【作者】 郑志鹏；

【导师】 周杰；

【作者基本信息】 南方医科大学 ， 肝胆外科， 2010， 硕士

【摘要】 自美国的Starzl于1963年在世界上首先行第一例人体原位肝移植手术以来,肝脏移植已经过近50年的发展,已经成为治疗终末期肝脏疾病、急性肝功能衰竭的一种最有效的选择。但肝移植术后真菌感染仍然是移植术后患者死亡的主要原因之一,国内外报道肝移植术后真菌感染的发生率高达15%～42%,病死率达40%～80%,高于急性排异反应、’肾功能衰竭和病毒感染等并发症。肝移植术后真菌感染起病隐匿,常缺乏典型的临床表现,临床诊断较为困难,由于肝移植患者病情、手术、用药等特殊性的存在,使得真菌感染在这一群体发病率更高、发病更早、病情更重、控制更难,其中侵袭性真菌感染是发生于术后早期一种常见的后果严重的并发症,是导致肝移植术后死亡的重要原因之一。肝移植术后真菌感染的流行病特点及易感因素均有其特殊性。随着人们对真菌感染的认识不断加深,针对肝移植术后真菌感染流行病学及易感因素的研究也愈发得到重视,也成为肝移植术后并发症研究的重要课题。笔者通过研究2004年8月至2009年1月南方医科大学附属南方医院118例肝移植患者术后真菌感染的流行性特点,研究肝移植术后真菌感染的真菌类型及菌谱变化及抗真菌药物耐药性变化规律；并根据本中心经验以及参考国内外相关文献综合选择多种肝移植围手术期的相关因素进行综合分析,以寻找出与真菌感染相关的危险因素。从而为临床上更有效地预防和治疗真菌感染提供理论依据。第一部分肝移植术后真菌感染的病原菌及其药物敏感性[目的]术后真菌感染仍是影响肝移植手术成功率和术后生存率的重要并发症,随着近几年来新的抗真菌措施的不断引入,围手术期广泛进行预防性抗真菌治疗等原因,国内外报道的肝移植术后真菌感染的发生率不降反升,真菌感染的菌谱已经发生了一些变化,真菌耐药率也逐渐增加。我们通过研究2004年8月至2009年1月南方医科大学附属南方医院118例肝移植术后真菌感染病例的真菌类型及耐药性的规律,从而更有效地预防和治疗真菌感染。[方法]1、标本来源以2004年8月至2009年1月南方医科大学附属南方医院118例肝移植患者为研究对象,术后定期(2-3次／周)清晨空腹抽血检测血清(1,3)-β-D葡聚糖和采集相关标本送真菌涂片检查,标本种类包括：呼吸道标本(痰液、咽拭子)、胃肠道标本(胃液、粪便)、腹水、胆汁、中段尿、血液。对血清(1,3)-β-D葡聚糖和(或)涂片检查结果阳性者反复多次采集相应标本送真菌培养及药敏试验。对临床表现疑似真菌感染者,无论血清(1,3)-β-D葡聚糖或涂片结果是否阳性亦反复采集临床标本送真菌培养及药敏试验。2、真菌的鉴定与药敏试验真菌培养鉴定选用郑州博赛生物制品公司的科马嘉显色培养基,吡咯类抗真菌药物的药敏试验方法参照美国国家临床试验标准化委员会(NCCLS)2003年公布的M38-A方案,其他药物使用丹麦Rosco真菌药敏纸片扩散法测定。3、参照2001年中华人民共和国卫生部发布的《医院感染诊断标准(试行)》及相关文献,规定以下诊断标准。(1)患者有发热、咳嗽、腹泻等全身或局部感染的临床表现,用其他并发症不能解释,经广谱抗生素和抗病毒治疗无效。(2)从无菌部位(血液、清洁中段尿、胆汁、胸水、腹腔引流液、静脉置管等)采集的标本中分离出真菌1次以上。(3)从同一有菌部位采集的标本进行真菌培养或病理检查,连续2次或2以上培养出同1种真菌或不同部位分离出同1种真菌。(4)多次涂片镜检发现大量真菌菌丝或芽孢并且通过至少1次真菌培养证实。(5)真菌定殖或皮肤真菌感染不纳入统计范畴。4、预防性使用抗真菌药物本组病例中对58例患者术后第1天开始预防性使用抗真菌药物：静脉使用氟康唑150～200mg/d,疗程为2-3周。5、统计学处理采用SPSS13.0统计软件计算频数及百分比。[结果]1、26例真菌疑似感染患者的确诊及临床资料根据1.3所述诊断标准共有26例患者被确诊为真菌感染,感染发生率为22.0%,其中男22例,女4例。平均年龄54.3(32～74)岁,平均住院时间71.4(33-193)d。原发病包括肝炎后肝硬化12例(其中3例合并急性肝功能衰竭),原发性肝癌13例,重症肝炎1例。26例患者术后均常规采用三联抗排斥治疗[他克莫司(FK506)、吗替麦考酚酯、甲基强地松龙；5d后改为FK506、吗替麦考酚酯、强地松),FK506的血药浓度维持在10～15ng/ml。26例患者术后均联合应用抗生素,平均疗程为35.9(20-50)d。2、感染部位及真菌种类26例患者中共分离出菌种6种,菌株49株,以白色念珠菌检出率最高,其次分别是曲霉菌、光滑念珠菌、热带念珠菌、近平滑念珠菌、克柔念珠菌。感染部位主要是呼吸道,其次是胃肠道、腹腔、胆道、血液、尿路。其中单系统(或器官)真菌感染22例(84.6%),多系统(或器官)真菌感染4例(15.4%),5例患者合并2种以上的真菌感染。3、真菌感染的时间分布感染发生时间平均为13.6(1-53)d,其中93.8%发生在术后1个月内。对真菌感染的时间分布进行分析发现术后1周检出率(42.9%)最高,随着时间的延长,检出率呈下降趋势。4、药敏试验结果氟康唑的总体敏感率最低(55.1%),伊曲康唑及伏立康唑最高(分别为90.0%、92.0%)。热带念珠菌与克柔念珠菌的总体耐药率最高(均为42.9%)。5、治疗及转归26例真菌感染患者均接受抗真菌治疗,即静脉滴注氟康唑150-400mg／d,疗程8-31d,其中4例因对氟康唑耐药而改为静脉滴注伊曲康唑200-400mg／d,使用时间为10-25d。26例中有19例治愈,7例死亡,病死率为26.9%；其中与真菌感染直接相关者5例,病死率为19.2%。另2例死亡直接原因是移植物抗宿主反应。[结论]1、肝移植术后真菌感染的病原菌仍以念珠菌属为主,包括白色念珠菌、光滑念珠菌、热带念珠菌、近平滑念珠菌、克柔念珠菌等,其中以白色念珠菌所占比例最高。病死率较高的曲霉菌(18.4%)的感染率也较国内外其他报道为高。提示近年来真菌感染菌谱发生了变化。2、感染部位主要是呼吸道和胃肠道,分别占75.5%和10.2%。真菌感染主要发生在术后1周(42.9%),随着术后时间的延长,真菌感染的发生率呈下降趋势,提示对于肝移植患者在易感期(术后1个月内,尤其是1周内)应加强对呼吸道、胃肠道等易感部位真菌感染的监测,力争早期发现真菌感染和及时治疗。3、本研究的药敏试验结果显示,伏立康唑、伊曲康唑对真菌有较高的敏感性,两性霉素B、氟胞嘧啶、氟康唑等药物对真菌的平均敏感率相对较低。各类抗真菌药物对不同种属的真菌敏感性存在一定的差异,伊曲康唑、伏立康唑对念珠菌属及曲霉菌的敏感率普遍较高,氟胞嘧啶、两性霉素B次之,而氟康唑对念珠菌及曲霉菌的敏感性普遍较低。随着抗真菌药物被广泛应用于肝移植术后预防性和经验性治疗,新的致病真菌及耐药菌株的不断出现,尤其是耐氟康唑菌株逐渐增多。4、抗真菌治疗应当综合病原菌的种类、药物的耐药特性等方面合理选择药物,确诊的患者应根据药敏结果选择敏感药物,并行足量、足疗程的抗真菌治疗,单用药物疗效不佳时也可以联合用药。近年来上市的伊曲康唑、两性霉素衍生物、伏立康唑等药物不良反应较小,对念珠菌属及曲霉菌均有较高的敏感性,是替代氟康唑较好的选择。5、近年来的研究认为预防性抗真菌治疗对降低肝移植术后深部真菌感染发生率有积极作用。本研究亦发现预防性抗真菌能有效防止真菌感染。第二部分肝移植术后真菌感染的危险因素分析[目的]深部真菌感染为医院获得性感染,易感人群多存在多种危险因素。目前报道较多的包括严重基础疾病患者、免疫功能低下、营养不良、长期使用抗生素和接受各种侵入性诊断和治疗患者。肝脏移植的对象主要是终末期肝病患者,如原发性肝癌、肝炎后肝硬化、肝功能衰竭等,受体术前一般情况和营养状态多较差,肝移植手术时间长、创伤大,术后免疫抑制治疗及抗感染治疗等特异性。因此,鉴于肝移植围手术期处理及肝移植手术本身的特殊性,有必要从肝移植术前、术后各种导致真菌感染的相关因素中寻找出主要的危险因素,为肝移植围手术期预防真菌感染提供理论依据。[方法]1、一般资料118例患者于2004年8月至2009年1月在南方医科大学附属南方医院接受肝脏移植手术。其中男100例,女18例,平均年龄47.2(16-74)岁,平均住院时间62.9(16～193)d,平均重症监护室(ICU)留观时间3.8(1～19)d。原发病包括肝炎后肝硬化42例,原发性肝癌70例,重症肝炎4例,布加综合征1例,肝豆状核变性1例。2、术式与免疫抑制方案经典原位肝移植78例,背驮式肝移植40例。免疫抑制剂使用方案：术后常规采用三联抗排斥治疗[他克莫司(FK506)、吗替麦考酚酯、甲基强的松龙；5d后改为FK506、吗替麦考酚酯、强地松)。FK506的血药浓度维持在10-15ng/mL。出现急性排斥反应的患者给予大剂量甲基强的松龙冲击治疗。3、相关因素的选择根据本中心经验以及参考文献综合选择如下44项相关因素进行统计分析。(1)术前因素：性别、年龄、体重、住院时间、吸烟史、肝肺综合征、其他肺部疾病(如肺部炎症、慢性阻塞性肺疾病、支气管哮喘等)、肝功能分级、恶性肿瘤、低蛋白血症、糖尿病、腹腔积液、术前1d检验[血清总胆红素(TBIL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、血浆凝血酶原时间(PT)、血清肌酐(Cr)、血尿素氮(BUN))。(2)术中因素：供肝热缺血时间、冷缺血时间、手术时间、无肝期、出血量、围手术期输血量。(3)术后因素：术后1d内检验(TBIL, ALB, ALT, AST, PT, Cr, BUN)、胸腔积液(包括术前已存在者)、重症监护室(ICU)留观时间、有创机械通气时间、胃肠外营养(TPN)时间、抗生素使用时间及种类、深静脉置管留置时间、尿管留置时间、腹腔引流管留置时间、急性排斥反应、手术并发症(如术后腹腔出血、胆瘘、胆道狭窄等)、并发细菌感染、连续肾替代治疗(CRRT),再次手术。4、统计学处理将符合上述诊断标准的病例归为真菌感染组,其余病例归为对照组。先对肝移植受体围手术期的主要独立变量进行单因素分析(其中计数资料比较采用x2检验,计量资料比较采用独立样本t检验),比较真菌感染组和对照组之间的差异,初步寻找出与感染相关的危险因素。鉴于某些因素可存在相互作用,将有统计学意义的相关因素纳入Logistic回归分析,找出主要的危险因素。采用SPSS13.0统计软件,按a=0.05检验水准,P<0.05为差异有统计学意义。[结果]1、相关因素单因素分析将上述44项围手术期相关因素进行单因素分析,发现术前低蛋白血症、肝功能衰竭、肝肺综合征、ICU留观时间、有创机械通气时间、胸腔积液、抗生素使用时间及种类、深静脉置管留置时间、腹腔引流管留置时间等9项相关因素在真菌感染组与对照组之间差异有统计学意义。2、危险因素多因素分析将上述经单因素分析有统计学意义的9个变量引入Logistic逐步回归分析,最终筛选出5个与肝移植术后真菌感染有显著相关性的危险因素。根据危险性(OR值)大小依次排序为：使用抗生素≥3种且时间≥2周,ICU留观时间≥5d,胸腔积液,有创机械通气时间≥48h及肝功能衰竭。3、感染患者与危险因素的关系26例中有19例治愈,7例死亡,病死率为26.92%；其中与真菌感染直接相关者5例,病死率为19.23%,5例患者中术前肝衰竭2例,术后合并胸腔积液3例,有创机械通气时间均大于48h,均在ICU留观超过5天,均使用广谱抗生素超过3种且时间超过2周。[结论]1、术前低蛋白血症、肝功能衰竭、肝肺综合征、ICU留观时间、有创机械通气时间、胸腔积液、抗生素使用时间及种类、深静脉置管留置时间、腹腔引流管留置时间等9项是肝移植术后真菌感染的相关因素。其中使用抗生素≥3种且时间≥2周,ICU留观时间≥5d,胸腔积液,有创机械通气时间≥48h及肝功能衰竭是肝移植术后真菌感染的主要危险因素。2、针对上述危险因素采取切实有效的预防和治疗措施,加强对高危患者在术后早期呼吸道、胃肠道等易感部位真菌感染的监测,力争早期发现真菌感染和及时治疗；有助于降低术后真菌感染发生率,提高手术成功率。更多还原

【Abstract】 Since Starzl successfully operated the first human liver transplantation in the world in 1963, the liver transplantation has underwent nearly 50 years’development, and became the most effective treatment for patients of last stage liver diseases and the acute liver function failure. But fungal infection is still one of the most important causes of death following the post-operative period in the liver transplantation, The incidence of fungal infections following liver transplantation reaches as high as 15%-42%, and the mortality reaches 40%-80%, which are higher than that of acute rejection, kidney failure and virus infections. Fungal infection after liver transplantation often lack of typical clinical manifestations, which is difficult for correct clinical diagnosis; because of the specificity of surgery and medication for patients who received liver transplantation, fungal infection is difficult to controlled and is a serious complication. The epidemiological features and risk factors of fungal infection after liver transplantation has its uniqueness. As the the growing awareness of fungal infection, the researches of the epidemiology and risk factors for fungal infections after liver transplantation are also increasingly being concerned and become an important subject. We made a retrospective research for epidemic characteristics of the fungal infections within 118 cases who received liver transplantation in Nanfang hospital from August 2004 to January 2009, studied and identified the fungi and drug resistance; selected independent variables to analyzed by univariate analysis and logistic regression to screen out the risk factors. Thus we can provide a theoretical basis for effectively prevention and treatment of fungal infections following liver transplantation.Patr One Analysis of epidemiology and drug resistance of fungal infection during the early postoperative period in liver transplantation[OBJECTIVE] Fungal infection is still the most important complication affecting the success rate and postoperative survival rate during the early postoperative period in liver transplantation.With the introduction of new anti-fungal measures and preventive treatment in recent years. As reported at home and abroad the incidence of fungal infections is still rising, meanwhile the bacterial spectrum has undergone some changes and the fungal resistance rate is gradually increased. In the purpose of making more effective prevention and treatment of fungal infections, we make a retrospective analysis of fungal infection after liver transplantation in 118 cases from August 2004 to January 2009 in Nanfang hospital, to Identify fungi types and drug resistance pattern.[MATERIALS AND METHODS]1. Cases Source The 118 cases who received liver transplantion from August 2004 to January 2009 were included in the research. We test the (1,3)-β-D-glucan of serum and fungal smear specimens 2-3 times a week. The specimens contained: respiratory tract specimens (sputum, throat swab), gastrointestinal tract specimens (gastric juice, faeces), ascites, bile, midstream urine, blood. Of which the positive serum (1,3)-P-D-glucan and (or) positive smear test results,We collected the specimens repeated several times to the appropriate fungal culture and sensitivity test. The patients who were suspected of fungal infections, we collected specimens for culture and sensitivity test repeatedly regardless of the outcome of serum (1,3)-β-D-glucan and smear.2. Fungi identification and susceptibility test We selected chromogenic medium frome Zhengzhou Bossay Bioproducts Co. for fungal culture and identification, The antifungal of piromidic susceptibility test methods refer to M38-A program publiced by the National Committee for clinical trials Standardization (NCCLS) 2003, other drug use Danish Rosco Determination of fungal susceptibility disk diffusion method.3. Diagnostic Criteria①Patients with systemic or local infection in the clinical manifestations and can not be explained by other complications, while the broad-spectrum antibiotics and anti-viral treatment are ineffective.②Fungi Specimens isolated from a sterile site (blood, cleaning the middle of urine, bile, pleural effusion, peritoneal drainage fluids, catheters, etc.) one or more times.③Continuous culture for the kind of fungi two times or more from the same parts by funal culture or pathological examination,or isolated the same kinds of fungi from different parts.④Repeated smear microscopy found that a large number of fungal hyphae or spores and confirmed by fungal culture at least once.⑤Fungal colonization or fungal skin infections are not incorporated into statistical areas.4. Prophylactic treatment with antifungal drugs 58 cases in this group were given preventive use of antifungal agents since the first day after operation: intravenous fluconazole 150～200mg/d,2～3 weeks.5. Statistical analysis SPSS 13.0 statistical software were used to calculate the frequency and percentage.[RESULTS]1. The diagnose and clinical data of 26 cases of suspected fungal infections 26 cases were confirmed to be fungal infections, infection rate was 22.0%, of which 22 male and 4 female. The average age of 54.3 (32～74) years, the average hospital stay was 71.4 (33～193) d. The primary disease including posthepatitic cirrhosis in 12 cases (including 3 cases of acute liver failure),13 cases of primary liver cancer, severe hepatitis in 1 case.26 patients were given triple anti-rejection therapy routinely postoperation [Tacrolimus (FK506), mycophenolate mofetil, methylprednisolone; and changed to FK506, mycophenolate mofetil, prednisone 5 days later]. Plasma concentration of FK506 were maintained at 10-15ng/ml. All cases of postoperative antibiotics were combined, with an average course of 35.9 (20～50) d.2. The site of infection and fungal species Six kinds of fungi were isolated, totally 49 fungi,With the highest detection rate of Candida albicans, Totally of 49 fungi strains were isolated, of which mainly were Candida albicans(57.1%), following the aspergillus, smooth candida, Candida tropicalis, Candida parapsilosis, Candida krusei. Infection site is mainly in respiratory tract, followed by the gastrointestinal tract, abdomen, biliary tract, blood, urinary tract. In which a single system (or organs) fungal infection in 22 cases (84.6%), multiple systems (or organs) fungal infection in 4 cases (15.4%),5 patients with combined more than two kinds of fungal infection.3. Time distribution of fungal infection The average time for infection 13.6 (1～53) d, of which 93.8%occurred within 1 month after surgery. Time distribution of the fungal infection was found after 1 week analysis of detection rate (42.9%) the highest, with time extended, and the detection rate of decline.4. The results of susceptibility test The overall sensitivity of fluconazole was lowest (55.1%), itraconazole and voriconazole was the highest (90.0%, respectively, 92.0%). The resistance rate of Candida tropicalis and Candida were highest (both 42.9%). 5. Treatment and outcome 26 cases of fungal infection were treated with anti-fungal treatment, that is, intravenous fluconazole 150-400mg/d,8-31d, of which 4 cases because of resistance to fluconazole than changed to intravenous infusion of itraconazole 200～00mg/d for 10～25d.19 patients were cured and 7 deaths, the mortality was 26.9%; of which 5cases were directly related with the fungal infection, The direct cause of the other two cases of death is graft-versus-host reaction.[CONCLUSION]1. The pathogenic fungal infections after liver transplantation in the still mainly Candida, including Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei, etc., of which the highest proportion of Candida albicans. Aspergillus with higher mortality (18.4%) of infection is also higher than other reports at home and abroad. Spectrum of fungal infections in recent years, prompted a change in bacteria.2. Infection site is mainly respiratory and gastrointestinal tract, accounting for 75.5%and 10.2%. Fungal infection mainly occurred in the postoperative 1 week (42.9%), with the time extened, the incidence of fungal infections showed a downward trend, suggesting that patients susceptible to liver transplantation period (within 1 month after operation, especially within 1 week) should strengthen the respiratory tract, gastrointestinal tract and other parts susceptible to fungal infection monitoring, and strive to early detection and timely treatment of fungal infections.3. Susceptibility test results of this study show that voriconazole, itraconazole against fungi have a higher sensitivity to amphotericin B, flucytosine, fluconazole and other drugs on fungi, the average sensitivity was relatively low. Various types of antifungal agents on the sensitivity of different species of fungi there are certain differences, itraconazole, voriconazole against Candida and Aspergillus sensitivity rates were generally higher, flucytosine, amphotericin B followed, while the fluconazole against Candida and Aspergillus sensitivity is generally low. As the antifungal agents are widely used in liver transplantation preventive and empirical therapy, and the continual emergence of drug-resistant strains, especially fluconazole-resistant strains increased gradually.4. Anti-fungal treatment should be integrated types of pathogens, drug resistance characteristics and so a reasonable choice of drugs, choice should be based on susceptibility-sensitive drugs, parallel enough, enough course of anti-fungal treatment, poor drug efficacy when used alone can also be changed to combined medication. Itraconazole, amphotericin derivatives, voriconazole with a minor dverse drug reactions which are more sentive to Candida and Aspergillus is a better choice alternative to fluconazole.5. Recent studies suggest that preventive anti-fungal therapy in reducing the liver transplantation the incidence of deep fungal infection has a positive effect. This study also found that preventive anti-fungal effective in preventing fungal infections.Patr Two Analysis and prophylaxis of the risk factors for fungal infection following liver transplantation[OBJECTIVE] Fungal infections are hospital-acquired infection, there are multiple risk factors in susceptible populations,As it’s recognized, patients with severe underlying diseases, immune dysfunction, malnutrition, long-term use of antibiotics and acceptance of a variety of invasive diagnosis and treatment of patients are all the risk factors. Liver transplantion is intended primarily for patients with end-stage liver disease, such as primary liver cancer, hepatitis, cirrhosis, liver failure and so on, the receptor preoperative conditions and nutritional status are always poor, together with the long time and large traumatic of surgry, immunosuppressive therapy and anti-infection treatment-specific after surgry. Therefore, in view of perioperative and operation inherent specificity, it is necessary to find out the major risk factors from a variety of factors leading to fungal infections for perioperative prevention and provide a theoretical basis.[MATERIALS AND METHODS]1. Clinical data 118 cases of patients received liver transplantation in the Nanfang hospital of the South Medical University for liver transplant from.100 cases were male and 18 female, mean age of 47.2 (16～74) years, the average hospital stay was 62.9 (16～193) d, the average intensive care unit (ICU) observation with the time 3.8 (1～19) d. The primary disease, including hepatitis,42 patients with liver cirrhosis, primary liver cancer in 70 cases,4 cases of severe hepatitis, Budd-Chiari syndrome in 1 case, hepatic degeneration in 1 case.2. Surgery program and immunosuppressive regimen Classic orthotopic liver transplantation in 78 cases, piggyback liver transplantation in 40 cases. All patients were given triple anti-rejection therapy routinely postoperation[Tacrolimus (FK506), mycophenolate mofetil, methylprednisolone; and changed to FK506, mycophenolate mofetil, prednisone 5 days later]. Plasma concentration of FK506 were maintained at 10-15ng/ml. All cases of postoperative antibiotics were combined, with an average course of 35.9 (20～50) d.3. The choice of relevant factors we selected 44 related factors as follows for statistical analysis according to the experience in our center and reference literature.①preoperative factors:gender, age, weight, length of stay in hospital, smoking history, hepatopulmonary syndrome, other lung diseases (such as lung inflammation, chronic obstructive pulmonary disease, bronchial asthma, etc.), liver function classification, malignant tumor in liver, hypoalbuminemia, diabetes, ascites, preoperative serum total bilirubin 1d before operation [(TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), serum creatinine (Cr), blood urea nitrogen (BUN)).②Intraoperative factors:liver warm ischemia time, cold ischemia time, operation time, anhepatic phase, blood loss, perioperative blood transfusion.③Postoperative factors:examine the (TBIL, ALB, ALT, AST, PT, Cr, BUN) 1d after operation, pleural effusion (including those which existed before surgery), intensive care unit (ICU) observation with time, there are invasive mechanical ventilation, parenteral nutrition (TPN) time, use of time and types of antibiotics, deep venous catheter indwelling time, catheter indwelling time, intra-abdominal drainage tube indwelling time, acute rejection, surgical complications (eg. postoperative abdominal bleeding, biliary fistula, biliary stricture, etc.), bacterial infections, continuous renal replacement therapy (CRRT), re-operation.4. Statistical analysis Cases consistent with the above-mentioned diagnostic criteria of cases classified as a fungal infection group, the remainder were classified as the control group. First, the major independent variables in perioperative period of the liver transplantion recipients were analyzed in univariate analysis (which count data compared with theχ2 test, measurement data used to compare the independent samples t test), compared with fungal infection group and the control group the difference between the initial search for out the risk factors associated with infection. In view of the existence of certain factors can interact, there will be statistically significant risk factors included in Logistic regression analysis to identify major risk factors. Using SPSS13.0 statistical software, according toα= 0.05 significance level, P<0.05 for the difference statistically significant.[RESULTS]1. Univariate analysis of the relevant factors 44 perioperative factors were analyzed in univariate analysis, found that preoperative hypoproteinemia, liver decompensation, hepatopulmonary syndrome, ICU observation with time, invasive mechanical ventilation, pleural effusion, the use of antibiotics time and type of deep venous catheter indwelling time, intra-abdominal drainage tube indwelling time etc, there are significant difference in the 9 related factors between the fungal infection group and control group statistically.2. Multivariate analysis of risk factors The nine factor which are statistical significance were include into Logistic regression analysis, than final selected five factors after liver transplantation was significantly related to risk factors. According to the risk (OR value) as followed:the use of antibiotics≥3 kinds and the time≥2 weeks, ICU observation with time≥5d, pleural effusion, invasive mechanical ventilation≥48h decompensated liver function.3. The connection between infection and risk factors 19 patients were cured and 7 deaths, mortality of 26.92%; of which are directly related with the fungal infection in 5 cases, mortality of 19.23%, in this 5 cases,preoperative liver failure in 2 cases, merger chest plot fluid in 3 cases, invasive mechanical ventilation were greater than 48h, observation more than five days in the ICU, the use of antibiotics≥3 kinds and the time≥2 weeks.[CONCLUSION]1. Preoperative hypoproteinemia, liver function decompensation, hepatopulmonary syndrome, Deep venous catheter indwelling time, intra-abdominal drainage tube indwelling time, pre-operative liver failure, duration of ventilator over 48 hours, pleural effusion, observation in ICU more than 5 days, the use of antibiotics more than 3 kinds and longer than 2 weeks are risk factors.And the last 5 are the most important risk factors2. We should take effective preventive and treatment measures In response to these risk factors, strengthen high-risk patients in monitoring in early postoperative,such as respiratory tract, gastrointestinal tract and other parts which susceptible to fungal infection. and strive to early detection and timely treatment of fungal infections. The above measures can help to reduce the incidence of postoperative fungal infections and improve the success rate of surgery.更多还原