丙型肝炎病毒感染至肝硬变进程影响因素的分析

目的探讨感染丙型肝炎病毒(HCV)时的年龄及既往发病情况、感染途径、性别等因素对患者向肝硬变发展病程的影响.方法对121例丙型肝炎后肝硬变患者分别按感染HCV时的年龄、既往有无急性肝病史、感染HCV途径、性别分组,对感染HCV至发展为肝硬变所需时间进行分析.结果感染HCV时的年龄越大,自感染HCV至发展为肝硬变所需时间越短(P＜0.01);既往有急性肝病史的患者自感染HCV至发展为肝硬变所需时间较无急性肝病史患者短(P＜0.01);输血感染HCV的患者自感染HCV至发展为肝硬变所需时间较非输血感染者短(P＜0.05);自感染HCV至发展为肝硬变所需时间男性与女性患者比较无显著性差异(P＞0.05).结论感染HCV至发展为肝硬变所需时间受感染HCV时年龄、既往急性发病史、感染途径等因素的影响,与性别关系不显著.     

肾移植受者与肝移植受者术后肺部感染的比较

目的 分析肾移植与肝移植术后肺部感染的异同点,探讨有效诊治措施.方法 对2004年1月至2008年12月间发生肺部感染的肾移植受者及肝移植受者进行回顾性分析,比较两组受者肺部感染的特点.结果 肾移植组肺部感染45例,肝移植组肺部感染23例,其肺部感染发生率分别分7.4%vs 56.1%(P<0.001),重症肺炎发生率2.6%vs 46.3%(P<0.001),肺炎诊断距移植中位时间(d)230(29-1080)vs 4(2-104)(P<0.001),肺炎病死率6.7%vs 17.4%(P=NS),肺部感染导致移植受者的死亡率0.5%vs 9.8%(P<0.001);两组细菌性感染的病原菌均以G-菌为主,但肝移植组受者多重耐药菌的比例较高(12.9%vs 37.0%,P=0.005).结论 了解肾移植及肝移植术后肺部感染的规律,能够为移植术后预防性抗感染治疗以及感染早期的经验性治疗提供依据,减少感染患者的死亡率及提高移植受者的存活率.     

肝移植受体巨细胞病毒活动性感染与补体C3、C4水平变化

目的研究肝移植受体发生巨细胞病毒（cytomegalovirus,CMV）活动性感染时补体C3、C4水平变化及其意义。方法应用速率散射比浊法分别检测三组人群肝移植受体外周血补体C3、C4水平。结果肝移植受体CMV活动性感染组C3、C4的水平明显高于无活动性感染组（P〈0.05）,与健康对照组比较无明显差异（P〉0.05）;而无活动性感染组补体C3、C4水平则明显低于健康组（P〈0.05）。结论肝移植术后CMV活动性感染时,补体系统处于激活状态,而激活的补体系统可能参与了移植器官排异过程。     

单剂抗IL-2受体单抗在重症肝炎肝移植患者中的初步观察

肝移植是目前救治重型肝炎的良好办法,但重型肝炎患者病情危重,变化快,手术耐受力差,行肝移植手术风险极大,术后并发症也较多,移植后肝性脑病、急性肾功能衰竭和肺部感染发生率高,影响患者预后.国内外多中心报道,抗IL-2受体单抗(抗IL-2R单抗)可以有效地减少器官移植后急性排斥反应(AR)的发生率,并可减少普乐可复(FK506)用量[1～3],但其在重型肝炎(简称重肝)肝移植中应用的经验不多.现将本中心重肝肝移植患者应用单剂抗IL-2R单抗的治疗体会报告如下.     

Acute tacrolimus overdose and treatment with phenytoin in liver transplant recipients

As a potent immunosuppressive agent, Tacrolimus is widely used in organ transplantation. Although complications due to chronic Tacrolimus use are rather well recognized, little is known about acute overdose and its treatment. Phenytoin, an anti-convulsant agent, can induce the Cytochrome P450 enzyme in the liver, which metabolizes Tacrolimus. Therefore, it can be considered as a potential treatment option for acute Tacrolimus toxicity. We hereby report two cases of acute Tacrolimus overdose after Orthotopic Liver Transplantation and the treatment with Phenytoin. Probable mechanisms of metabolism and interactions of these two drugs are discussed and the literature is reviewed.     

Polymorphisms in cytokine genes and their association with acute rejection and recurrence of hepatitis B in Chinese liver transplant recipients

BACKGROUND: Acute rejection (AR) and hepatitis B virus (HBV) recurrence after liver transplantation (LT) are the two major complications leading to chronic graft dysfunction. Genomic polymorphisms in interleukin (IL)-10, tumor necrosis factor (TNF)alpha and transforming growth factor (TGF)beta1 genes have been found to affect the susceptibility to certain diseases. However, the relationship between cytokine gene polymorphisms and risk of AR as well as HBV recurrence after LT in Han Chinese has not been reported. The objective of the present study was to investigate the association of polymorphisms within these cytokine genes with the risk of AR as well as HBV recurrence. METHODS: One hundred eighty six Chinese LT recipients in which 41 patients developed AR and 29 patients experienced HBV recurrence were enrolled; 151 age- and gender-matched healthy individuals were selected as controls. Single-nucleotide polymorphisms (SNPs) at loci of IL-10 -1082, -819, -592, and TNFalpha -308, -238, as well as TGFbeta1 -988, -800, -509, +869, and +915 were determined by using DNA sequencing and then confirmed by restriction fragment length polymorphism (PCR-RFLP). Analyses of linkage disequilibrium and haplotype frequency were performed using Haploview program. RESULTS: The -819 and -592 polymorphisms in the IL-10 gene were in complete linkage (r(2) = 1). Another linkage was found at -509 and +869 in the TGFbeta1 gene (r(2) = 0.66). A significant difference was observed in the distribution of allelic frequencies at position -819 and -592 in the IL-10 gene between ARs and non-ARs (p = 0.036, OR = 1.134, 95% CI 0.999-1.287 and p = 0.036, OR = 1.134, 95% CI 0.999-1.287, respectively). After adjustment for a Bonferroni correction, there was no significant difference between the polymorphism and AR (p >0.05). Furthermore, the overall genotype distribution between HBV recurrence patients and non-HBV recurrence patients was also not significantly different (p >0.05). CONCLUSIONS: Our study suggests that gene polymorphisms of IL10, TNFalpha, and TGFbeta1 do not have a major independent role in AR and HBV recurrence after LT and may not be risk factors of AR and HBV recurrence after LT in Chinese liver transplant recipients.     

肝移植术后乙肝主动免疫重建受体停用乙肝免疫球蛋白和(或)抗病毒药物的可行性

目的 探讨乙肝肝移植术后乙肝主动免疫重建成功受体停用乙肝免疫球蛋白(HBIG)和(或)抗病毒药物的可行性及临床指征.方法 检测乙肝主动免疫重建成功受体体内的HBV DNA和ccc DNA的水平,并监测其停用HBIG和(或)抗病毒药物后的乙肝复发情况.结果 共20例乙肝主动免疫重建成功受体纳入本研究.所有受体血浆均未检测到HBV DNA,1例受体的外周血单个核细胞中检测出微量HBV DNA (0.023 6 copies/cell),另1例受体的肝组织中检测出微量HBV DNA,但均未检测到ccc DNA.随访期间,所有受体均停用HBIG,13例停用抗病毒药物.1例外周血单个核细胞中检测到HBV DNA的受体有乙肝复发,并检测出HBV变异(变异位点G145R).结论 乙肝肝移植术后乙肝主动免疫重建成功受体停用HBIG和(或)抗病毒药物是安全可行的,但必须在停药前检测体内的HBV和病毒变异情况.     

MANF蛋白在乙型肝炎病毒慢性感染后肝纤维化进展中的无创监测价值

目的 探索中脑星形胶质细胞源性神经营养因子(MANF)在乙型肝炎病毒(HBV)慢性感染后肝纤维化进展中的表达差异及无创诊断价值.方法 对169例慢性HBV感染者进行肝脏穿刺病理学检查,并于穿刺当日检测患者肝功能等临床指标计算FIB-4和APRI指数,采用酶联免疫吸附方法检测健康对照和169例接受肝穿病理检查的慢性HBV感染患者外周血中MANF蛋白的表达水平,以肝脏病理结果为金标准,分别绘制MANF蛋白的受试者工作曲线(AUC),计算曲线下面积、特异度和敏感度,并与FIB-4、APRI指数等无创肝纤维化预测模型进行比较,评价MANF蛋白对显著肝纤维化和严重肝纤维化的预测价值.结果 健康对照组、轻微肝纤维化(S0-1)组、显著肝纤维化(S2)组和严重肝纤维化(S3-4)组4组间MANF蛋白的表达差异有统计学意义(F=17.55,P=0.00);进一步组间两两分析显示,除S0-1和S2组两组间差异无统计学意义外,其余组间两两比较差异均有统计学意义(P<0.05).随着肝纤维化程度的加重,MANF蛋白水平与肝纤维化呈正相关性(rs=0.431,P<0.001),与APRI指数和FIB-4肝纤维化的相关性基本一致.MANF蛋白在诊断慢性HBV感染者显著肝纤维化(S≥S2)的AUC为0.670,灵敏度和特异度分别为64.5%和68.7%,诊断严重肝纤维化(S≥S3)的AUC分别为0.736,灵敏度和特异度分别为92.9%和46.6%.结论 MANF蛋白表达水平随肝纤维化程度加重逐渐升高,对慢性HBV感染患者肝纤维化程度的预测有一定临床价值.