干扰素α联合拉米夫定治疗慢性乙型肝炎临床观察

采用重组干扰素α联合接米夫定治疗慢性乙型肝炎患者３１例（Ａ组）,并与３１例仅行保肝和对症治疗的慢乙肝患者（Ｂ组）进行疗效比较,结果显示,两组临床,生化指标均获改善;Ａ组ＨＢｅＡｇ阴转率为６５．５％,Ｂ组仅１０．７％,两组比较差异显著;Ａ组ＨＢＶ－ＤＮＡ均转阴,而Ｂ组无１例阴转,认为干扰素α联合拉来夫定治疗慢乙肝可改善患者的肝功、稳定病情,提高ｅ抗原阴转率。     

拉米夫定用于干扰素治疗失败的慢性乙型肝炎的疗效观察

慢性乙型肝炎(CHB)的发病机制复杂,但乙型肝炎病毒(HBV)的持续复制是肝脏损伤的起始因素,因此,抗病毒治疗一直是CHB治疗的重要一环。α-干扰素是公认的对HBV有效的抗病毒药物,但其疗效仍不尽人意,治疗后仍有60％左右的患者达不到完全效应。为了探讨对IFN治疗失败的CHB的抗病毒治疗,我们应用拉米夫定对这类患者进行了治疗观察。     

拉米夫定与α干扰素联合治疗慢性乙型肝炎

目的 观察拉米夫定(LAM)联合干扰素α1b(IFNα1b)治疗慢性乙型肝炎的近期疗效和安全性。方法 HBV DNA和HBeAg均阳性的90例慢性乙型肝炎患者，按1：1：1的比例进入三个不同的治疗组。联合治疗组：用IFNα1b 5MU，隔日肌肉注射，及口服LAM 100mg／d，共6个月，随后单用口服LAM 100mg／d6个月；LAM组：口服LAM 100mg／d共12月：IFN组：IFN α1b 5MU，隔日肌肉注射，共6个月。结果 治疗结束时，HBV DNA转阴率，联合治疗组为90．0％，LAM组为80％，IFN组为46．7％。丙氨酸氨基转移酶(ALT)复常率，联合治疗组为90．0％，LAM组为80．0％，IFN组为53．3％。HBeAg／抗HBe血清转换率，联合治疗组为46．7％，LAM组为13．3％，IFN组为33．3％。联合治疗组患者治疗结束时无一例检测到YMDD变异。结论 联合治疗组对HBV DNA抑制作用及ALT复常率高于单用干扰素组，与单用拉米夫定组接近。HBeAg／抗HBe血清转换率高于拉米夫定组，与单用干扰素组相近。初步显示联合治疗组发生YMDD变异较少。     

拉米夫定治疗儿童慢性乙型肝炎新进展

在国外,拉米夫定被用于2岁以上儿童慢性乙型肝炎的治疗,而国内对12岁以下儿童的治疗问题尚在探讨中。本文重点讨论了儿童慢性乙型肝炎的特点、拉米夫定应用的安全性和临床疗效等,认为在严格掌握治疗适应证的同时,对于2～11岁的儿童,建议可常规应用拉米夫定治疗。     

α-干扰素与拉米夫定治疗慢性乙型肝炎的疗效对比观察

目的探讨α-干扰素与拉米夫定治疗慢性乙型肝炎的疗效。方法将86例慢性乙型肝炎病人随机分成2组，一组采用α-干扰素5MU治疗，另一组采用拉米夫定100mg／日治疗12个月。结果在谷丙转氨酶复常率、HBeAg血清学转换率、HBV DNA阴转率方面，两组相比无显著性差异。结论仅一干扰素和拉米夫定治疗慢性乙型肝炎患者都有较好的抗病毒效果。     

拉米夫定治疗儿童慢性乙型肝炎疗效及安全性Meta分析

目的应用Meta分析评价拉米夫定治疗儿童慢性乙型肝炎(CHB)的疗效和安全性。方法计算机检索中英文数据库中有关拉米夫定治疗儿童CHB的临床随机对照试验。结果选中8项随机对照试验,包括1309例儿童CHB患者。Meta分析显示:拉米夫定组HBeAg阴转率、HBeAg血清学转换率和ALT复常率均明显高于安慰剂组:①HBeAg/抗HBe血清转换率:48周[OR=2.96,95%CI(1.71,5.12),P<0.001];②HBeAg阴转率:24周[OR=2.96,95%CI(1.71,5.12),P<0.001]。48周[OR=6.64,95%CI(3.47,12.7);Z=5.72,P<0.00001]。52周[OR=2.52,95%CI(1.44,4.42),P<0.01]。96周[OR=10.98,95%CI(3.26,37.05),P<0.001];③ALT复常率:12周[OR=2.84,95%CI(1.61,5.00),P<0.001]。24周[MD=4.56,95%C(I 1.46,14.28),P<0.01]。48周[OR=6.17,95%C(I 3.2,11.92),P<0.00001]。然而,在治疗12周和24周,患者HBV DNA阴转率与对照组比,差异无明显统计学意义[OR=56.66,95%CI(0.12,27661),P>0.05]、[OR=120.84,95%CI(0.67,21659.97),P>0.05],而在治疗48周[OR=66.02,95%CI(3.65,1195.7),P<0.01]、52周[OR=4.97,95%CI(2.35,10.51),P<0.0001]和96周[OR=46.92,95%CI(3.27,673.4),P<0.0001]时,HBV DNA阴转率明显提高。随访发现:拉米夫定治疗儿童CHB不影响正常的身高与体重的增长。结论拉米夫定可有效提高CHB患儿HBeAg阴转率、HBeAg血清学转换率和ALT复常率,治疗48周后HBVDNA阴转率才有明显提高。拉米夫定治疗儿童CHB,无明显的副作用,安全性较好。     

用拉米夫定治疗对干扰素α无应答的慢性乙型肝炎患者

目的探讨拉米夫定对干扰素α治疗无应答的慢性乙型肝炎的疗效。方法经重组干扰素α-1b 5MU治疗无应答的慢性乙型肝炎35例为治疗组,选择同期未接受抗病毒治疗的慢性乙型肝炎35例为对照组。两组患者均给予拉米夫定100 mg口服每天一次,疗程2年以上,观察两组患者的肝功能、HBV标志及YMDD变异的发生率。结果拉米夫定治疗两年后,治疗组ALT复常率、HBeAg阴转率、HBeAg血清转换率、HBVDNA阴转率分别为85.71%、68.57%、42.86%和74.29%,显著高于对照组的65.71%、42.86%、20.00%和51.43%,两组比较,有显著性差异（P〈0.05）。拉米夫定治疗两年后,治疗组YMDD变异的发生率为8.57%,显著低于对照组的37.14%（P〈0.01）。结论拉米夫定可显著提高干扰素α无应答慢性乙型肝炎的抗病毒疗效,并明显降低拉米夫定YM-DD耐药变异的发生率。     

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     

干扰素联合拉米夫定治疗YMDD变异株慢性乙型肝炎

新一代核苷类似物拉米夫定作为抗乙型肝炎病毒(HBV)感染的有效药品用于临床已取得了较好疗效，但因YMDD变异株的出现，又使部分慢性乙型肝炎(CHB)的治疗复杂化。目前尚无理想的抗YMDD变异病毒治疗方案，我们用干扰素联合拉米夫定治疗YMDD变异株CHB近两年，效果比较满意。     

拉米夫定和干扰素序贯疗法治疗慢性乙型肝炎的疗效观察

目的我们设计拉米夫定和IFN-α序贯疗法,治疗慢性乙型肝炎患者。方法治疗组28例患者。平均年龄40岁,对照组28例患者,平均年龄40岁。治疗组单用拉米夫定100mG/d 20周,而后联合IFN-α2b 5Mu tiw和拉米夫定4周。最后单用IFN-α24周。结果 拉米夫定治疗结束时,全部血清HBVDNA转阴;序贯治疗结束后6个月,血清HBVDNA持续阴性16/28,HBeAg转为抗-HBe 10/28,HBeAg和HBsAg均出现血清学转换6/28,全部应答患者ALT复常。结论 本临床研究结果表明,拉米夫定和IFN-α序贯疗法治疗慢性乙型肝炎患者可诱导包括抗-HBs血清学转换的持续应答,此治疗方案值得在临床实践中进一步评价。     

Lamivudine therapy for children with chronic hepatitis B

AIM: To assess the effectiveness and side-effects of lamivudine therapy for children with chronic hepatitis B (CHB) who fail to respond to or have contraindications to interferon-α(IFN-α) therapy. METHODS: Fifty-nine children with CHB were treated with 100 mg lamivudine tablets given orally once daily for 12 mo. Alanine aminotransferase (ALT) activity was evaluated monthly during the therapy and every 3 months after its discontinuation. HBe antigen, anti-HBe antibodies, HBV DNA level in serum were evaluated at baseline and every six months during and after the lamivudine therapy. Sustained viral response (SVR) to lamivudine therapy was defined as permanent (not shorter than 6 mo after the end of the therapy), namely ALT activity normalization, seroconversion of HBeAg to anti-HBe antibodies, and undetectable viral HBV-DNA in serum (lower than 200 copies per mL). The analysis of the side-effects of the lamivudine treatment was based upon interviews with the patients and their parents using a questionnaire concerning subjective and objective symptoms, clinical examinations, and laboratory tests performed during clinical visits monthly during the therapy, and every 3 mo after the therapy. RESULTS: ALT normalisation occurred in 47 (79.7%) patients between the first and 11th mo of treatment (mean 4.4±2.95 mo, median 4.0 mo), and in 18 (30.5%) of them after 2 mo of the therapy. There was no correlation between the time of ALT normalization and the children's age, the age of HBV infection, the duration of HBV infection, inflammation activity score (grading), staging, ALT activity before treatment, serum HBV DNA level, and lamivudnie dose per kg of body weight. HBeAg/anti HBe seroconversion was achieved in 27.1% of cases. The higher rate of seroconversion was connected with lower serum HBV DNA level and longer duration of HBV infection. There was no connection between HBeAg/ anti HBeAb seroconversion and the children's age, age of HBV infection, grading, staging, ALT activity before treatment, and lamivudnie dose per kg of body weight. No complaints or clinical symptoms were observed during lamivudine therapy. Impairment of renal function or myelotoxic effect was noted in none of the patients. CONCLUSION: One year lamivudine therapy for children with chronic hepatitis B is effective and well tolerated. Seroconversion of HBeAg/HBeAb and SVR are connected with lower pre-treatment serum HBV DNA level.     

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.     

拉米夫定治疗慢性乙型肝炎的经济学评价

目的 评估拉米夫定治疗慢性乙型肝炎的经济学价值。方法 运用临床试验和相关文献资料，采用Markov模型对拉米夫定治疗慢性乙型肝炎进行经济学评价。结果 与安慰剂相比，拉米夫定每延长1年寿命，所需医疗费用在25000元以下，疗程较长者的拉米夫定治疗与疗程较短者相比，每延长1年寿命所需的医疗费用在38500元以下。结论 拉米夫定具有成本效果，疗程越长，成本效果越好。     

Safety of lamivudine treatment for chronic hepatitis B in early pregnancy

AIM: To evaluate the safety of lamivudine (LAM) treatment for chronic hepatitis B in early pregnancy.METHODS: A total of 92 pregnant women who received LAM treatment either before pregnancy or in early pregnancy were enrolled in this study. All of the pregnant women volunteered to take lamivudine during pregnancy and were not co-infected with hepatitis C virus, human immunodeficiency virus, cytomegalovirus, or other viruses. All infants received passive-active immunoprophylaxis with 200 IU hepatitis B immunoglobulin and three doses of 10 μg hepatitis B vaccines (0-1-6 mo) according to the guidelines for the prevention and treatment of chronic hepatitis B. Adverse events were observed throughout the entire pregnancy and perinatal period, and the effectiveness of lamivudine treatment for blocking mother-to-infant transmission of hepatitis B virus (HBV) was evaluated. All adverse events in mothers and infants during pregnancy and the perinatal period and the HBV mother-to-infant transmission blocking rate were compared with the literature.RESULTS: Among the 92 pregnant women, spontaneous abortions occurred in 11 cases, while 3 mothers had a second pregnancy after the initial abortion; 72 mothers delivered 73 live infants, of whom 68 infants were followed up for no less than 6 mo, and 12 mothers were still pregnant. During pregnancy, the main maternal adverse events were vaginitis (12/72, 16.7%), spontaneous abortion (11/95, 11.6%), and gestational diabetes (6/72, 8.3%); only one case had 1-2 degree elevation of the creatine kinase level (195 U/L). During the perinatal period, the main maternal adverse events were premature rupture of the membranes (8/72, 11.1%), preterm delivery (5/72, 6.9%), and meconium staining of the amniotic fluid (4/72, 5.6%). In addition, 2 infants were found to have congenital abnormalities; 1 had a scalp hemangioma that did not change in size until 7 mo, and the other had early cerebral palsy, but with rehabilitation training, the infant’s motor functions became totally normal at 2 years of age. The incidence of adverse events among the mothers or abnormalities in the infants was not higher than that of normal mothers or HBV-infected mothers who did not receive lamivudine treatment. In only 2 cases, mother-to-infant transmission blocking failed; the blocking rate was 97.1% (66/68), which was higher than has been previously reported.CONCLUSION: Lamivudine treatment is safe for chronic HBV-infected pregnant mothers and their fetuses with a gestational age of less than 12 wk or throughout the entire pregnancy.     

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)。     

拉米夫定治疗重度黄疸型慢性乙型肝炎临床疗效观察

目的评估拉米夫定治疗重度黄疸型慢性乙型肝炎(CHB)的短期疗效,观察血清HBV DNA水平与血清总胆红素(TBIL)水平之间的关系.方法179例重度黄疸型慢性乙型肝炎患者分为观察组101例和对照组78例.观察组给予拉米夫定100mg,每天1次口服,同时给予常规护肝治疗,治疗12周.对照组给予常规护肝治疗,治疗12周.结果观察组血清HBV DNA的下降水平明显好于对照组(P＜0.01),血清HBV DNA阴转率(＜5×102拷贝/ml)为91.1%,而对照组仅为14.1%.观察组丙氨酸转氨酶、TBIL下降水平均明显好于对照组(P值均＜0.01).线性回归分析y=85.534x-153.4,R2=0.9661(P＜0.01).结论短期应用拉米夫定治疗重度黄疸型CHB疗效明显好于常规护肝治疗,观察组血清HBV DNA水平与TBIL水平间存在相关性.     

长疗程干扰素α-2b联合拉米夫定治疗慢性乙肝的临床观察

目的观察干扰素α-2b联合拉米夫定较长疗程治疗慢性乙型肝炎患者的疗效。方法将慢性乙型肝炎患者137例,随机分为两组,观察组61例,用干扰素α-2b（5万U/次,肌注）隔日1次,连用52周停药,52周后用拉米夫定100mg/d口服,1次/d,用至104周。对照组76例,单用拉米夫定,用法、用量、疗程同观察组。结果治疗104周后两组HBVDNA转阴率、ALT正常率差异无统计学意义（P=0.24）,观察组的HBeAg/抗-HBe血清转换率为42.6%,高于对照组的26.3%（P=0.045）,观察组的HBVYMDD变异率为14.5%,低于对照组的40.8%（P=0.001）。结论干扰素α-2b联合拉米夫定治疗慢性乙型肝炎,疗程2年,疗效优于单用拉米夫定,且能减少病毒YMDD变异。     

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。