乙型肝炎病毒基因型与干扰素-α2b疗效的关系

目的研究乙型肝炎病毒基因型与干扰素-α2b治疗疗效的关系。方法采用DNA测序法对222例慢性乙型肝炎患者进行HBV基因分型。其中106例接受干扰素-α2b治疗6个月，观察治疗后应答率与基因型的关系。结果在106例接受干扰素-α2b治疗的患者，C基因型患者肝组织学改变明显重于B基因型。在6个月治疗结束时，B型感染者HBVDNA阴转、HBeAg血清转换和ALT复常率分别为41．9％，38．7％和58．1％，均显著高于C型患者（P〈0．05）。结论HBV基因型与肝损害程度及对干扰素-α2b的应答率有一定的关系。     

乙型肝炎病毒基因型对干扰素α2b应答的影响

在HBV基因型特异引物下聚合酶链反应(PCR)扩增并检测1020例慢性乙型肝炎患者血清HBVDNA。其中136例接受干扰素α2b治疗,疗程6个月;观察患者乙型肝炎病毒血清标志物、HBVDNA、丙氨酸转氨酶(ALT)。1020例乙型肝炎患者中966例有基因分型结果;136例接受干扰素α2b治疗综合疗效(HBeAg阴转、HB-VDNA阴转、ALT复常)B型患者为40.9%(18/44),优于C型25.8%(16/62)及B/C混合型16.7%(5/30)(P>0.05)。乙型肝炎病毒不同基因型可以对干扰素α2b应答产生影响。     

慢性乙型肝炎病毒基因型与干扰素治疗应答的关系

观察慢性乙型肝炎病毒基因型与α -干扰素治疗慢性乙型肝炎患者疗效的关系。利用限制性片段长度多态性分析技术 ,由限制性内切酶AvaⅡ和DpnⅡ作用于前S区扩增片段建立的简便的HBV基因型分型方法 ,对 6 0例经干扰素治疗的慢性乙型肝炎患者的血清HBV进行基因型测定 ,显示B基因型 31例 (5 1 7% ) ,C基因型 2 6(43 3% ) ,D基因型 3例 (5 0 % )。B型、C型与干扰素应答无明显差异 (P >0 0 5 ) ,3例D型均有效。由于我国大部分地区HBV基因型以B型和C型为主 ,HBV基因型可能不是预测干扰素疗效的重要因素。D型对干扰素应答率高 ,有待进一步研究。     

聚乙二醇干扰素α-2a治疗慢性丙型肝炎病毒／乙型肝炎病毒共感染临床疗效

目的研究慢性丙型肝炎（CHC）与丙型肝炎病毒/乙型肝炎病毒（HCV/HBV）共感染者用聚乙二醇干扰素α-2a（PEG-IFNα-2a）抗病毒治疗疗效的观察。方法治疗前后定期采集31例CHC、30例HCV/HBV共感染者的外周血,检测HCV RNA、HBV DNA和肝脏纤维化指标。结果治疗后CHC患者血清中HCV RNA含量51.6%〈102拷贝/ml,HCV/HBV共感染者HCV、HBV下降均不理想。结论 PEG-IFNα-2a抗病毒治疗HCV/HBV共感染者疗效较单纯丙型肝炎患者差,但对HBV、HCV有抑制作用,并部分改善机体免疫功能及肝功能。     

慢性乙型肝炎病毒基因型与拉米夫定疗效关系的研究

目的：研究乙型肝炎病毒(HBV)基因型对拉米夫定抗病毒疗效的影响。方法：回顾性调查286例拉米夫定治疗组和对照组患者的临床资料。结果：HBV优势基因型是B(34％)和C(48％)型，共235例。135例患者接受拉米夫定抗病毒治疗，对照组100例。拉米夫定有效率在B、C两基因型中分别为92．9％和75．9％(P=0．02)，而对照组分别为9．8％和8．5％(P=0．59)；YMDD变异发生率为8．9％和22．8％(P=0．028)。Multivariate分析发现，B基因型、ALT升高、HBV DNA低水平是影响抗病毒应答的预测因素。在ALT升高患者中，B、C基因型拉米夫定有效率分别为93％和77％(P=0．01)，对照组为13％和8％(P=0．45)。Multivariate分析发现，B基因型、HBV DNA低水平是预测较好疗效的独立因素。结论：B基因型HBV对拉米夫定的应答率高于C型，而变异YMDD发生率低于C型，基因型是影响拉米夫定疗效和诱导变异的重要因素之一。     

兰州地区慢性乙型肝炎病毒基因与干扰素治疗的关系

目的观察兰州地区慢性乙型肝炎病毒基因型与干扰素治疗的关系.方法用套式PCR方法扩增69例经干扰素治疗的慢性乙型肝炎病人的S基因,利用限制性内切酶Sty Ⅰ和Bsr Ⅰ平行酶切鉴别乙型肝炎病毒基因型,并追踪其治疗效果.结果B型19例(27.5%),C型35例(50.7%),D型12例(17.3%).对于干扰素治疗的应答率,B型与C、D型有显著性差异(P＜0.05),C型与D型无显著性差异(P＞0.05).结论B型病人对干扰素治疗有较好的应答,HBV基因型可能是预测干扰素治疗的因素之一.     

拉米夫定联合干扰素-α1b抗乙型肝炎病毒疗效观察

慢性乙型肝炎治疗的关键是抗病毒治疗，但单用一种抗乙型肝炎病毒(HBV)药物疗效往往不佳，目前国内外公认的抗HBV药物为拉米夫定和干扰素-α，国内有学者认为采用拉米夫定干扰素-α序贯疗法进行治疗，虽能减少YMDD变异，但不能提高抗HBV疗效。因此我们采取两者开始联合应用以了解其能否提高抗病毒疗效，现总结如下。     

乙型肝炎病毒基因型与抗病毒药物疗效关系的研究进展

乙型肝炎在全球发病率高,严重危害人类健康.随着HBV基因型研究的深入,大量研究显示HBV基因型与临床疾病谱密切相关.目前抗病毒治疗是慢性乙型肝炎治疗的最主要措施,越来越多的学者对HBV基因型与抗病毒药物疗效的关系进行了研究,本文就目前国内外关于HBV基因型与抗病毒疗效关系的研究进展作一综述.     

α1b干扰素治疗小儿乙型肝炎病毒相关性肾炎的远期疗效

鉴于皮质醇激素治疗小儿乙型肝炎病毒相关性肾炎（ＨＢＶ－ＧＮ）的各种不良反应，现应用国产人α１ｂ基因工程干扰素治疗８例小儿ＨＢＶ－ＧＮ，剂量为３００万Ｕ／ｍ＾２体表面积隔天肌注，４个月后改为每周肌注２次持续２个月，总疗程６个月，用药期间无严重副反应，结果是５例尿蛋白消失，肾病缓解，２例尿蛋白减少，１例无进步，６例血清总蛋白，白蛋白上升，有３例血清ＨＢＶ抗原转阴（其中２例ＨＢｅＡｇ，ＨＢｓＡｇ均转阴，     

乙肝病毒基因型与干扰素近期疗效探讨

目的：探讨HBV基因型与干扰素近期疗效的关系。方法：分析240例HBVDNA阳性的患者基因型，比较不同基因型患者干扰素近期疗效。结果：240例HBV感染者中HBV基因B型144例，占60．0％，C型90例，占37．5％，B、C混合型6例，占2．5％；干扰素的疗效以B型为高。结论：干扰素近期疗效以HBV基因型B型为好。     

聚乙二醇化干扰素α-2b与干扰素α-2b治疗e抗原阳性慢性乙型肝炎的疗效和安全性的随机对照多中心研究

目的比较聚乙二醇化干扰素α-2b（PEG-1FN α-21））和干扰素α-2b（IFNα-2b）治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性。方法选择HBeAg阳性慢性乙型肝炎患者230例，按照1：1的比例随机给予PEGIFN α-2b（1．0μg／kg．每周1次、皮下注射）或IFNα-2b（3MU、每周3次、皮下注射）治疗24周，停药后随访24周。结果（I）治疗24周和随访24周时，PEGIFNα-2b治疗组的完全应答率、HBVDNA阴转率、HBeAg血清转换率、HBeAg阴转率均高于IFNα-2b组，但除随访24周时的HBeAg阴转率外，差异均无统计学意义。（2）治疗过程中两组患者血清中HBVDNA均持续下降。24周时PEG—IFNα-2b治疗组病毒量平均下降值明显大于IFNα-2b组（2、22log10对1．68log10，P〈0.05）。（3）两组总的不良事件发生率．药物相关的不良事件种类及各自的发生率差异无统计学意义。结论PEG—IFN、α-2b（1．0μg／kg、每周1次、皮下注射）治疗HBeAg阳性慢性乙型肝炎的应答率，从数值上看优于IFNα-2b（3MU／次，每周3次、皮下注射），但除随访24周时的HBeAg阴转率外，差异均无统计学意义。两组的安全性相似。     

α干扰素治疗HBeAg阳性慢性乙型肝炎疗效的预测指标

目的探讨α干扰素(IFN-α)治疗HBeAg阳性慢性乙型肝炎(CHB)疗效的预测指标。方法 165例HBeAg阳性CHB患者接受干扰素-α1b治疗24周,以ALT、HBV DNA基线、IFN-α剂量、肝组织炎症程度为预测指标,分析这些指标与抗病毒应答的相关性。结果 5 ULN1×106copies/mL组(P<0.05,P<0.01),中、重度CHB的有效应答率高于轻度CHB(P<0.01);IFN-α剂量与疗效未显示相关性(P>0.05)。结论干扰素疗效与治疗前ALT、HBV DNA水平及肝组织炎症程度等有密切的关系,可以作为预测IFN-α抗HBV疗效的指标。     

Expression of bcl-2 protein in chronic hepatitis C： Effect of interferon alpha 2b with ribavirin therapy

AIM: Mechanisms responsible for persistence of HCV infection and liver damage in chronic hepatitis C are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic protein bcl-2 expression on liver tissue as well as the influence of interferon alpha 2b (IFNa2b) and ribavirin (RBV) were analyzed in patients with chronic hepatitis C. METHODS: In 30 patients with chronic hepatitis C (responders - R and non-responders - NR) treated with IFNα2b+RBV, protein bcl-2 was determined in hepatocytes and in liver associated lymphocytes before and after the treatment. RESULTS: The treatment diminished bcl-2 protein accumulation in liver cells in_patients with hepatitis C (P<0.05). Before and after the therapy, we detected bcl-2 protein in R in 87±15% and 83±20% of hepatocytes and in 28±18% and 26±10% of liver-associated lymphocytes, respectively. In NR, the values before treatment decreased from 94±32% to 88±21% of hepatocytes and 39±29% to 28±12% of lymphocytes with bcl-2 expression. There was no statistical correlation between bcl-2 expression on liver tissue with inflammatory activity, fibrosis and biochemical parameters before and after the treatment. CONCLUSION: IFNα2b+RBV treatment, by bcl-2 protein expression decrease, enables apoptosis of hepatocytes and associated liver lymphocytes, which in turn eliminate hepatitis C viruses.     

Modification of the immune response against hepatitis B virus by the human immunodeficiency virus

Summary Hepatitis B virus and the human immunodeficiency virus are similarly transmitted. Individuals with preexisting HIV infection have a higher chance to become HBsAg carriers than do anti-HIV negative persons. Cytotoxic T cells with specificity for HBcAg, that are under the control of HBcAg-specific helper T cells, are responsible for liver injury. There is good evidence that HIV infection lowers inflammatory activity, is associated with milder liver histology, high levels of viral replication and low seroconversion rates. In addition interferon alpha therapy is less effective in anti-HIV positive subjects. The immune response against HBsAg is helper T-cell dependent and vaccination against hepatitis B is of low effectiveness. In addition, vaccination against hepatitis B may activate the HIV disease and is, therefore, presently not to be recommended.     

Hepatitis B genotypes and the response to interferon therapy

BACKGROUND/AIMS: Possible pathogenic differences among hepatitis B virus (HBV) genotypes have been observed; however, the response to interferon therapy among HBV genotypes remains unknown. We therefore analyzed the efficacy of interferon alfa in the treatment of chronic hepatitis B patients with different HBV genotypes. METHODS: Fifty-eight genotype B or C infected chronic hepatitis B patients who had been treated with interferon alfa-2b were retrospectively studied. The response to interferon was defined as normalization of serum aminotransferase level, loss of hepatitis B e antigen and HBV DNA 48 weeks post-treatment. RESULTS: Baseline data of both groups of patients were comparable; however, genotype C patients had a higher serum aminotransferase level and a higher frequency of core promoter mutation. The response rate was 41% and 15% in genotype B and C patients, respectively (p=0.045). In those with higher serum aminotransferase levels, the response rate was 50% and 17%, respectively (p=0.025). Additionally, younger age and genotype B infection may predict a better response to interferon alfa. CONCLUSIONS: HBV genotype C, compared to genotype B, is associated with a higher frequency of core promoter mutation, and a lower response rate to interferon alfa therapy.     

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。     

不同亚型干扰素α的抗乙型肝炎病毒活性研究

我们用Abbot试剂盒检测干扰素(IFN)α-2b、IFN α-2a、IFNα-1b对HepG2.2.15细胞分泌的HBsAg,HBeAg的抑制率,用RT-PCR、Westem blot以及荧光定量PCR方法检测基因应答水平上信号传导分子STAT1 mRNA及蛋白质表达水平,比较信号传导分子的表达水平与1 FN α对HBsAg和HBeAg抑制率的关系,以探讨用信号分子STAT1作为一种新的抗病毒评价标准的可能性.同时通过不同试验方法的比较,以寻求一种更好的评价IFN α抗病毒活性的方法.     

Lamivudine and 24 weeks of lamivudine/interferon combination therapy for hepatitis B e antigen-positive chronic hepatitis B in interferon nonresponders

BACKGROUND/AIMS: Lamivudine is effective in treatment-naive patients with chronic hepatitis B, but its role in interferon nonresponders has not been described. We assessed lamivudine treatment, with or without added interferon, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had failed interferon therapy previously. METHODS: Patients were randomized to lamivudine (100 mg) or placebo for 52 weeks or to a 24-week regimen of lamivudine plus interferon. Primary treatment comparisons were at week 52, with a 16-week posttreatment follow-up period. Measurements included histology (primary endpoint), HBeAg response, normalization of alanine aminotransferase, reduction of hepatitis B virus (HBV) DNA, and safety. RESULTS: Among 238 patients, histologic response was significantly more common in patients treated with lamivudine (52 versus placebo 25%, P=0.002) or the combination regimen (32%, P=0.01). HBeAg loss was also more common with lamivudine (33 versus 13 versus 21%), as were virologic and alanine aminotransferase responses. Among 28 subjects with HBeAg loss/seroconversion, 71% had durable responses 16 weeks posttreatment. CONCLUSIONS: Lamivudine for 52 weeks is as effective in interferon nonresponders as in previously reported treatment-naive patients; however, a combination of lamivudine for 24 weeks and interferon for 16 weeks was not effective in this population.     

拉米夫定联合干扰素α治疗慢性乙型肝炎疗效观察

目的研究拉米夫定联合干扰素α对慢性乙型肝炎病人的疗效。方法对1999~2001年深圳市东湖医院慢性乙型肝炎病人87例,随机分为2组,观察组36例,用拉米夫定(100mg/d)联合干扰素α(每次5mU)隔日1次肌注,26周后单用拉米夫啶至104周。对照组51例,单用拉米夫啶100mg/d,疗程104周,并评估疗效。结果两组HBVDNA转阴率差异无显著性(P=0.24),联合治疗组的HBeAg/抗-HBe血清转换率高于拉米夫定组(38.9%对17.6%,P=0.03)。联合治疗组的HBVYMDD变异率较低(22.2%对43.1%,P=0.04)。结论联合治疗的2年疗效优于单用拉米夫定,且能减少病毒YMDD变异。     

乙型肝炎病毒基因组变异对干扰素治疗的影响

目的 研究乙型肝炎病毒基因组Ｘ区和前Ｃ／Ｃ区多部位变异对干扰素（ＩＦＮ）治疗的影响。方法 利用套式聚合酶链反应产物直接测序技术,测定１７例慢性乙型肝炎患者ＩＦＮ治疗前病毒核苷酸序列。结果 ５例Ｔ＾１７６２－Ａ＾１７６４变异株感染者均对ＩＦＮ治疗有应答,而在１２例无Ｔ＾１７６２－Ａ＾１７６４突变患者中仅３例有应答。在８例Ａ＾１８９６变异株感染者中,５例同时伴Ｃ区Ｂ细胞表位ａａ１０７￣１１８突变,其中