135例慢性HBV感染者阿德福韦酯抗病毒疗效与基因型的关系

目的探讨秦皇岛地区慢性乙型肝炎患者阿德福韦酯抗病毒疗效与基因型的关系。方法慢性HBV感染者135例予以阿德福韦酯10 mg/d口服,疗程48周,用药前采用A-D基因型乙型肝炎病毒（HBV）全长逆转录酶区（PCR）方法测定基因型,用药中检测HBV DNA阴转率、HBeAg血清转换率、ALT复常率、治疗有效率。结果秦皇岛地区慢性乙型肝炎患者基因型以C型为主占75.56%,其次为B型占17.78%,B/C混合型占6.67%。在阿德福韦酯治疗中,B、C、B/C混合型在HBV DNA阴转率、HBeAg血清转换率、ALT复常率、治疗有效率方面均无统计学差异（P〉0.05）。结论慢性HBV感染者阿德福韦酯抗病毒疗效与基因型无关。     

不同乙型肝炎病毒基因型感染与阿德福韦酯疗效的相关性

目的探讨HBV基因型对阿德福韦酯的抗病毒治疗效果的影响及HBV耐药变异情况。方法对应用阿德福韦酯初治的336例慢性乙型肝炎(乙肝)患者治疗前行HBV基因分型检测;治疗48周和96周分别对临床疗效及HBV耐药变异率进行比较。结果治疗48周B基因型HBV感染者(B基因型)血清HBV-DNA均值较基线下降幅度及血清HBV-DNA转阴(血清HBV-DNA<1×103copies/mL)率优于C基因型HBV感染者(C基因型),P<0.05;B基因型与C基因型者血清ALT复常率及血清学应答(血清HBeAg转阴或血清HBeAg/抗-HBe转换)率比较无统计学意义。血清HBV-DNA阴性者继续阿德福韦酯单药治疗至96周,B基因型与C基因型者血清学应答率和HBV耐药变异率比较均无统计学意义。结论感染B基因型HBV者阿德福韦酯的治疗效果优于感染C基因型者;血清ALT复常率、血清学应答率及HBV耐药变异率与HBV基因型无明显关系。     

HBV基因型与干扰素抗病毒疗效的关系

目的:探讨HBV不同基因型对α-干扰素抗病毒疗效的影响.方法:选取应用α-干扰素进行抗病毒治疗的慢性乙型肝炎患者作为研究对象,观察其抗病毒疗效.患者的HBV基因型采用PCR微板核酸杂交-ELISA方法检测;血清HBV DNA复制水平采用荧光定量PCR检测;HBV前C区和BCP(基础核心启动子)区基因位点变异采用HBV基因多态性芯片进行检测.结果:94例慢性乙型肝炎患者的HBV基因型以C型、B型为主,未发现A、E、F基因型.HBV DNA高复制水平明显与C基因型及混合基因型有关.B基因型对α-干扰素抗病毒治疗的应答明显优于C、D型,而混合基因型对α-干扰素的应答最不敏感.仅B基因型对α-干扰素治疗产生完全应答.部分应答及无应答时HBeAg的转阴与HBV前C区nt 1 896位点变异、以及BCP区nt 1 762、nt 1 764双位点变异有关.C基因型HBV前C区及BCP区基因变异发生率明显高于B型.结论:HBV基因型与HBV DNA复制水平、HBV基因变异以及α-干扰素抗病毒疗效均有一定的相关性,提示HBV基因分型有重要的临床意义.     

B和C基因型乙型肝炎病毒对阿德福韦酯治疗的病毒学应答比较

目的 阐明不同基因型HBV对阿德福韦酯治疗反应是否存在差异.方法 首先利用型特异引物PCR法结合型特异核苷酸分析法检测HBV基因型,然后根据基因型对阿德福韦酯Ⅲ期临床资料进行分析及统计学处理(计量资料用t检验,计数资料用卡方检验).结果 177例临床标本检出B基因型HBV感染者102例,C基因型感染者65例,B+C混合型感染者6例,B+D混合型感染者4例.治疗第12、24周时,B基因型组和C基因型组血清HBV DNA下降均值分别为2.2log10>拷贝/ml、2.1log10拷贝/ml和2.7log10拷贝/ml、2.4log10拷贝/ml,两组差异均无统计学意义(P>0.05),第48周时两组HBV DNA分别下降3.6log10拷贝/ml和3.1log10拷贝/ml,差异有统计学意义(P<0.05).治疗结束时(48周)B基因型组和c基因型组分别有43例(42.2%)和22例(33.8%)出现血清HBV DNA转阴,差异有统计学意义(P<0.05);两组患者HBeAg阴转率抗-Hbe血清转换率分别为30.4%、29.2%和21.6%、20.0%,差异无统计学意义(P>0.05).两组患者血清ALT复常率在治疗第12、24、36周和48周时分别为35.3%、33.9%,51.0%、53.9%,63.4%、61.5%和83.3%、81.5%,各时间段两组ALT复常率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48周时,部分病毒学指标(如血清HBV DNA下降均值和HBV DNA阴转率)B基因型优于C基因型HBV感染者.但由于阿德福韦酯起效较慢,抑制病毒作用相对较弱,有必要延长治疗时间进一步证实这一现象.     

秦皇岛市136例慢性乙型肝炎患者拉米夫定的疗效及其与HBV基因型的关系

目的:探讨秦皇岛市慢性乙型肝炎(CHB)患者拉米夫定治疗疗效与基因型的关系。方法:136例CHB患者口服拉米夫定,100mg/次,1次/d,疗程48周,用药前采用PCR方法测定乙型肝炎病毒(HBV)A～D基因型。结果:秦皇岛市CHB患者基因型以C型为主,占75.74%,其次为B基因型占16.91%,B/C混合型占7.35%,B基因型在拉米夫定抗病毒治疗48周时显示HBV DNA阴转率、HBeAg血清转换率、ALT复常率、治疗有效率4方面均高于C型及B/C基因型(P0.05),B基因型HBV感染者有较低的YMDD变异发生率。结论:拉米夫定抗病毒疗效与基因型有关,HBV基因型测定可作为预测拉米夫定抗病毒疗效的指标。     

不同HBV基因型感染慢性乙型肝炎患者对核苷(酸)类药物治疗的应答反应比较

目的研究与探讨HBV基因型与慢性乙型肝炎患者肝组织病理学变化及对核苷(酸)类抗病毒药物疗效的关系。方法随机将慢性HBV感染者541例分为4组:拉米夫定组136例、替比夫定组135例、恩替卡韦组135例和阿德福韦组135例,各治疗48周。治疗前应用聚合酶链反应法确定HBV基因型,并于治疗前和治疗48周时分别检测肝功能、HBV DNA和HBV M。其中109例行肝组织病理学检查。结果本组HBV B基因型94例(17.38%),C型410例(75.79%),B/C混合型37例(6.84%),未检出其他基因型;在B型感染者,肝组织G3占37.3%、S313.0%,C型感染者G3占8.7%、S3占22.7%,B基因型与C基因型之间比较,有统计学意义(P<0.05);在拉米夫定、恩替卡韦和替比夫定治疗患者,B型、C型和B/C混合型之间疗效的比较,有统计学差异(P<0.05),而在阿德福韦酯治疗患者,几种不同的基因型感染患者疗效无统计学差异(P>0.05)。结论 HBV基因型与患者肝组织病理学改变及对核苷类抗病毒治疗的疗效密切相关。     

e抗原阳性慢性乙型肝炎患者感染病毒的基因型与抗病毒治疗疗效的关系

目的 探讨HBV基因型与抗病毒治疗疗效的关系。方法 应用PCR-微板核酸分子杂交ELISA法检测90例HBeAg阳性CHB患者的HBV基因型,对其中41例患者给予拉米夫定（100 mg／d）抗病毒治疗48周,49例患者给子干扰素α（3 MU／次,隔日1次）抗病毒治疗48周,治疗前、治疗过程中和治疗结束时分别检测血清生化指标（ALT）、病毒学血清标志物（HBeAg和抗-HBe）和HBV DNA水平。结果 90例CHB患者中HBV B基因型者16例,C基因型者74例。41例患者应用拉米夫定治疗,感染B和C基因型患者48周时对拉米夫定治疗应答率分别为33.3％和20%,差异无统计学意义;49例患者应用干扰素α治疗,48周时感染基因B型患者的ALT复常率、HBeAg消失率和HBV DNA阴转率均高于感染基因C型患者（分别为60.0％和20．5％,50．0％和17．9％, 50．0％和17．9％）,两组比较差异有统计学意义,但HBeAg血清转换率差异无统计学意义。结论 基因B和C型对拉米夫定抗病毒治疗的疗效无影响,基因B型对干扰素α治疗的疗效优于C型。     

干扰素治疗慢性乙型肝炎疗效与HBV基因型的关系

目的: 探讨HBV不同基因型对干扰素抗病毒治疗的影响.方法: 对30名HBV患者进行干扰素抗病毒治疗, PCR-RFLP检测HBV基因型, 观察不同基因型HBV对干扰素的应答水平.结果: 30例患者HBV基因型以B型(40.0%)和C型(56.67%)为主, C型患者HBV DNA水平显著高于B型患者(6.03±1.35 vs 5.45±1.21,P<0.05), B型患者对干扰素应答率显著高于C型患者, 在无应答患者中分别有1名B型和C型转变为D型.结论: HBV基因型与HBV DNA复制水平、抗病毒疗效均有一定的相关性, 在治疗过程中可发生基因型改变.     

延安地区乙型肝炎病毒基因型与干扰素抗病毒治疗的效果

目的 了解延安地区不同HBV基因型临床特征及其干扰素抗病毒治疗的效果.方法 用PCR鉴定延安地区130例慢性乙型肝炎患者的HBV基因型,并对患者应用干扰素α-2b抗病毒治疗12个月,随访12个月,对治疗及随访资料进行回顾性分析.统计学处理采用x2检验.结果 延安地区HBV基因型以B、C基因型为最常见;B基因型HBeAg阳性率明显低于C基因型,且B+C基因型HBeAg阳性率也明显低于C基因型;B基因型与B+C基因型、B基因型与D基因型、C基因型与D基因型、D基因型与B+C基因型的HBeAg阳性率比较,差异均无统计学意义.B基因型对干扰素的完全应答率、持续应答率明显高于C基因型,而无应答率低于C基因型;B+C基因型的干扰素应答率低于B、C基因型.结论 延安地区B、B+C基因型HBeAg阳性率明显低于C基因型;B基因型对干扰素的完全应答率高于C基因型,B+C基因型的干扰素应答率低于B、C基因.     

乙型肝炎病毒基因型和早期病毒学应答对干扰素-α2b治疗慢性乙型肝炎疗效的预测价值

目的观察乙型肝炎病毒基因型以及早期HBV DNA应答对干扰素-α2b疗效的影响。方法136例慢性乙型肝炎患者接受干扰素-α2b治疗6个月,观察治疗结束时患者乙型肝炎病毒血清标志物、HBV DNA和ALT的变化。结果在完成治疗的129例患者中,C型感染者57例,B型感染者42例,B/C感染者30例。在治疗结束时,B型患者的综合应答率为42%,优于C型28%及B/C混合型16%。多变量Logistic回归分析显示,治疗3月时HBV DNA呈现应答者,治疗结束时应答率高（HBV DNA快速应答的偏回归系数=0.801,P=0.001,优势比=4.5,优势比的95%可信区间为3.01～5.28）。结论快速病毒学应答和感染病毒的基因型可以预测干扰素-α2b治疗慢性乙型肝炎的疗效。     

Effect of Hepatitis B Virus Genotypes on the Efficacy of Adefovir Dipivoxil Antiviral Therapy

Background:

Hepatitis B is a common infectious disease in China. Many studies have shown that the genotype of hepatitis B virus (HBV) is probably associated with the efficacy of some antiviral drugs such as interferon α (IFN-α) and Lamivudine (LAM). However, the association between HBV genotype and adefovir dipivoxil (ADV) is controversial. ADV is the most popular antiviral drug in China due to its low price, good antiviral efficacy, few side effects, and convenient of administration.

Objectives:

This study focused on the effect of HBV genotypes on antiviral efficacy of ADV in patients with chronic hepatitis B infection (CHB).

Patients and Methods:

A total of 526 HBeAg-positive patients with CHB were randomly allocated into two groups. One group took ADV and another group took placebo. Nested Polymerase Chain Reaction (PCR) with multiple pairs of genotype-specific primers (nPCR-MPP) was used to analyze genotypes of HBV in these patients. Antiviral efficacy after treatment for three, six, 12 months was compared among the patients with different HBV genotypes.

Results:

Genotype B (73.6%) and genotype C (26.4%) were detected in these patients. After treatment for 12 months, the rate of HBV DNA seroclearance, ALT normalization, and HBeAg seroconversion were significantly higher in ADV group than in placebo group (P < 0.05). However, there were no significant differences in these three rates between patients infected with genotype B and C (P > 0.05).

Conclusions:

HBV genotypes B and C have no significant difference in virologic, biochemical, and immunologic response to ADV.     

阿德福韦酯治疗不同HBV基因型感染慢性乙型肝炎患者48周疗效分析

目的观察阿德福韦酯初始治疗慢性乙型肝炎患者48周疗效及其与HBV基因型的关系。方法 75例慢性乙型肝炎患者接受国产阿德福韦酯治疗48周,观察治疗期间ALT、AST、HBV DNA、HBeAg等指标变化,并检测患者HBV基因型。结果在75例中检出B基因型49例（65.3%）,C基因型22例（29.3%）,B/C基因型4例（5.3%）;治疗48周时ALT复常率和HBV DNA转阴率分别为58.7%和50.7%,HBeAg消失率为34.9%,HBeAg血清转换率为1.5%;在治疗12周时,B基因型组ALT复常率和HBV DNA阴转率分别为26.5%和38.8%,48周时为55.1%和53.1%,在治疗12周时,C基因组ALT复常率和HBV DNA阴转率为13.6%和31.8%4,8周为59.1%和36.4%（P〉0.05）。结论基线HBV DNA〉1×105copies/ml的慢性乙型肝炎患者初始采用ADV治疗,HBeAg血清学转换率较低,ADV治疗的疗效与HBV基因型无关。     

阿德福韦酯治疗HBeAg阴性慢性乙型肝炎疗效与HBV基因型的关系

目的探讨阿德福韦酯（ADv）治疗HBeAg阴性慢性乙型肝炎（chronic hepatitis B,CHB）的疗效与HBv基因型的关系。方法选择71例HBVDNA〉1×10^4copies／ml、ALT〉2倍正常值上限、TBIL正常的HBeAg阴性cHB患者,其中B基因型40例,C基因型31例,所有患者均口服ADV 10mg,1／d,治疗52周,动态观察治疗过程中HBV DNA和ALT水平的变化。结果在治疗12、24、52周时,B基因型患者ALT变化、血清HBVDNA水平下降≥2log。完全抑制比例与C基因型患者相比差异无统计学意义（P〉0．05）。结论ADV能有效抑制HBeAg阴性CHB患者HBV复制,促进肝功能好转,其疗效与HBV基因型B或C型无关。     

未经治疗的慢性乙型肝炎患者乙型肝炎病毒耐药变异、基因型和血清型研究

目的 研究未经核苷(酸)类似物(NA)治疗的慢性乙型肝炎患者HBV耐药变异、基因型、基因亚型和血清型特点.方法 从北京大学附属医院收集97例未经NA治疗的慢性乙型肝炎患者血清,用半巢式聚合酶链反应-直接测序法获得HBV全长逆转录酶区序列,用生物信息学技术筛查该区内11个经典耐药变异位点并鉴定基因型、基因亚型和血清型.用统计分析软件SPSS11.0进行t检验和χ~2检验. 结果 HBV在11个经典耐药变异位点上均为野生型氨基酸;B基因型和C基因型分别占36.1%(35/97)和63.9%(62/97),前者均属B2亚型,后者C2亚型占91.9%(57/62),C1亚型占6.5%(4/62),1例未能分出亚型.已知出生地的患者中,71.9%(23/32) B基因型感染者出生于我国南方地区,81.6%(40/49) C基因型感染者出生于北方地区,基因型地域分布特点明显,χ~2=23.19,P<0.01.血清型为adr者占60.8%(59/97),与C基因型相关;为adw者占38.1%(37/97),与B基因型相关,χ~2=87.83,P<0.01.结论 未经NA治疗的慢性乙型肝炎患者体内野毒株为优势株,其基因型、基因亚型和血清型与患者出生地有关.     

Hepatitis B virus with the rtL80V/I mutation is associated with a poor response to adefovir dipivoxil therapy

Background/Aims: Lamivudine (LAM) resistance is frequently associated with various types of genomic changes in hepatitis B virus (HBV)‐DNA including YMDD mutations (rtM204V/I). We intended to examine the effects of these genotypic variants on the antiviral efficacy of adefovir dipivoxil (ADV) therapy. Methods: A total of 97 chronic hepatitis B (CHB) patients with YMDD mutants who had been treated with ADV for >12 months were analysed. Mutations of the entire polymerase domain of HBV were determined by direct sequencing. Results: All the 97 patients had genotype C HBV associated with rtM204V/I mutations; 63 (65%) rtM204I, 27 (28%) rtM204V and seven (7%) both. The rtL80V/I and rtL180M variants were identified in 66 (68%) and 67 (69%) patients respectively. The rtM204I and rtM204V variants were strongly associated with rtL80V/I and rtL180M respectively (P<0.01). There was no difference in antiviral response at 12 months after ADV therapy between patients in relation to the type of YMDD mutation or the presence of rtL180M. However, interestingly, after ADV therapy for 12 months, patients with rtL80V/I achieved a much smaller reduction in serum HBV‐DNA titre than those without it (mean, ?3.43 vs. ?4.43 log₁₀ copies/ml; P=0.018). In addition, patients with rtL80V/I had lower rates of undetectable HBV‐DNA (20 vs. 26%), alanine aminotransferase normalization (70 vs. 81%) and HBeAg loss (16 vs. 26%) than those without it, although none of these differences was statistically significant. Conclusions: These results provide evidence that rtL80V/I variants of HBV may be associated with a poor antiviral response to ADV in CHB patients with YMDD mutants.     

Antiviral efficacy of adefovir dipivoxil versus lamivudine in patients with chronic hepatitis B sequentially treated with lamivudine and adefovir due to lamivudine resistance

AIM： To compare the antiviral efficacy of adefovir （ADV） in lamivudine （LMV）-resistant patients with LMV treatment in nucleoside-naive patients, using serum samples collected sequentially during the course of treatment progressing from LMV to ADV.
METHODS： Forty-four patients with chronic hepatitis B （CHB） were included. The patients were initially treated with LMV and then switched to ADV when LMV resistance developed. Antiviral efficacy was assessed by measuring the following： reduction in serum HBV DNA from baseline, HBV DNA negative conversion （defined as HBV DNA being undectable by the hybridization assay）, and HBV DNA response （either HBV DNA level ≤ 10^s copies/mL or a ≥ 2 log10 reduction from baseline HBV DNA level）.
RESULTS： After two and six months of treatment, HBV DNA reduction was greater with LMV compared to ADV treatment （P = 0.021）. HBV DNA negative conversion rates were 64% and 27% after one month of LMV and ADV treatment respectively （P = 0.001）. Similarly, HBV DNA response rates were 74% and 51% after two months of LMV and ADV treatment respectively （P = 0.026）. The time taken to HBV DNA negative conversion and to HBV DNA response were both delayed in ADV treatment compared with LMV.
CONCLUSION： The antiviral efficacy of ADV in LMV-resistant patients is slower and less potent than that with LMV in nucleoside-naive patients during the early course of treatment.     

慢性乙型肝炎和肝硬化患者血清HBV基因型分析

目的 分析慢性乙型肝炎和肝硬化患者血清乙型肝炎病毒(HBV)分型分布情况。方法 2015年6月～2018年5月南京中医药大学附属南京市第二医院就诊的慢性乙型肝炎患者261例,乙型肝炎肝硬化患者30例,肝细胞癌4例,采用测序法检测血清HBV基因型。结果 在295例HBV感染者中,有132例(44.7%)为B型感染,161例(54.6%)为C型感染,2例(0.7%)为D型感染;慢性乙型肝炎患者与肝硬化患者血清TBIL、ALT和AST水平比较差异均无统计学意义(P>0.05);肝硬化患者血清肝纤维化指标(P<0.05)、血清HBV DNA载量(P<0.05)和血清HBeAg阳性率(x²=5.798,P<0.05)均显著高于慢性乙型肝炎患者;乙型肝炎肝硬化患者和肝细胞癌患者C型感染比例均显著高于慢性乙型肝炎患者,差异具有统计学意义(P<0.05)结论 慢性乙型肝炎和肝硬化患者HBV感染以B基因型和C基因型为主,而肝硬化患者以C型感染居多,提示C型感染患者可能比B型患者更容易出现严重的肝损伤,并产生严重的临床结局。     

Rapid HBV DNA decrease (week 12) is an important prognostic factor for first-line treatment with adefovir dipivoxil for chronic hepatitis B

Background  The aim of the study was to estimate the effect of viral factors (HBV genotype, viral load and kinetics) to treatment response in chronic hepatitis B (CHB) and first-line therapy with adefovir dipivoxil (ADV). Methods  Sixty-six patients (60% males, 65% HBeAg negative) were treated with 10 mg ADV QD. Quantitative HBV DNA and ALT levels were determined at weeks 4, 12, 24, 48, 72 and 96. Nonresponse or viral resistance to ADV was assessed in patients with either persistent elevated HBV DNA levels (week 24) or with an increase in HBV DNA of at least 1 log after initial decline. Results  Most patients were infected with genotype D (66.7%; genotype A: 27.3%; genotype E: 6%); 86.4% achieved a virological (VR) and 54.5% a biochemical response (BR) in week 48, more often in patients with genotype A (P < 0.01). In week 96, BR increased to 60.5%, whereas a negative HBV DNA was observed in 83.3%. In 3% an ADV-induced viral resistance was detected. As an important predictive parameter for VR, a rapid decline of viral load at week 12 was observed. Of the patients with a negative PCR or drop of viral load of at least 3 log, 96% were still HBV DNA negative at the end of week 96; 77% of patients with a partial response achieved a VR. In contrast, no patient with nonresponse (week 12) reached a negative PCR at week 96 (P < 0.0001). Conclusions  These results underline the importance of early viral kinetics to assess treatment response in CHB. In ADV nonresponders (week 12), an advanced antiviral therapy or switch to another nucleoside analogue should be considered.