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.     

HBeAg阴性慢性乙型肝炎患者初始拉米夫定治疗后血清HBsAg转阴3例

病例1,男,49岁。2002年6月查体发现HBV感染,肝功能正常,未治疗。2002年11月自觉乏力明显,化验肝功能A坍378U／L,ALB40．6g／L,TBIL17．61xmol／L。HBV血清标志物（Roche公司,电化学发光法）HBsAg3360COI,HBeAg0．37COI,抗-HBe0．56COI．HBVDNA3．2×10^4eopies／ml。肝脏组织病理学检查结果为G3S3。     

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与HBeAg血清转换持久性研究进展

拉米夫定作为治疗慢性乙型肝炎(CHB)的有效药物已广泛应用于临床。HBeAg血清转换常作为判断抗乙肝病毒(HBV)疗效的指标。拉米夫定疗效及HBeAg血清转换持久性受多种因素的影响。在决定拉米夫定治疗前应注意考虑患者的多因素影响,把握好适应证,才能获得更好的疗效和持久的HBeAg血清转换。     

慢性乙型肝炎拉米夫定治疗后HBeAg早期血清学转换的临床随访观察

目前拉米夫定已广泛应用于乙型肝炎的抗病毒治疗,然而治疗中及停药后可出现病情复发.本文对应用拉米夫定治疗后出现HBeAg/抗-HBe早期血清学转换(服药6个月内)的46例慢性乙型肝炎病人进行临床随访,旨在探讨病情复发的影响因素,指导合理用药.     

拉米夫定治疗慢性乙型肝炎疗程的建议

拉米夫定有很强的抑制ＨＢＶ的作用 ,这已由国内外大量的临床实践得到证明。但由于该药是ＨＢＶ的抑制药 ,而不是杀灭药 ,因此 ,也有很多不尽人意之处。《2 0 0 1年拉米夫定临床应用专家共识》和 1999、2 0 0 0年的《拉米夫定临床应用指导意见》均提出疗程应在 1年以上 ;对获得部分应答的病例 ,应继续服药 ,直至达到完全应答后再服药半年。这样就有很大一部分病人服药要 2年、3年……。随着时间的推延 ,耐药株出现的机率逐步升高 ,可使病情出现反复 ;长期应用后未达到完全应答及少部分获得完全应答的病例停药后也会出现病情反复 ,个别病例发…     

拉米夫定治疗慢性乙型肝炎的临床观察

新一代核苷类似物拉米夫定是一种很强的抑制乙型肝炎病毒复制的抗病毒药物。 1999年 9月～ 2 0 0 0年 9月 ,我们用拉米夫定治疗 10 0例慢性乙型肝炎患者 ,诊断符合 1995年第 5次全国传染病与寄生虫病学术会议修订的标准案。现报告如下 :材料和方法一、病例Ａ组 (拉米夫定组 ) 10 0例 ,按“拉米夫定临床应用指导意见”符合“适合治疗对象”者 82例 ,年龄均在 16岁以上 ,ＨＢＶＤＮＡ拷贝数 >1× 10 2 拷贝 /Ｕｌ(荧光法ＰＣＲ) ,ＡＬＴ高于正常 ,胆红素低于 5 0 μｍｏｌ/Ｌ (3ｍｇ/ｄｌ)。其中 72例ＨＢｅＡｇ阳性 ;10例ＨＢｅＡｇ阴性 ,抗 …     

拉米夫定治疗慢性乙型肝炎疗效观察

1999年12月至2002年12月，我院应用拉米夫定治疗慢性乙型肝炎88例，效果较好。现报告如下。     

拉米夫定治疗慢性乙型肝炎安全性观察的建议

本着学术争鸣的精神 ,本期发表了数篇关于拉米夫定临床应用的经验介绍 ,但在临床实践中也不乏失败的病例 ,因此在临床应用时还应严格参照拉米夫定专家小组指导意见和共识处理。此外 ,长期使用拉米夫定治疗时 ,建议仔细观察和记录有关事项。一、血清ＡＬＴ经治疗ＡＬＴ复常后 ,继续治疗可能出现ＡＬＴ反跳。此时需记录 :(一 )ＡＬＴ反跳出现的时间　是发生在治疗中、治疗停止后、出现ＨＢｅＡｇ/抗 ＨＢｅ血清转换后 ,抑或出现ＹＭＤＤ变异后 ,并要指出多少时间 (月 )。(二 )ＡＬＴ增高的水平、持续的时间和随访结果　由于各医院ＡＬＴ正常…     

拉米夫定和泛昔洛韦联合治疗慢性乙型肝炎

背景现有的抗病毒药物单用均难以完全清除乙型肝炎病毒(HBV)感染。体外研究证明,拉米夫定(LMD)和Penciclovir[泛昔洛韦(FCV)的活性代谢物]联合应用对HBV复制具有相加或协同抑制作用。目的研究LMD和FCV联合疗法对慢性乙型肝炎感染的疗效。方法21例慢性乙型肝炎患者在联合治疗前曾接受6个月以上的LMD治疗,但均未取得改善。所有患者均为血清乙型肝炎表面抗原(HBsAg)阳性,具有高水平HBVDNA和丙氨酸转氨酶(ALT),17例乙型肝炎e抗原(HBeAg)阳性。12例HBeAg阳性患者的诊断得到组织学证实。联合用药方案为治疗期LMD100mgqd+FCV500mgtid口服4个月;随访期(5～10个月)单用LMD,剂量同前。结果21例患者的血清HBVDNA水平在治疗前为1×10819±0.58copies/ml,治疗期末为1×104.55±1.18copies/ml,随访期为1×105.25±1.82copies/ml(P＜0.01);ALT水平从联合治疗前的225U/L±110U/L降至治疗期末的79U/L±50U/L和随访期的81U/L±48U/L(P＜0.01)。17例HBeAg阳性患者中,8例(47.1％)发生HBeAg/抗HBe血清转换;与此同时,血清ALT均正常化,HBVDNA降至1×104copies/ml以下(P＜0.01)。4例HBeAg阴性患者中,3例HBVDNA降至1×104copies/ml以下,ALT同时降至正常或明显降低。共有2例患者在随访期复发,其中1例HBeAg再次转为阳性,但HBVDNA和ALT均低于治疗前水平。10例接受肝活检复查的患者中,分别有8例(80％)和4例(40％)肝脏炎症活动度和纤维化程度得到改善(P＜0.05),无一例病变加重。结论LMD和FCV有协同或相加性抗HBV作用,可作为慢性乙型肝炎可供选择的治疗方法。     

拉米夫定治疗慢性重型肝炎的疗效和预后观察

目的:研究拉米夫定对慢性乙型重型肝炎的疗效、安全性及对预后的影响。方法:对慢性乙型重型肝炎患者采用常规治疗加口服拉米夫定100mg/d。连续30天,并与对照组比较。结果;拉米夫定组的好转率(75％)高于对照组(53％),P<0.05,且无明显不良反应,经随访,继续服用者肝功能基本正常,生活质量良好。结论:采用常规疗法联合拉米夫定治疗慢性重型肝炎为一种较好的治疗方案,可改善患者临床症状,促进肝功能恢复,提高患者的存活率。     

拉米夫定治疗慢性乙型肝炎过程中外周血单核细胞产生Th_1/Th_2类细胞因子的动态观察

目的:观察拉米夫定治疗慢性乙型肝炎过程中外周血单核细胞(PBMC)产生Th_1/Th_2类细胞因子(IFN-γ/IL-10)的动态变化。方法:用ELISA法分别检测20例慢性乙型肝炎患者在拉米夫定治疗前、治疗3个月、治疗6个月、治疗9个月时PBMC在PHA(100μg/ml)、HBcAg(1μg/ml)、HBeAg(1μg/ml)诱导下体外培养48h后培养上清液IFN-γ和IL-10的水平。结果:在拉米夫定治疗3个月时,无论是在非特异性抗原PHA还是特异性抗原HBcAg/HBeAg诱导下,同治疗前相比PBMC产生INF-γ和IL-10的水平无显著变化,在治疗6个月时,仅PHA诱导组产生IFN-γ的水平同治疗前相比显著升高,在治疗9个月时,备诱导组同治疗前相比,PBMC产生IFN-γ的水平显著增高,同时IL-10的水平也明显降低。结论:拉米夫定治疗慢性乙型肝炎过程中,随着治疗时间的延长,乙型肝炎患者PBMC产生Th_1类细胞因子IFN-γ水平逐渐增强;产生Th_2类细胞因子IL-10水平逐渐减弱,提示拉米夫定治疗慢性乙型肝炎不但具有抑制病毒作用,而且长时间治疗可增强Th_1类细胞优势应答,抑制Th_2类细胞功能...     

Adefovir Dipivoxil Alone or in Combination with Lamivudine for Three Months in Patients with Lamivudine Resistant Compensated Chronic Hepatitis B

We studied clinical and laboratory effects of 3 months of lamivudine with adefovir combination and adefovir dipivoxil (AD) alone in the treatment of patients with lamivudine-resistant hepatitis B virus (HBV) infection. Eligible patients were hepatitis B surface antigen-positive men and women with compensated liver disease who were given lamivudine at least more than 6 months and had HBV polymerase gene mutation. Patients were assigned to receive adefovir 10 mg/day (Group 1) or adefovir 10 mg once daily and lamivudine 100 mg once daily combination during first 3 months, and then stopped lamivudine and continued adefovir (Group 2). Median age was 48 years (34 males and 20 females, and 35 were HBeAg-negative). Baseline median ALT, AST, and HBV DNA levels were 66 IU/l, 49 IU/l, and 6.7 log₁₀ copy/ml, respectively. Median adefovir therapy time and ALT normalization time were 9 and 3.5 months, respectively. There was no significant difference between groups according to the baseline HBV DNA, ALT, HBe Ag status, age, gender, and lamivudine resistance time. Virological and biochemical responses were similar in both groups during therapy. Two patients (8%) had ALT flare more than five times upper limit of normal without any clinical decompensation in Group 1. Mild ALT elevation according to baseline levels were found in 8 (27.6%) and 4 (17.4%) patients, respectively, in Group 2 and Group 1, and no statistically significance between two groups. In conclusion, this study showed that it is not necessary to continue lamivudine therapy while switching to AD therapy. Adefovir alone is effective in the treatment of patients with lamivudine resistant HBV infection and compensated liver disease, without significant clinical and laboratory flares. However, it is not easy to say that switching to AD with cessation of lamivudine is safe, because the study population is not enough for precise conclusion and resistance may be a considerable problem against AD in patients using long-term treatment.     

拉米夫定对慢性乙型肝炎患者肝脏MMP-1及TIMP-1的影响

目的:观察拉米夫定对慢性乙型肝炎患者肝脏基质金属蛋白酶-1(MMP-1)及金属蛋白酶组织抑制因子-1(TIMP-1)的影响,探讨其防治肝纤维化的作用。方法:25例慢性乙型肝炎患者予拉米夫定100mg/d,连用1年,治疗前后作2次肝穿活捡,常规HE染色及Gordon Sweet、Masson染色,作炎性活动度及纤维化程度计分,作MMR-1、TIMP-1的免疫组化学分析。结果:25例患者中21例HBV DNA转阴,炎性活动度计分由5.40±3.04降至3.88±1.42(P<0.01),纤维化程度计分由3.44±1.45降至3.16±1.34(P<0.05),MMP-1由3.142±0.024增至4.009±0.310(P<0.05),TIMP-1由5.063±0.610降为4.107±0.131(P<0.05)。结论:拉米夫定强效抑制HBV,使肝脏TIMP-1活性降低、MMP-1活性增强而起到防治肝纤维化的作用。     

拉米夫定联合乙肝转阴合剂治疗慢性乙型肝炎的临床研究

目的观察拉米夫定联合乙肝转阴合剂治疗慢性乙型肝炎的抗病毒效果和安全性。方法将139例HBsAg、HBeAg及HBVDNA均为阳性的慢性乙型肝炎患者随机分为3组Ⅰ组45例,口服拉米夫定100mg/次,1次/d,同时口服乙肝转阴合剂20ml/次,3次/d。Ⅱ组44例,口服拉米夫定100mg/次,1次/d。Ⅲ组50例,口服乙肝转阴合剂20ml/次,3次/d。疗程均为52周,3组患者常规用维生素、甘利欣等护肝药物。结果Ⅰ组患者的HBVDNA阴转率和HBeAg血清转换率均明显高于Ⅲ组(P<005);Ⅰ组和Ⅱ组相比,HBVDNA阴转率相似(P>005),但两组在HBeAg阴转率和血清转换率方面比较差异有显著性意义(P<005或P<001)。结论拉米夫定联合乙肝转阴合剂治疗慢性乙型肝炎不仅可提高抗病毒疗效,而且可减少停药后的反跳现象,具有良好的临床应用价值。     

晶珠肝泰舒联合拉米夫定治疗慢性乙型肝炎临床疗效观察

目的:观察晶珠肝泰舒联合拉米夫定治疗慢性乙型病毒性肝炎(慢乙肝)的效果。方法:将60例慢乙肝患者随机分成晶珠肝泰舒联合拉米夫定组(治疗组)、拉米夫定组(对照组)各30例,疗程均为3个月,观察临床症状、生化指标、病毒复制指标,以及特异性细胞免疫指标IFN-γ、IL-4水平的变化。结果:治疗3个月后,两组在HBsAg、HBeAg、HBV DNA阴转,肝功能复常,以及症状、体征的恢复等方面差别无统计学意义(P>0.05),但IFN-γ、IL-4水平变化则有显著性差异。结论:在较短期的疗程中,晶珠肝泰舒联合拉米夫定治疗慢乙肝,对调整特异性细胞免疫指标IFN-γ、IL-4有较好作用。     

Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients

Background/Aims

Hepatitis B core antigen is known to be a major target for virus-specific T cells and also reflects the progression of liver dissease and viral replication. Hepatitis B core antigen expression in hepatocytes leads to altered histological activity, viral replication, and immune response. The purpose of this study is to evaluate whether the topographical distribution of hepatitis B core antigen expression can predict the viral response to entecavir in patients with chronic hepatitis B.

Methods

We enrolled 91 patients with treatment-naïve chronic hepatitis B. All the patients underwent liver biopsy, and the existence and pattern of hepatitis B core antigen evaluated by immunohistochemistry. All patients received 0.5 mg of entecavir daily following a liver biopsy. We checked the viral response at 3, 6, and 12 months during antiviral therapy.

Results

Of the 91 patients, 64 (70.3%) had hepatitis B core antigen expression. Of the subcellular patterns, the mixed type was dominant (n=48, 75%). The viral response was significantly higher in the hepatitis B core antigen-negative group than in the hepatitis B core antigen-positive group (88.9% and 54.7%, respectively; p=0.001) after 12 months of entecavir therapy.

Conclusions

Chronic hepatitis B patients who are hepatitis B core antigen-negative have a better response to entecavir therapy than do hepatitis B core antigen-positive patients.     

The Seroconversion Rate of Hepatitis A Virus Vaccination among Patients with Hepatitis B Virus-Related Chronic Liver Disease in Korea

Background/Aims

The aim of this study was to evaluate the seroconversion rate of a hepatitis A virus (HAV) vaccination in patients with hepatitis B virus (HBV)-related chronic liver disease (CLD).

Methods

Analyses were conducted using clinical records from 94 patients with chronic HBV infection who were seronegative for IgG anti-HAV antibodies between September 2008 and June 2009. Two doses of an HAV vaccine were administered 24 weeks apart. A third vaccine dose was administered only for patients seronegative for anti-HAV antibodies at week 48.

Results

The seroconversion rate of anti-HAV following the two-dose vaccination was 86.17%. The seroconversion rate of anti-HAV was not significantly different according to age or status of liver disease. The rate was higher in female than in male patients. A third HAV vaccine dose was administered to 13 patients seronegative for anti-HAV after the two-dose regimen, and 84.62% of these patients showed seroconversion at week 72.

Conclusions

HAV vaccination is effective in most Korean patients with HBV-related CLD, and it might be necessary to evaluate three-dose vaccination approach for non-responders to the conventional regimen to maximize the success of an HAV vaccination program.     

Entecavir Versus Lamivudine Therapy for Patients With Chronic Hepatitis B-Associated Liver Failure: A Meta-Analysis

Background:

Nucleoside analogues are recommended as antiviral treatments for patients with hepatitis B virus (HBV)-associated liver failure. Clinical data comparing entecavir (ETV) and lamivudine (LAM) are inconsistent in this setting.

Objectives:

To compare the efficacy and safety of ETV and LAM in patients with chronic hepatitis B (CHB)-associated liver failure.

Patients and Methods:

A literature search was performed on articles published until January 2014 on therapy with ETV and LAM for patients with CHB-associated liver failure. Risk ratio (RR) and mean difference (MD) were used to measure the effects. Survival rate was the primary efficacy measure, while total bilirubin (TBIL), prothrombin activity (PTA) changes and HBV DNA negative change rates were secondary efficacy measures. A quantitative meta-analysis was performed to compare the efficacy of the two drugs. Safety of ETV and LAM was observed.

Results:

Four randomized controlled trials and nine retrospective cohort studies comprising a total of 1549 patients were selected. Overall analysis revealed comparable survival rates between patients received ETV and those received LAM (4 weeks: RR = 1.03, 95%CI [0.89, 1.18], P = 0.73; 8 weeks: RR = 0.98, 95% CI [0.85, 1.14], P = 0.84; 12 weeks: RR = 0.98, 95% CI [0.90, 1.08], P = 0.70; 24 weeks: RR = 1.02, 95% CI [0.94, 1.10], P = 0.66). After 24 weeks of treatment, patients treated with ETV had a significantly lower TBIL levels (MD = -37.34, 95% CI [-63.57, -11.11], P = 0.005), higher PTA levels (MD = 11.10, 95% CI [2.47, 19.73], P = 0.01) and higher HBV DNA negative rates (RR = 2.76, 95% CI [1.69, 4.51], P < 0.0001) than those treated with LAM. In addition, no drug related adverse effects were observed in the two treatment groups.

Conclusions:

ETV and LAM treatments had similar effects to improve 24 weeks survival rate of patients with CHB-associated liver failure, but ETV was associated with greater clinical improvement. Both drugs were tolerated well during the treatment. It is suggested to perform further studies to verify the results.