FAS抗原与慢性丙型肝炎关系的研究

目的通过观察慢性丙型肝炎(CHC)患者肝组织及外周血单核细胞(PBMC)FAS抗原表达对CHC病情的影响,进而探讨FAS系统及HCV RNA水平与CHC的关系及临床意义.方法采用肝活检组织病理、免疫组织化学、PCR及血液生化等方法检测41例CHC患者的肝组织和PBMC中FAS抗原、血清HCV RNA及肝功能,观察肝组织和PBMC中FAS抗原表达情况与血清HCV RNA水平及肝损伤的关系.结果(1)CHC患者PBMC的FAS阳性率为41.5%(17/41),肝组织FAS阳性率为65.6%(21/32).(2)CHC患者PBMC FAS阳性组血清HCV RNA和ALT水平均显著高于FAS阴性组(P＜0.05).结论(1)CHC患者肝组织和PBMC中FAS表达与肝组织炎症及血清病毒载量有关;(2)FAS系统可作为观察CHC病情的新指标,协助诊断与治疗.     

TNF-α基因多态性与慢性乙型肝炎患者干扰素治疗前后Th1/Th2细胞因子水平变化相关性研究

目的 研究TNF-α-238、308基因多态性与慢性乙型肝炎患者干扰素治疗6个月前后Th1/Th2细胞因子水平变化的相关性,探讨乙型肝炎发病机制和治疗策略.方法 以接受α干扰素正规治疗的77例慢性乙型肝炎患者作为研究对象,运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测77例慢性乙型肝炎患者TNF-α-238、-308位点基因多态性,并用ELISA检测干扰素治疗前后血清细胞因子水平,最后根据患者不同应答水平及基因型分组分别进行统计分析.结果 (1)应答组治疗前血清IL-2、IFN-γ水平较无应答组高(P<0.05),IL-10水平较无应答组低(P<0.05),IL-4水平在应答组和无应答组间无显著性差异(P>0.05);(2)干扰素治疗6个月后应答组、无应答组IL-2、IFN-γ水平均升高(P<0.01),IL-4、IL-10水平均降低(P<0.01),应答组IL-2、IFN-γ水平平均升高浓度高于无应答组(P<0.05),IL-4、IL-10水平平均降低浓度也高于无应答组(P<0.05);(3)治疗前TNF-α-308G/A基因型患者血清IFN-γ水平较G/G型高(P<0.05),IL-2、IL-4、IL-10水平在两种基因型间无显著性差异(P>0.05).TNF -α-238G/G、G/A基因型患者血清IL-2、IFN-γ、IL-4和IL-10水平均无显著性差异(P>0.05);(4)TNF-α-238G/G、G/A基因型, TNF-α-308G/G、G/A基因型各组间在干扰素治疗后IL-2、IFN-γ、IL-4和IL-10平均浓度变化无显著差异(P>0.05);(5)TNF-α-238、TNF-α-308位点各基因型在α干扰素治疗应答组和无应答组的分布差异无显著性意义(P>0.05).结论 (1)干扰素治疗不同应答水平与血清Th1/Th2细胞因子水平有关;(2)干扰素治疗后不同应答水平与治疗前后Th1/Th2细胞因子变化水平有关;(3)TNF-α-308 G/A基因型可能与慢性乙型肝炎患者外周血高IFN-γ水平有关;(4) TNF-α-238、-308位点基因多态性可能与干扰素治疗后IL-2、IFN-γ、IL-4和IL-10水平变化无关;(5)TNF-α-238、-308基因多态性与干扰素治疗不同应答水平无相关性.     

橙皮苷对急性肝损伤模型小鼠肿瘤坏死因子 α和干扰素 γ表达的影响

目的 研究橙皮苷对刀豆蛋白A（Con A）致小鼠急性肝损伤的保护作用及其对肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）表达的影响。方法72只SPF级C57BL/6雄性小鼠,随机均分为正常对照组、模型对照组和橙皮苷组。橙皮苷组给小鼠连续灌胃橙皮苷悬浊液1 000 mg.kg-1,灌胃10 d,模型对照组灌胃等量0. 5%羧甲基纤维素钠,模型对照组和橙皮苷组均用Con A诱导小鼠急性肝损伤模型,测定血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的含量;苏木精 伊红（HE）染色检查肝组织病理变化,反转录 聚合酶链反应（RT-PCR）法检测肝组织TNF-α和IFN-γ mRNA水平,酶联免疫吸附测定（ELISA）法检测血清TNF-α和IFN-γ水平。结果橙皮苷预处理后,与模型对照组比较,橙皮苷组ALT和AST水平显著降低（P<0. 01）,肝细胞坏死及炎性细胞浸润明显减轻,肝组织TNF-α和IFN-γ mRNA表达明显下调（P<0. 01）。橙皮苷组血清TNF-α和IFN-γ水平2 h分别为（717. 05±205. 22）,（611. 06±92. 82）pg.mL-1,6 h分别为（811. 56±167. 47）,（786. 19±215. 44）pg.mL-1。橙皮苷组TNF-α和IFN-γ水平较模型对照组明显降低（P<0. 01）,但Con A注射6 h,橙皮苷组TNF-α水平与模型对照组比较,差异无统计学意义（P＞0. 05）。结论橙皮苷预处理对Con A致小鼠急性肝损伤具有保护作用,其作用机制与其抑制TNF-α和IFN-γ的表达有关。     

聚乙二醇化干扰素α-2a、聚乙二醇化干扰素α-2b和干扰素α-2b联合利巴韦林治疗慢性丙型肝炎的疗效

目的观察聚乙二醇化干扰素(PegIFN)α-2a、PegIFN-α-2b和干扰素(IFN)α-2b联合利巴韦林治疗慢性丙型肝炎(CHC)患者的疗效。方法回顾性观察278例CHC患者的临床资料,分为接受PegIFN-α-2a、PegIFN-α-2b和IFN-α-2b联合利巴韦林抗病毒治疗组。比较患者治疗前、治疗第4、12、24、48周时各组患者HCV基因分型、HCV RNA载量、ALT和AST的变化。分析各组患者治疗期间ALT/AST复常率、病毒学应答,不同基因型或HCV RNA载量与病毒学应答的相关性。结果停药后随访24周时,各治疗组患者肝功能复常率差异具有统计学意义(χ~2=23.06、P0.001),以PegIFN-α-2a(180μg)组与PegIFN-α-2b(80μg)组患者复常率较高(分别为76.7%和83.0%)。各治疗组患者快速病毒学应答(RVR)、治疗结束时病毒学应答(ETVR)及持续病毒学应答(SVR)差异均具有统计学意义(χ~2=9.79、P=0.04,χ~2=11.33、P=0.02,χ~2=11.99、P=0.02),以PegIFN-α-2a(180μg)组与PegIFN-α-2b(80μg)组患者较高(分别为62.8%、88.4%、64.0%和64.2%、83.0%、65.1%)。普通IFN-α-2b(600万单位)组、PegIFN-α-2a(180μg)组、PegIFN-α-2b(80μg)组患者依次有13例、54例和68例获得RVR,依次有11例(84.6%)、50例(92.6%)和62例(91.2%)最终获得SVR。入组患者中1b基因型患者243例,其RVR、完全早期病毒学应答(cE VR)和SVR均优于非HCV 1b基因型患者(χ~2=8.23、P0.001,χ~2=46.26、P=0.01,χ~2=10.22、P0.001)。普通IFN-α-2b(600万单位)组、PegIFN-α-2a(180μg)组、PegIFN-α-2b(80μg)组低病毒载量(HCV RNA6.0 Log_(10)拷贝/ml)患者的SVR均优于高病毒载量患者(χ~2=4.10、P=0.04,χ~2=20.89、P0.001,χ~2=19.60、P0.001)。结论聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎具有较好疗效,早期RVR对SVR的获得具有很强的预测作用,非基因HCV 1b型和低病毒载量患者疗效优于HCV 1b基因型和高病毒载量患者。     

RNA干扰Kupffer细胞肿瘤坏死因子-α减轻大鼠肝脏缺血再灌注损伤

目的 观察RNA干扰肝脏Kupffer细胞肿瘤坏死因子-α(TNF-α)对大鼠肝脏缺血再灌注损伤的保护作用.方法 构建针对大鼠TNF-α基因的短发夹状RNA(shRNA)真核表达载体.肝脏缺血再灌注损伤前48 h经门静脉注射磷酸盐缓冲液(PBS)、空载体或TNF-α shRNA.实验随机分为4组,假手术组、PBS组、空载体组和shRNA组.阻断大鼠70%入肝血流40 min,再灌注6 h检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、肝脏Kupffer细胞TNF-α mRNA、血清TNF-α、肝组织中丙二醛(MDA)以及超氧化物岐化酶(SOD)含量.结果 与PBS组和空载体组比较,shRNA组再灌注6 h后血清ALT和AST水平显著降低(P＜0.05),Kupffer细胞TNF-α mRNA水平、血清TNF-α水平(56.6±6.7 pg/ml比87.8±8.7 pg/ml和96.5±7.3 pg/ml,P＜0.05)、肝组织中MDA含量(93.4±13.3 nmol/mg比133.5±12.4 nmo1/mg和136.7±13.6 nmol/mg,P＜0.05)显著降低,SOD活性显著升高(22.4±4.6 U/mg比12.2±3.1 U/mg和11.4±2.9 U/mg,P＜0.05).结论 RNA干扰Kupffer细胞TNF-α基因的表达可以减轻大鼠肝脏缺血再灌注损伤.     

肝囊型包虫病患者外周血单个核细胞表面程序性死亡受体配体1的表达及其与干扰素-γ的关系

目的 探讨肝囊型包虫病患者外周血单个核细胞(PBMC)表面程序性死亡受体配体1(PD-L1)的表达及其与血清1FN-γ水平之间的关系.方法 回顾性分析2010年6月至2011年2月新疆医科大学第一附属医院收治的63例肝囊型包虫病患者的临床资料.根据世界卫生组织包虫病专家组包虫病标准化分型原则将患者分为肝包虫活性组(38例)和肝包虫无活性组(25例),20例肝血管瘤患者及健康志愿者作为正常对照组.采用流式细胞仪及免疫组织化学法检测PD-L1阳性表达率,ELISA法检测血清IFN-γ的表达水平.组间比较采用成组设计资料￡检验和单因素方差分析,进一步两两比较采用LSD检验,总体分布采用x2检验,PD-LI阳性表达率和IFN-γ的表达水平的相关性分析采用Pearson检验.结果 流式细胞仪检测肝包虫活性组、肝包虫无活性组和正常对照组PBMC表面PD-L1的阳性表达率分别为12.1％士3.8％、10.9％士2.5％和9.1％±2.5％,肝包虫活性组与正常对照组PD-L1的阳性表达率比较,差异有统计学意义(t =3.327,P＜0.05).免疫组织化学检测肝包虫活性组、肝包虫无活性组和正常对照组PBMC涂片中PD-L1的阳性表达率分别为11.9％±3.4％、10.6％±2.9％和9.5％±3.6％,肝包虫活性组与正常对照组PD-L1的阳性表达率比较,差异有统计学意义(t=2.470,P＜0.05).肝包虫活性组、肝包虫无活性组和正常对照组血清IFN-γ表达分别为(141±38) μg/L、(124±32) μg/L和(105±42) μg/L,肝包虫活性组与正常对照组IFN-γ表达水平比较,差异有统计学意义(t=3.280,P＜0.05).流式细胞仪和免疫组织化学检测PBMC的PD-L1阳性表达率与血清IFN-γ表达水平均呈明显正相关(r=0.59,0.61,P＜0.05).结论 PD-L1可能在IFN-γ的作用下发挥着促进肝包虫免疫逃避的重要作用.     

环孢素A对不明原因复发性流产患者外周血IFN-γ、TNF-α的调控

目的探讨环孢素A(CsA)对不明原因复发性流产(uRM)患者外周血干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)表达的影响。方法收集79例正常育龄期妇女的外周血标本,采用流式细胞仪检测其外周血CD3~+CD4~+T细胞中IFN-γ、TNF-α的表达水平,制定正常参考范围。入选36例IFN-γ、TNF-α表达量异常升高的uRM患者,于月经第1天口服CsA50mg,2次/d,直至黄体中期;收集uRM患者治疗前后的外周血,采用流式细胞仪检测IFN-γ、TNF-α的表达水平并进行比较。结果正常育龄期妇女外周血CD3~+CD4~+T细胞中IFN-γ、TNF-α的表达水平呈正态分布,以百分位数P10~P90(分别为6.7%~30.5%,12.6%~41.0%)作为正常参考范围。IFN-γ和/或TNF-α异常升高的uRM患者服用CsA后,其表达量均显著降低[IFN-γ:(36.7±9.3)%vs.(28.5±11.0)%,TNF-α:(52.8±7.2)%vs.(40.9±13.8)%,P<0.01]。结论CsA可以下调uRM患者外周血中IFN-γ、TNF-α的表达量,但其具体机制尚需进一步研究。     

丙型肝炎病毒感染至肝硬化的影响因素分析

目的探讨感染丙型肝炎病毒（HCV）的时间、感染途径、性别、肝功、HCVRNA、基因型、肝穿病理、治疗与否等因素对疾病发展至肝硬化的影响。方法351例丙型肝炎患者分为LC组和CHC组,对感染HCV至发展为肝硬化的各种可能影响因素进行统计学分析。结果LC组基线AST水平高于CHC组（t=2．015,P=0．045）,LC组与CHC组ALT水平无显著差异（t=-1．158,P=0．248）;LC组HEY RNA水平与CHC组HCV RNA水平无显著差异（t=0．718,P=0．473）;基因型1b患者更易发展为肝硬化;感染HCV的时间越长。越容易发展为肝硬化（t=5．652,P〈0．001）;输血感染HCV的患者自感染HCV至发展为肝硬化所需时间较非输血感染者短（t=14．439,P〈0．001）;LC组接受抗病毒治疗的患者比率明显低于CHC组（P〈0．001）;LC组与CHC组男女性别构成无差异（P=0．081）。结论感染HCV至发展为肝硬化受感染时间,感染途径,AST水平,病毒基因型、治疗与否等因素影响,与ALT水平、HCV RNA、性别关系不显著。     

γ干扰素与肿瘤坏死因子α对肠上皮屏障功能影响的实验研究

目的 观察炎症介质γ干扰素及TNF-α联合作用对肠上皮屏障功能的影响并探讨其分子机制.方法建立人肠上皮细胞株Caco-2单层细胞培养模型,分别在预处理的24孔板与6孔板中采用DMEM培养基培养.将2种培养板中细胞均按随机数字表法分为对照组(常规培养)、γ干扰素组(加入终浓度为10 ng/mL γ干扰素培养)、TNF-α组(加入终浓度为10 ng/mL TNF-α培养)、γ干扰素+TNF-α组(加入终浓度均为10 ng/mL的γ干扰素与TNF-α培养).24孔板细胞处理后0 h(即刻)及6、12、24、36、48 h,用电阻测定仪检测肠上皮细胞跨上皮电阻(TER);于48 h分别采用异硫氰酸荧光素-葡聚糖荧光示踪法与免疫荧光法,检测肠上皮细胞通透性及紧密连接咬合蛋白的分布与形态变化.6孔板细胞处理24 h时,用蛋白质印迹法检测咬合蛋白、磷酸化肌球蛋白轻链(pMLC)、肌球蛋白轻链激酶(MLCK)蛋白表达.对数据进行单因素方差分析与t检验.结果 (1)对照组各时相点肠上皮细胞TER无明显变化(F=0.86,P＞0.05);γ干扰素组与TNF-α组TER虽逐渐降低,但与处理后0 h比较差异均无统计学意义(F值分别为1.69、2.47,P值均大于0.05);γ干扰素+TNF-α组TER从24 h起显著低于处理后0 h(t=4.97,P＜0.05),并明显低于其余3组(F=11.54,P＜0.05).(2)γ干扰素+TNF-α组的肠上皮细胞通透性[(1197±215)pmo1]显著高于对照组、γ干扰素组与TNF-α组[(303±93)、(328±76)、(797±177)pmol,t值分别为4.8、5.0、6.9,P值均小于0.01].(3)24 h时各组咬合蛋白表达量无明显变化(F=0.26,P＞0.05).48 h时对照组咬合蛋白排列规则;γ干扰素组及TNF-α组咬合蛋白排列不规则;而γ干扰素+TNF-α组咬合蛋白排列不连续,发生明显重分布,胞质内分布增加.(4)γ干扰素+TNF-α组pMLC蛋白表达量(0.95±0.05)显著高于对照组、γ干扰素组与TNF-α组(0.57±0.12、0.56±0.07、0.59±0.10,F=17.97,P＜0.01),MLCK蛋白表达量(1.57±0.36)也显著高于其余3组(0.85±0.18、1.04±0.23、1.00±0.07,F=9.05,P＜0.05).结论γ干扰素与TNF-α联合作用通过增加MLCK及pMLC蛋白表达,引起肠上皮屏障功能损害.

Abstract：

Objective To investigate the effect of combination of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha ( TNF-α ) on intestinal epithelial barrier function. Methods The Caco-2 monolayers were cultured in DMEM nutrient solution, and then they were inoculated in 24-well or 6-well plate with Transwell inserts. They were divided into control group ( ordinary treatment), IFN-γ group ( with addition of 10 ng/mL IFN-γ), TNF-α group (with addition of 10 ng/mL TNF-α), and IFN-γ plus TNF-α group (with addition of 10 ng/mL TNF-α and 10 ng/mL IFN-γ ). Monolayers inoculated in 24-well plate were collected for determination of transepithelial electrical resistance (TER) with an ohmmeter at post treatment hour (PTH) 0, 6, 12, 24, 36, and 48, the permeability of monolayers with fluorescein isothiocyahate-labeled dextran (FITC-dextran) tracer method at PTH 48, the distribution and morphological change of tight junction occludin with immunofluorescence assay at PTH 48. Monolayers inoculated in 6-well plate were collected for determination of protein expression of occludin, myosin light chain kinase (MLCK), and phosphorylated MLC (pMLC) with Western blot at PTH 24. Data were processed with one-way analysis of vaiiance and t test. Results ( 1 ) There was no obvious difference in TER in control group at each time point ( F = 0. 86, P ＞ 0.05 ). TER in IFN-γgroup and TNF-α group were gradually decreased during PTH 6-48,but showed no statistical difference as compared with that at PTH 0 ( with F value respectively 1.69, 2.47,P values all above 0.05 ). TER in IFN-γplus TNF-α group was significantly decreased from PTH 24 as compared with that at PTH0 ( t =4.97, P ＜0.05) and that in each of the other three groups ( F =11.54,P ＜ 0.05 ). (2) The permeability of monolayers in IFN-γplus TNF-α group [( 1197 ± 215 ) pmol] was significantly higher than that in control group, IFN-γ group, and TNF-α group [( 303 ± 93 ), ( 328 ± 76),(797 ± 177) pmol, with t value respectively 4.8, 5.0, 6.9, P values all below 0.01]. (3) There was no statistical difference in occludin expression at PTH 24 among four groups ( F = 0.26, P ＞ 0.05). The occludin in control group at PTH 48 was regular in arrangement, while that in IFN-γand TNF-α groups was irregular in arrangement. The arrangement of occludin in IFN-γ plus TNF-c group at PTH 48 was interrupted,with obvious redistribution in cytoplasm. (4) The protein expression of pMLC in IFN-γ plus TNF-α group (0.95 ±0.05) was significantly higher than that in control group, IFN-γ group, or TNF-α group (0.57 ±0.12, 0.56 ±0.07, 0.59 ±0. 10, respectively, F = 17.97, P ＜0.01). The protein expression of MLCK in IFN-γplus TNF-α group (1.57 ±0.36) was also significantly higher than that in control, IFN-γ, TNF-α groups (0.85 ± 0.18, 1.04 ± 0. 23, 1.00 ± 0.07, respectively, F = 9.05, P ＜ 0.05 ). Conclusions Combination of IFN-γand TNF-α can induce intestinal epithelial barrier dysfunction by up-regulating MLCK protein expression and promoting MLC phosphorylation.     

卵巢早衰患者血清抗透明带抗体和肿瘤坏死因子-α、γ-干扰素及白细胞介素-2的分析

目的 :探讨抗透明带抗体 ( Azp Ab)和肿瘤坏死因子 -α( TNF-α) ,γ-干扰素( IFN-γ)及白细胞介素 -2 ( IL-2 )在卵巢早衰 ( POF)发病中的作用及其临床意义。方法 :以定量酶联免疫吸附试验 ( EL ISA)测定 POF患者血清中 Azp Ab水平 ,放射免疫测定 IFN-γ、IL-2和 TNF-α的水平。结果 :POF组 Azp Ab明显高于正常对照组 ( P<0 .0 0 1 ) ,TNF-α和 IL -2显著降低 ( P<0 .0 0 1 ) ,IFN-γ明显升高 ( P<0 .0 1 )。 POF患者中 ,Azp Ab阳性组 ,以上三种细胞因子水平均明显高于 Azp Ab阴性组。结论 :Azp Ab,TNF-α,IFN-γ和IL-2在自身免疫性 POF的发病中起着重要作用。     

HCV antigen instead of RNA testing to diagnose acute HCV in patients treated in the Dutch Acute HCV in HIV Study

Introduction : Affordable and sensitive screening methods for acute hepatitis C (HCV) are necessary to successfully intervene in the current HCV epidemic among HIV‐positive men having sex with men. HCV core antigen (Ag) testing has been proven effective in diagnosing chronic HCV‐infected patients at low costs. We studied the characteristics of HCV Ag testing in acute HCV‐infected HIV‐positive patients. Methods : Plasma samples were selected from acutely HCV genotype 1‐infected patients treated with peginterferon, ribavirin and boceprevir in the Dutch Acute HCV in HIV Study. The control group consisted of HIV‐positive patients with a newly raised alanine aminotransferase (ALT) (>41 U/L) in whom HCV RNA was undetectable and who were tested for HCV Ag. Spearman correlation coefficient between HCV RNA and HCV Ag was calculated together with the sensitivity and specificity of HCV Ag testing at acute HCV diagnosis. Results and discussion : Upon acute HCV diagnosis, HCV Ag was identified in 39 out of 44 patients with detectable HCV RNA levels. In all 23 control patients without detectable HCV RNA in plasma, HCV Ag was undetectable as well. This resulted in a sensitivity and specificity of HCV Ag of respectively 89% (95% CI 75–96) and 100% (95% CI 82–100). The correlation between HCV Ag and HCV RNA was 0.97 (p < 0.001) upon diagnosis. Conclusion : The data presented in this study suggest that HCV Ag testing is a sensitive and specific method that can be used in diagnosing AHCV in HIV‐infected patients.     

HCV infection and hemodialysis

Hepatitis C virus (HCV) infections are frequent in hemodialyzed patients and are mainly related to transfusions and nosocomial contamination. HCV-related infection may result in cirrhosis in 10% of dialysis patients and is worsened by transplantation because of the immunosuppressive therapy for prevention of graft rejection. Because there is a risk for significant liver disease and because cirrhosis contraindicates a renal transplantation, a liver biopsy should be performed early in HCV-RNA positive hemodialysis patients to evaluate histologic impact of the liver disease. A combined liver-kidney transplantation should be discussed in dialysis patients with cirrhosis. Standard alpha-interferon is the only treatment for HCV in dialysis patients because ribavirin is contraindicated by a high risk for hemolytic anemia. It leads to an overall 30% rate of sustained viral eradication. It is indicated in dialysis patients with acute hepatitis C, significant liver disease (fibrosis score > or =2), or symptomatic cryoglobulinemia, and to candidates for renal transplantation, whatever the severity of the liver disease. Indeed, alpha-interferon is contraindicated in kidney recipients given the risk for rejection. Preventive treatment for HCV is only respect for universal hygiene rules in the dialysis setting because there is no available vaccine.     

Campath induction in HCV and HCV/HIV‐seropositive kidney transplant recipients

Alemtuzumab (AZ) induction in hepatitis C‐seropositive (HCV+) kidney transplant (KTX) recipients may negatively affect patient survival; however, available information is scant. Using US registry data from 2003 to 2010 of adult HCV+ deceased‐donor KTXs (n = 4910), we examined outcomes by induction agent – AZ (n = 294), other T cell‐depleting agents, (n = 2033; T cell), IL‐2 receptor blockade (n = 1135; IL‐2RAb), and no induction (n = 1448). On multivariate analysis, induction therapy was associated with significantly better overall patient survival with AZ [adjusted hazards ratio (aHR) 0.64, 95% confidence interval (CI) 0.45, 0.92], T cell (aHR 0.52, 95% CI 0.41, 0.65) or IL‐2RAb (aHR 0.67, 95% CI 0.53, 0.87), compared to no induction. A significant protective effect was also seen with AZ (aHR 0.63, 95% CI 0.40, 0.99), T cell (aHR 0.62, 95% CI 0.49, 0.78), and IL2R‐Ab (aHR 0.62, 95% CI 0.47, 0.82) in terms of death‐censored graft survival relative to no induction. There were 88 HIV+/HCV+ coinfected recipients. Compared to noninduction, any induction (i.e. three induction groups combined) was associated with similar overall patient survival (P = 0.2255) on univariate analysis. Induction therapy with AZ, other T cell‐depleting agents, or IL‐2RAb in HCV+ KTX is associated with better patient and death‐censored graft survival compared to noninduction. In HCV/HIV coinfected patients, induction is not contraindicated.     

Hepatitis C virus (HCV)-related cryoglobulinemia after liver transplantation for HCV cirrhosis

The aim of this study was to analyze the clinical impact of hepatitis C virus (HCV)-related cryoglobulinemia in patients that had received liver transplants after HCV cirrhosis. Thirty patients who had received transplants between 1990 and 1996 for HCV cirrhosis and who had a follow-up longer than 1 year were studied. Serum HCV RNA levels, HCV genotype, cryoglobulinemia, rheumatoid factor, serum C3 and C4, IgA, IgG, IgM levels, liver tests, and liver histology were studied 30 +/- 16 months post-transplant. Cryoglobulinemia was found in 9 of 30 patients (30.0%) and was symptomatic in 4 of the 9 cases (glomerulonephritis, 1 case; palpable purpura, 3 cases). Age, sex distribution, alanine aminotransferase (ALAT) activity, and Knodell score did not differ, whether cryoglobulinemia was present or not. Rheumatoid factor (209.5 +/- 70.4 IU/l vs 12.0 +/- 4.4 IU/l, P = 0.004) and IgM levels (3.2 +/- 0.5 g/l vs 1.6 +/- 0.9 g/l, P = 0.0001) were significantly higher, and C4 levels (0.16 +/- 0.16 g/l vs 0.30 +/- 0.10 g/l, P = 0.009) were significantly lower in patients with cryoglobulinemia. One patient died from cryoglobulin-related renal failure. We concluded that, after liver transplantation (LT) for HCV cirrhosis, cryoglobulinemia was frequent and often symptomatic. Cryoglobulinemia did not seem to be associated with more severe graft damage. Cryoglobulinemia-associated morbidity must be taken into account in the management of post-transplant HCV infection.     

Diffusion of HCV through peritoneal membrane in HCV positive patients treated with continuous ambulatory peritoneal dialysis

Purpose of the Study. We evaluated the presence of HCV in the peritoneal effluents of viraemic patients treated with continuous ambulatory peritoneal dialysis (CAPD) to evaluate the risk of transmitting the infection with this procedure. Procedure. Fifteen of 81 CAPD patients (18.5%) had anti-HCV antibodies and eight were viraemic. At the beginning of CAPD two of the viraemic patients had ascites with a clinical picture of chronic active hepatitis and cirrhosis. Peritoneal dialysates were collected after an overnight exchange with 1.36% glucose and after a 4-h exchange with 3.86% glucose. Fluids from the overnight exchange were spun to obtain a cellular pellet and the supernatant 100-fold concentrated. Results. No viral genome could be detected in unconcentrated samples and in cellular pellets, while HCV-RNA at low titre was detected in concentrated dialysates from the two patients with active liver disease. Conclusions. Our findings confirm that HCV may be present in the CAPD effluent of some patients; however, the titre of virus in the effluent was extremely low, at the limit of detection of the PCR assay. Peritoneal fluids originating from patients with HCV associated severe liver disease may be a potential source of infection.     

丙肝病毒相关冷球蛋白血症性肾炎

丙肝病毒感染可引起冷球蛋白血症以及肾小球肾炎,冷球蛋白血症相关膜增生性肾小球肾炎是HCV相关肾炎的主要类型,本文主要就近年HCV相关冷球蛋白血症性MPGN的发病机理以及治疗进展作一综述。