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 …     

拉米夫定治疗慢性重型乙型肝炎短期临床疗效观察

慢性重型乙型肝炎病情凶险，死亡率高，其抗病毒治疗，目前临床上无突破性进展。用拉米夫定治疗慢性重型乙型肝炎，初步观察其短期临床效果，结果如下：     

拉米夫定联合左旋咪唑涂布剂治疗慢性乙型肝炎疗效观察

本文比较拉米夫定联合左旋咪唑涂布剂和单用拉米夫定治疗慢性乙型肝炎的疗效和不良反应。对门诊及住院患者126例慢性乙型肝炎患者随机分为2组,该两组从年龄、性别、病情和乙型肝炎病毒标志的阳性率方面均有可比性。每组为63例,治疗组用拉米夫定100mg,l次/d,口服,加左旋咪唑涂布剂每周2次,每次1支(500mg)外用;对照组单用拉米夫定100mg/d,口服,疗程均为3个月,停药后作     

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35例疗效观察

目的 观察拉米夫定治疗慢性乙型肝炎的疗效。方法 使用拉米夫定100mg口服每日一次，疗程一年。结果 拉米夫定对HBV DNA转阴率、ALT复常率效果显著。结论 拉米夫定有强烈抑制HBV DNA复制作用，能改善肝功能。     

拉米夫定治疗慢性乙型肝炎及HBsAg携带者的临床疗效

我院自 1999年 9月～ 2 0 0 1年 1月应用拉米夫定治疗慢性乙型肝炎 (ＣＨＢ)及无症状ＨＢｓＡｇ携带者 (ＡＳＣ)共 14 1例 ,现将治疗结果报道如下。资料与方法一、病例选择入选病例均为我院门诊及住院ＨＢｓＡｇ、ＨＢｅＡｇ和ＨＢＶＤＮＡ阳性的ＣＨＢ及ＡＳＣ患者 ,共 2 2 8例。诊断依据 1995年全国第五次传染病与寄生虫病学术会议修订的标准。其中男178例 ,女 5 0例 ,年龄在 16～ 5 2岁之间 ,平均年龄 ( 33± 12 )岁 ,伴有或不伴有转氨酶升高。将所有患者分为 3组 ,治疗 1组 5 2例 ,为ＡＳＣ组 ;治疗 2组 89例 ,对照组 87例 ,均为反复多…     

拉米夫定联合胸腺肽治疗慢性乙型肝炎疗效的初步观察

我院应用拉米夫定联合胸腺肽对慢性乙型肝炎进行临床治疗观察 ,取得较好效果 ,现报道如下。资料与方法一、病例选择根据 1995年北京第五次全国传染病与寄生虫病会议制订的标准。选择我院 1999年 11月以来住院或门诊患者共 5 8例 ,随机分为治疗组 (拉米夫定联合胸腺肽治疗 ) 2 8例 ,其中男 17例 ,女 11例 ,年龄 18～ 47岁 ,病程为 ( 35± 19)个月 ,ＡＬＴ为48Ｕ/Ｌ～ 2 82Ｕ/Ｌ ;对照组 (拉米夫定治疗 ) 30例 ,其中男 18例 ,女 12例 ,年龄 2 1岁～ 5 9岁 ,病程 ( 32± 18)个月 ,ＡＬＴ为 5 1Ｕ/Ｌ～ 2 76Ｕ/Ｌ ,两组病例血清ＨＢｅＡｇ、ＨＢ…     

拉米夫定治疗慢性重型乙型肝炎近期临床疗效观察

目的 观察拉米夫定治疗慢性重型乙型肝炎的疗效。方法 31例患者给予拉米夫定100mg口服,每日一次,观察患者病死率、病毒量、血清病毒标志物及生化指标的改变。结果 治疗组病死率为32.2％,较对照组54.8％明显下降,病毒量明显减少,生化指标改善。结论 拉米夫定治疗慢性乙型重型肝炎似有一定的近期疗效。     

拉米夫定加泛昔洛韦联合治疗慢性乙型肝炎的疗效观察

为了提高拉米夫定抗病毒的疗效 ,我们采用拉米夫定加泛昔洛韦联合治疗慢性乙型肝炎 ,探讨其抗病毒的效果。材料和方法一、病例选择82例患者均为我院 1999年起在门诊、住院治疗的慢性乙型肝炎患者 ,分两组分别接受不同方案治疗。病例入选标准 :血清ＡＬＴ >正常值 1.5倍以上 ,胆红素 <2 5 μｍｏｌ/Ｌ ,ＨＢｅＡｇ阳性或ＨＢＶＤＮＡ阳性。随机分为两组 :甲组 5 2例 ,男 34例 ,女18例 ,平均年龄 30岁 ( 18～ 5 4)岁 ;乙组 30例 ,男 2 0例 ,女 10例 ,平均年龄 2 6岁 ( 19～ 46岁 )。二、治疗方法甲组单用拉米夫定 ,10 0ｍｇ ,每日 1次 ,共 72…     

拉米夫定治疗慢性乙型肝炎三年疗效观察

目的　评估拉米夫定治疗慢性乙型肝炎 3年的长期疗效和安全性 ,以及病毒变异的发生率和影响。方法　采用多中心双盲、随机、安慰剂、对照临床试验及开放试验。 4 2 9例HBsAg、HBeAg阳性的慢性乙型肝炎病人 ,先按 3∶1随机分成拉米夫定组和安慰剂组 ,治疗 12周 ,以后所有病人均服拉米夫定 10 0mg/d ,共 3年。结果　治疗 12周 ,拉米夫定组HBVDNA累计阴转率 (<1 6pg/ml)为 92 2 % ,安慰剂组仅为 14 1% (P <0 0 1)。服药 3年后 ,血清HBVDNA仍持续降低 ,非变异组病人其中位值 ,低于可检测水平 ,变异组则可有轻度或中度回升 ,中位值为 86mEq/ml (bDNA法 ,相当于液相杂交法的 10pg/ml)。第 3年结束时 ,HBeAg阴转率为 2 0 3% ,HBeAg/抗 HBe血清转换率为17 3%。此与治疗前ALT水平有显著关系。治疗前ALT基础值 >2倍正常值上限 (2ULN)和 >5ULN者 ,3年时HBeAg阴转率分别为 4 2 2 %和 6 6 7% ,血清转换率分别为 34 4 %和 6 1 1%。治疗前ALT增高的病人 ,3年治疗后 ,ALT的复常率为 5 8 8%。第 1、2和 3年的YMDD变异率分别为 12 1%、4 9 7%和 70 5 %。发生变异后 ,继续服药 ,HBVDNA大多仍抑制 ,少数可回升 ,中位值为 86mEq/ml,仍继续有HBeAg阴转和血清转换 ,分别为 2 0 0 %和 15 1% ,低于非变异组病人。ALT增     

拉米夫定治疗慢性重型肝炎疗效观察

将45例慢性重型乙型肝炎患者随机分为治疗组22例、对照组23例.治疗组在综合保肝治疗的基础上口服拉米夫定100mg、每日1次,对照组仅用综合保肝治疗,疗程均为1年;观察症状、体征、肝功能、血清HBVM和HBVDNA的变化.结果显示,治疗后两组患者症状体征均有一定程度的改善;治疗结束时,治疗组治愈好转率(95.45%)高于对照组(73.91%),病死率(4.5%)低于对照组(17.39%),P均＜0.05.治疗前治疗组13例HBVDNA阴性、9例阳性(650.47±597.22fg/ml),治疗后阴性者持续阴性,阳性者均逐渐转阴;对照组15例HBVDNA阴性、8例阳性(579.52±542.86fg/ml),治疗后阴性者6例阳转,阳性者持续阳性.治疗3个月时,治疗组ALT复常率高于对照组;治疗8个月后治疗组复发率4.7%(1/21),对照组为57.14%(8/14),P＜0.01.提示拉米夫定治疗慢性重型乙型肝炎可使病毒持久转阴,复发率和病死率低.     

拉米夫定对慢性乙型肝炎疗效的组织病理学分析

目的从病理组织学和免疫组织化学改变的角度分析拉米夫定的疗效.方法13例慢性乙型肝炎患者予拉米夫定100 mg/d,连用1年.治疗前后在超声导向下行肝脏活检,切片HE染色和网纤染色,对炎症活动度(HAI)和纤维化程度作计分评价.HBsAg和HBcAg用免疫组化(LSAB)法检测.结果13例患者拉米夫定治疗后血清HBV DNA全部转为阴性(＜1.6 pg/ml),组织学炎症活动度计分由5.23±2.99降为3.54±1.55(P＜0.05);纤维化程度计分由2.61±1.15降为1.92±1.21(P＞0.05).免疫组化5例HBsAg由弥漫性胞浆型表达转变为散在包涵体样型表达,其中4例HBcAg由胞浆型表达为主转变为核型表达为主.结论拉米夫定持续用药可使肝组织炎症活动度计分尤其是碎屑坏死改善(P＜0.05);血清HBV DNA阴转,肝组织HBsAg、HBcAg表达量减少.     

拉米夫定治疗慢性乙型肝炎出现血清转换的持续性研究

目的观察拉米夫定治疗慢性乙型肝炎患者5年的血清转换率和持续血清转换率及多元因素对两者的影响。方法81例慢性乙型肝炎患者,每天服用拉米夫定100 mg,持续5年。出现血清转换后, 继续服拉米夫定6个月以上(每3个月随访1次,至少2次以上),仍为乙型肝炎e抗原(-)和抗-HBe( ), 则停药并继续随访6-12个月。所需观察项目有丙氨酸氨基转移酶、血清病毒学标志物、乙型肝炎病毒DNA 载量及基因分型、YMDD变异等。结果(1)共有26例患者出现血清转换。总血清转换率为32.10% (26/81)。第1-5年,每年累积的血清转换率为16.05%、19.75%、27.16%、28.40%和32.10%。(2)停药后4例出现复发,持续血清转换率为84.62%(22/26)。(3)经Logistic多元回归分析,得出近期血清转换率和持续血清转换率与治疗前丙氨酸氨基转移酶水平呈正相关,与治疗前乙型肝炎病毒DNA水平呈负相关。持续血清转换与血清转换后继续服药时间有相关性。结论慢性乙型肝炎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。对持续血清转换的影响因素为治疗前丙氨酸氨基转移酶和乙型肝炎病毒DNA水平(P<0.05)。     

拉米夫定治疗后慢性乙型肝炎患者的生活质量测评

目的　评价拉米夫定对慢性乙型肝炎患者生活质量的影响 ,探讨临床防治重点。方法　应用健康状况调查问卷 ,对中南大学湘雅第二医院传染科 2 0 0 2 - 0 7～ 2 0 0 3- 0 7的 15 0例慢性乙型肝炎患者及 5 0名健康者生活质量研究 ,并对拉米夫定治疗前后的临床客观指标和生活质量主观指标进行对照分析 ,综合评价拉米夫定的疗效。结果　慢性乙型肝炎患者生活质量评分与对照组相比差异有显著意义 (P <0 0 1) ;拉米夫定治疗前后临床症状、血液学和病原学检查等客观指标及生活质量评分均差异有显著意义 (P <0 0 1)。结论　慢性乙型肝炎患者的生活质量普遍下降 ,拉米夫定能改善临床客观指标和提高患者的生活质量 ;在慢性乙型肝炎的防治中 ,生活质量可以作为效果评价指标 ,指导临床治疗方法的选择和决策。     

国产拉米夫定治疗慢性乙型肝炎少年患者的疗效与安全性研究

目的 探讨国产拉米夫定治疗慢性乙型肝炎(CHB)少年患者的疗效及安全性。方法 随机对105例l2～16岁的CHB病毒感染者予以口服国产拉米夫定片剂100mg／d，共52周，基线丙氨酸氨基转移酶(ALT)水平异常者为第1组，基线ALT水平正常者为第2组。评价治疗前后患者血清乙型肝炎病毒(HBV)DNA、HBV标志物、ALT变化，同时记录不良事件。结果 治疗52周时血清HBV DNA阴转率第1组为92．0％，第2组为76．1％;第1组在治疗12、24、52周时ALT复常率分别为59．0％、66．7％和76．0％；HBV DNA阴转伴ALT复常率分别为44．9％，64．1％与70．7％。治疗52周时，第1组乙型肝炎e抗原(HBeAg)血清转换率为23．9％，HBeAg血清转换并有I{BVDNA阴转率为22．5％，第2组均为14．2％，两组比较差异无显著性；在治疗期间发生的不良事件中，仅有6例次可能与拉米夫定有关，无严重不良事件发生。结论 有HBV活动复制的CHB少年患者，用国产拉米夫定治疗52周安全有效，能迅速抑制HBV复制，并使大多数患者ALT正常化，部分患者发生HBeAg阴转或血清转换且有随基线ALT水平升高而增加的趋势。     

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.     

Extended treatment with lamivudine and adefovir dipivoxil in chronic hepatitis B patients with lamivudine resistance

Purpose

We and others have reported that adding adefovir dipivoxil (adefovir) to lamivudine results in virological and biochemical improvement in cases of lamivudine resistance. The current study assessed the efficacy and safety of combined therapy after 104 weeks of combined treatment and analyzed the frequency of persistent lamivudine resistant HBV.

Methods

A total of 78 patients with compensated CHB (Group A) were maintained on either adefovir 10 mg daily (n = 38) or placebo (n = 40) while continuing lamivudine. An additional 38 patients with decompensated cirrhosis or post liver transplantation (Group B) received lamivudine plus adefovir. The primary endpoint was HBV DNA response at year 2.

Results

At week 104 of therapy, a significantly greater proportion of patients in Group A on combination therapy (76%) had a decline in serum HBV DNA to ≤10⁵ copies or >2 log₁₀ reduction from baseline compared to those receiving lamivudine alone (13%; p < 0.001). Fifty-two percent of Group A patients on combination treatment continued to have the M204V/I HBV mutation compared to 92% receiving lamivudine alone (p = 0.0013). Virologic response occurred less frequently in patients expressing persistent lamivudine resistant HBV. In Group B, 87% of patients had HBV DNA response at week 104 (median change from baseline of −5.84 log₁₀ copies/mL).

Conclusions

The combination of lamivudine and adefovir for 2 years generally proved effective in lamivudine-resistant cases, but there was a persistently high rate of detection of lamivudine resistant mutants and impaired virologic response in compensated patients.     

Combination therapy of lamivudine and adefovir in Japanese patients with chronic hepatitis B

Purpose  This study aimed to clarify the long-term efficacy of the lamivudine treatment in Japanese patients with chronic hepatitis B either with or without lamivudine resistance or with or without adefovir add-on treatment. Methods  We followed 110 patients who received lamivudine for more than 12 months, including 67 hepatitis B e antigen (HBeAg)-positive and 43 HBeAg-negative patients. Results  The median follow-up after the onset of lamivudine was 48 (range = 12–86) months. In all the patients with or without lamivudine resistance, the level of alanine aminotransferase (ALT) normalization decreased from 70.0% at 1 year to 36.4% at 5 years and the loss of serum HBV DNA level decreased from 72.7% at 1 year to 31.8% at 5 years. Sixty patients (54.6%) developed a lamivudine-resistant mutation, and this occurrence was more frequently observed in those who were HBeAg-positive (P < 0.01), those with a low level of ALT (P < 0.05), and those with a high level of serum HBV DNA (P < 0.01). Thirty-six of 60 patients received adefovir in addition to lamivudine to treat breakthrough hepatitis. A Cox proportional hazards model analysis revealed the level of baseline HBV DNA to be the best predictive factor for the virus recrudescence (risk ratio = 0.466, 95% confidence interval [CI]: 0.246–0.842, P = 0.011) and the breakthrough hepatitis (risk ratio = 0.444, 95% CI: 0.218–0.879, P = 0.019). We carefully monitored the efficacy of this treatment both in patients who received adefovir and in those who did not since the beginning of the lamivudine treatment. The normalization level of ALT was 61.4% at 5 years and the loss of serum HBV DNA was 61.4% at 5 years since lamivudine was started. A histologic improvement was observed in patients with ALT levels less than two times the upper limit of normal at the time of a second liver biopsy. Conclusions  Although the efficacy of lamivudine is limited because of breakthrough hepatitis, adefovir was used as a salvage treatment of patients with lamivudine-resistant chronic hepatitis B. In addition, lamivudine was used for the treatment of Japanese patients with chronic hepatitis B with or without lamivudine resistance, and was found to be useful regarding the long-term virologic and biochemical responses. An erratum to this article can be found at     

Lamivudine-to-entecavir switching treatment in type B chronic hepatitis patients without evidence of lamivudine resistance

Purpose  A considerable number of chronic hepatitis B (CH-B) patients remain under continuous lamivudine treatment, although switching treatment to entecavir could be beneficial. We investigated the antiviral efficacy of switching treatment to entecavir in CH-B patients without apparent evidence of lamivudine resistance during the preceding lamivudine treatment. Methods  Forty-four CH-B patients, who underwent lamivudine treatment for more than 6 months and showed no evidence of lamivudine resistance, switched to entecavir. Serial changes in hepatitis B virus (HBV) DNA were correlated with the patients' baseline HBV DNA at the commencement of entecavir administration. The entecavir-resistant substitution was examined by PCR-direct sequencing. The median follow-up period of entecavir treatment was 20 (10–23) months. Results  All 31 patients with baseline HBV DNA <2.6 logcopies/ml maintained HBV DNA-negative status during entecavir treatment. Of seven patients having HBV DNA of 2.6–<4.0 logcopies/ml, all achieved undetectable HBV DNA at the end of follow-up. As for six patients having HBV DNA ≥4.0 logcopies/ml, three patients achieved undetectable HBV DNA, whereas virological breakthrough was observed in one patient at month 15. An entecavir-resistant virus having rtM204V, rtL180M and rtS202G substitutions was detected in this patient. Conclusions  The lamivudine-to-entecavir switching treatment may be generally recommendable in CH-B patients without evidence of lamivudine resistance during the preceding lamivudine treatment. However, great care should be taken with respect to the emergence of entecavir-resistance, especially in patients who do not respond well to the preceding lamivudine treatment.     

阿德福韦酯联合拉米夫定治疗拉米夫定耐药的慢性乙型肝炎患者48周疗效观察

目的 观察阿德福韦酯（ADV）联合拉米夫定（LAM）治疗LAM耐药的慢性乙型肝炎患者的临床疗效。方法 2011年1月～2013年6月我科诊治的对LAM耐药的慢性乙型肝炎患者85例,43例接受ADV组治疗,42例接受ADV联合LAM治疗,观察治疗48 w时的疗效。结果 在治疗24 w和48 w时,联合治疗组患者肝功能指标改善情况优于阿德福韦治疗组（P<0.05）;在治疗24 w和48 w时,联合治疗组患者血清HBV DNA阴转率分别为54.7%（23/42）和92.8%（39/42）,显著高于阿德福韦治疗组[分别为37.2%（16/43）和67.4%（29/43）,P<0.05];在治疗48 w时,联合治疗组血清HBeAg阴转率为24.1%（7/29）,显著高于阿德福韦组的[3.2%（1/31）,P<0.05]。结论 ADV联合LAM治疗LAM耐药的慢性乙型肝炎患者有较好的临床疗效。