肝移植术后新发糖尿病危险因素研究进展

肝移植术后新发糖尿病(NODAT)是肝移植术后常见的并发症,因其发病率高、危害大,严重的影响移植物功能和受者生存质量,受到了广大学者的关注。NODAT的危险因素有许多,大致可分为不可调控性危险因素及可调控性危险因素。不可调控性危险因素主要包括年龄、性别、供肝脂肪变性、肝硬化、糖尿病家族史等;可调控性危险因素包括肥胖、钙调磷酸酶抑制剂、糖皮质激素、肝炎病毒感染、巨细胞病毒感染及移植前血糖等。笔者结合近年相关研究报道对NODAT的发生机制及危险因素进行综述。     

肝移植术后糖尿病及其危险因素

本文就肝移植术后糖尿病的诊断标准、危险因素、发病情况,以及预防、治疗等进行了阐述.     

肝移植术后急性肾功能衰竭危险因素分析

目的 探讨围手术期因素对肝移植术后急性肾功能衰竭的发生的影响。方法 回顾性分析我院移植中心1999--2002年之间的资料齐全的89例肝移植患者的围手术期病例资料，利用单因素Logistic回归分析筛选肝移植术后急性肾功能衰竭的相关因素。结果 在单因素分析中患者的术中输血量及手术时间与患者术后急性肾功能衰竭的发生有相关性（P=0．041，P=0．005）。患者术后30d内的不良预后与急性肾功能衰竭的发生有相关性。在多因素分析中，仅有手术时间与术后急性肾功能衰竭的发生相关（P=0．026）。结论 术中输血量和手术时间为发生肝移植术后急性肾功能衰竭的危险因素，其中手术时间为一独立危险因素。     

肝移植术后代谢综合征及危险因素分析

目的 研究肝移植术后代谢综合征(metabolic syndrome,MS)及相关症状在肝移植长期生存者中的发生率与危险因素.方法 参照2005年美国心脏协会修订后的美国国家胆固醇教育计划成人治疗方案第3次报告(NCEP-ATPⅢ)标准,评估肝移植术后生存期≥5年的102例受体MS的发生率.选择手术年龄＞50岁、男性、吸烟史、术前指标肥胖、高血压、糖尿病(DM)、高甘油三酯血症(TG)、低高密度脂蛋白血症(HDL)等因素,用Logistic回归分析其中的危险因素.结果 102例肝移植受体中,肥胖、高血压、DM、低HDL、高TG的发生率在术后明显高于术前.术前与术后MS的发生率分别为29.3％及51.9％.术后MS与非MS组相比,术前肥胖、DM、高血压、高TG、高龄、男性、吸烟史更多见于MS组.结论 MS高发于长期生存的肝移植受体人群中.高龄(＞50岁)、术前肥胖及术前DM为发生肝移植术后代谢综合征的独立危险因素.     

影响肝移植术后新发糖尿病逆转的相关因素

目的 探讨影响肝移植术后新发糖尿病(PTDM)逆转的相关因素.方法 回顾分析232例肝移植受者的临床资料,术后共有62例患者发生PTDM,发生率为26.7%.根据PTDM是否发生逆转,将62例患者分为暂时性PTDM组(34例)和持续性PTDM组(28例).对两组患者的性别、年龄、体重指数、糖尿病家族史、乙型肝炎病毒感染情况、术前空腹血糖水平、免疫抑制剂使用及其血药浓度、皮质激素的使用时间等相关因素进行分析.结果 两组间患者的性别、体重指数、糖尿病家族史、术前空腹血糖水平、免疫抑制方案中皮质激素的持续使用时间、术后血他克莫司浓度及使用环孢素A的患者比例等因素的差异均无统计学意义(P＞0.05).与持续性PTDM组相比,暂时性PTDM组患者移植时年龄较轻,分别为(54±8)岁和(42±6)岁(P＜0.05);发生PTDM的术后时间较晚,分别为术后(18±23)d和(35±42)d(P＜0.05);免疫抑制方案中联合运用吗替麦考酚酯(MMF)或西罗莫司(SRL)的患者比例较高,分别为0和8.9%(P＜0.05).经多因素Logistic回归分析显示,只有移植时年龄是PTDM逆转的独立预测因子(比值比为1.312,95%可信区间为1.005～1.743).结论 患者移植时年龄、发生PTDM时的术后时间及免疫抑制方案中使用MMF或SRL的患者比例等因素与肝移植术后PTDM逆转相关,但只有移植时年龄是PTDM逆转的独立预测因子.

Abstract：

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

肝移植术后医院感染相关危险因素分析

目前,肝移植已成为治疗终末期肝病的有效手段,而移植术后医院感染的发生成为影响患者恢复及导致患者死亡的主要因为.文献报道,我国肝移植术后早期医院感染率为25%～50%,是继排斥反应后的第2大常见并发症~（[1-2]）.因此,了解肝移植术后医院感染的发病特点和相关危险因素,采取有效的防治措施,对改善患者预后、提高生存率有重要意义.笔者就第二军医大学附属长征医院收治的75例肝移植患者发生医院感染及相关危险因素进行分析,报道如下.     

肝移植术后腹腔积液的危险因素分析

目的对肝移植术后腹腔积液并发症进行原因分析，了解其危险因素，从而指导肝移植术后腹腔积液的预防和治疗。 方法回顾性分析2015年1月至2016年12月中山市人民医院47例肝移植患者临床资料，根据术后腹腔积液发生情况，分为腹腔积液组（24例）和无腹腔积液组（23例），采用单因素分析、Logistic多元回归分析以及ROC曲线分析肝移植术后发生腹腔积液的危险因素以及敏感度、特异度。 结果Logistic回归分析显示，术后第1天白蛋白（ALB）水平、供体胆碱酯酶（ChE）、脑死亡时间是肝移植术后腹腔积液的危险因素（P=0.017、0.044、0.035）。术后第1天ALB水平每增加评分一级、供体ChE每增加1 U、脑死亡时间增加1 h，患者术后腹腔积液风险分别增加6.531、1.000、1.052倍。ROC曲线分析发现，供体ChE的最佳截断值为5 142 U/L，判断术后腹腔积液发生风险敏感度为79.2%，特异度为56.5%，曲线下面积为0.676（P=0.039，95% CI：0.520~0.832）；供体脑死亡时间截断值为21.5 h，判断术后腹腔积液发生风险敏感度为62.5%，特异度为73.9%，曲线下面积为0.674（P=0.041，95% CI：0.520~0.828）。 结论提高术后第1天ALB水平，选择相对低ChE水平供体及减少供体脑死亡后等待时间可降低肝移植术后腹腔积液发生风险。     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

肝移植术后糖尿病的诊治策略

目的探讨肝移植术后糖尿病(PTDM)的临床特征和诊治措施。方法回顾性分析我院自2003年10月到2008年8月的58例PTDM患者的临床资料。70.7%(41/58)的患者予胰岛素治疗,激素组23例口服激素的PTDM患者中有15例激素减量或停用;FK506组16例使用单药他克莫司(FK506)免疫抑制方案的PTDM患者,转换为霉酚酸酯(MMF)或西罗莫司(RPM)为主的免疫抑制方案,随访3个月,观察改变免疫抑制方案对PTDM的影响。结果 89.7%(52/58)的PTDM患者临床症状不典型,激素组有5例患者空腹血糖正常,出现糖尿病逆转;11例患者胰岛素用量显著降低或停用,无一例发生急性排斥反应。FK506组有2例患者糖尿病逆转,10例患者胰岛素用量显著降低或停用,1例患者发生急性排斥反应,在FK506加量后排斥反应得以控制。结论肝移植术后PTDM的临床症状不典型,胰岛素治疗占主体。减低激素和FK506用量,转换MMF或RPM为主的免疫抑制方案,可能是防治PTDM的有效手段。     

原位异体肝移植术后新发慢性肾脏病的危险因素和预后分析

目的:探索术前估测肾小球滤过率（estimated glomerular filtration rate, eGFR）正常的成年人肝移植术后新发慢性肾脏病（new-onset chronic kidney disease, NOCKD）的围手术期危险因素,为NOCKD高危人群的筛查提供早期预测模型。方法:采用回顾性病例...     

心脏移植术后患者新发糖尿病危险因素的Meta分析

目的 系统评价心脏移植术后患者新发糖尿病的危险因素,为临床防治心脏移植术后新发糖尿病提供依据.方法 计算机检索PubMed、Embase、Cochrane、Web of Science、CINAHL、中国知网、万方数据库、中国生物医学文献数据库和维普数据库,检索时间均为建库至2020年9月,收集心脏移植术后新发糖尿病危险因素的观察性研究.由2名研究者提取资料并进行偏倚风险评价,用RevMan5.3软件进行Meta分析.结果 共纳入14项研究9808例研究对象,心脏移植术后新发糖尿病总发病率为20.22％(1983/9808).Meta分析结果显示,不可干预的危险因素有年龄、糖尿病家族史(OR=1.21、2.15,均P<0.01);可干预的危险因素有体重指数、术前空腹血糖、使用他克莫司、使用类固醇、冷缺血时间(OR=1.08～5.13,P≤0.01).结论 心脏移植术后新发糖尿病受较多因素影响,医护人员应识别其危险因素,采取针对性干预措施,提高治疗效果与移植成功率.     

肾移植术后糖尿病的临床特性及高危因素

目的 研究肾移植术后糖尿病（ＰＴＤＭ）的临床特性及高危因素。方法 将５１２例肾移植患者分为２组,其中４８例ＰＴＤＭ患者为糖尿病组。其余４６４例患者为非糖尿病组。定期监测患者体重、用药情况、生化指标、病毒抗体,并用血清学方法及聚合酶链反应（ＰＣＲ）方法检测主要组织相容性抗原（ＨＬＡ）。结果 糖尿病组的平均年龄及术后６个月内激素的用量明显高于非糖尿病组。肾移植术后半年内易出现ＰＴＤＭ,且全部ＰＴＤＭ     

肝、胰Ⅰ期联合移植治疗合并糖尿病的良性终末期肝病一例

目的 对1例原位肝、异位胰腺I期联合移植进行总结.方法 对1例终末期肝病合并2型糖尿病的患者施行肝、胰I期联合移植,肝脏为原位移植,胰腺异位移植于右侧髂窝,胰液空肠引流.术后采用他克莫司、霉酚酸酯及糖皮质激素预防排斥反应,并辅以两剂达利珠单抗.结果 术后移植胰腺功能良好,第2天即停用胰岛素.术后14 d,移植肝出现轻度急性排斥反应,调整他克莫司的用量后逆转.受者已存活15个月,移植肝脏及胰腺功能均正常.结论 肝、胰联合移植是治疗终末期肝病合并糖尿病的有效方法.     

肝移植围手术期糖尿病防治的初步研究

目的研究肝移植围手术期糖尿病对患者的影响及防治措施。方法回顾性分析131例肝移植患者临床资料，观察患者围手术期糖尿病的发生及对术后并发症的影响，探讨移植术后新发糖尿病与原发疾病、术后免疫抑制药物等因素的关系。结果移植术后新发糖尿病发生率为19．3％（21／109），与糖尿病家族史和术后使用大剂量激素有关，与非糖尿病患者相比，围手术期糖尿病患者急性排斥反应、细菌感染、高血压等并发症的发生率显著升高（P〈0．05），术前及术后早期（2周内）将血糖降至正常可减少感染的发生。结论围手术期出现糖尿病会增加肝移植患者术后并发症的发生率，应该有效控制血糖以减少感染并发症的发生，同时肝移植术后早期应避免使用大剂量激素.     

原位肝移植术后肺部感染与易感因素分析

目的 探讨原位肝移植（OLT）术后肺部感染的特点和易感因素。方法 回顾性总结128例原位肝移植的临床资料,分析肺部感染的主要致病菌、感染发生的时间及易感因素。结果 128例患者OLT术后共发生肺部感染48例（37．5％）,其中27例（56．3％）发生在术后7d内,34例（70．8％）为混合感染;死亡6例（12．5％）,其余治愈。致病菌前几位依次为铜绿假单胞菌,鲍曼／溶血不动杆菌、金黄色葡萄球菌和曲霉菌。结论 多种病菌可致肝移植术后肺部感染,并与受者的体质、机械通气及免疫抑制剂应用等诸多因素有关。     

原位肝移植术后消化道出血的病因与治疗

目的 探讨原位肝移植术后消化道出血的病因与治疗.方法 回顾性分析16例肝移植术后消化道出血患者的临床资料,总结其病因与治疗经验.结果 16例患者发生消化道出血的时间在肝移植术后2 d～4.5年.经检查发现患者的出血原因主要为食道静脉曲张破裂出血4例,急性胃黏膜病变出血3例,门脉高压性胃病出血3例,十二指肠球部多发性溃疡出血2例,十二指肠降段黏膜下小动脉出血、十二指肠乳头肌切开后出血、胆道出血及不明原因出血各1例.有2例经止血治疗无效而死亡,1例在肝移植围手术期死于多器官功能衰竭,1例死于急性心肌梗死,2例死于晚期肿瘤,其他患者经过积极止血治疗后好转,并长期存活.结论 肝移植术后消化道出血的病因主要为食道静脉曲张破裂出血、急性胃黏膜病变、门脉高压性胃病及消化性溃疡等.采用及时的止血治疗,必要时行剖腹探查手术止血是治疗成功的关键.     

HLA-DR、DQ基因与肾移植术后糖尿病的相关性的研究

目的探讨肾移植术后糖尿病与HLA-DR、DQ基因的相关性。方法28例患者肾移植术后并发糖尿病,术前进行了HLA分型。另以同期进行HLA分型肾移植术后无糖尿病的患者132例作为对照,二者在性别构成比及年龄方面的差异无统计学意义。术后采用环孢素A(CsA)、硫唑嘌呤和泼尼松(Pred),或采用CsA、霉酚酸酯和Pred预防排斥反应。结果HLA-DRB1*03、DRB1*02、DQB1*03与肾移植术后糖尿病呈显著正相关(相对危险度分别为2.16、1.74和1.99,P值均<0.05)。HLA-DRB3、HLA-DQB1*06与糖尿病发生呈显著负相关(相对危险度分别为0.59和0.55,P值均<0.05)。两种免疫抑制方案间糖尿病发病率的差异无统计学意义(P>0.05)。结论肾移植术后糖尿病的发生与某些HLA基因(糖尿病易感基因)相关。