拉米夫定阻断乙型肝炎病毒宫内传播的临床探讨

【目的】研究拉米夫定对HBsAg阳性孕妇的乙肝病毒 (HBV)宫内阻断作用。【方法】拉米夫定组 43例 ,孕 2 8周起口服拉米夫定 ,每天 10 0mg至产后 30d。对照组 5 2例 ,未予用药。两组孕妇均于孕 2 8周、分娩前 ,其新生儿于生后 2 4h内免疫接种前抽静脉血检测HBsAg、HBeAg及HBV的定量。【结果】拉米夫定组孕妇HBV的DNA水平显著下降 (P <0 0 5 ) ,其新生儿宫内感染率 (16 3% )明显低于对照组 (32 7% ) ,P <0 0 5。两组孕妇及其新生儿未发现有不良反应。【结论】携带HBV孕妇产前服用拉米夫定可有效减少HBV宫内感染发生率。     

Inhibition of hepatitis B virus DNA replicative intermediate forms by recombinant interferon-γ

AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine. METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support productive HBV infection in vitro. Expression of HBsAg and HBeAg in infected HepG2 culture medium was detected by commercial enzyme immunoassays. HBV DNA replication intermediates were detected in infected cells by Southern hybridization and viral DNA load was determined by dot hybridization. RESULTS: IFN-γat 0.1 to 5μg/L efficiently down regulated HBsAg expression in transduced HepG2 cells. At 5μg/L, IFN-γalso suppressed HBV DNA replication in these cells. While treatment with a combination of lamivudine and IFN-γshowed no additive effect, sequential treatment first with lamivudine and then IFN-γwas found to be promising. In this culture system the best HBV suppression was observed with a pulse of 2μmol/L lamivudine for two days, followed by 1μg/L IFN-γfor another four days. Compared to treatment with lamivudine alone, the sequential use of 0.2μmol/L lamivudine for two days, followed by 5μg/L IFN-γfor six days showed a 72% reduction in HBV cccDNA pool. CONCLUSION: This in vitro study warrants further evaluation of a combination of IFN-γand lamivudine, especially in IFN-αnon-responder chronic hepatitis B patients. A reduced duration of lamivudine treatment would also restrict the emergence of drug-resistant HBV mutants.     

Detection of YMDD motif mutants by oligonucleotide chips in lamivudine-untreated patients with chronic hepatitis B virus infection

Lamivudine, a nucleoside analogue, has been used widely as an effective antiviral agent for the treatment of patients with chronic hepatitis B virus (HBV) infection. However, the YMDD motif mutation of HBV polymerase resistant to lamivudine occurs very frequently after long term therapy. We developed an oligonucleotide chip for the detection of YMDD motif mutants resistant to lamivudine and investigated the prevalence of the mutants in patients with chronic HBV infection who had not been treated by lamivudine before. Forty patients who had not been treated with lamivudine were included in this study. Serum samples were tested by the oligonucleotide chips designed for detection of wild-type YMDD motif, M552V and M552I. Samples were confirmed by restriction fragment length polymorphism (RFLP) and direct sequencing. M552I mutants were detected by the oligonucleotide chips in 7.5% (3/40) of chronic HBV infected patients (2 chronic hepatitis and 1 cirrhosis). The results were in accordance with those of RFLP. YMDD motif mutants occur as natural genome variabilities in patients with chronic HBV infection who had not been treated with lamivudine before. Oligonucleotide chip technology is a reliable and useful diagnostic tool for the detection of mutants resistant to antiviral therapy in chronic HBV infection.     

拉米夫定联合胸腺五肽治疗慢性乙型肝炎疗效观察

目的：探索抗病毒药物联合免疫调节药物治疗慢性乙型肝炎的疗效。方法：采用拉米夫定联合胸腺五肽治疗慢性乙型肝炎，同期单用拉米夫定或胸腺五肽作对照，动态观察血清HBV复制指标及肝功能。结果：治疗结束时联合组血清HBeAg阴转及抗HBe阳转率明显优于拉米夫定组（P＜0．05），与胸腺五肽组比较差异无显著性（P＞0．05）；联合组的HBV DNA阴转率优于胸腺五肽组（P＜0．05），与拉米夫定组比较差异无显著性（P＞0．05）。治疗结束后6个月、12个月的病毒复制指标变化与治疗结束时无明显变化。联合组的显效率及总有效率均高于其他两组，且ALT复常率保持在85％以上。结论：拉米夫定联合胸腺五肽治疗慢性乙型肝炎，可达到有效而持续的抗病毒作用。亦有利于ALT持久复常。     

干扰素α-1b联合拉米夫定治疗慢性乙型肝炎

目的 探讨干扰素α-1b联合拉米夫定治疗慢性乙型肝炎患者的临床疗效。方法 将103例CHB分为三组：干扰素组应用干扰素α-1b6个月，随访6个月；拉米夫定组应用疗程12个月；联合治疗组为干扰素α-1b联合拉米夫定。采用电化学发光法、荧光定量聚合酶链反应及多点基因正链检测技术对血清ALT、HBV—DNA、HBV-M等指标进行了观察。结果 联合治疗组HBV-DNA阴转率高于干扰素组（均P〈0．01）；HBeAg阴转率和抗-HBe阳转率均高于拉米夫定组（均P〈0．01）；ALT复常率优于干扰素组和拉米夫定组（P〈0．01）。结论 IFNα-1b联合拉米夫定治疗慢性乙型肝炎的疗效优于单一用药。     

不同基因型慢性乙型肝炎病人对拉米呋定应答反应的初步观察

[目的 ]　观察拉米呋定治疗B、C基因型慢性乙型肝炎病人的临床疗效。 [方法 ] 3 5例B型慢性乙型肝炎病人及 18例C型慢性乙型肝炎病人同时给予拉米呋定 10 0mg ,每天 1次 ,疗程 1年 ,观察血清病毒学指标、肝功能变化及药物不良反应。　 [结果 ]　B型慢性乙型肝炎病人治疗后HBV -DNA阴转率、ALT复常率均显著高于C型慢性乙型肝炎病人 ,差异均有显著性 (P <0 .0 5 )。　 [结论 ]　拉米呋定对B基因型的慢性乙型肝炎病人的临床疗效高于C基因型慢性乙型肝炎病人。拉米呋定用于治疗有病毒复制的慢性乙型肝炎病人安全有效     

拉米夫定联合α干扰素治疗HBeAg阳性慢性乙型肝炎

目的 :观察拉米夫定和干扰素联合治疗HBeAg阳性慢性乙型肝炎的疗效及其影响因素。方法 :64例HBeAg阳性的慢性乙型肝炎患者随机分成治疗组和对照组。治疗组32例 ,同时使用α干扰素及拉米夫定9个月 ,随后单用拉米夫定15个月,对照组32例 ,单用拉米夫定24个月 ,定期检测丙氨酸转氨酶 (ALT)、HBeAg、抗 -HBe、HBVDNA ,并作YMDD变异检测 ,两组在治疗结束时进行疗效评价。结果 :治疗组ALT复常率为90.6 % (29/32) ,对照组ALT复常率为87.5 % (28/32) ,两组差异无显著性 (P>0.05),治疗组HBeAg阴转率为68.8 % (22/32) ,对照组HBeAg阴转率为37.5 % (12/32) ,两组比较差异有显著性 (P<0.05) ,治疗组HBeAg/抗 -HBe血清转换率为53.1 % (17/32) ,对照组HBeAg/抗 -HBe血清转换率为25 % (8/32) ,两组比较差异有显著性 (P<0.05),治疗组HBVDNA阴转率为78.1 % (25/32) ,对照组HBVDNA阴转率为59.4 % (19/32) ,两组比较差异无显著性 (P>0.05) ,治疗组YMDD变异率为21.9 % (7/32) ,对照组YMDD变异率为40.6 % (13/32) ,两组比较差异无显著性 (P>0.05) ,同时治疗组ALT复常率、HBeAg转换率、HBVDNA阴转率与治疗前ALT及HBVDNA基线水平有关。结论 :α干扰素联合拉米夫定治疗HBeAg阳性的慢性乙型肝炎对于ALT中度升高、HBVDNA高水平复制     

苦参素体内抗乙型肝炎病毒作用研究

目的观察苦参素对鸭乙型肝炎病毒感染的治疗效果。方法采用一日龄麻鸭静脉注射鸭乙型肝炎病毒，7天后开始给鸭口服苦参素75、150和300mg／kg3个剂量，每天2次，给药10天，观察药物对鸭的毒性和鸭血清乙肝病毒DNA（DHBV—DNA）的影响。结果苦参素在150mg／kg组对鸭乙型肝炎病毒感染有可重复的显著治疗效果。300mg／kg组有较好的效果，75mg／kg组无抑制作用。结论苦参素有良好的抗鸭乙肝病毒效果。     

复方甘草酸苷与甘草酸二铵治疗拉米夫定停药后反跳的疗效观察

目的 :观察复方甘草酸苷与甘草酸二铵治疗拉米夫定停药后慢性乙型肝炎 (CHB)患者病情反跳的疗效 ,并比较其差异。方法 :将76例停用拉米夫定后CHB病情反跳的患者分为复方甘草酸苷组和甘草酸二铵组。观察和记录患者症状、体征的变化及药物不良反应 ,定期检测肝功能、HBV血清免疫学标志物、HBV -DNA定量等项目 ,随访12个月。结果 :复方甘草酸苷组与甘草酸二铵组总有效率分别为79 49 %和75 68 % ,两组间无显著性差异 (P>0 05) ;两组在AST复常方面有显著性差异 (P<0 01) ;复方甘草酸苷组显效率为69 23 % ,甘草酸二铵组显效率为48 65 % ,两组亦有显著性差异 (P<0 05)。结论 :复方甘草酸苷与甘草酸二铵治疗拉米夫定停药后CHB患者病情反跳均有明显的疗效 ,前者停药后病情反跳率低 ,疗效稳定、持久。