抗病毒治疗对乙型肝炎病毒感染者肾移植术后临床转归的影响

目的 探讨乙型肝炎病毒感染者肾移植术后临床转归及治疗对策.方法 将术前乙肝病毒标志物阳性(HBsAg阳性、HBeAg阳性或HBeAb阳性、HBV DNA阳性或阴性)的32例肾移植术后患者分为抗病毒治疗组和无抗病毒治疗组两组.观察两组(术前1周至术后9年)的肝功能(ALT、AST、TBIL、PT)变化、病毒复制(HBV DNA)及存活情况.结果 抗病毒治疗组23例患者肝功能损害复常率为82.60%,存活率为82.60%,HBV DNA(PCR法)下降(≥2 log10)或保持低复制率为86.95%;未抗病毒组9例患者肝功能损害复常率为22.22%,存活率为11.11%,HBV DNA(PeR法)下降(≥2log10)或保持低复制率为11.11%.抗病毒组肝功能复常率、存活率及HBV DNA下降或保持低复制率高于无抗病毒组,两组比较差异有统计学意义(P<0.05).19例拉米夫定治疗患者6例出现病毒学反弹31.58%,1例加用阿德福韦酯,2例换用恩替卡韦后好转,其余3例肝功能衰竭死亡.结论 持续有效的抗病毒治疗可以有效控制乙肝病毒复制,促进肝功能恢复,减少肝衰竭发生,提高乙肝病毒感染者肾移植术后患者存活率.在治疗过程中出现病毒学反弹应及时换用或加用有效药物减少肝衰竭发生.     

慢性乙肝患者血清趋化因子RANTES水平与肝功能生化指标等的相关性研究

Objective To investigate the level of the serum chemokine RANTES and its correlation with serum biochemical indices of liver function test, HBeAg and HBV DNA load in patients with chronic hepatitis B.Methods 144 patients with chronic hepatitis B (observed group) and 18 normal cases (control group) were enrolled in this study. The serum level of chemokine RANTES was detected with an ABC-ELISA assay. Statistical analysis was performed on the software of SPSS13.0. Results The serum chemokine RANTES level in the observed group (3930.12 ng/ml±2856.96) ng/ml was significantly higher than that in the control group (329.46 ng/ml±152.23) ng/ml. The results from the observed group indicated the positive correlation of serum RANTES level with indices of liver function test, including ALT (r=0. 197, P=0.018), AST(r=0.239, P=0.004) and TBil (r=0.316, P=0.001), but did not with PTA (r=-0.078, P=0.357). Neither difference of serum chemokine RANTES level between HBeAg-positive group and HBeAg-negative group nor that between high HBV DNA load group (≥105 copies/ml) and low HBV DNA load group (< 105 copies/ml) were statistically significant (P=0.407 and 0.185, respectively). Conclusions Serum chemokine RANTES level in patients with chronic hepatitis B elevates significantly and is not affected by HBeAg or HBV DNA load. Its positive correlation with indices of liver function test indicates that RANTES might play an important rule in the pathogenesis of chronic hepatitis B.     

抗病毒治疗对乙型肝炎病毒感染者肾移植术后临床转归的影响

目的 探讨乙型肝炎病毒感染者肾移植术后临床转归及治疗对策.方法 将术前乙肝病毒标志物阳性(HBsAg阳性、HBeAg阳性或HBeAb阳性、HBV DNA阳性或阴性)的32例肾移植术后患者分为抗病毒治疗组和无抗病毒治疗组两组.观察两组(术前1周至术后9年)的肝功能(ALT、AST、TBIL、PT)变化、病毒复制(HBV DNA)及存活情况.结果 抗病毒治疗组23例患者肝功能损害复常率为82.60%,存活率为82.60%,HBV DNA(PCR法)下降(≥2 log10)或保持低复制率为86.95%;未抗病毒组9例患者肝功能损害复常率为22.22%,存活率为11.11%,HBV DNA(PeR法)下降(≥2log10)或保持低复制率为11.11%.抗病毒组肝功能复常率、存活率及HBV DNA下降或保持低复制率高于无抗病毒组,两组比较差异有统计学意义(P<0.05).19例拉米夫定治疗患者6例出现病毒学反弹31.58%,1例加用阿德福韦酯,2例换用恩替卡韦后好转,其余3例肝功能衰竭死亡.结论 持续有效的抗病毒治疗可以有效控制乙肝病毒复制,促进肝功能恢复,减少肝衰竭发生,提高乙肝病毒感染者肾移植术后患者存活率.在治疗过程中出现病毒学反弹应及时换用或加用有效药物减少肝衰竭发生.     

慢性乙肝患者血清趋化因子RANTES水平与肝功能生化指标等的相关性研究

Objective To investigate the level of the serum chemokine RANTES and its correlation with serum biochemical indices of liver function test, HBeAg and HBV DNA load in patients with chronic hepatitis B.Methods 144 patients with chronic hepatitis B (observed group) and 18 normal cases (control group) were enrolled in this study. The serum level of chemokine RANTES was detected with an ABC-ELISA assay. Statistical analysis was performed on the software of SPSS13.0. Results The serum chemokine RANTES level in the observed group (3930.12 ng/ml±2856.96) ng/ml was significantly higher than that in the control group (329.46 ng/ml±152.23) ng/ml. The results from the observed group indicated the positive correlation of serum RANTES level with indices of liver function test, including ALT (r=0. 197, P=0.018), AST(r=0.239, P=0.004) and TBil (r=0.316, P=0.001), but did not with PTA (r=-0.078, P=0.357). Neither difference of serum chemokine RANTES level between HBeAg-positive group and HBeAg-negative group nor that between high HBV DNA load group (≥105 copies/ml) and low HBV DNA load group (< 105 copies/ml) were statistically significant (P=0.407 and 0.185, respectively). Conclusions Serum chemokine RANTES level in patients with chronic hepatitis B elevates significantly and is not affected by HBeAg or HBV DNA load. Its positive correlation with indices of liver function test indicates that RANTES might play an important rule in the pathogenesis of chronic hepatitis B.     

慢性乙肝患者血清趋化因子RANTES水平与肝功能生化指标等的相关性研究

Objective To investigate the level of the serum chemokine RANTES and its correlation with serum biochemical indices of liver function test, HBeAg and HBV DNA load in patients with chronic hepatitis B.Methods 144 patients with chronic hepatitis B (observed group) and 18 normal cases (control group) were enrolled in this study. The serum level of chemokine RANTES was detected with an ABC-ELISA assay. Statistical analysis was performed on the software of SPSS13.0. Results The serum chemokine RANTES level in the observed group (3930.12 ng/ml±2856.96) ng/ml was significantly higher than that in the control group (329.46 ng/ml±152.23) ng/ml. The results from the observed group indicated the positive correlation of serum RANTES level with indices of liver function test, including ALT (r=0. 197, P=0.018), AST(r=0.239, P=0.004) and TBil (r=0.316, P=0.001), but did not with PTA (r=-0.078, P=0.357). Neither difference of serum chemokine RANTES level between HBeAg-positive group and HBeAg-negative group nor that between high HBV DNA load group (≥105 copies/ml) and low HBV DNA load group (< 105 copies/ml) were statistically significant (P=0.407 and 0.185, respectively). Conclusions Serum chemokine RANTES level in patients with chronic hepatitis B elevates significantly and is not affected by HBeAg or HBV DNA load. Its positive correlation with indices of liver function test indicates that RANTES might play an important rule in the pathogenesis of chronic hepatitis B.     

慢性乙型肝炎血清透明质酸和抗-HBe与肝组织病理的相关性

目的： 探讨慢性乙型肝炎血清透明质酸（ Ｈ Ａ） 和抗 Ｈ Ｂｅ 与肝组织病理改变的关系。方法：对１７０ 例慢性乙型肝炎患者进行肝活检,观察肝组织病理分级（ Ｇ） 和分期（ Ｓ） 情况,同时检测 Ｈ Ａ 及肝炎病毒标志物。结果：①血清 Ｈ Ａ 与肝组织病理分级和分期关系密切,随着病理分级和分期的升高, Ｈ Ａ 也逐渐升高, Ｇ４ 、 Ｓ４ 的血清 Ｈ Ａ 分别比 Ｇ１ 、 Ｓ１ 显著升高（ Ｐ ＜ ０００１） 。②肝组织病理分级、分期与血清抗 Ｈ Ｂｅ 的出现情况也密切相关, Ｇ４ 、 Ｓ４ 的抗 Ｈ Ｂｅ 阳性率分别比 Ｇ１ 、 Ｓ１ 显著升高（ Ｐ ＜ ００５） ;③抗 Ｈ Ｂｅ 阳性者中 Ｈ Ａ 值显著高于抗 Ｈ Ｂｅ 阴性病人（ Ｐ ＜ ０００１） 。结论： Ｈ Ａ 与抗 Ｈ Ｂｅ 有一定的相关性,在 Ｈ Ａ 显著升高或／ 和抗 Ｈ Ｂｅ 阳性的慢性乙型肝炎病人中,其肝组织的炎症、坏死及肝纤维化的程度较严重。     

一种新的乙型肝炎病毒全基因组克隆技术的建立

目的建立一种乙型肝炎病毒(HBV)全基因组扩增及克隆的新方法。方法设计含SalⅠ、NotⅠ酶切位点的引物,用一片段PCR法扩增HBV全基因组,经双酶切后将PCR产物克隆入pBlueScript-(SK-)载体,进行HBV全基因组序列测定。结果用此方法成功获得35例HBV全基因组DNA序列。同时以重组质粒为模板进行敏感性和保真性测定,其敏感性为102个初始模板,核苷酸的人为突变率为1.6bp/kb。结论此方法可用于大规模HBV全基因组扩增和序列分析,为HBV的基础和临床研究提供了一种新方法。     

丙型肝炎病毒包膜蛋白E2的原核表达及鉴定

 【目的】构建丙型肝炎病毒（HCV）包膜蛋白E2基因的重组原核表达质粒，并获得E2蛋白的高效表达。【方法】通过RT-PCR法从HCV RNA阳性的血清标本中扩增出HCVE2区基因595bp，PCR产物分别经BamHⅠ和Hind Ⅲ双酶切后连接到经同样酶切的原核表达载体PET22b（＋）上，转化大肠杆菌DH5α菌株，获得阳性重组质粒PETB，阳性质粒转化BL21（DE3），IPTG诱导表达，表达产物经SDS-PAGE和Westemblot鉴定。【结果】成功地克隆了HCVE2区基因，构建了其原核表达质粒，并在BL21（DE3）菌中表达HCVE2重组蛋白，Western blot显示表达蛋白具有抗原性。【结论】HCVE2重组蛋白的表达和鉴定为进一步了解HCV糖蛋白E2的功能及其与CD81二者的相互关系打下基础。     

HCV在中国流行多样性和独特生长史的分析

目的 探讨中国丙型肝炎患者中HCV的基因型分布类型,并进行HCV在中国流行病学历史分析,进而研究HCV在中国的分子流行病学和进化动力学特征.方法 从423例丙型肝炎患者的血清中提取HCV RNA并进行cDNA反转录,扩增E1和NS5B两个基因区的核苷酸序列,排除不合格及不适合分析的病毒株序列,再对合格序列进行系统发育分析（phylogenetic analysis）.运用BEAST软件中的Bayesian MCMC （Markov Chain Monte Carlo）算法来进行Coalescence分析,通过重构BSPs（Bayesian skyline plots）图回溯HCV的流行病学历史.结果 HCV分离株的基因分型如下：共包括6个基因型,12个基因亚型（1b：65.9％,6a：17.1％,2a：7.4％,3a：3.6％,3b：3.3％,6e：0.76％,1a,1c,2b,2f,4d以及5a共占0.25％）,以及2个新基因型6变异体.所产生的5个BSP曲线图均凸显1993年至2000年这一时间段,中国的HCV感染数量呈现指数增长,随后则陡然下降.结论 证实了HUV在中国多样性的流行现状,反映了HCV不断变化的基因型流行模式;1993年至2000年期间由于“单采血浆”事件的影响,HCV在中国的感染数量经历了一段“指数”增长期.     

聚乙二醇干扰素α-2a序贯替比夫定治疗HBeAg阳性慢乙肝的短期疗效与安全性

目的 观察聚乙二醇干扰素α-2a初治48周疗效欠佳的HBeAg阳性慢乙肝患者序贯应用替比夫定治疗48周的疗效与安全性.方法 聚乙二醇干扰素α-2a初治的27例在48周时未发生HBV DNA转阴（＜100 IU/ml）及HBeAg血清学转换的患者,序贯替比夫定继续治疗,设为A组.替比夫定初治的HBeAg阳性慢性乙肝患者54例,设为B组.比较治疗48周后两组的疗效及安全性.结果 治疗至12周,A、B两组患者的ALT复常率、HBeAg血清学转换率、HBV DNA转阴率分别为59.3％、14.8％、66.7％ vs 75.9％、5.6％、46.3％;治疗至24周,两组患者的ALT复常率、HBeAg血清学转换率、HBV DNA转阴率分别为92.6％、25.9％、70.3％ vs 92.6％、7.4％、85.2％;治疗至48周,两组患者的ALT复常率、HBeAg血清学转换率、HBV DNA转阴率分别为88.9％、29.6％、81.5％vs 98.1％、28.0％、83.3％.在各观察点两组间各观察指标的差异均无统计学意义,但A组的HBeAg血清学转换率均高于B组.治疗48周时,A组未观察到病毒学突破的发生,B组的病毒学突破的发生率为14.8％.治疗过程中有38.3％的患者出现肌酸激酶（CK）升高,A组患者在各观察点CK值均明显高于B组,但两组间的差异均无统计学意义.治疗期间未出现1例因药物严重不良反应而停药.结论 聚乙二醇干扰素α-2a初治48周疗效欠佳的患者序贯应用替比夫定治疗,短期内仍可取得较好疗效,安全性好.