肝移植术后腹泻的病因及治疗

腹泻是肝移植术后常见并发症。肝移植术后腹泻确切发生率仍不清楚，根据其他实质器官移植及骨髓移植的研究资料，其发生率为10％～43％。感染是肝移植术后腹泻的最常见病因，包括巨细胞病毒感染，艰难梭状芽孢杆菌感染，偶有非典型肠道感染。免疫抑制疗法是肝移植术后腹泻的另一常见病因。吗替麦考酚酯、环孢素A、他克莫司、西罗莫司均与肝移植术后腹泻相关。少数情况，移植物抗宿主反应、淋巴组织异常增殖、炎症性肠病及结肠癌也可引起腹泻。肝移植术后腹泻病因仍有1／3难以确定。本文对相关文献进行了综述，为肝移植术后腹泻的诊治提供参考。[第一段]     

中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)

肝脏虽为"免疫特惠器官",肝移植术后急性排斥反应发生率及严重程度明显低于其他器官移植,但术后排斥反应仍较为常见,规范的免疫抑制治疗是保证移植效果的关键。为进一步规范肝移植术后免疫抑制治疗及排斥反应诊疗,中华医学会器官移植学分会组织肝移植专家,总结国内外相关研究最新进展,并结合国际指南和临床实践,针对肝移植术后免疫抑制剂应用原则、常用方案及各类型排斥反应的诊断与治疗,制订《中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)》。     

中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)

肝脏虽为“免疫特惠器官”,肝移植术后急性排斥反应发生率及严重程度明显低于其他器官移植,但术后排斥反应仍较为常见,规范的免疫抑制治疗是保证移植效果的关键。为进一步规范肝移植术后免疫抑制治疗及排斥反应诊疗,中华医学会器官移植学分会组织肝移植专家,总结国内外相关研究最新进展,并结合国际指南和临床实践,针对肝移植术后免疫抑制剂应用原则、常用方案及各类型排斥反应的诊断与治疗,制订《中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)》。     

依维莫司在肝细胞癌肝移植术后的临床应用

目的阐述依维莫司(everolimus,EVR)的作用机制以及EVR在肝细胞癌(hepatocellular carcinoma,HCC)患者肝移植术后的应用和疗效及常见不良反应。方法通过万方、知网、PubMed等网站检索近年来的相关文献,进行阅读、分析、总结,得出结论。结果目前用于HCC患者肝移植术后的免疫抑制剂种类众多,免疫抑制治疗方案也多种多样且尚无统一标准。现今临床上使用较为广泛的用于移植术后的免疫抑制剂为钙调磷酸酶抑制剂(calcineurin inhibitors,CNIs),但由于其肾毒性及增加HCC复发概率等副作用,CNIs在HCC患者肝移植术后的使用逐渐受到限制,而哺乳动物雷帕霉素靶点(mammalian target of rapamycin,mTOR)抑制剂则开始受到重视,逐步走入临床,为肝移植术后免疫抑制治疗提供了新思路。EVR作为一种mTOR抑制剂,正逐步应用于HCC患者肝移植术后。结论 EVR作为近年来才被批准使用于HCC患者肝移植术后的mTOR抑制剂,相关文献研究均显示它在提高移植成功率、对肾功能的保护及抑制HCC复发等方面发挥了重要作用。     

肝癌肝移植研究进展

原发性肝细胞癌是常见的恶性肿瘤,肝移植是全世界公认的治疗终末期肝脏疾病的最有效方法。在我国,肝癌仍是肝移植的主要适应证。本文从肝癌肝移植的适应证、病人免疫抑制剂的个体化应用及肿瘤术后复发的防治等方面对肝癌肝移植研究进展进行综述。     

原位肝移植术后脑病的治疗

目的　探讨同种异体原位肝移植术后脑病可能的病因及治疗。方法回顾性分析 5 1例肝移植的临床资料。结果本组 6例患者并发了肝移植术后脑病 ,发生率为 11.8% (6/ 5 1) ,均发生在术后一月内。经应用镇静剂、多巴胺受体阻断剂 (氟哌啶醇 )治疗 ,6例患者全部治愈。结论肝移植术后脑病可能与多种因素有关 ;术前、术后的代谢紊乱 ,术中的血液动力学的异常 ,术后免疫抑制剂的应用等可能是肝移植术后脑病发生的重要因素 ;应用镇静剂、多巴胺受体阻断剂治疗肝移植术后脑病效果良好。     

肝移植术后感染的炎症标志物研究进展

近年来随着受体选择、外科技术及免疫抑制剂治疗的发展,肝移植术已成为治疗终末期肝病的常规手段。肝移植术后感染是影响器官移植患者预后的重要因素之一,亦是肝移植术后的主要致死原因[1]。Gao等[2]认为,缺血-再灌注是肝移植术中引起炎症反应最主要的原因,而术后大剂量应用免疫抑制剂,进一步降低了患者的免疫功能,极易被感染。肝移植术后的感染常表现为脓毒血症,最初是     

肝移植术后精神并发症的早期诊断与治疗

目的探讨肝移植术后精神并发症的早期诊断和治疗。方法回顾性分析24例原位肝移植患者的临床资料,分析肝移植术后精神并发症的发生原因和诊断,总结治疗经验。结果15例患者于术后1周内出现不同程度的精神并发症,其中5例症状较为明显。临床表现为亢奋、蹂狂、抑郁、焦虑、睡眠障碍、震颤及认知改变等。术前有无肝性脑病、术后感染及使用免疫抑制剂与术后精神并发症的发生有关。结论肝移植术后精神并发症的发生率较高。病因与多种因素有关,临床表现形式多样。需排除脑桥中央髓鞘溶解症。针对不同病因和及时处理,可有效改善与控制症状。     

肝移植术后疑诊急性移植物抗宿主病1例报告:附文献复习

目的探讨肝移植术后移植物抗宿主病(GVHD)的病因、诊断及治疗。方法回顾性分析天津市第一中心医院1例肝移植术后疑诊GVHD患者的病情进展、组织学特点及治疗经过,并进行相关文献复习。结果患者于外院行肝移植术,术后2周先后出现发热、癫痫、皮疹、骨髓造血停滞等症状,经抗感染治疗无效,病史结合皮肤活检、骨髓涂片镜检、T细胞亚群等检查,考虑GVHD,停用免疫抑制剂,甲泼尼龙1 g静脉滴注,皮疹消褪,但整体病情进展,于术后3周患者死于多器官功能衰竭。结论肝移植术后GVHD为一种致命的并发症,病死率高达75%以上,目前尚无确诊标准,本文结合该病例特点,复习肝移植术后GVHD相关文献,并提出待解决问题,以期提高对该疾病的认识,并指导临床工作。     

免疫检查点抑制剂药物在肝癌肝移植中的研究进展

本综述介绍了免疫检查点抑制剂在肝癌肝移植中的研究进展,总结了近几年国内外对肝癌肝移植术后免疫检查点抑制剂药物应用的临床报道,分别从免疫检查点抑制剂的作用机制、临床应用、发生排斥反应的相关因素及机制等方面做了详细描述,以期为临床管理人员制定肝癌肝移植术后诊疗计划提供参考。     

肝移植术后高胆红素血症的原因及处理

目的：探讨原位肝移植术后胆红素升高的原因及其处理方法.方法：回顾性分析了我院肝移植术后出现高胆红素血症40例患者的临床资料,采用临床表现与肝穿刺活检及ERCP检查的方法明确原因,分析总结其原因及相关处理方法.结果：40例肝移植患者发生术后高胆红素血症的病因包括：急性排斥反应16例（40.0%）、保存性损伤11例（27.5%）、胆道并发症7例（17.5%）、药物反应6例（15.0%）.无原发性肝脏无功能者,受者1年生存率约为90%,高胆红素血症临床治愈率为95%.结论：肝移植术后发生高胆红素血症的原因较多,机制复杂,以急性排斥反应、保存性肝损伤、胆道并发症和药物反应常见,临床上应根据其病因,进行综合处理,常可取得较好的临床效果.     

Diarrhea in liver transplant recipients: etiology and management.

Diarrhea is common after liver transplantation (LT). The true incidence of diarrhea in liver transplant recipients is unknown but possibly ranges from 10% to 43% based on a few published studies in other solid organ and bone marrow transplantation. Infectious etiologies, including cytomegalovirus (CMV), Clostridium difficile, and occasional atypical intestinal infections, are the most common causes. Diarrhea is also a frequent side effect of immunosuppressive medications. To variable extents, mycophenolate mofetil (MMF), cyclosporine A (CSA), tacrolimus, and sirolimus are all known to be associated with diarrhea. Rarely, graft-versus-host disease (GVHD), lymphoproliferative disorder, de novo inflammatory bowel disease (IBD), or colon cancer may present as diarrhea. Flare-up of preexisting IBD is also not uncommon after LT. However, the cause of acute diarrhea remains unidentified in 1 of 3 patients. This review summarizes the literature and provides recommendations on the management of acute diarrhea after LT. Although our focus is on LT, the etiology and management recommendations apply to most transplant recipients.     

肝移植术后早期高胆红素血症的临床研究

目的探讨原位肝移植术后1月内导致高胆红素血症的原因,并提出其防治措施。方法通过对41例原位肝移植患者1月内的临床表现、实验室检查、影像学及移植肝病理学检查等资料回顾性分析,确定肝移植术后早期高胆红素血症的原因,并提出相应的防治措施。结果本组术后早期发生高胆红素血症的主要原因包括：保存（含再灌注损伤）（35例,85．4％）,胆道并发症（18例,43．9％）,急性排斥反应（13例,31．7％）,血管并发症（5例,12．2％）,感染并发症（20例,48．8％）,术前高胆红素血症（12例,29．2％）,药物毒性反应（4例,9．8％）。通过对其原因及时处理,于术后满1月时28例高胆红素血症基本消失,临床治愈率为68．3％（28／41）,6例效果不明显,7例死亡。结论肝移植术后早期高胆红素血症通常是多种原因同时或相继作用所致,其中保存及再灌注损伤、胆道并发症、急性排斥反应以及感染并发症是最常见的原因,早期病因诊断、根据不同的病因作相应的处理是提高其治愈率的关键。     

Two- to three-fold increase in blood tacrolimus (FK506) levels during diarrhea in liver-transplanted children

BACKGROUND: The diagnosis and treatment of diarrhea in liver transplant recipients often pose a challenge owing to the variety of infectious and non-infectious causes. However, diagnosis is principally focused on ruling out an infectious etiology. Tacrolimus, an immunosuppressive agent generally used after liver transplantation, is absorbed mainly from the duodenum through the upper jejunum. It can be assumed that metabolism of the drug will be influenced by diarrhea. METHODS: Four liver transplant recipients who developed an episode of acute gastroenteritis. Infectious etiology was confirmed; trough tacrolimus levels were measured before, during and after gastroenteritis. RESULTS: All patients presented a two- to three-fold increase in blood tacrolimus levels after the onset of gastroenteritis. CONCLUSIONS: Until the role played by the intestine in the metabolism of tacrolimus is fully understood, it is prudent to recommend early dose reduction of tacrolimus and careful monitoring of trough levels during diarrheal disorders of any nature in pediatric liver-transplanted patients.     

肝移植术后胆道并发症病因及预防

目的分析原位肝移植术后胆1道并发症的病因。方法回顾性分析307例尸体供肝和40例活体供肝原位肝移植的临床资料,总结术后胆道并发症的病因。结果40例活体肝移植受体术后胆道并发症的发生率5.0%,307例尸体供肝肝移植受体术后胆道并发症的发生率为18.9%;肝内胆道狭窄和胆道铸型结石形成等严重胆道并发症在活体肝移植和放置“T”管的尸肝移植未发生。结论缺血时间尤其热缺血时间是导致严重胆道并发症的最主要的原因,放置“T”管引流能降低胆道并发症的发生率。     

肝移植术后早期黄疸的原因分析

目的 探讨肝移植术后早期黄疸的原因。方法 回顾性分析87例肝移植患者术后早期黄疸发生的原因及临床特征。结果 87例患者中，术后46例（52．87％）发生黄疸，共发生21种并发症，有17种（80．95％）并发症伴发黄疸，导致黄疸发生的常见原因依次为缺血．再灌注损伤（n=25，28．73％）、胆道并发症（n=23，26．44％）、急性排斥反应（n=19，21．84％）、药物性肝损害（n=4，4．60％）、移植肝病毒感染（n=4，4．60％）、腹腔内或全身严重感染等（n=3，3．45％），有2例（2．30％）原因不明；46例中，部分病例同时存在多个原因。不同原因所致的黄疸，在发生时间、胆红素水平的变化等方面均呈现相应的特征。结论 黄疸是肝移植术后早期较常见的临床表现，导致黄疽的原因复杂，甄别其主要原因，对指导治疗至关重要。     

Intrahepatic biliary strictures after liver transplantation

Biliary complication has been one of the most common complications after liver transplantation. Nonanastomotic strictures and dilatations involving the intrahepatic biliary tree have been recognized as biliary complications. These lesions were reported to be associated with hepatic artery thrombosis; prolonged preservation time; ABO-incompatible organs; and immunological injury, including injuries to vascular endothelial cells (chronic rejection) and the bile duct (primary sclerosing cholangitis). However, the etiology of these lesions appeared to be mostly related to ischemic injury. Anatomical research on the arterial supply of the bile duct has provided further insights into bile duct blood supply and its surgical implications. The biliary tract is supplied with arterial blood by a vasculature called the peribiliary vascular plexus. Any injury to the peribiliary vascular plexus may contribute to ischemic death of the biliary system mucosa. At many points, the process of liver transplantation exposes the endothelial cells and peribiliary vascular plexus to ischemic injury. The majority of intrahepatic biliary strictures (IHBS) are diffuse or bilateral. A percutaneous or an endoscopic approach has been used as the initial treatment. However, a low threshold for surgical intervention (retransplantation) should be adopted, because these patients demonstrate high mortality. The aim of this article is to review the anatomy, etiology, clinical picture, diagnosis, management, and prognosis of IHBS after liver transplantation.     

Use of short tandem repeats for DNA fingerprinting to rapidly diagnose graft-versus-host disease in solid organ transplant patients

BACKGROUND: Graft-versus-host disease (GVHD) is a rare complication following liver transplantation and carries a poor prognosis with mortality approaching 90-95%. Diagnosis of GVHD is often delayed due to early symptoms mimicking more common, entities such as drug reactions and viral syndromes. To date, definitive diagnosis has been difficult and has relied on a constellation of clinical and histopathologic variables. We present the use of short tandem repeat DNA "fingerprinting" technology as a method of early, definitive diagnosis of GVHD in patients after liver transplantation. METHODS: A patient status-postorthotopic cadaveric-liver transplant, with an uncomplicated immediate posttransplant course, presented 4 weeks after transplant with fever, diarrhea, and maculopapular rash on her palms, soles, and back. The patient's condition worsened despite empiric treatment for an infectious etiology. Skin and rectal biopsies were suspicious for GVHD. RESULTS: DNA was isolated from the skin and rectal biopsies as well as from a donor lymph node. PCR amplification was done for nine highly polymorphic short tandem repeats for each specimen and a unique DNA "fingerprint" was obtained from each. DNA from skin and rectum demonstrated mixed chimerism with both donor and recipient alleles detected. Thorough analysis confirmed GVHD. CONCLUSION: Short tandem repeats for DNA fingerprinting represents an efficient and reproducible method for the definitive diagnosis of GVHD after liver transplantation. Rapid detection of GVHD using this technology, coupled with early initiation of therapy, may lead to improved survival for patients with GVHD after solid organ transplant.     

Chronic graft-versus-host disease after liver transplantation: a case report

Graft-versus-host disease (GVHD) after orthotopic liver transplantation (OLT) is a rare but significant complication, occuring in 1%-2% of cases with a mortality rate of 85%- 90%. It occurs when donor passenger lymphocytes mount an alloreactive response against the host's histocompatibility antigens. It presents as fever, rash, and diarrhea with or without pancytopenia. Between March 2002 and September 2011, among 656 OLT patients 1 (0.15%) had acute GVHD. A biopsy at the 7th posttransplantation month revealed chronic GVHD. Consequently, in the cases that had fever, rash, and/or desquamation of the any part of body after liver transplantation, GVHD must be considered and skin biopsies must be planned for the diagnosis.     

肝移植术后胆道并发症的介入治疗

目的探讨原位肝移植术后胆道并发症的介入治疗疗效。方法回顾性分析我院2002年6月至2005年9月诊治的173例原位肝移植患者的临床资料。结果术后出现胆道并发症14例(8.1%),其中胆管狭窄6例,胆管狭窄合并胆漏1例,胆泥淤积或结石3例,肝断面胆漏2例(劈离式肝移植患者),T管拔除后胆漏1例,Oddi括约肌功能失常1例。除1例胆道狭窄再次行肝移植,因发生严重感染导致肝功能衰竭死亡外,其余患者经介入治疗均获得满意的效果。结论介入治疗是诊断和治疗肝移植术后胆道并发症的首选方法。