拉米夫定加肝络欣治疗慢性乙型肝炎疗效及对YMDD变异的影响

观察拉米夫定加肝络欣联合治疗慢性乙型肝炎的疗效及对慢性乙型肝炎病毒P基因(YMDD)变异的影响。收集乙型肝炎病毒(HBV)HBeAg、HBVDNA阳性的慢性乙型肝炎患者6 7例,分为拉米夫定加用肝络欣组(A组)、单用拉米夫定组(B组)。分别检测血清HBeAg、抗-HBe、HBVDNA ,肝脏生化指标和基因YMDD变异。在治疗5 6周时,拉米夫定联合肝络欣组HBeAg/抗-HBe转换率(39. 4 % ) ,优于拉米夫定组(P <0 .0 5 )。HBVDNA阳性率及YMDD变异率都比拉米夫定组低(P <0 . 0 5 )。拉米夫定联合肝络欣能在一定程度上提高治疗慢性乙型肝炎的疗效并可减少YMDD变异。     

苦参素治疗乙肝所致肝纤维化的临床观察

观察苦参素治疗乙肝所致肝纤维化的作用。苦参素治疗肝纤维化患者前后检测血清肝纤维化四项指标与乙肝病毒标志物 ,并与γ -干扰素对照。LN、HA、Pc -Ⅲ、Ⅳ -C在苦参素治疗前后有显著性差异 (P <0 0 1,P<0 0 5 ) ;与γ -干扰素组比较无显著差异 (P <0 5 ,P <0 2 5 ) ,说明两者疗效相仿。苦参素治疗组HBsAg、HBeAg与HBV -DNA转阴率分别是 3 3%、2 2 8%、2 0 0 % ,略低于γ -干扰素组 ,但两组比较无显著性差异 (P >0 5 ,P >0 75 )。苦参素是治疗肝纤维化与抗乙肝病毒有效的药物之一     

干扰素α联合拉米夫定治疗慢性乙型肝炎的短期疗效及其影响因素

目的　了解干扰素α和拉米夫定联合治疗的效果及其影响因素。方法　 71例HBeAg阳性的慢性乙型肝炎患者随机分成治疗组与对照组。治疗组 34例 ,同时使用干扰素α及拉米夫定 2 6周 ,随后单用拉米夫定 2 6周 ;对照组 37例 ,单用拉米夫定 5 2周。治疗前做肝穿刺活检 ,疗程中定期检测丙氨酸转氨酶 (ALT)、HBeAg、抗 HBe、HBVDNA ,并作YMDD变异检测。结果　全部患者完成1年治疗。治疗组与对照组血清转换率分别为 41.2 %( 14/34)和 2 1.6 %( 8/37) ,两组差异无显著性(P =0 .0 8)。治疗组未发现YMDD变异 ,对照组则有 5例。治疗组的血清ALT及HBVDNA基线水平与血清转换率明显相关 (P =0 .0 4) ;在ALT >2ULN及血清HBVDNA >1× 10 7拷贝 /ml的患者中 ,治疗组HBeAg/抗 HBe血清转换率明显高于对照组 (分别为 5 2 .0 %和 2 5 .8%,P =0 .0 4及 6 3 .2 %和 2 8.6 %,P =0 .0 3)。治疗组血清转换率与肝组织炎症活动度、肝组织纤维化程度及肝细胞HBVDNA表达水平无相关性。在肝组织HBVDNA表达水平较高的患者中 ,治疗组血清转换率高于对照组 (分别为 46 .2 %和 9.5 %,P =0 .0 3)。结论　干扰素α与拉米夫定联合治疗对于ALT中度以上升高、HBVDNA高水平复制及肝组织HBVDNA高水平表达者短期疗效优于单用拉米夫定 ,并对于延迟及     

干扰素α-2b联合苦参素治疗慢性乙型肝炎的临床研究

目的　探讨干扰素α 2b(IFNα 2b)联合苦参素治疗慢性乙型肝炎 (CHB)患者的临床疗效。方法　将 14 6例CHB ,随机分为A、B、C、D 4组。在常规保肝治疗 (D组 )基础上 ,A组加用IFNα 2b联合苦参素治疗 ;B组单用IFNα 2b ;C组单用苦参素 ,疗程 6个月 ,随访 6个月。采用免疫组织化学、放射免疫法及酶联免疫吸附法 ,对治疗前后肝组织学、肝组织转化生长因子 β(TGF β)的表达及血清TGF β、HBeAg、HBVDNA等指标的变化进行了观察。 结果　治疗后A组组织学肝纤维化程度计分、肝组织TGF β的表达及血清TGF β、HBeAg、HBVDNA等指标均显著下降 ,与B、C组比较差异有显著性 (P <0 .0 5或P <0 .0 1) ,肝组织TGF β的表达与肝脏纤维化的动态变化相一致 ;B组与C组相比差异无显著性 (P >0 .0 5 )。结论　IFNα 2b联合苦参素治疗慢性乙型肝炎的疗效优于单一用药。     

慢性乙肝YMDD变异患者肝纤维化指标、血清标志物的检测及意义

探讨慢性乙肝患者(CHB)发生YMDD变异后肝纤维化指标及血清标志物的变化意义.检测接受拉米夫定治疗285例CHB患者YMDD变异情况,根据结果分为无突变组和突变组;又各分为继续使用拉米夫定治疗组和未继续治疗组;并测定各组乙肝病毒拷贝数(HBV-DNA)、乙肝两对半(HBV M)、常规肝功能指标、透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CIV)水平.结果显示285例患者中发生YMDD突变144例,以YIDD型最常见;突变组HBeAg阳性率、HBV-DNA水平高于无突变组(P＜0.01、P＜0.05);无突变病例中继续治疗组CIV、PCⅢ、HBV-DNA水平比未继续治疗组出现下降(P＜0.01、P＜0.05).YMDD突变组HBeAg阳性率、病毒拷贝数高于无突变组,而纤维化指标无差异;继续使用拉米夫定治疗,可改善无突变组患者肝组织纤维化.     

HBeAg阴性乙型肝炎病毒携带者血清HBV DNA水平与肝纤维化指标相关性研究

目的 研究HBeAg阴性乙型肝炎病毒携带者血清HBVDNA水平与肝纤维化指标的相关性。方法 选取HBeAg阴性的乙型肝炎病毒携带者110例，检测其HBVDNA水平和肝纤维化指标。结果在HBVDNA〉10Scopies／ml者，其肝纤维化四项指标较10^3〈HBVDNA〈10^5 copies／ml者和HBVDNA低于检测值者均略有升高，但经统计学处理，无显著性差异（P〉0．05）.结论HBeAg阴性HBV携带者血清HBVDNA复制活跃程度与肝纤维化四项指标之间关联度不大。     

乙型肝炎患者血清HBVDNA负荷与其肝功能及肝组织损害的关系研究

探讨乙肝患者血清HBVDNA含量与其肝功能及肝组织损害的关系。检测 380例未经治疗的乙肝患者血清HBVDNA、肝功能 ,其中 71例进行了肝活检。乙肝患者血清HBVDNA含量与其病情的严重程度不一致 ;临床各型乙肝中HBVDNA阳性组与阴性组间ALT、TBil均无显著差异 (P >0 0 5 ) ;肝组织炎症分级Gi～G4和纤维化分期S1～S4各组间HBVDNA值均无明显差异 (P >0 0 5 )。乙肝患者血清HBVDNA含量不能反映其病情的临床严重程度 ,与肝组织炎症和纤维化程度无关     

拉米夫定治疗失代偿期乙型肝炎肝硬化的临床观察

目的　研究拉米夫定对失代偿期乙型肝炎肝硬化的临床疗效和安全性。方法　 2 8例乙型肝炎肝硬化患者给予拉米夫定 10 0mg/d口服 ,连用 2 4个月 ,设立对照组。在治疗开始前、治疗开始后 6个月、12个月和 2 4个月分别记录Child Pugh得分 ,并进行肝功能、肝纤维化标志物、HBV血清标志物以及血清HBVDNA定量检测。结果　 2 8例肝硬化患者拉米夫定治疗后 ,血浆白蛋白显著升高 ,血清丙氨酸转氨酶和胆红素明显降低 ,血清Ⅲ型前胶原、Ⅳ型胶厚、层粘连蛋白和透明质酸水平较治疗前显著降低 ,血清HBVDNA阴转率明显高于对照组 (P <0 .0 0 5 ) ,HBVDNA水平较治疗前显著降低。治疗组Child Pugh计分平均降低 2 .5 ,5 4.2 %患者提高了分级 (12例从B到A ,1例从C到B) ,而对照组仅有10 .5 %的患者Child Pugh分级得到了改善 ,治疗组显著高于对照组 (P <0 .0 1)。不良反应的发生率为 3 2 .1% (9/2 8)。结论　拉米夫定能使HBV复制指标阳性的活动性肝硬化患者的病毒复制受到抑制 ,肝功能改善 ,肝纤维化程度降低 ,病情缓解。应用拉米夫定治疗肝硬化患者安全可靠。     

慢性乙型肝炎患者拉米夫定治疗24周时YMDD变异对疗效的影响

目的 使用基因芯片方法检测乙型肝炎病毒(HBV)YMDD变异的发生情况,研究YMDD变异发生与肝功能损伤和HBV复制水平指标之间的关系。方法 120例以常规剂量(100mg/d)口服拉米夫定的慢性乙型肝炎患者,治疗前和治疗第24周抽取血清检测丙氨酸氨基转移酶(ALT)、HBV DNA(定量)水平,对24周HBV DNA阳性的17例患者血清样本,以基因芯片方法检测其治疗前和治疗24周时血清中YMDD变异是否存在,并分析该变异发生和ALT、HBV DNA的关系。结果 (1)120例入选患者治疗24周时有17例患者HBV DNA仍为阳性,除外治疗前已存在的1例感染变异病毒,基因芯片共检出7例变异,变异率为5.8％。其中纯变异2例,YIDD变异1例,YVDD变异1例,混合变异5例,其中YMDD/YVDD变异3例,YVDD/YMDD变异2例。(2)变异组在治疗前和治疗24周时ALT定量水平与非变异组相比,差异无显著性,P>0.05。(3)变异组在治疗前和治疗24周时HBV DNA定量水平与非变异组相比,差异无显著性,P>0.05。结论 在拉米夫定治疗过程中,YMDD基因变异发生对肝脏炎症活动度和病毒复制的抑制作用无显著影响。     

拉米夫定治疗中乙型肝炎病毒YMDD野毒株和变异株的变化

目的 观察慢性乙型病毒性肝炎(CHB)患者应用拉米夫定治疗前后,YMDD野毒株及变异株的动态变化,并分析其临床意义。方法 取5例CHB患者治疗前与治疗48周的10份血清标本,先用PCR法扩增包括YMDD基序的乙型肝炎病毒(HBV)部分核苷酸序列,然后进行DNA序列测定,同时分别进行克隆,每份标本随机挑选20～24株单克隆,用实时荧光PCR法检测YMDD野毒株及其变异株。结果 5例CHB患者治疗前PCR产物直接测序结果未检出YMDD变异,治疗48周时有4例检出YMDD变异,但对每株克隆的分别检测显示：治疗前YMDD变异株(YIDD／YvDD)所占比率分别为0％、9．5％、0％、4．5％、5．6％;治疗48周时所占比率分别为100％、100％、65％、100％、0％。其中1例患者治疗前检出YIDD变异株,而治疗48周时YVDD变异株则变成优势株。治疗52周时,4例YMDD变异患者中2例HBVDNA和血清丙氨酸转氨酶(ALT)突破,1例患者ALT突破,但HBVDNA为阴性。结论 YMDD变异株在拉米夫定治疗前的血清中已存在,在服用拉米夫定后,由于选择性抑制了野毒株,使YMDD变异株由弱势株变成优势株,部分患者可导致拉米夫定临床耐药。YVDD变异株可能比YIDD变异株的复制能力强。     

248例慢性乙型肝炎患者血清HBV DNA水平与肝组织HBsAg／HBcAg表达的相关性研究

目的 探讨慢性乙型肝炎患者血清HBV DNA水平与肝组织病理学损害和HBsAg／HBcAg表达的关系。方法 对248例慢性乙型肝炎患者进行肝穿刺活检,采用免疫组织化学法检测HBsAg和HBcAg,同时检测患者血清HBVDNA水平。结果 在肝脏炎症程度G1～G4四组患者之间血清HBV DNA水平无显著性差异（P〉0．05）,肝纤维化程度S1～S4四组患者之间血清HBV DNA水平也无显著性差异（P〉0．05）;在肝组织HBsAg表达强度-～＋＋＋四组患者之间血清HBV DNA水平无显著性差异（P〉0．05）,而肝组织HBcAg随血清HBV DNA水平的增高而表达增强。结论 慢性乙型肝炎患者肝组织炎症活动度和纤维化程度与血清HBV DNA水平无相关性。     

YMDD mutations and genotypes of hepatitis B virus in northern China

The objective of this research was to determine the relationship between YMDD mutations and the genotypes of hepatitis B virus (HBV) during lamivudine treatment. HBV genotypes were determined by nested PCR with 6 pairs of HBV genotype-specific primers (A to F) in serum specimens from 142 hepatitis B patients receiving lamivudine antiviral therapy. YMDD mutations were detected by fluorescent hybridization bioprobe PCR and melting curve assay (FH-PCR-MC). Among 142 serum specimens, 13 samples were genotype B (9.2%), 125 samples were genotype C (88%), 4 samples were genotype D (2.8%), and 80 YMDD mutations were found. The YMDD mutation rates were 69.2 and 54.4% in genotype B and genotype C, respectively. There was no significant difference in the YMDD mutation rate between genotypes B and C. Nine genotype B sera with YMDD mutations were found, including 2 YIDD mutations and 7 YVDD (M + V) mutations. Sixty-eight genotype C sera with YMDD mutations were found, including 34 mutations I (M + I) and 17 mutations V (M + V). There was a significant difference in the YMDD mutation types between genotypes B and C. Our results suggested that the YMDD mutation rate was 56.3% in patients treated with lamivudine for 2-4 years. YIDD was the main mutation type. The YMDD mutation rate showed no significant difference between HBV types B and C (P > 0.05), while the YMDD mutation types showed a significant difference between HBV types B and C in Northern China (chi2 test = 4.6, P < 0.05).     

阿德福韦酯和拉米夫定治疗乙型肝炎肝硬化失代偿期的临床观察

目的观察阿德福韦酯和拉米夫定治疗肝炎肝硬化失代偿期患者48周的疗效和不良反应。方法采用随机分组法,将62例肝炎肝硬化失代偿期患者,随机分为阿德福韦酯组32例,给予阿德福韦酯10mg/d,拉米夫定组30例,给予拉米夫定100mg/d,疗程均为48周。均给予常规护肝及支持、对症治疗。观察两组患者的肝功能、HBeAg、HBV DNA、肝纤维化标志物Ⅲ型前胶原、Ⅳ型胶原、层黏连蛋白、透明质酸、肾功能及Child-Pugh分级、药物不良反应。结果两组患者肝功能各项指标的复常率、血清HBV DNA下降水平及转阴率、HBeAg转阴率及HBeAg/抗-HBe转换率均随着治疗疗程的延长而增加,但两组比较,差异无统计学意义。治疗至48周时拉米夫定组有2例发生YMDD变异,变异率6.7%,阿德福韦酯组无病毒变异发生。两组患者血清肝纤维化标志物治疗至24周时与治疗前相比明显下降,且随着疗程的延长进一步降低,两组比较差异无统计学意义。两组患者治疗前后Child-Pugh分级比较,差异无统计学意义。两组患者均未发现药物相关的肾功能损害,两组中各有2例患者出现轻度不良反应,但均能耐受。结论肝炎肝硬化失代偿期患者48周的抗病毒治疗,阿德福韦酯的疗效与安全性均与拉米夫定相似,而病毒耐药突变率较拉米夫定低。     

YMDD mutations in patients with chronic hepatitis B untreated with antiviral medicines

AIM: To polymerase P region (YMDD) mutations of hepatitis B virus gene (HBV DNA) in patients with chronic hepatitis B (CHB) untreated with antiviral medicines and to explore its correlation with pre-c-zone mutations, HBV genotypes and HBV DNA level, and to observe its curative effect. METHODS: A total of 104 cases (38 cases in group of familial aggregation and 66 cases in group of non-familial aggregation) were randomly chosen from 226 patients with CHB who did not receive the treatment of lamivudine (LAM) and any other antivirus drugs within the last one year. Their serum YMDD mutations were detected by microcosmic nucleic acid and cross-nucleic acid quantitative determination, HBV genotypes by PCR-microcosmic nucleic acid crossELISA, HBV DNA quantitative determination and fluorescence ration PCR analysis, hepatitis B virus markers (HBVM) by ELISA. LAM was taken by 10 patients with YMDD mutations and its curative effect was observed. RESULTS: Twenty-eight cases (26.9%) had YMDD mutations, of them 11 cases (28.9%) were in familial aggregation group (38 cases) and 17 cases (25.8%) in nonfamilial aggregation group (66 cases) with no significant difference between the two groups. Twenty-seven point one percent (16/59) cases were positive for HBeAg YMDD mutations, and 26.7% (12/45) cases were negative for HBeAg and positive for anti-HBe. There was also no significant difference between the two groups. Different YMDD incidence rate existed in different HBV genotypes. HBV DNA level did not have a positive correlation with the incidence of YMDD mutations. LAM was effective for all patients with mutations. CONCLUSION: Wild mutant strains in HBV and their incidence rate have no significant difference between familial aggregation and non-familial aggregation. It may have no significant relationship between YMDD mutations and pre-c-zone mutations. HBV DNA level may not have a positive correlation with YMDD mutations. LAM is clinically effective for CHB patients with YMDD mutations.     

慢性乙型肝炎患者肝组织HBV cccDNA、总HBV DNA与血清HBV DNA的相关性及其与临床的关系

目的探讨慢性乙型肝炎患者肝组织HBV共价闭合环状DNA（cccDNA）、肝组织总HBV DNA（HBV tDNA）与血清HBV DNA之间的相关性及其与临床的关系。方法 78例慢性乙型肝炎患者入选本研究。肝组织β- globinDNA、HBV cccDNA和HBV tDNA采用实时荧光定量PCR方法检测,平均每个肝细胞HBV cccDNA和HBV tDNA含量（拷贝/cell）=HBV cccDNA（实测值）/β-globin DNA（实测值）和HBV tDNA（实测值）/β3-globin DNA（实测值）,肝组织HBV cccDNA和HBV tDNA含量的计算单位定义为log₁₀拷贝/10⁶cell;采用实时荧光定量PCR、ELISA法检测血清HBVDNA和HBV标志物;采用免疫组织化学方法检测肝细胞中HBsAg和HBcAg的表达。统计分析采用pearson相关分析及t检验。结果 （1）肝组织HBV cccDNA与HBV tDNA定量呈正相关（r=0.696,P<0.001）;肝组织HBV cccDNA与血清HBV DNA定量呈正相关（r=0.304,P<0.01）;肝组织HBV tDNA与血清HBV DNA定量呈正相关（r=0.341,P<0.01）;（2）肝细胞内HBcAg定性检测阳性患者的血清HBV DNA定量明显高于阴性患者,且差异有统计学意义（P<0.05）;肝细胞内HBcAg定性检测阳性患者与阴性患者的肝组织HBV cccDNA和HBV tDNA定量差异均无统计学意义和（P均>0.05）;（3）肝细胞内HBsAg定性检测阳性患者的血清HBV DNA定量明显高于阴性患者,且差异有统计学意义（P<0.05）;肝细胞内HBsAg定性检测阳性患者与阴性患者的肝组织HBV cccDNA和HBV tDNA定量差异均无统计学意义（P>0.05）;（4）HBeAg（+）/抗-HBe（-）患者血清HBV DNA定量明显高于HBeAg（-）/抗-HBe（+）患者,且差异有统计学意义（P<0.05）;HBeAg（+）/抗-HBe（-）患者肝组织HBV cccDNA和HBV tDNA定量与HBeAg（-）/抗-HBe（+）患者比较差异均无统计学意义（均P>0.05）;（5）肝组织HBV cccDNA、HBV tDNA以及血清HBV DNA三者与肝脏炎症活动度及纤维化程度均无显著相关性（P>0.05）。结论 （1）血清HBV DNA定量结果并不一定能完全反映患者肝组织中HBV cccDNA和HBV tDNA含量,尤其在血清HBV DNA<500拷贝/mL时,肝组织中仍存在HBV cccDNA和HBV tDNA,且含量大小不等。（2）肝细胞内HBcAg定性检测阳性或者HBsAg定性检测阳性患者的血清HBV DNA定量均明显高于阴性患者;而两者的肝组织HBV cccDNA和HBV tDNA定量均没有显著差异;（3）HBeAg（+）/抗-HBe（-）患者血清HBV DNA定量明显高于HBeAg（-）/抗-HBe（+）患者,而两者的肝组织HBV cccDNA和HBV tDNA均没有显著差异;（4）肝组织HBV cccDNA、HBV tDNA及血清HBV DNA与肝脏炎症活动度和纤维化程度均无显著相关性。     

Clinical characteristics and distribution of hepatitis B virus genotypes in Guangxi Zhuang population

AIM: To investigate the distribution of HBV genotypes and their YMDD mutations in Guangxi Zhuang population, China, and to study the relationship between HBV genotypes and clinical types of HB, ALT, HBV DNA, HBe system as well as the curative effect of Lamivudine (LAM) on hepatitis B. METHODS: A total of 156 cases were randomly chosen as study subjects from 317 patients with chronic hepatitis B (CHB). HBV genotypes were determined by PCR-microcosmic nucleic acid cross-ELISA. YMDD mutations were detected by microcosmic nucleic acid cross-nucleic acid quantitative determination. HBV DNA was detected by fluorescence ratio PCR analysis. LAM was given to 81 cases and its curative effect was observed by measuring ALT, HBV DNA load, HBeAg, and HBeAg/HBeAb conversion rate. RESULTS: HBV genotypes B, C, D, and non-classified genotypes were found in Guangxi Zhuang population, accounting for 25.6%, 47.4%, 58.3%, and 16.0%, respectively. Seventy-four cases were CD-, CB-, BD-mixed genotypes (47.7%). Forty-six (29.5%) cases had YMDD mutations. Genotype B was mostly found in mild and moderate CHB patients. Genotypes C, D and mixed genotype mostly occurred in severe CHB cases. Genotypes D and CD HBV-infected patients had higher ALT and HBV DNA than patients with other types of HBV infection. There was no significant difference among the genotypes in YMDD mutations, clinical types, ALT and HBV DNA level. Non-classified types geno had a significantly lower positive rate of HBeAg than other genotypes (X2=12.841,P<0.05). There was no significant difference in ALT recovery rate, HBV DNA load, HBeAg, and HBeAg/HBeAb conversion rate, 48 wk after LAM treatment between groups of genotypes D, CD, and non-classified type. CONCLUSION: Genotypes B, C, and D, non-classified and mixed genotype of HBV are identified in the Guangxi Zhuang population. Variations in genotypes are associated with clinical severity and serum ALT levels, but not with YMDD mutation or HBV DNA load. Therapeutic effects of LAM on clinical parameters are not influenced by differences in genotypes. Further studies are needed to gain an in-depth understanding of the relationship between HBV genotypes and serum HBeAb and HBeAg.     

慢性乙型肝炎患者血清HBV DNA载量与肝组织病理学变化关系研究

探讨慢性乙型肝炎轻度患者血清HBV DNA载量与肝组织病理学变化的关系。方法根据血清HBeAg状态将310例慢性乙型肝炎轻度患者分为HBeAg阳性和HBeAg阴性,应用荧光定量PCR技术检测血清HBV DNA水平,常规进行肝活检术和病理学观察,分析血清HBV DNA载量与肝组织病理学变化的关系。结果224例HBeAg阳性患者肝组织炎症程度以G0（42.0%）为主,纤维化程度以S0（58.0%）为主;86例HBeAg阴性患者炎症程度以G0（29.1%）、G1（30.2%）、G2（34.9%）为主,纤维化程度以S0（51.2%）为主;HBeAg阳性患者血清HBV DNA水平与肝组织炎症程度无明显相关（r=-0.098,P＞0.05）,与纤维化分期间存在负相关关系（r=-0.309,P＜0.01）;HBeAg阴性患者血清HBV DNA水平与肝组织炎症程度存在正相关关系（r=0.306,P＜0.01）,与纤维化程度无明显相关（r=0.112,P＞0.05）。结论 HBeAg阳性与HBeAg阴性患者血清HBV DNA载量与肝组织病理学变化的关系存在显著差别,应区别分析其临床意义。     

Hepatitis B virus DNA in sera and liver tissue of HBsAg negative patients with chronic hepatitis C

BACKGROUND/AIMS: Hepatitis B virus (HBV) DNA has been detected in HBsAg-negative patients with hepatitis C. We determined the rate and explored the clinical significance of HBsAg negative HBV coinfections in Austrian patients with chronic hepatitis C. METHODS: Sera (n=82, group I) or liver tissue (n=16, group II) from 98 HBsAg negative Austrian patients with chronic hepatitis C were examined for HBV DNA by nested polymerase chain reaction (PCR). For control purposes, sera from 15 patients with chronic HBV infection (8 HBsAg positive, 7 HBsAg negative, all HBV PCR positive) were examined. RESULTS: HBV DNA was detected in 22% of sera and 19% of liver tissue specimens of patients with chronic hepatitis C. No significant difference in mean aminotransferase values, markers of HBV infection, inflammatory disease activity, or degree of hepatic fibrosis was observed in patients with or without HBV DNA. Anti-HBc alone as a marker of past HBV infection was more frequent in chronic hepatitis C patients compared to control individuals. Negative HCV PCR was more common (p=0.009) among patients with positive HBV PCR in serum. When examining repeat sera for HBV DNA, positive results were obtained in previously negative, but also negative results in previously positive patients. CONCLUSIONS: Coinfection with HBV can be demonstrated by PCR in a considerable number of HBsAg negative Austrian patients with chronic hepatitis C. HBV infection seems to suppress HCV replication even in HBsAg negative patients with dual infection. HBV coinfection in HCV infected patients cannot be excluded by negative HBsAg status alone. Repeat PCR examinations are needed to exclude dual infections.     

乙型肝炎病毒基因型、YMDD变异与拉米夫定治疗后HBV DNA反弹关系的研究

目的探讨HBV基因型、YMDD变异与拉米夫定抗病毒治疗后HBV DNA反弹的关系。方法应用多引物对巢式PCR法、PCR-序列分析法检测拉米夫定治疗的27例乙型肝炎患者和19例从未用过抗病毒治疗的患者HBV基因型和P区（YMDD）的突变位点。结果在27例HBV DNA反弹的患者中，13例（48．15％）检出YMDD变异，而对照人群无YMDD变异（P〈0．05）。YMDD变异的位点为rtM204V／I（C区）±rtL180M（B区）；在治疗组YMDD变异的患者中，B、C基因型构成比（46．15％和59．26％）与对照组（53．85％和68．42％）比较无显著性差异（P〉0．05）。结论YMDD变异是拉米夫定治疗后出现耐药导致HBV DNA反弹的主要原因；YMDD变异的常见位点依然为rtM204V／I（C区）±rtL180M（B区）；YMDD变异在B、C基因型病人中无差别。