拉米夫定治疗HBeAg阳性和阴性慢性乙型肝炎探讨

目的:探讨HBeAg阳性和阴性慢性乙肝患者经拉米夫定治疗后HBVYMDD变异、HBV DNA消失率、ALT复常率情况。方法:将病例分成两组,HBeAg阳性48例,HBeA阴性48例,均口服拉米夫定100mg/d。治疗前和治疗9个月、12个月、18个月、24个月分别检测血清标本HBVYMDD变异、HBV DNA消失率、ALT复常率。结果:治疗前和治疗9个月两组HBVYMDD变异率无差别(P>0.05);治疗12个月、18个月、24个月两组HBVYMDD变异率均有显著性差异(P<0.05)。治疗前和治疗9个月、12个月、18个月、24个月两组HBV DNA消失率、ALT复常率均无显著性差异(P>0.05)。结论:HBeAg阳性乙肝患者经拉米夫定治疗后较HBeAg阴性患者易发生HBVYMDD变异,但治疗效果无明显差异。     

拉米夫定治疗慢性乙型肝炎过程中血清HBeAg动态变化与YMDD变异的相关性研究

近年来,在对与拉米夫定治疗相关变异的研究中发现,拉米夫定治疗前患者血清HBeAg的状态可以预测YMDD变异的发生,即治疗前血清HBeAg阳性者较血清HBeAg阴性者容易发生YMDD变异,但对于治疗过程中血清HBeAg动态变化与YMDD变异发生的相关性研究鲜有报道。本文通过对48例拉米夫定治疗过程中发生YMDD变异以及39例治疗已达3年尚未发生YMDD变异患者的血清HBeAg动态变化的回顾与分析,探讨其与YMDD变异发生的可能相关性。     

拉米夫定治疗HBeAg阴性慢性乙型肝炎的疗效观察

HBeAg阴性慢性乙型肝炎(CHB)是乙型肝炎中的一种独立类型,有学者称其为非典型型。常迁延不愈,预后差,用灵敏检测方法检查,多数患者体内仍有病毒复制。α-干扰素对其疗效较差。近两年我们使用拉米夫定治疗20例该类患者,疗效满意,现将结果报告如下。     

HBeAg阴性HBV DNA阳性慢性HBV感染者治疗的预测分析

目的 研究HBeAg阴性乙肝病毒(hepatitis B virus,HBV)DNA阳性慢性乙肝病毒感染者达到治疗时间的预测指标.方法 将入组的108例患者,根据肝脏病理结果分为治疗组和随访组,将年龄、性别、感染家族史、HBsAg定量水平、HBV DNA载量纳入单因素分析,有统计学意义的变量进行Logistic多变量回...     

拉米夫定治疗慢性HBV感染的研究进展

拉米夫定(Lamivudine)是新一代核苷类似物。全称2′3′-双脱氧-3-硫代胞嘧啶核苷,简称3TC。对HBV有明显抑制作用。继加拿大、美国批准上市后,我国也已批准进入临床应用并制定出临床应用的指导意见。本文简述近几年用3TC治疗慢性HBV感染的研究进展。     

HBeAg阴性慢性乙型肝炎的药物治疗

本文根据近年来最新的研究进展 ,就HBeAg阴性慢性乙型肝炎的用药指征、治疗目标、停药指征、疗效评价、安全性评估及未来治疗发展方向做一讨论。一、HBeAg阴性慢性乙型肝炎用药指征、治疗目标、停药指征及疗效评价所有的HBeAg阴性慢性乙型肝炎病人都需要接受治疗 ,但治疗前必须与HBsAg携带者进行鉴别诊断 ,因为两者的血清病毒学检查非常相似 ,都表现为HBsAg阳性及HBeAg阴性 ,且通常其抗 HBe为阳性 ,持续时间多长于 6个月。HBeAg阴性慢性乙型肝炎的诊断指标为 :( 1)血ALT升高 (随机测值大于正常值 2倍或持续 1个月大于正常值的 1…     

拉米夫定联合苦参碱序贯疗法治疗慢性乙型肝炎 HBeAg/抗HBe转换的临床观察

拉米夫定对慢性乙型肝炎的疗效经多年来的临床验证表明是有效的,且耐受性好,服用方便。但拉米夫定治疗6～9个月后,可出现YMDD变异,且随着疗程的延长,YMDD变异率升高。为了减少耐药株的发生并巩固疗效,我们采用拉米夫定治疗一段时间后再联合苦参碱治疗,然后再单用拉米夫定这种序贯疗法。本文研究的目的旨在评价单用拉米夫定的疗效与使用拉米夫定联合苦参碱序贯疗法的效果。[第一段]     

拉米夫定治疗慢性乙型肝炎过程中HBV YMDD变异与临床

目的:探讨拉米夫定治疗慢性乙型肝炎过程中HBV YMDD变异与临床的关系。方法:对应用拉米夫定治疗的19例慢性乙型肝炎患者进行肝功能、乙肝病毒血清学标志物、HBV YMDD变异检测,个别病例进行肝组织病理学检查。结果:ALT异常率为47％,HBeAg血清转换率为15.8％,HBV YMDD变异发生率为25％,肝组织中HBsAg和HBcAg依然阳性。结论:运用拉米夫定治疗慢性乙型肝炎6个月后可出现HBV YMDD变异,随着治疗时间延长,其变异发生率越高;该药远期降酶作用不够理想;HBeAg血清转换率不高;肝组织内仍处于炎症状态。     

Biochemical response to lamivudine treatment in HBeAg negative chronic hepatitis B patients in Iran

AIM: To study the effect of a one-year lamivudine regimen in patients with chronic hepatitis B. METHODS: Medical records of HBeAg negative hepatitis B patients who attended a hepatitis clinic in Tehran between March 2002-March 2004 were evaluated. The patients received 100 mg lamivudine tablets once daily for at least 12 mo. Liver enzymes and complete blood count were checked at baseline and the end of treatment (12th mo) and 6 mo after discontinuation of treatment. RESULTS: Of all patients, 24 were excluded. Of 71 patients left, 58 (81.7%) were men. Mean age of the patients was 38±14 years. Mean level of ALT in serum was 1437±205 nkat/L at baseline with a significant reduction at the end of treatment to a mean level of 723±92 nkat/L (P = 0.002). In 38 patients (53.5%), the ALT level was normal after one-year treatment. Five patients (7.3%) relapsed (biochemically) within 6 mo after discontinuing lamivudine therapy (the patients with good end of treatment response). Mean level of AST in serum was 1060±105 nkat/L at baseline which decreased significantly to 652±75 nkat/L at the end of treatment (P = 0.002). CONCLUSION: Over half (53.5%) of chronic hepatitis B patients with HBeAg negative have normal liver enzyme level at 12-mo lamivudine therapy.     

免疫疗法联合拉米夫定治疗慢性乙型肝炎应用研究

目的 探讨免疫疗法联合拉米夫定对慢性乙型肝炎(CHB)的抗病毒治疗效果。方法 治疗组(免疫疗法 拉米夫定)76例，对照组(单用拉米夫定)38例。2组病例根据血清ALT、HBV标志物水平分为免疫耐受期、免疫清除期。免疫疗法包括应用乙型肝炎疫苗、绿脓杆菌菌毛注射液、胸腺肽注射液。结果 免疫清除期病例的HBeAg阴转率治疗组为15／34(44．1％)，对照组为2／17(11．8％)，P＜0．05。HBV DNA阴转率2组分别为82．5％和70．6％。免疫耐受期病例的HBeAg阴转率治疗组为11／42(26．2％)，对照组1／21(4．8％)，P＜0．05。HBV DNA阴转率治疗组为23／42(54．8％)，对照组6／21(28．6％)，P＜0．05。结论 免疫疗法联合拉米夫定可以提高CHB患者HBeAg及HBV DNA阴转率。     

Efficiency and safety of lamivudine therapy in patients with chronic HBV infection, dialysis or after kidney transplantation

AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well tolerated and safe in patiente with renal insufficiency undergoing hemodialysis and kidney-transplantation. However, in the latter group, high incidence of YMDD mutation after lamivudine treatment was observed.     

Effect of lamivudine in HBeAg-positive chronic hepatitis B： Discordant effect on HBeAg and HBV DNA according to pretreatment ALT level

AIM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9+/-0.4 mo. RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs 2, P = NS; groups 1 vs 3, P = 0.002; groups 1 vs 4, P<0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P = NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs 2, P = 0.02; groups 1 vs 3, P = NS). CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.     

拉米夫定治疗慢性乙型肝炎患者定量检测HBeAg的意义

目的探讨拉米夫定治疗的慢性乙型肝炎患者血清HBeAg和HBV DNA载量的变化规律。方法采用免疫化学发光和荧光定量聚合酶链反应技术分别检测了64例HBeAg阳性的慢性乙型肝炎患者在接受拉米夫定治疗过程中血清HBeAg和HBV DNA水平的变化。结果治疗12个月,HBV DNA完全转阴49例(76.6%),HBeAg转阴17例(26.6%),他们的HBV DNA和HbeAg水平呈同步下降趋势;11例治疗无效的患者血清HBV DNA和HBeAg水平也呈下降趋势,但始终未转阴;4例HBV DNA短暂转阴的患者,在治疗6个月后又转为阳性,HbeAg也未阴转。结论在拉米夫定抗病毒治疗过程中动态检测HBeAg水平可用于评估抗病毒的效果。     

Quantitative assessment of serum hepatitis B e antigen, IgM hepatitis B core antibody and HBV DNA in monitoring the response to treatment in patients with chronic hepatitis B

Virological response to treatment of chronic hepatitis B is defined as the loss of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The quantitative measurement of HBV DNA is useful for monitoring and predicting the response to therapy with interferon-α (IFN-α). In this study, we evaluated whether quantitative measurement of serum HBeAg and IgM antibody to hepatitis B core antigen (HBcAb) could also be used in this manner. Using a microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence rate vs HBeAg concentration was constructed to provide quantitative results. The IgM HBcAb index was also measured using a microparticle enzyme immunoassay and serum HBV DNA was measured by a solution hybridization assay. We studied 48 patients who were initially positive for HBeAg and HBV DNA and who were treated with IFN-α2b. Their sera were serially evaluated for HBeAg concentration, and results were compared with HBV DNA levels. In the 14 patients who responded to IFN, similar disappearance curves were observed with good intraindividual correlation between the levels of the two markers. In the 34 non-responders, HBeAg levels decreased during treatment but never became negative; HBV DNA levels also decreased during treatment and became transiently undetectable in six patients, falsely suggesting treatment success. The IgM HBcAb index paralleled changes in alanine aminotransferase (ALT) concentration and did not provide additional information. Multiple logistic regression indicated that baseline ALT and HBeAg concentrations were independent predictors of the response to treatment and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude that quantitative measurement of HBeAg provides information similar to that of HBV DNA in monitoring and predicting the response to treatment; this technique could be readily adaptable to clinical laboratories.     

拉米夫定治疗HBeAg阳性慢性乙型肝炎患者血清转换持久性的研究

目的观察拉米夫定长期治疗慢性乙型肝炎(CHB)3年以上患者的血清转换率和停药后持久率,及影响疗效的有关因素.方法167例CHB患者,每天服用拉米夫定100mg,持续3年以上,连续2次以上出现血清转换(间隔3个月),即HBeAg转阴和抗HBe转阳,继续服药6～12个月后,停药并随访1年以上.服药第1年每月,以后第3个月观察临床症状和血清病毒学标志、丙氨酸转氨酶(ALT)、HBV DNA定量及YMDD变异等项目.HBV基因分型应用型特异性PCR方法.结果共有45例患者出现血清转换(27.0%),继续服药6～12个月后停药并随访1年以上,9例出现血清学重新激活,血清转换持久率为80.0%.经单因素统计和Logistic多元回归分析,得出血清转换率和停药后持久率与基线ALT水平呈正相关,与基线HBV DNA水平和治疗后YMDD变异呈负相关.结论CHB患者出现血清转换后继续应用拉米夫定治疗6个月以上,大多数患者可达到持续转换.对血清转换率和持久率有显著影响意义的因子为基线ALT、治疗后YMDD变异.     

拉米夫定治疗慢性乙型肝炎病毒感染的近期疗效

目的评价拉米夫定治疗不同临床类型慢性乙型肝炎病毒（HBV）感染的近期疗效。方法口服拉米夫定150mg,每日1次,连服6个月,治疗慢性乙型肝炎病人40例,肝炎肝硬化18例,慢性重型肝炎10例。观察其临床、生物化学、血清学和病毒学改变。结果（1）慢性乙型肝炎病情缓解。对照组病毒血症持续,27．5％病人于随访期内肝炎复发（P＜0．001）。同时观察拉米夫定联用干扰素治疗病人20例,未见提高疗效。（2）肝炎肝硬化病情渐趋稳定,肝功能好转,Child—Pugh积分下降。（3）慢性重型肝炎除2例服药不足3个月死亡外,余8例病情缓解,随着肝功能改善,生活质量显著好转。结论拉米夫定适用于治疗慢性乙型肝炎,对处于HBV复制状态的肝硬化和重型肝炎也有效。     

Pegylated IFN-α 2b added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B

AIM: To investigate the role of pegylated-interferon (IFN) alpha-2b in the management of patients with lamivudine-resistant chronic hepatitis B.METHODS: Twenty consecutive anti-HBe positive patients were treated with pegylated IFN alpha-2b (100 mug sc once weekly) for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison.RESULTS: Nine patients (45%) had a partial virological end-treatment response; seven patients (35%) showed complete virological end-treatment response. Eight patients (40%) showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders (four out of seven patients vs none out of six patients, respectively; P=0.1). Patients without virological end-treatment response showed significant worsening of fibrosis [median score 2 (range, 1 to 3) vs median score 3 (range, 1 to 4)], in the first and second biopsy respectively (P=0.014), whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies (n=5). Nevertheless, after 12 mo of follow-up, only one patient (5%) showed sustained virological response and only 2 patients (10%) showed sustained biochemical response. Two patients (10%) discontinued pegylated IFN both after 6 mo of treatment due to flu-like symptoms.CONCLUSION: Pegylated IFNalpha-2b, when added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B, induces sustained responses only in a small minority of cases.