乙型肝炎病毒基因型、基础核心启动子和C区变异与干扰素疗效的观察

目的 探讨HBV基因型、基础核心启动子(BCP)和C区变异与IFNα抗病毒疗效的相关性.方法 选择IFNα-1b治疗6个月的HBeAg阳性慢性乙型肝炎(CHB)患者,随访6个月.应用限制性片段长度多态性(RFLP)法检测HBV基因型,PCR测定BCP、前C/C区核苷酸序列.计量资料采用t检验、方差分析,计数资料采用卡方检验、Fisher确切概率法,并进行多因素条件Logistic回归分析.结果 共39例CHB患者完成观察,治疗结束时,应答16例,占41.0%;随访结束时,应答者中持续应答12例,占30.8%,复发4例,占10.3%.其中B基因型29例,占74.4%,C基因型10例,占25.6%.基因型型别差异与IFNα-1b疗效无关.8例患者BCP区T1762/A1764双变异,占20.5%,与IFNα-1b疗效无相关.8例患者检出A1896变异,占20.5%,随访结束时获得疗效的3例A1896变异株感染者均复发.C区非淋巴细胞表位测序发现,15例患者L60V变异,占38.5%,14例为I97L变异,占35.9%.与60V比较,表现为60L的患者在随访结束时的HBeAg血清学转换率和HBV DNA阴转率明显低(Fisher确切概率法,P=0.0126、0.0069).与97L比较,表现为97I的患者在治疗结束时和随访结束时的HBV DNA阴转率明显低(Fisher确切概率法,P=0.0484、0.0024).Logistic回归分析显示,基因型、C区变异与IFNα-1b疗效无相关.结论 HBV基因型、BCP双变异与IFNα的疗效无关,C区非淋巴细胞表位L60V及I97L变异可能有利于IFNα的治疗.

Abstract：

Objective To investigate the association between hepatitis B virus (HBV)genotype, the mutations in HBV basic core gene promoter(BCP), pre C/C gene region and treatment response to interferon (IFN)α-1b. Methods Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients were treated with IFNα-Ib for 6 months and were followed up for 6 months after the end of treatment. Restriction Fragment Length Polymorphism (RFLP) was used for determining HBV genotype. HBV DNA was amplified by polymerase chain reaction (PCR) and analyzed for BCP and pre C/C gene region by sequencing. Measurement data were compared using t test and analysis of variance. Enumeration data were compared using chi-square test, Fisher exact probability test.Logistic regression analysis was utilized for multi-factor analysis. Results There were 39 patients who completed the treatment and follow up in this study. At the end of treatment, 16(41.0%) patients showed response to the IFNα-lb treatment. At the end of follow-up, four out of 16 patients who achieved on treatment response relapsed. Among 3a patients, 29 (74.4 %) were infected with genotype B and 10 (25. 6%) with genotype C. The treatment response rates were not significant different between the groups with different genotypes. The double mutation pattern (T1762/A1764) was found in eight (20. 5%) patients. The response rates to IFNα-lb treatment were not significant different between the group with and without double mutation pattern. A1896 mutation was detected in eight patients at baseline. Three of them became HBeAg negative at the end of treatment and returned to HBeAg positive during follow-up. The non-lyphocyte epitope mutations, L60V and I97L, were found in 15 patients (38. 5%) and 14 patients (35.9%), respectively. At the end of follow-up, the patients with 60V had a significantly lower HBeAg seroconversion rate and HBV DNA undetectable rate compared to the patients with 60L (Fisher exact probability test; P = 0.0126 and 0.0069,respectively). The HBV DNA undetectable rates in the patients with 97I were significantly lower than those in patients with 97L both at the end of treatment and the end of follow-up (Fisher exact probability test; P= 0.0484 and 0. 0024, respectively). Logistic regression analysis results showed that there was no association between the above viral mutations and the treatment response to IFNαlb. Conclusions There is no association between HBV genotype, BCP double mutation pattern and IFN-α treatment response. The non-lyphocyte epitope mutations, L60V and I97L, may have impact on IFN-α treatment response.     

胸腺肽α1治疗慢性乙型重型肝炎的临床疗效观察

目的观察胸腺肽α1治疗慢性乙型重型肝炎患者的效果。方法 79例慢性乙型重型肝炎患者在常规治疗的基础上给予胸腺肽α1治疗,观察疗效。结果患者治疗后TBIL、血清HBV DNA均有显著性降低,PTA均有明显升高,并发症明显减少,存活率增加。结论胸腺肽α1治疗慢性乙型重型肝炎有效。     

部分脾动脉栓塞术31例分析

目的：探讨部分脾动脉栓塞术对脾功能亢进的治疗疗效观察。方法：收集近几年在我院治疗肝硬化、肝癌所致脾功能亢进患者31例,行选择性部分脾动脉栓塞术。结果：本组31例脾功能亢进者,行部分脾动脉栓塞术后,白细胞在3～5d升高,血小板在1～2周内升高,29例好转,2例疗效差。结论：对脾功能亢进患者,可进行选择性脾动脉栓塞术,术后可保留部分脾脏功能,有利于白细胞、血小板、红细胞的恢复。同时门静脉高压可缓解20％～30％。     

成年小鼠肝组织中长期体外培养的探讨

目的探讨成年肝组织(AHT)体外中长期培养的各项活性指标,寻求以AHT替代成年肝细胞(AHC)培养的方法。方法以0.5mm3大小的肝组织贴壁于盖破片上,静置培养48h后改为旋转培养,每2天作半量换液1次,并取盖玻片作HE染色观察肝组织内细胞存活状况,第26天时结束培养观察;取培养第6天的肝组织设对照组、大黄素实验组、胆红素代谢组,分别行大黄素抗内毒素实验和胆红素代谢实验。结果在对照组,AHT染色鲜明、细胞存活良好;大黄素实验组呈现大黄素的抗内毒素作用而明显提高AHT的细胞活性;胆红素代谢实验组的总胆红素、直接胆红素、间接胆红素分别下降13.69%、19.85%、10.38%。结论AHT保持了体内三维立体结构,体外培养存活期可达26天,生物代谢活性良好,并有省时、操作简便、低成本的优点。     

重症肝炎并发急性胰腺炎25例临床分析

重症肝炎是一种死亡率极高的疾病,近年来,随着医学的进步,其死亡率有所下降,但仍为难治性疾病。临床上重症肝炎合并急性胰腺炎并不少见,但报道较少。其临床表现不典型,如果临床医生对该病认识不足,易造成漏诊,以致贻误病情,造成不良后果。本文对重症肝炎合并急性胰腺炎患者的临床资料进行回顾性分析,     

成年动物肝细胞基本培养法筛选暨胆红素代谢实验

目的探讨成年动物肝细胞(adult animal hepatocytes,AAH)基本培养法和胆红素代谢、尿素氮生成的生物活性,寻找体外生物人工肝支持系统(extracorporeal bioartificial liver support system,EBLSS)更理想的生物材料。方法①三种基本成分:合成培养基、血清、胰岛素对成年小白鼠肝细胞作15种组合培养观察最长存活期;②用重肝高胆红素血清培养AAH,观察胆红素代谢、尿素氮生成活性。结果含20%同种异体雄性小白鼠灭活血清、10U/ml胰岛素的高糖型DMEM培养基作高密度培养时,第14天时仍有20%的存活率;AAH3h使总胆红素、直接胆红素、间接胆红素各下降28.88%、21.13%、33.63%。结论本模式可作为AAH的基本培养法;AAH可成为EBLSS更理想的生物材料。     

闽西产叶下珠治疗慢性乙型肝炎98例

叶下珠为大戟科油柑属植物，是近年来发现有苗头的抗乙型肝炎病毒（ＨＢＶ）的中草药。笔者自１９９３年至１９９８年６月应用闽西产叶下珠（Ｐｈｙｌａｎｔｈｕｓｕｒｉｎａｒｉ－ａＬ）水煎剂治疗慢性活动型乙型病毒性肝炎９８例，取得较好效果。１一般资料共１９５例患...     

654-2联合大剂量黄芪治疗肝硬化低蛋白血症30例

1 临床资料1.1 病例选择:本组病例均选自1999年6月至2001年12月本院收治的乙型肝炎后肝硬化患者,所有病例均符合1995年全国传染病和寄生虫病学术会议制定的诊断标准。选取血清蛋白<35 g/L的肝硬化低蛋白血症患者,并随机分为2组。治疗组30例,其中男25例,女5例;平均年龄42.3岁。对     

益气补肺汤治疗肺炎衣原体感染患儿临床观察

目的 探讨益气补肺汤治疗肺炎衣原体感染患儿的临床效果。方法 将龙岩市第二医院2019年6月—2021年5月收治的150例肺炎衣原体感染患儿随机分为2组,各75例。参照组给予常规西医治疗,研究组在参照组基础上给予益气补肺汤治疗。治疗前后检测2组白细胞介素-2(IL-2)、白细胞介素-17(IL-17)、Toll样受体2(TLR2)、免疫T细胞亚群及肺功能指标,记录临床症状体征消失时间。结果 研究组患儿IL-17、TLR2水平低于参照组(P<0.05),IL-2水平高于参照组(P<0.05);研究组患儿CD4⁺、CD4⁺/CD8⁺高于参照组,CD8⁺低于参照组(P<0.05);研究组患儿FEV₁、PEF、FVC、MMF高于参照组(P<0.05);研究组退热、咳嗽消失时间及胸片阴影吸收时间短于参照组(P<0.05)。结论 益气补肺汤可改善肺炎衣原体感染患儿呼吸功能,抑制炎症反应,提升机体免疫功能,利于患儿康复。     

孙家敏运用银翘散临证思路探讨

银翘散是吴鞠通治疗温病之名方,孙家敏老师继承并发扬,将其加减变方运用于临床,取得了良好疗效。