Liver transplantation in patients with Caroli's disease and recurrent cholangitis

Caroli's disease is an uncommon congenital disorder of the intrahepatic biliary tree. It is characterized by multiple and segmental dilatations of the bile ducts. The clinical course of Caroli's disease is often complicated by recurrent episodes of bacterial cholangitis that seriously impair the patient's quality of life. Despite wide spectrum antimicrobial agents, medical treatment of cholangitis is frequently unsuccessful in patients with Caroli's disease due to the persistence of bacteria in dilatated bile ducts. Other therapies, including internal or external biliary drainages and various surgical or endoscopic procedures, have been used in the treatment of Caroli's disease, with poor results. There are no previous reports in the literature of liver transplantation for recurrent cholangitis in patients with Caroli's disease. We present two such cases, in which cholangitis is resolved. Received: 16 July 1996 Received after revision: 4 February 1997 Accepted: 5 February 1997     

Liver transplantation in a 7-month-old girl with Caroli's disease

Caroli's disease (including Caroli's syndrome) is a rare autosomal recessive disorder of the liver characterized by diffuse cystic dilatation of the intrahepatic bile ducts. The disease may present at any age and is characterized by recurrent episodes of biliary obstruction, cholangitis, hepaticolithiasis, and liver abscesses. Caroli's syndrome is further associated with congenital hepatic fibrosis and portal hypertension. Patients with recurrent complications or cirrhosis may die because of recurrent infection, portal hypertension, liver failure, or cholangiocarcinoma. Liver transplantation is the treatment of choice for these complicated patients. Here we describe the youngest reported patient with Caroli's syndrome treated successfully using liver transplantation and review the recent literature.     

背驮式原位肝移植术治疗Caroli''s病

目的 总结背驮式原位肝移植技术治疗Caroli's病的经验。方法 回顾性分析2例Caroli's病病人行背驮式原位肝移植手术的临床资料。结果 2例Caroli's病病人背驮式原位肝移植手术获得成功，手术效果好，已分别存活17及18个月，已恢复工作和正常生活，结论 背驮式原位肝移植是目前治疗弥漫的伴反复胆管炎的Caroli's病的有效方法。     

Living-donor liver transplantation in adults

End-stage liver disease is being treated by liver transplantation. Despite legislative and social efforts, the number of cadaveric organs suitable for liver transplantation has not grown to match the increasing demand. The insufficient number of grafts results in high mortality for patients on the waiting list and prolonged waiting times with increasing morbidity. Following the success of living related-donor segmental liver transplantation in children, an amended concept has been applied to the adult patients. The early experience with this technique, the process concerning the selection of the donor for the recipient, the risks of the donor, and the future evolution of living related-donor liver transplantation are the topics of this article. Received: 15 October 1999 Accepted: 20 October 1999     

Caroli's病的研究现状

Caroli's病是一种罕见的常染色体隐性遗传病,由于该病发病率低,临床医师认识不足,临床表现隐匿且复杂,常容易导致误诊及漏诊.为了更好的认识此病,本文对本病的病因、分型、病理、临床表现、诊断和治疗现状做以综述.     

The place of liver transplantation in Caroli''s disease and syndrome

Caroli's disease (CD) or syndrome (CS) are rare inherited disorders which may cause severe, life-threatening, cholangitis or which may lead to hepatobiliary degeneration. The typical cystic biliary anomalies are often associated to congenital hepatic fibrosis (CHF) and, less frequently, to cystic renal disease especially autosomic recessive polycystic kidney disease (ARPKD). The place of liver transplantation (LT) in the treatment of CD or CS is evaluated based on our own experience of three successfully transplanted patients, the literature review of 19 patients and the European experience with 110 patients collected in the European Liver Transplant Registry. LT should be proposed as a definitive therapeutic option once severe cholangitis or (suspicion of) malignant transformation is present. The frequently used radiological, endoscopical or surgical biliary drainage procedures carry a high morbidity and mortality rate. In case of concomitant symptomatic CHF and renal failure, combined or sequential hepatorenal transplantation should be carried out, dependent on the evolution of the hepatic and renal disease. In case of associated ARPKD, renal transplantation is often indicated early on because of the more rapid progression of the renal component of the disease.     

Living related liver transplantation for polycystic liver disease

Polycystic liver disease (PCLD) is a rare inherited disorder, often associated with polycystic disease of the kidney. Although liver failure is unusual, some patients suffer from hepatic enlargement associated with severe complications such as abdominal distention, cachexia and dyspnea. Until recently, many surgical attempts had been made to reduce hepatic size, however, results have been unsatisfactory [3, 9, 10]. Today, liver transplantation is recommended as a therapeutic option, and excellent outcome has been demonstrated [1, 2, 4, 5, 6, 8, 11]. In this paper, we present the first case study of total hepatectomy and partial liver transplantation for PCLD, from a living, related donor. The patient is a 38-year-old man with PCLD who underwent living related liver transplantation (LRLT). He is alive and well 21 months after the operation, with complete resolution of the symptoms. He has returned to his previous job, with a marked improvement in his quality of life. Our experience demonstrates that LRLT can be an option for treatment of PCLD.     

Living-donor liver transplantation in children

Introduction: Living- related liver transplantation (LRLT) for paediatric recipients was developed 10 years ago to overcome the high mortality on the waiting list. Since then, liver transplantation programs around the world have begun to employ this method with encouraging results. This review describes the actual status of LRLT in children, aspects of donor selection, donor risks, and surgical technique, as well as an update of the results of the leading LRLT programs in the world. The donor operation has matured to the stage of being a standardised, teachable procedure with a low risk of morbidity or mortality. However, there is a percentage of potential donations that have to be declined for medical or socio- psychological reasons. LRLT provides grafts of excellent quality and short cold ischemic times. A major advantage is the fact that the optimal moment for the transplantation procedure can be chosen. Together with split-liver techniques, LRLT has a positive effect on the general situation of the paediatric waiting list for liver transplantation, with a reduction of pre-transplant mortality to nearly 0%. Received: 14 October 1999//Accepted: 20 October 1999     

Living-donor liver transplantation: an overview

It has been 16 years since the first successful living-donor liver transplant was performed from a parent to a child. The overall recipient and graft survival, together with a low morbidity and mortality in donors, have resulted in the widespread acceptance of the procedure by both the transplant community and the public at large. Adult-to-adult living-donor liver transplantation has been evolving over the past decade. Despite living-donor transplant patients being better-risk candidates than those who receive a graft from a deceased donor, and well-established and experienced units achieving satisfactory results, overall recipient and graft survival recorder by registries can only be described as suboptimal. This, combined with the high morbidity and not-insignificant mortality amongst donors makes expansion of adult-to-adult liver transplantation hard to justify on a risk-benefit analysis.     

活体肝移植治疗终末期肝病

目的 探讨活体肝移植(1iving donor liver transplantation,LDLT)供、受者术前评估和手术方式的选择.方法 回顾性分析1995年1月至2007年10月我中心95例LDLT患者的临床资料.良性终末期肝病92例,其中Wilson病45例;肝脏恶性肿瘤3例.结果 供肝切取不带肝中静脉右半肝31例,带肝中静脉右半肝3例,带肝中静脉左半肝51例,不带肝中静脉左半肝或左外叶10例.所有供者术后顺利恢复,均未出现严重并发症.受者随访1～86个月,良性终末期肝病受者1、3、5年累积生存率分别为89%(82例)、78%(71例)和73%(67例),其中Wilson病受者1、3、5年累积生存率分别为92%(42例)、89%(40例)和76%(34例).3例肝脏恶性肿瘤患者死亡2例,1例长期生存.供、受者铜代谢均恢复正常.结论 建立供者安全保障体系是LDLT开展的先决条件,选择合理的手术方式是提高受者生存率的关键.亲体肝移植是治疗Wilson病的有效手段.     

原位肝移植治疗多囊肝病的临床分析

目的 探讨肝移植治疗多囊肝病中的效果和经验.方法 回顾分析我中心2000年1月至2008年12月9例多囊肝行肝移植的病例,对患者术前MELD评分、肝肾功能,术中输血、失血,手术时间、无肝期以及术后并发症、存活时间等方面进行总结.结果 9例患者术前MELD平均(16±9)分,5例同时患有多囊肾,除1例出现肝硬化外其他8例无明显肝功能损害但因明显的压迫症状而严重影响生活质量,3例有肾功能异常需要透析.术中平均输血(1800±1600)ml,失血(3500±2600)ml,平均手术时间(7.2±1.5)h,无肝期(52.7±15.4)min.术后3例分别因腹腔出血、急性排斥反应及循环衰竭导致多器官衰竭而早期死亡;6例患者均存活1年以上,现最长存活时间8年.本组1年和2年存活率分别为77.8%和66.7%.结论 肝移植是治疗多囊肝疾病的有效方法,比较其他的肝移植受者手术时间长,失血量较大,手术难度较高,但预后良好.     

Living-donor liver transplantation for homozygous familial hypercholesterolemia from a donor with heterozygous hypercholesterolemia

Familial hypercholesterolemia is a rare inherited disease with an incidence of approximately one per million. Severe hypercholesterolemia is observed from the time of birth onwards. It is associated with severe atherosclerosis in childhood, leading to death from myocardial infarction before the age of 20 years. Liver transplantation is the only effective treatment for this disease. We experienced the case of an infant aged 2 years 5 months who had homozygous familial hypercholesterolemia and who received a liver graft from his father, who had familial heterozygous hypercholesterolemia. The pre-operative plasma cholesterol level was >800 mg/dl. After liver transplantation, the recipient's cholesterol level decreased to 250 mg/dl after we administered the HMG-CoA reductase inhibitor. At present, 6 months after transplantation, the patient is doing well and free from a special diet. We can thus conclude that the combination therapy of liver transplantation from a donor with heterozygous familial hypercholesterolemia on cholesterol-lowering drugs is an effective therapy for a patient with the homozygous type of hypercholesterolemia.     

肝移植治疗Caroli病七例报道

目的 探讨肝移植治疗Caroli病的临床效果.方法 回顾性分析1999年9月至2008年2月期间7例弥漫型Caroli病患者行肝移植治疗后的临床资料.对其临床特征、手术方式、并发症类型以及随访情况进行分析.结果 7例患者术前均表现为复发性胆管炎症状并最终确诊为弥散型Caroli病.其中男性3例,女性4例;年龄10～31岁,平均16岁.6例患者肝移植术前接受保守治疗,1例曾行胆囊切除、T型管引流术.4例患者行劈离式肝移植,2例行全肝移植,1例行亲属活体供肝肝移植.其中2例患者术中采用静脉-静脉转流术.手术平均耗时9.1 h.术后并发症包括:肺部感染3例、急性排斥反应2例、胸腔积液2例、肝断面胆汁漏1例.经抗感染、调整免疫抑制方案及用量、胸腔穿刺抽吸及经皮穿刺引流等对症保守治疗后症状得到控制.1例肝移植受者术后19 d死于急性肾功能衰竭合并多器官功能衰竭,其余6例受者均存活.随访发现,存活的6例受者健康状况良好,其中最长存活已达7年.结论 应用肝移植治疗弥散型Caroli病具有良好的临床效果.     

再次肝移植治疗首次肝移植术后肝癌肝内复发的效果分析

目的 探讨肝癌肝移植术后复发肝癌的病理特点及再次肝移植治疗的意义及其预后.方法 回顾性分析肝移植术后21例肝癌复发患者的临床资料,其中9例接受再次肝移植治疗,12例行姑息治疗.所有患者原发病均为乙型肝炎后肝硬化合并肝癌,肝移植术后肿瘤均为肝内复发,无法局部切除.结果 9例患者首次和再次肝移植时肿瘤病理分析,肿瘤均为肝细胞肝癌,最大肿瘤直径分别平均为6.2 cm和4.8 cm,多发肿瘤者分别占67％和89％,有微血管侵犯者分别占100％和56％,肿瘤分化为Ⅱ级、Ⅲ级和Ⅳ级者分别为33％、67％、0和22％、22％、56％,复发肝脏肿瘤的平均最大直径和分化程度与原发肝脏肿瘤比较,差异均有统计学意义(P＜0.01).首次肝移植术后再次移植组患者无瘤存活时间中位数为15.0个月,再次肝移植术后无瘤存活时间中位数为2.5个月,再次移植术后存活时间中位数为5.8个月,总体存活时间中位数为21.8个月;姑息治疗组受者肝移植术后无瘤存活时间中位数为13.0个月,总体存活时间中位数为17.6个月;再次移植组和姑息治疗组术后1、2、3年累积存活率分别为89％、44％、33％和91％、45％、9％,两组间存活率比较,差异无统计学意义(P＞0.05).结论 血管侵犯为肝癌复发的高危因素;复发肿瘤分化程度更低;首次肝移植术后肝癌肝内复发可能是术前和术中肿瘤全身播散的早期临床特点和局部表现,不建议再次肝移植治疗肝癌肝移植术后肝癌肝内复发.     

Primary liver disease as a determinant for acute rejection after liver transplantation

Background: Graft rejection and infection remain major problems following liver transplantation; both are heavily influenced by the immunosuppressive regimen. Despite the disparity in the primary disease leading to transplantation, all patients receive the same post-transplant immunosuppressive treatment in a given center. The aim of this study is to detect a possible effect of the underlying disease on the incidence of early acute rejection episodes after orthotopic liver transplantation (OLT). Patients and Methods: Retrospective analysis on all 101 consecutive liver transplants performed in 95 patients between 1983 and March 1998; five of these patients, surviving less than 30 days, were not included. The immunosuppressive regimen was based on conventional triple therapy during the whole study period. The diagnosis and treatment of acute rejection within the first 30 days post-OLT was uniform throughout the whole study period. Results: Though there were no differences with respect to patients' characteristics [age, child classification, number of HLA-mismatches or cytomegalovirus (CMV)-serocompatibility], patients with primary biliary cirrhosis (PBC) showed a significant increase of acute rejection after OLT compared with the other patients transplanted for other liver diseases (P = 0.024). The incidence of infection was not elevated in patients transplanted for PBC when compared with other diagnoses. Conclusion: Our results indicate that primary liver disease may be a determinant for acute graft rejection in PBC. Furthermore, these results suggest that immunosuppressive regimens based on the underlying disease should be considered. Received: 19 October 1998 Accepted: 28 January 1999     

原位肝移植治疗成人尼曼匹克病一例

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经颈静脉肝内门体分流术(TIPSS)与肝移植

目的 经颈静脉肝内门体分流术（TIPSS）正逐渐成为控制食管曲张静脉破裂出血和肝移植之间的桥梁。目前国内没有有关TIPSS对原位肝移植手术影响的报道。方法 回顾性研究接受术前TIPSS治疗的肝移植病人，即评价TIPSS作为肝移植桥梁的有效性和是否影响移植手术。结果 匹兹堡移植中心5例术前接受TIPSS的肝移植病人。行TIPSS与肝移植间隔时间为9．6（0．2－24．7）个月，3例病人在肝移植前能有效地控制出血。4例病人的支架位于肝实质内，并不影响手术；1例部分突出于肝外门静脉，术中需要移去支架。术后随访时间平均4.2(2-7)个月，无门静脉血栓形成。手术时间和术中输血量无显著性差异。结论 TIPSS是一种有效的桥梁，并没有增加移植术后并发症发生率和死亡率；鉴于有潜在的手术风险，支架最好放置在肝实质内，但肝外支架并不构成移植手术的反指征。     

原位肝移植治疗终末期自身免疫性肝病

目的 评价肝移植治疗终末期自身免疫性肝病的疗效并总结临床经验.方法 回顾性分析2003年9月至2009年7月间因终末期自身免疫性肝病接受肝移植手术的11例患者的临床资料,其中8例为原发性胆汁性肝硬化,2例为自身免疫性肝炎,1例为原发性硬化性胆管炎.平均年龄为(44.2±8.7)岁.手术方式均采用附加腔静脉整形的改良背驮式肝移植术.术后免疫抑制治疗采用他克莫司或环孢素A联合激素的二联免疫抑制方案,部分患者使用骁悉和熊去氧胆酸.结果 本组11例患者中2例原发性胆汁性肝硬化患者死亡,其中1例于术后第5天死于肺部感染和多器官功能衰竭,另1例于术后964 d死于脓毒症和移植肝失功.5例患者术后1个月内出现急性排斥反应,加强免疫抑制治疗后痊愈.9例患者生存良好并存活至今,随访期7～62个月,中位随访时间为38个月.受体1年存活率为91%,3年存活率为82%,最长存活期5年.随访期间未发现复发病例.结论 肝移植是治疗终末期自身免疫性肝病的惟一有效手段,手术时机的正确把握和有效的免疫抑制治疗是减少肝移植术后并发症的关键.

Abstract：

Objective To evaluate the effect of liver transplantation for end-stage autoimmune liver disease (ESALD) and summarize the clinical experience of liver transplantation in the treatment of ESALD.Methods The clinical data of 11 ESALD cases who underwent liver transplantation from September 2003 to July 2009 were analyzed retrospectively. There were 2 males and 9 females ( median age, 44. 2 ± 8. 7years). The indication of liver transplantation was end stage of primary biliary cirrhrosis (8 cases),autoimmune hepatitis (2 cases), and primary sclerosing cholangitis ( 1 case). In all cases, modified piggyback liver transplantation with venacavaplasty was carried out. Postoperatively all patients were treated with immunosuppressive agents including tacrolimus (or cyclosporine A) and prednisone, some patients were treated additionally with mycophenolate mofetil and ursodeoxycholic acid. Results Postoperatively 2patients of primary biliary cirrhosis died, one of lung infection and multiple organ failure on the 5th postoperative day, the other dying of sepsis and graft dysfunction on the 964th postoperative day. Five cases suffered from episodes of acute cellular rejection within 1 month after transplantation and was successfully reversed by strengthened immunosuppressive therapy. Nine patients recovered satisfactorily and with excellent life quality until now. Patients were followed up from 7 months to 62 months with the median follow-up time of 38 months. The recipient survival rate at 1 year and 3 years was 91% and 82% ,respectively. One patient has now survived for 5 years. No recurrent ALD case was found during follow up.Conclusions Orthotopic liver transplantation is an exclusive treatment for ESALD. Optimum operation timing and effective immunosuppressive treatment are very important for decreasing occurrence of complications.