肝癌患者血清HBV基因型、外膜大蛋白定量检测的临床意义

目的探讨血清乙型肝炎病毒(HBV)基因型及HBV外膜大蛋白(LHBs)水平与肝细胞癌的关系。方法对61例肝癌、65例慢性活动性乙型肝炎患者及10例HBV携带者的血清HBV基因型、HBV LHBs进行检测。结果136例中,B基因型56例(41.0%),C基因型76例(55.9%),B、C混合型1例(0.7%),B、D混合型3例(2.2%);随病情加重,C基因型比例增加;不同基因型HBV感染的肝癌患者间HBV DNA、HBV LHBs水平存在明显差异;慢性活动性肝炎患者二者无统计学差异。结论本地区HBV以B、C基因型为主,不同基因型HBV感染在肝癌的发生中可能存在不同机制。     

乙型肝炎病毒基因分型及其临床意义

目的了解慢性乙型肝炎病毒(HBV)感染者HBV基因分型及其对慢性肝病的影响,为制定针对不同HBV基因型抗病毒的个体化方案提供分子病毒学依据。方法临床确诊的慢性乙型肝炎、乙型肝炎肝硬化及肝癌患者314例,采用RDB法对HBV进行基因分型检测。结果山西地区的200例慢性乙型肝炎患者所感染的HBV均为B和C基因型,分别占56%、26%,并存在混合感染(17%);C与B基因型患者相比,血清病毒载量高、肝脏损伤严重;混合感染的患者与单一基因型感染者相比病毒载量更高、肝损伤更严重;肝硬化患者感染的HBV主要为C基因型及B、C混合感染,且肝损害严重、病毒复制率高;肝癌患者中C基因型感染占42.19%,B、C混合感染占37.5%,B基因型感染可能与年轻患者肝癌的发生有关。结论B基因型HBV感染与C基因型及混合感染相比,病毒载量低、肝损害轻,但年轻患者应监测肝癌的发生;C基因型及混合感染的患者预后较差,肝硬化、肝癌发生率高,应进行积极有效的治疗,防止严重肝病发生。     

乙型肝炎病毒基因分型与拉米夫定临床应用反应

目的了解常州地区乙型肝炎病毒(HBV)基因型分布特征,探讨基因型与肝功能损害、病毒复制水平及其与拉米夫定疗效关系.方法 76例慢性乙型病毒性肝炎患者每天口服拉米夫定100mg治疗,并于治疗4～6周时测定不同基因型患者的丙氨酸转氨酶(ALT)和HBV DNA,治疗48周后测定HBV DNA反跳和YMDD变异.采用巢式聚合酶链反应(nest PCR)法扩增HBV S基因区,以4色荧光标记PCR产物末端,在以毛细管高压电泳为核心技术的核酸序列分析仪上自动测序,将测序结果与基因库中登录的标准基因型序列相比较.结果 76例慢性乙型肝炎患者血清HBV DNA基因分型示B型株感染26例(34.2%),C型株感染50例(65.8%).B和C基因型患者ALT值分别为(246.3±138.8)U和(283.7±125.6)U,(t=0.335,P>0.05),HBV DNA含量分别为107.124±101.49和107.189±101.56拷贝/ml(t=0.138, P>0.05),HBeAg阳性数分别为20例和41例(χ2=0.159,P>0.05).拉米夫定治疗4～6周后,B基因型和C基因型患者ALT、HBV-DNA(阴转)、HBV DNA(拷贝/ml)均呈良好恢复状态,两组间差异无显著性.治疗48周后,HBV DNA反跳者B基因型20例,C基因型16例(χ2=13.49,P<0.001).结论常州地区HBV DNA基因型以单一B或C型为主;不同基因型患者ALT水平、病毒复制水平以及HBeAg表达水平差异均无显著性,拉米夫定对C基因型患者的疗效优于B基因型.     

慢性乙型肝炎病毒基因型和亚型分布及与临床关系的探讨

目的了解乙型肝炎病毒(HBV)基因型和亚型分布情况,探讨其与临床的关系。方法采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对2006年1月至4月邯郸市传染病医院收集的108份HBV感染者的血清进行乙型肝炎病毒基因型和亚型分型,分析乙型肝炎病毒基因型与患者临床特点的相关性。结果108例慢性乙型肝炎患者感染的HBV主要以C基因型为主,占93.5%,B基因型占6.5%;B基因型中均为Ba型,C基因型中C2亚型为主,占C基因型的88.1%。不同性别感染基因型和C1、C2亚型分布差异无显著性意义。肝生化指标丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)比较提示C基因型患者的肝脏炎症较B基因型患者重,但差异无显著性意义。C基因型患者血清乙型肝炎病毒e抗原(HBeAg)阳性率显著高于B基因型患者。C基因型患者血清HBV-DNA略高于B基因型,但差异无显著性意义。C1、C2亚型间在肝功能、HBeAg阳性率和血清HBV-DNA载量方面差异均无显著性意义。结论慢性乙型肝炎患者感染的HBV主要以C基因型(C2亚型)为主。C基因型的患者血清HBeAg阳性率高于B基因型,C基因型患者与B基因型相比肝脏炎症程度、HBV-DNA载量差异无显著性意义。C1和C2亚型患者的临床特点相似。     

厦门市乙型肝炎患者病毒基因型的分析

目的:采用多对型特异性引物,通过巢式PCR法检测厦门市乙型肝炎患者血清中乙型肝炎病毒(HBV)基因型的分布情况.方法:收集250例HBV感染患者血清,提取血清中HBV DNA作为模板,设计HBV前S1基因和S基因中区域内设计出10条内外引物,并将其中8条型特异性内引物分成A,B两组,分别扩增A,B,C和D,E,F型HBV,然后将第2轮PCR产物以用30g/L琼脂糖进行电泳,根据PCR产物电泳显示的产物长度判定HBV基因型,以了解厦门HBV基因型分布情况.结果:共120例确定了HBV基因型.患者群中慢性乙型肝炎90例,占75.0%,急性乙型肝炎、肝炎肝硬化、原发性肝癌分别占5.8%(7/120)、6.7%(8/120)和12.5%(15/120).分型结果:B型58例(48.3%)、C型30例(25.0%),B/C混合型32例(26.7%).HBeAg阳性患者中B基因型占63.8%,B/C型混合感染21.9%;抗-HBe阳性患者中以B/C型混合感染68.8%,B型25.9%,HBeAg阳性组与抗-HBe组之间比较发现B型和B/C混合型之间(P<0.05).结论:厦门乙型肝炎患者HBV基因型以B型为主,B/C混合感染是一个值得重视的问题.     

乙型肝炎病毒基因型检测的临床价值探讨

目的探讨乙型肝炎病毒基因型检测的临床价值,对临床表型分析有重要意义。方法 HBV阳性乙型肝炎等相关肝病患者245例,抽取空腹静脉血,采用HBV基因分型检测试剂盒对HBV DNA进行基因分型,采用荧光定量PCR法检测HBV DNA载量,同时收集患者相关临床资料进行统计学分析。结果 HBV DNA为B基因型患者占64.49%(158/245),C基因型患者占25.71%(63/245),BC混合基因型患者占9.80%(24/245)。158例HBV DNA为B基因型患者中,男性85例,女性73例,分别占53.80%和46.20%;63例HBV DNA为C基因型患者中,男性35例,女性28例,分别占55.56%和44.44%;24例HBV DNA为BC基因型患者中,男性14例,女性10例,分别占58.33%和41.67%。HBV DNA为B基因型、C基因型、BC混合基因型的患者DNA表达载量分别为(6.32±0.10)×10~5 copy/ml、(8.56±2.08)×10~5 copy/ml和(7.32±1.20)×10~5 copy/ml,患者年龄分别为(46.91±3.15)岁和(46.76±2.96)岁、(46.29±1.87)岁。B型患者中慢性乙型肝炎、肝硬化、原发性肝癌病例数分别为104、43和11例,分别占65.82%、27.22%和6.96%;C型患者中慢性乙型肝炎、肝硬化、原发性肝癌的患者数分别为25、38和0例,分别占39.68%、60.32%和0;BC型患者中慢性乙型肝炎、肝硬化、原发性肝癌病例数分别为6、7和11例,分别占25.00%、29.17%和45.83%。结论人感染HBV DNA基因型以B基因型居多,男性为易感人群。及时监测HBV DNA表达载量,对感染HBV的表型分析和临床治疗有重要意义。     

鄂西北地区慢性乙型肝炎患者HBV基因型与耐药突变的研究

目的:分析鄂西北地区慢性乙型肝炎患者乙型肝炎病毒(HBV)基因分型与耐药突变的分布及其临床特点。方法:回顾性研究2011.1-2016.11太和医院感染科病房及门诊基因测序法和基因芯片法检测的324例慢性乙型肝炎患者的HBV基因型、常见核苷(酸)类似物(NAs)耐药突变位点、肝功能指标、HBV DNA定量及临床特点等,并分析其相关性。结果:基因测序法检测238例,芯片法86例,其基因分型均以B型为主,基因芯片法中可以检测到少量D型及混合基因型。共132例患者检测出NAs耐药,耐药突变位点以204位点最多见,B、C基因型耐药率及临床表现的差异无统计学意义,耐药位点整体分布存在差异,但NAs耐药分布一致,均以拉米夫定耐药为主。结论:鄂西北地区慢性乙型肝炎患者的HBV基因分型以B型为主,C型次之,B、C基因型患者耐药突变位点的分布存在一定差异,但其耐药率、临床表现及NAs耐药分布差异无统计学意义。B型患者无NAs抗病毒治疗史患者NAs耐药率高于C型患者。     

山西省HBV基因型分布特点和临床意义

目的:了解山西省常见的乙型肝炎病毒(HBV)基因型,探讨HBV各基因型与血清HBV-DNA水平以及疾病进展的临床意义.方法:随机收集山西省HBV DNA阳性病例680例进行基因分型,并结合临床资料进行统计学分析.结果:680例HBV感染者中,有65例(9.6％)未测出基因型.在可检出基因型的615例患者中,基因型B、C、B/C分别占8.9％、82.6％、8.5％.C型、B/C型的HBV DNA载量明显高于B型(P＜0.05);各基因型与肝病的严重程度间差异有显著性意义(P＜0.05).结论:山西省HBV基因型中以C型为优势,其次为B/C和B型.基因C型和B/C型在慢性重型肝炎中较为常见,基因C型更易发生肝硬化和肝癌.     

湖北省地区乙型肝炎病毒基因分型及其临床意义

目的探讨湖北省地区乙型肝炎病毒(HBV)基因型分布及其临床意义。方法随机选取HBVDNA阳性病例276例,其中慢性无症状携带者(其中30例经病理学证实)78例,慢性乙型肝炎110例,重症肝炎32例,肝硬化30例,肝细胞癌26例,取其外周血,采用乙型肝炎病毒核酸扩增荧光定量检测试剂盒检测HBVDNA载量,采用微板核酸杂交-ELISA法测定HBV基因型。结果湖北省地区基因型主要以C型和B型为主,基因型C型的HBVDNA载量均值水平为1.2×106copies/m l,显著高于其它类型,男女性别在HBV基因型构成比中无差异。混合型及基因型C与较严重的肝脏疾病有关,更易发生重症肝炎、肝硬化及肝癌。结论湖北省地区基因型主要以C型和B型为主,基因型C的HBVDNA载量均值水平显著高于其它类型,混合型及基因型C与较严重的肝脏疾病有关,湖北省地区存在基因型共同感染问题。     

乙型肝炎病毒基本核心启动子突变与基因型的关系

目的研究乙型肝炎病毒（HBV）基本核心启动子（BCP）突变与HBV基因型的关系。方法随机选取我院68例慢性乙型肝炎患者外周血，采用荧光定量PCR结合TaqmanMGB探针技术检测HBV基因型，并用基因扩增和DNA测序方法检测BCPT1762／A1764双突变。结果68例患者HBV分型中，B基因型20例，C基因型46例，B、C混合型1例，未分型（非B非C型）1例。66例B、C两基因型中，B基因型组T1762／A1764双突变5例，突变率25．0％（5／20），C基因型组T1762／A1764双突变24例，突变率52．2％（24／46），C基因型T1762／A1764双突变率明显高于B基因型（P〈0．05）。结论苏州地区慢性乙型肝炎患者基因型以C型和B型为主，C基因型比B基因型更易发生T1762／A1764双突变。     

乙型肝炎病毒基因型检测及其临床应用

目的:探讨HBV基因型的检测及其在临床上的应用.方法:用微板核酸分子杂交-ELISA方法检测468例HBV DNA阳性的慢性乙型肝炎患者血清HBV基因型.分析HBV基因型与病毒复制、基本C基因启动子(BCP)变异、肝病病情轻重、干扰素疗效的关系.结果:深圳地区HBV基因型以B和C基因型为主,分别占25.0%和64.9%;C基因型的HBeAg阳性率(68.8%)高于B基因型的HBeAg阳性率(35.0%)(P＜0.01);C基因型的血清HBV DNA水平也明显高于B基因型(1g 6.74 copies/ml vs. 1g 5.44 copies/ml, P＜0.01);轻中度慢性肝炎以B基因型为主,而重度慢性肝炎以C基因型为主;B基因型对干扰素的有效应答率为47.2%,C基因型的有效应答率为28.9%,两组比较差异有显著性意义(P＜0.05).结论:HBV基因分型有助于临床判断病情、估计预后及抗病毒治疗疗效预测.     

Hepatitis B viral genotypes: clinical relevance and molecular characteristics

Hepatitis B virus (HBV) infection is a global health problem and the clinical outcome of chronic HBV infection depends on the frequency and severity of hepatitis flares in the immune clearance phase. Currently, four subtypes and seven genotypes of HBV are identified and most have specific geographic distributions. The impact of HBV genotypes on the clinical outcome of chronic HBV infection has been partially clarified. In Taiwan, genotype C is associated with more severe liver disease and genotype B is associated with the development of hepatocellular carcinoma (HCC) in young non-cirrhotic patients. In contrast, genotype B has a relatively good prognosis in Japan and China and is rarely associated with the development of HCC. Similarly, genotype D is associated with more severe liver disease than genotype A in India and may predict occurrence of HCC in young patients. Although superinfection of HBV on top of hepatitis B carriers occurs in Taiwan, it is rarely associated with acute exacerbations. As to the response to antiviral treatment, genotypes C and D are associated with a lower response rate to interferon therapy compared with genotypes B and A. In addition, the subtype adw is reported to be associated with a higher risk of lamivudine resistance than ayw. In HBV subtype adw-infected HCC patients, genotype B responds better to embolization therapy and has a lower rate of HCC recurrence than genotype C. In summary, pathogenic and therapeutic differences do exist among HBV genotypes and determining the genotype in patients with chronic HBV infection would help gain further information for etiologic, clinical, virologic and anthropologic investigations. Further studies to clarify the molecular virological factors that contribute to these differences are awaited.     

Hepatitis B virus genotypes and clinical manifestation among hepatitis B carriers in Thailand

BACKGROUND: Hepatitis B virus (HBV) genotypes have distinct geographic distributions. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Thailand. METHODS: Hepatitis B virus genotypes among 107 hepatitis B carriers residing in Thailand were evaluated using serologic and genetic methods. They were clinically classified into asymptomatic carriers with normal serum alanine transaminase (ALT) levels and patients with chronic liver disease, such as those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). RESULTS: Hepatitis B virus genotype distribution among the 107 patients was 25.2% for genotype B, 72.0% for genotype C and 2.8% for genotype D. The serum ALT levels, HBV-DNA and hepatitis B e antigen positivity were significantly higher in carriers infected with genotype C HBV than in those infected with genotype B (P < 0.05). The proportion of genotype B HBV was higher in asymptomatic carriers than in patients with CH and those who developed liver disease, such as LC and HCC (45.5, 16.9 and 25.0%, respectively; P < 0.05). In contrast, the proportion of genotype C HBV was higher in patients who developed liver disease and CH than in asymptomatic carriers (68.7, 83.0 and 50.0%, respectively; P < 0.05). Phylogenetic analysis based on entire genome sequences revealed three HBV isolates, which were classified into a subgroup of genotype C in isolates from South-East Asian countries. CONCLUSIONS: Genotypes B and C are the predominant types among hepatitis B carriers residing in Thailand and those genotypes influence the clinical manifestation in carriers with chronic hepatitis B infection.     

Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan

BACKGROUND: Hepatitis B virus (HBV) infection is a major health problem. HBV genotypes may be associated with progression of liver disease. The distribution and clinical implications of HBV genotypes in southern Taiwan are evaluated. METHODS: We used a polymerase chain reaction-restriction fragment length polymorphism genotyping method to determine HBV genotypes. RESULTS: The genotype distribution for 265 patients with chronic HBV infection was as follows: A, 3 (1%); B, 158 (60%); C, 90 (34%); D, 7 (2.5%); E, 0: F, 0; and unclassified, 7 (2.5%). Compared with genotype B patients, genotype C patients had a higher hepatitis B e antigen positive rate and higher fibrosis score. There was no significant difference in the mean age between genotype B and genotype C patients with hepatocellular carcinoma (HCC). However, when patients were stratified by age, the prevalence of genotype C was significantly higher in young HCC patients (<50 years of age) than in age-matched asymptomatic carriers (40% versus 10%, P < 0.001). Using multivariate analysis, the significant risk factors for advanced liver disease (cirrhosis or HCC) for patients with chronic HBV infection were old age, male gender and genotype C. CONCLUSIONS: These results suggest that genotype C is associated with more severe liver diseases than the B variant.     

兰州地区HBV基因型的分布及临床意义

目的观察兰州地区HBV基因型的分布及其与病情严重性的相关性。方法采用荧光PCR法对163例乙肝患者血清进行基因分型。结果兰州地区乙肝患者HBV基因分型以C型为主,占92.02%,B型占4.33%,B＋C型占3.64%。基因C型患者中,肝硬化患者明显多于慢乙肝患者,（49.33% vs34.00%）,但差异无统计学意义。进一步分析年龄、HBVDNA对病情的影响,肝硬化与肝癌患者在年龄方面明显大于慢乙肝患者,在HBVDNA水平方面低于慢乙肝患者,差异有统计学意义。结论兰州地区以C型为主,符合北方以C型为主的研究结果 ;除外基因型对病情及预后的影响外,还需要结合患者的年龄、病程的长短、HBVDNA水平等多种因素来分析病情。     

Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent

BACKGROUND AND AIM: Certain hepatitis B virus (HBV) genotypes have been alleged to be associated with the development of cirrhosis and hepatocellular carcinoma (HCC), and the response to interferon therapy in Taiwanese patients. We undertook to study the prevalence and significance of HBV genotypes in the Indian subcontinent. METHODS: One hundred and thirty histopathologically proven chronic HBV-infected patients, including 52 incidentally detected asymptomatic hepatitis B surface antigen (HBsAg)-positive subjects (IDAHS) with chronic HBV infection (group I), 48 cirrhotics (group II) and 30 hepatocellular carcinoma (HCC; group III) patients were studied. Hepatitis B virus genotypes were determined by using restriction fragment length polymorphism, and direct sequencing of the s gene including the 'a' determinant region. RESULTS: Only genotypes A (46%) and D (48%) were found in the chronic HBV-infected patients. A mixed infection with genotypes A and D was seen in 6% of patients. Genotype A was found in 42, 48 and 50%, and genotype D in 48, 50 and 47% of group I, II and III patients, respectively (P = NS). The patients who had mixed genotypes were significantly younger (P < 0.05). In group I (IDAHS) patients infected with genotype D, none had a histological activity index (HAI) of < four. Genotype D was significantly more common in group I patients with HAI > 4 as compared to genotype A (53 vs 32%, P < 0.05). Similarly, genotype D was associated with more severe liver diseases (61 vs 30%, P < 0.05). Genotype D was more prevalent in HCC patients of < 40 years of age, as compared to IDAHS (63 vs 44%, P = 0.06). CONCLUSIONS: (i) Hepatitis B virus genotypes A and D are prevalent in chronic liver disease patients of Indian origin; and (ii) HBV genotype D is associated with more severe diseases and may predict the occurrence of HCC in young patients.     

乙肝病毒基因型与患者临床预后关系的研究

研究不同HBV基因型感染者临床特征的异同。选取慢性HBV感染者297例,用特异性引物PCR法测定其HBV基因型,并比较不同基因型者在临床各方面表现有何异同。297例样本中B型占12．8％,C型占87.2％, 未发现其他基因型。B型者与C型者相比,年龄≤35岁者较多,血清ALT、AST水平较低,两组的血清HBVDNA水平无明显差异。B型在慢性HBsAg携带者、慢性肝炎、肝硬化及肝癌患者中所占比例逐步下降,而C型所占比例则逐步上升。B型者HBeAg阳性率低,HBeAg血清学转换率高。B型、年龄小者及女性者容易呈慢性HBsAg携带者状态。在17例死于肝病者中,B型者死亡时感染HBV时间较长。B型者对抗病毒治疗应答比C型者好。C型HBV 感染与严重肝脏疾病的发生有关,感染B型HBV者临床预后较好,对抗病毒治疗的应答较好。     

Is There Any Value to Hepatitis B Virus Genotype Analysis?

Hepatitis B may cause a varying spectrum of diseases ranging from an asymptomatic or mild anicteric acute illness, to severe or fulminant hepatitis. Similarly, the outcome of chronic hepatitis B is variable. Viral factors associated with outcome of chronic hepatitis B virus (HBV) infection include hepatitis B e antigen status, HBV DNA, genotype, and HBV variants. HBV genotypes and subgenotypes have been associated with differences in clinical and virological characteristics, indicating that they may play a role in the virus-host relationship. A total of ten hepatitis B virus genotypes have been defined with a distinct geographical distribution. Hitherto, genotypes A, B, C and D have been studied most extensively. The HBV genotype appears to influence not only the natural history of HBV related liver disease but also the response to HBV treatment. HBV genotypes are also linked with both core promoter and BCP mutations. Progression to chronic infection appears to occur more frequently following acute infection with genotypes A and D than with the other studied genotypes. Genotypes A and B appear to have higher rates of spontaneous HBeAg seroconversion. More advanced liver disease and progression to HCC is more often seen in chronic infection with genotypes C and D in contrast to genotypes A and B. More specifically, genotypes A1, C, B2–B5 and H appear to be associated with more serious complications than genotypes A2, B1 and B6. These observations suggest important pathogenic differences between HBV genotypes. Genotypes A and B have higher response rates to interferon based therapy than genotypes C and D. Knowledge of HBV genotype enables clinicians to identify those patients at increased risk of disease progression whilst aiding the selection of appropriate antiviral therapy. Genotyping and monoclonal subtyping can provide useful information for epidemiological studies. In conclusion, genotyping of chronic HBV infections can help practicing physicians identify those at risk of disease progression and determine optimal anti-viral therapy.     

Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B

BACKGROUND & AIMS: Six genotypes (A-F) of hepatitis B virus (HBV) have been identified; however, the genotype-related differences in the pathogenicity of HBV remain unknown. Therefore, we investigated the prevalence of HBV genotypes in Taiwan and the association between distinct genotypes and severity of liver disease in a cross-sectional study. METHODS: Using a molecular method, HBV genotypes were determined in 100 asymptomatic carriers and in 170 patients with histologically verified chronic liver disease and hepatocellular carcinoma (HCC). RESULTS: All genotypes except genotype E were identified in Taiwan, and genotypes B and C were predominant. Genotype C was prevalent in patients with cirrhosis and in those with HCC who were older than 50 years compared with age-matched asymptomatic carriers (60% vs. 23%, P < 0.001, and 41% vs. 15%, P = 0.005, respectively). Genotype B was significantly more common in patients with HCC aged less than 50 years compared with age-matched asymptomatic carriers (80% vs. 52%, P = 0.03). This predominance was more marked in younger patients with HCC (90% in those aged 相似文献