重要的临床意义。     

ADV联合LMV治疗LMV耐药慢性乙型肝炎临床疗效

目的 观察ADV联合LMV治疗LMV耐药慢性乙型肝炎临床疗效和安全性.方法 选择YMDD变异株患者68例,随机分为对照组(A组、34例)和治疗组(B组、34例),对照组继续予拉米夫定100 mg/d口服治疗、治疗组联合ADV10 mg/d口服治疗,疗程6月.检测肝、肾功能、HBV DNA,HB-sAg,治疗过程中的病情变化和不良事件的发生率.结果 B组在第6月时,ALT、HBV DNA水平下降明显,与A组比较有显著性差异(P<0.05);A组与B组比较,AL T复常率有显著性统计学差异(P<0.05),HBV DNA转阴率比较无显著性差异(P>0.05),在使用ADV联合LMV治疗过程中,监测肾功能均在正常范围内,未发现明显的毒副作用.结论 ADV联合LMV治疗LMV耐药慢性乙型肝炎患者具有良好的疗效和安全性.     

阿德福韦酯治疗拉米夫定耐药性HBeAg阳性慢性乙型肝炎的疗效及安全性分析

目的观察并分析阿德福韦酯（ADV）治疗拉米夫定（LAM）耐药性乙肝病毒e抗原（HBeAg）阳性慢性乙型肝炎的疗效及安全性。方法选择2006年6月至2007年6月期间来自我院的76例LAM耐药性HBeAg阳性慢性乙型肝炎患者,分别采用ADV及LAM继续治疗。治疗1年后,分别观察两组的血清丙氨酸转氨酶（ALT）、HBeAg、乙肝病毒（HBV）DNA变化情况,并进行安全性分析。结果治疗1年后,两组患者HBeAg转阴率比较,差异无统计学意义（P〉0．05）,而ADV组的血清ALT复常率明显高于LAM组,差异有统计学意义（P〈0．05）。ADV组HBVDNA水平明显下降,且显著低于LAM组治疗后HBVDNA水平,差异有统计学意义（P〈0．05）。两组均未见严重不良反应。结论ADV治疗LAM耐药性HBeAg阳性慢性乙型肝炎具有良好的临床疗效及安全性。     

南通地区乙型肝炎病毒P区耐药突变与基因型及其临床意义

目的 探讨南通地区乙型肝炎病毒P区耐药基因突变特征与基因型,为临床合理用药提供科学依据。方法 选择158例经核苷(酸)类似物治疗至少2年以上慢性乙型肝炎(CHB)患者和30例未接受过核苷(酸)类似物治疗的CHB患者作为研究对象,采用PCR产物直接测序法检测HBV P区耐药基因和基因型,同时观察三种主要突变模式与ALT和HBV DNA水平的关系。结果 158例CHB患者检出B基因型42例(26.58%),C基因型116例(73.42%)。131例发生P区不同位点突变,突变率为82.91%。共检出11个HBV突变位点,主要突变位点是M204I,L180M,M204V,A181V和A181T,耐药频率依次为41.14%,37.34%,22.15%,11.39%和10.13%,11个突变位点有21种突变模式。拉米夫定(LAM)耐药相关突变中以L180M和M204V合并出现为主,其次以M204I单独出现; 阿德福韦酯(ADV)耐药相关突变中以A181V为主; 恩替卡韦(ETV)耐药率较低。结论 南通地区HBV基因型以B和C型为主,C型为优势基因型; 耐药突变主要集中在拉米夫定和阿德福韦酯耐药相关的突变位点,而恩替卡韦耐药率较低。多位点耐药突变检测有助于及时发现病毒耐药,更好地指导临床治疗。     

乙型肝炎病毒耐药基因变异位点与基因型及病毒载量的关系

目的：研究81例慢乙型肝炎患者乙型肝炎病毒（HBV）耐药基因位点变异状况及其基因型分布特征,并探讨其与HBV-DNA、乙型肝炎 E 抗原（HBeAg）、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）的关系。方法采用荧光定量PCR 和基因芯片反向斑点杂交技术检测81例慢乙型肝炎患者血清 HBV-DNA 载量、基因型和6种常见耐药位点;用电化学发光法检测 HBeAg 的含量,用酶法检测患者血清中 ALT、AST 的浓度。结果81例慢乙型肝炎患者中,HBV 基因型 B 型38例占46．9％;C 型38例占46．9％;B、C 混合型5例占6．2％;未发现其他基因型。检测出的43例耐药基因位点发生变异：B 基因型26例突变率为60．5％,C 基因型17例突变率为39．5％;其中 rt204V 变异率为9．3％;rt204I 变异率为34．9％;rt180M＋rt204I／rt204V 变异率为41．9％;rt181V 变异率为9．3％;rt236T 变异率为4．7％。在43例出现基因位点变异的患者中,发生 rt204I 变异的 B 基因型占60％,HBV-DNA（U／mL）的对数值为5．73±1．77;C 基因型占40％,HBV-DNA（U／mL）的对数值为6．93±2．12;发生 rt204V 变异的 B 基因型占75％,HBV-DNA（U／mL）的对数值为6．85±2．06;C 基因型占25％,HBV-DNA（U／mL）的对数值为4．17±1．15;发生 rt180M＋rt204I／rt204V 变异的 B 基因型占22．2％,HBV-DNA（U／mL）的对数值为5．89±1．95;C 基因型占77．8％,HBV-DNA（U／mL）的对数值为5．58±1．56;发生 rt181V 变异的全部为 C 基因型。结论HBV 发生变异的位点以rt204I 位点变异和 rt180M＋rt204I／rt204V 混合位点变异为主;在 HBV 发生变异的不同位点中 C 基因型更易发生 rt181V 位点和 rt180M＋rt204I／rt204V 混合位点变异,B 基因型可能更易发生 rt204V 位点和 rt204I 位点变异;在发生 rt204V 位点和 rt236T位点的突变中,HBV-DNA 的载量 B 基因型组明显高于 C 基因型组,在发生 rt204I 位点的突变中 HBV-DNA 的载量 C 基因型组则明显高于 B 基因型组,C 基因型较 B 基因型更易发生耐药位点变异。     

拉米夫定联合阿德福韦酯治疗LAM耐药慢性乙型肝炎患者的疗效分析

目的探讨拉米夫定(LAM)联合阿德福韦酯(ADV)治疗LAM耐药慢性乙型肝炎患者的疗效。方法选取2017年1月至2019年1月于我院治疗的LAM耐药慢性乙型肝炎患者86例,回顾性资料分析,分为观察组和对照组,对照组给予ADV治疗,观察组患者在ADV治疗基础上进行LAM联合治疗,观察LAM联合ADV治疗的LAM耐药慢性乙型肝炎患者治疗效果,对患者血清IL-17水平表达的影响以及治疗后生活质量评分。结果对两组患者治疗前后的HBV DNA载量进行比较发现,治疗前两组患者的HBV DNA载量无明显差异,治疗后虽均有下降,但是观察组患者的HBV DNA载量明显低于对照组患者,且随着治疗时间的增加其HBV DNA载量差距越来越大(P0.05)。对两组患者治疗前后血清IL-17、ALT水平比较,发现治疗前两组患者的IL-17、ALT水平无明显差异,治疗3个月检测发现,观察组患者的IL-17、ALT水平明显低于对照组患者(P0.05)。观察两组患者治疗后HBeAg血清转换率发现,随着治疗时间的增加两组患者的HBeAg血清转换率增加,同时观察组患者的HBeAg血清转换率明显高于对照组患者(P0.05)。对两组患者治疗后不良反应比较发现,观察组患者中不良反应发生率为4.65%,对照组患者不良反应发生率为6.98%,差异无统计学意义(P0.05)。结论 LAM联合ADV可以有效降低HBV-DNA的载量,增加患者HBeAg血清转换率,同时降低血清内IL-17、ALT水平,值得临床进一步探索。     

Hepatitis B virus genotype-associated variability in antiviral response to adefovir dipivoxil therapy in Chinese Han population

It is well known that different genotypes of hepatitis B virus (HBV) have a different sensitivity to interferon-alpha or lamivudine (nucleoside analogue) antiviral therapy. However, for adefovir dipivoxil (ADV, a nucleotide analogue), the antiviral response of the different genotypes remains to be clarified. In order to evaluate the response of HBV genotypes to ADV therapy and to identify factors that might affect initial virological response, we performed a retrospective analysis on patients with chronic hepatitis B (CHB) in Chinese Han population. The study included 183 patients, who had been tested positive for hepatitis B e antigen (HBeAg) and had been treated with ADV (10 mg/day) for 48 weeks. The numbers of patients infected with HBV genotype B and genotype C were 98 and 75 cases, respectively, and the remaining 10 patients were mixture infection of genotypes B plus C or genotypes B plus D. The mean HBV-DNA reduction and HBV-DNA seroclearance of genotypes B and C at 48 weeks were 3.6 log(10) and 3.1 log(10) copies/ml (p < 0.05) and 41.8% and 34.6% (p < 0.05), respectively. There were no statistically significant differences between genotypes B and C in terms of HBeAg loss, anti-HBe seroconversion and normalization of serum alanine aminotransferase (ALT). Multivariate analysis showed that young age, low pretreatment HBV-DNA and/or elevated ALT level might be independent predictive factors associated with initial virological response. Thus, in Han CHB patients who are HBeAg-positive, HBV genotype B shows a better virological response to ADV therapy than does genotype C.     

慢性乙型肝炎基因分型与阿德福韦酯疗效相关性研究

目的 调查本地区乙型肝炎病毒(HBV)基因分型的分布情况,观察乙型肝炎基因分型对阿德福韦酯抗病毒疗效的影响.方法 对285例慢性乙型肝炎(其中HBV基因型B型219例,C型66例)用阿德福韦酯治疗的慢性乙型肝炎的患者进行分析,观察治疗12周、24周、48周及96周丙氨酸转氨酶(ALT)、HBV DNA定量、乙型肝炎病毒e抗原(HBeAg)乙型肝炎病毒e抗体定量.结果 阿德福韦酯治疗12周时B组以及C组HBV DNA转阴率为30.6%及36.4%,HBV DNA下降均值为(1.36±0.98)eopies/ml及(1.31±1.40)copies/ml(P>0.05);治疗24周两组HBV DNA转阴率分别为33.8%及42.4%,HBV DNA下降均值为(2.19±1.18)copies/ml及(2.22±1.10)copies/ml(P>0.05).治疗48周两组HBV DNA转阴率分别为38.8%及45.5%,HBV DNA下降均值为(2.98±1.24)copies/ml及(2.97±0.92)copies/ml(P>0.05).治疗96周两组HBV DNA转阴率分别为44.8%及48.5%,HBV DNA下降均值为(3.41±1.68)copies/ml及(3.50±1.72)copies/ml(P>0.05).治疗12周后B、C两组HBeAg转阴HBeAb出现分别为10.6%vs 8.6%及11.6%vs 9.3%,24周后B、C两组HBeAg转阴/HBeAb出现分别为14.6%vs 11.3%及16.3%vs 11.6%,48周后B、C两组HBeAg转阴/HBeAb出现分别为27.8%vs 21.2%及25.6%vs 20.9%,96周后B、C两组HBeAg转阴/HBeAb出现分剐为36.4%vs 25.2%及39.5%vs 25.6%,两组差异均无统计学意义(P>0.05).两组ALT复常率12周为59.8%vs 47.0%(P<0.05),24周为60.3%vs 63.6%,48周为76.3%vs 77.3%,96周为80.0%vs 80.3%,两组差异均无统计学意义(P>0.05).结论 阿德福韦酯治疗慢性乙型肝炎B型及C型,病毒应答、生化应答及血清学应答相当,阿德福韦酯时HBV基因B型及C型疗效无明显影响.本地区HBV基因型以B型为主,C型次之,未发现A、D型.     

HBV基因分型和耐药突变基因检测

目的探讨东营地区乙型肝炎病毒(HBV)基因型分布,乙型肝炎患者耐药情况,HBV基因型别与耐药以及突变位点关系。方法收集乙型肝炎患者血清300例,采用离心柱法提取HBV-DNA,聚合酶链反应(PCR)-反向点杂交法检测HBV分型和耐药突变。结果 300例HBV-DNA阳性患者中,检出B型、C型、B/C型及其他未检测出的基因型,未检出D型分型,检出结果中以C型为主,占81.8%;HBV患者耐药药物以拉米夫定和替比夫定的联合耐药为主,占43.6%;HBV耐药突变基因型主要为rt204I(24.35%)、rt204V(17.39%)及rt180M(17.39%);B型和C型的耐药突变率分别为30.77%和42.42%,差异有统计学意义(P0.05)。结论东营地区HBV基因C型多于B型,C型容易产生耐药,以rt204I,rt204V及rt180M基因突变型多见,拉米夫定和替比夫定的联合耐药多见,应根据基因分型和耐药突变结果对乙型肝炎患者选择适合的治疗方案。     

Hepatitis B virus genotypes B and C do not affect the antiviral response to lamivudine

To date, there have been no studies examining the role of hepatitis B virus (HBV) genotypes on the response to lamivudine therapy and the development of YMDD mutations. The present study aimed at determining any differences in the antiviral response and risk of YMDD mutations between lamivudine-treated patients with HBV genotype B and genotype C. Eighty-two patients receiving lamivudine were recruited. HBV genotypes at baseline and YMDD mutations at week 52 were determined by line probe assays (LiPA). HBV DNA levels were determined by the Cobas Amplicor HBV Monitor Test. Seventeen (20.7%) and sixty-four (78%) patients had single genotypes of B and C, respectively. At both week 24 and 52 there were no differences in the median reduction of HBV DNA levels (median 4 logs drop), the median reduction of alanine aminotransferase (ALT) levels, and the proportion with normalization of ALT [8/8 (100%) vs 26/37 (70.3%), P=0.19] between patients with genotypes B and C. The rate of HBeAg seroconversion [3/17 (17.6%) vs 6/64 (9.4%), P=0.39] and the chance of YMDD mutation development [3/17 (17.6%) vs 12/64 (18.8%), P=1.0] at week 52 were also similar between patients with genotype B and C, respectively. In conclusion, there was no difference in the antiviral response and the rate of development of YMDD mutations in Chinese patients with genotype B and C after 1 year of lamivudine. Determination of HBV genotypes before lamivudine therapy was probably not an important pretreatment investigation to predict antiviral responses in Chinese patients.     

Hepatitis B genotypes in chronic hepatitis B and lamivudine therapy

The influence of hepatitis B virus (HBV) genotypes on the natural history and the response to treatment of patients with chronic hepatitis B are of potential interest. Compared to the patients with HBV genotype C, those with genotype B were of a younger age and had a higher cumulative rate of hepatitis B e antigen (HBeAg) seroconversion during the initial 6 years of follow-up. The earlier HBeAg seroconversion in the patients with genotype B, however, did not provide them with a benefit in terms of a reduced risk of developing long-term complications. The response to lamivudine therapy was evaluated in 21 patients infected with HBV genotype B (all of subtype Ba) and 61 with genotype C. There were no differences in the virological response to lamivudine therapy, based on the reduction in median logarithmic HBV DNA titer as well as alanine aminotransferase (ALT) levels, normalization of ALT and the rate of HBeAg seroconversion between the patients with genotypes B and C. No differences were noted either, in the frequency of YMDD mutants at week 52 or the cumulative risk of HBV DNA breakthroughs with YMDD mutations during long-term lamivudine therapy (median 37.5 months). In conclusion, there is no influence of HBV genotypes on the development of long-term complications and lamivudine therapy in Hong Kong.     

Efficacy of lamivudine therapy and factors associated with emergence of resistance in chronic hepatitis B virus infection in Japan

OBJECTIVE: Several reports have examined the efficacy of long-term lamivudine therapy and the risk factors involved in emergence of viral resistance in Japanese patients with hepatitis B virus (HBV) infection. However, the patient cohorts in such studies are relatively small. METHODS: We analyzed 234 chronically HBV-infected Japanese patients who were treated with lamivudine for more than 12 months. They comprised patients with HBV genotype A (n = 8), genotype B (n = 21), genotype C (n = 203) and other HBV genotypes (n = 2). RESULTS: In most patients, lamivudine resulted in normalization of alanine transaminase (ALT) levels at 6 and 12 months, and suppression of serum HBV DNA to undetectable levels by the branched chain DNA probe assay (bDNA). Rates of ALT normalization and non-detection of HBV DNA were higher among patients with genotype B than genotype C disease. The proportions of patients who achieved HBeAg loss were 27, 42 and 45% after 6 months, 1 year and 2 years, respectively. The emergence of mutations was not different among genotypes A, B and C by the Kaplan-Meier method. Multivariate analyses identified high HBV DNA level (bDNA >or=100 MEq/ml) as an independent factor associated with emergence of the YMDD motif mutation in all patients. Among patients with genotype C disease, which is the predominant HBV genotype in Japan, multivariate analysis also identified high HBV DNA level and HBeAg positivity as factors associated with emergence of resistance. CONCLUSION: Patients exhibiting these factors at the commencement of lamivudine treatment must be monitored carefully at regular intervals for emergence of viral resistance.     

Hepatitis B genotypes and response to antiviral therapy: a review

The aim of this review is to examine the impact of hepatitis B virus (HBV) genotypes on biochemical and virologic response to antiviral drugs (alfa-interferon and pegylated-interferon alfa-2b, lamivudine, and adefovir dipivoxil) actually used for the treatment of chronic hepatitis, HBV related. International literature evidences that HBV genotypes D and C are associated with a lower rate of favorable response to alfa-interferon and pegylated-interferon alfa-2b therapy than genotypes A and B. The rate of resistance to lamivudine was higher in patients with genotype A infection than in patients infected by genotype D, whereas no difference in the risk of lamivudine resistance is found between patients with genotype B and patients with genotype C. In regard to the new nucleotide analogue, adefovir dipivoxil, a preliminary trial appears to provide no evidence of any difference in virologic response among the different HBV genotypes. The current study has determined that the different HBV genotypes have a very important impact on response to antiviral therapy, in particular interferon treatment. For this reason, determining the HBV genotype could be helpful for predicting the outcome of antiviral therapy in patients affected by chronic hepatitis B.     

某地区乙型肝炎病毒基因型分布和P区耐药突变模式分析

目的探讨十堰地区乙型肝炎病毒(HBV)基因型分布和P区耐药突变模式及两者的相关性。方法将在该院进行治疗的224例慢性乙型肝炎患者纳入本研究,提取患者血液标本中的HBV DNA,利用ABI 3730型遗传分析仪对DNA进行测序,通过SeqMan软件实施序列比对,分析HBV DNA的基因型和P区耐药突变的情况。结果检出HBV基因型为B型者136例,占60.71%;为C型者62例,占27.68%。二者比例均高于D型、B+C型及未分型者,差异有统计学意义(P0.05)。78例明确出现耐药突变,其中B基因型对于拉米夫定以及阿德福韦的耐药率分别为18.38%与9.56%,与C基因型对于二者的耐药率16.13%与9.68%相比,差异均无统计学意义(P0.05)。B基因型患者M204V、M204I耐药突变的发生率分别为38.60%、17.54%,C基因型患者则分别为28.57%与38.10%,两种基因型患者比较差异无统计学意义(P0.05)。B、C型基因突变患者间YMDD突变(M204V、M204I)及非YMDD突变所占比例比较,差异均无统计学意义(P0.05)。B基因型及C基因型分别与M204V及M204I两种突变均呈正相关。结论十堰地区HBV的基因型主要是B型及C型,发生的HBV耐药突变则以M204I和M204V为主,在临床治疗时应按照基因分型以及耐药突变情况合理选择药物进行慢性乙型肝炎的治疗。