自身免疫性肝病与肝移植

肝移植是目前公认的治疗终末期肝病的惟一有效手段。自身免疫性肝病(AILD)主要包括自身免疫性肝炎(AIH)、原发性胆汁性胆管炎(PBC)、原发性硬化性胆管炎(PSC),其肝移植适应证与其他急、慢性肝病类似。尽管AILD患者行肝移植术预后良好,但术后复发较为常见,影响了患者的术后管理和移植物的存活率。此外需注意的是,非AILD肝移植患者术后会新发AIH。本文就AILD的肝移植适应证和预后作一概述。     

肝移植术后机械通气时间延长的预测因素及干预措施

近年来肝移植技术和围手术期管理水平有了很大的提高,但仍有许多围手术期并发症导致受体预后不良。其中术后机械通气时间延长(PMV)是术后早期常见的并发症。PMV导致更易发生术后并发症,住ICU和住院时间延长,病死率增加。近年已有较多研究肝移植术后PMV的文献报道,但尚无总结性统计归纳,也无预防术后PMV的措施。整理归纳了肝移植术后PMV的相关影响因素及可干预手段,以期为临床减少肝移植术后机械通气时间、改善受体预后提供有价值的信息。     

肝移植术后早期死亡因素的研究进展

正肝脏移植术已成为治疗终末期肝脏疾病和急性肝功能衰竭最有效的方法,随着外科技术的发展,新型免疫抑制剂的应用,肝移植术后长期存活率不断提高,但其1年生存率仍然低于85%,分析影响预后的危险因素是提高肝移植效果的重要手段~([1])。由于我国大陆肝移植手术普及开展明显晚于国外,供体受体的客观条件与国外不尽相同,因此,总结分析我国目前条件下肝移植术后早期(存活期1年)的死亡原因,及早采取     

血管内支架植入治疗部分肝移植术后流出道狭窄

目的 探讨血管内支架治疗肝移植术后流出道狭窄的适应症、手术时机、操作要领、后续治疗等。方法 总结我院2例左半肝移植术后流出道狭窄患者的诊断和治疗经过,通过股静脉进行肝静脉造影并测压,证实2例患者存在肝静脉-下腔静脉吻合口狭窄,经球囊血管扩张后置入血管内支架。结果 2例患者经血管支架治疗后,肝静脉内压力迅速回降,腹水等症状逐渐消失,肝功能恢复正常。观察6个月,无相关并发症发生,最终解决了肝静脉流出道狭窄的问题。结论 肝移植术后流出道狭窄严重影响患者近期和远期预后,早期诊断、早期干预是治疗肝移植术后流出道狭窄的关键。介入下血管内支架植入是肝移植术后流出道狭窄的有效治疗措施之一,可以一定程度改善患者预后。     

原位肝移植中移植肝功能影响因素分析

肝移植术后原发性移植物功能不良是原位肝移植术后的早期主要并发症,其直接对移植肝和受者的存活造成影响。全文对可能导致原发性移植物功能不良的因素作一综述(包括供体相关因素、受体相关因素、术中影响因素等),并小结在肝移植术前及术后可用于评估手术后早期肝脏功能的各种检验方法,为进一步指导临床治疗提供依据。     

脾动脉盗血综合征：一个被忽视的肝病治疗靶点

肝脏对动脉低灌注所致的缺氧非常敏感,这在肝移植术后移植物并发症（如肝动脉血栓形成、动脉瘤）中已经得到证实,可导致严重的胆道缺血性损害、移植物失功能、甚至受体死亡等严重并发症。脾动脉盗血综合征（SASS）是肝移植术后一种较少认识的动脉并发症。SASS本质是粗大的脾动脉＂盗走＂肝动脉血流而导致肝动脉灌注不良;不及时干预,SASS亦可导致严重的移植物并发症。目前临床上尚未形成＂肝硬化性SASS＂概念,更未认识其危害性。肝硬化性SASS是慢性肝病损害的结果,并加重肝损害的病理过程,临床上无特异性,多表现为基础肝病合并脾脏肿大等异常。我们通过三维CT血管成像及血管造影证实失代偿期肝硬化患者普遍存在SASS,并证实纠正SASS后肝硬化患者的肝功能指标、Child-Pugh评分、评级等显著改善,并降低了消化道出血风险。因此,该文在国际上首次提出了肝硬化性SASS概念,并证实SASS是失代偿期肝硬化患者改善肝功能的一个有效治疗靶点,可作为等待肝移植的架桥性治疗措施。     

异甘草酸镁在肝移植术后的应用

肝移植已成为治疗终末期肝病和急性肝功能衰竭的最有效手段。而术后患者肝功能的尽快恢复显得尤为重要。本研究对异甘草酸镁在60例原位肝移植患者术后肝功能恢复中的作用进行分析。     

肝移植患者术后早期心血管并发症

肝移植已成为终末期肝病和暴发型肝功能衰竭的一种有效治疗方式。但由于手术本身的特点和术前患者的基础状况较差,术后易并发心血管系统的并发症,并影响全身各器官功能,进而影响预后。本文重点阐述肝移植术后早期心血管并发症—高血压、心力衰竭、心肌缺血和肺动脉高压的原因及其防治策略。     

肝移植术治疗自身免疫性肝炎(附1例报告)

目的探讨肝移植术在自身免疫性肝炎(AIH)中的治疗价值。方法对1例AIH肝硬化患者行肝移植手术。结果患者术后恢复顺利,随访1年未出现排斥反应及复发,抗核抗体(ANA)转阴,肝功能正常。结论肝移植术可作为终末期AIH的有效治疗手段。     

肝移植术后早期肝功能的动态变化及其对预后的价值

目的动态观察肝移植术后1周内肝功能的变化,明确变化规律及术式对其的影响,以筛选对判断预后有价值的指标。方法回顾性分析149例肝移植受者术前、术后1、3、7d时ALT、AST、总胆红素(TB)、直接胆红素(DB)及凝血酶原时间(PT)、部分凝血活酶时间(APTT)、纤维蛋白原的变化情况,采用logistic回归筛选与预后有关的指标。结果肝移植术后1个月内生存的患者在术后1周内肝功能呈单峰变化。术后1d,纤维蛋白原恢复;术后3d,PT、APTT恢复;术后7d,ALT、AST下降至正常值附近。术后1个月内死亡的患者胆红素出现双峰,PT、APTT高峰前移,各项指标恢复时间延迟。背驮式肝移植受者前期恢复慢于经典式受者,但在术后1周内两组均可恢复,且术式与预后无关。术后7d的AST水平,术前及术后1、3、7d的TB水平,术后1、3d的DB水平及术后1d的PT值与预后相关。结论肝移植术后1周内肝功能出现单峰改变,术后7d基本可恢复正常;肝移植术后1周内AST、TB、PT与术后早期预后相关。术后高峰形状及位置改变提示并发症的出现,对术后管理和判断预后有积极意义。     

Transplantation for cystic fibrosis: outcome following early liver transplantation

BACKGROUND AND AIM: Life expectancy in patients with cystic fibrosis (CF) has recently improved due to numerous factors, including a multidisciplinary approach to their management. Prolonged survival may have led to an increasing impact of liver disease on the prognosis of CF patients. The aim of this study was to assess the role of liver transplantation in patients with CF. METHODS: The factors influencing outcome in 24 patients (15 adults and nine children) with CF who have received single liver transplantation, triple heart-lung-liver transplantation (tx) or died while being assessed for triple grafting, were analyzed. RESULTS: Median age at tx in single liver recipients (13 years) was lower than in triple graft recipients (21 years) and those who died (23 years). All patients who received single liver tx made an excellent recovery, including significant improvement of their respiratory function (mean forced vital capacity (FVC) increased from 61% before transplantation to 82% of expected, 6-9 months after tx). Four out of five patients who received triple tx died (0-2 months) after operation. On the basis of our retrospective review, we propose modifications to an existing scoring system for liver tx assessment in CF by scoring additional points for elevated white blood count, bilirubin, and impaired pulmonary function. These changes will need to be evaluated prospectively to confirm their predictive value. CONCLUSIONS: Liver transplantation is effective therapy in young patients with cystic fibrosis, portal hypertension and hepatic dysfunction, and is indicated before a critical stage of deteriorating lung function is reached. In patients with both end-stage liver and lung disease, triple tx has a poor prognosis. Pre-emptive liver tx in younger patients with CF not only has a better outcome but improves lung function.     

Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation

Extended-criteria donors (ECDs) have an impact on early allograft dysfunction (EAD), biliary complications, relapse of hepatitis C virus (HCV), and survivals. Early allograft dysfunction was frequently seen in grafts with moderate and severe steatosis. Donors after cardiac death (DCD) have been associated with higher rates of graft failure and biliary complications compared to donors after brain death. Extended warm ischemia, reperfusion injury and endothelial activation trigger a cascade, leading to microvascular thrombosis, resulting in biliary necrosis, cholangitis, and graft failure. The risk of HCV recurrence increased by donor age, and associated with using moderately and severely steatotic grafts. With the administration of protease inhibitors sustained virological response was achieved in majority of the patients. Donor risk index and EC donor scores (DS) are reported to be useful, to assess the outcome. The 1-year survival rates were 87% and 40% respectively, for donors with a DS of 0 and 3. Graft survival was excellent up to a DS of 2, however a DS >2 should be avoided in higher-risk recipients. The 1, 3 and 5-year survival of DCD recipients was comparable to optimal donors. However ECDs had minor survival means of 85%, 78.6%, and 72.3%. The graft survival of split liver transplantation (SLT) was comparable to that of whole liver orthotopic liver transplantation. SLT was not regarded as an ECD factor in the MELD era any more. Full-right-full-left split liver transplantation has a significant advantage to extend the high quality donor pool. Hypothermic oxygenated machine perfusion can be applied clinically in DCD liver grafts. Feasibility and safety were confirmed. Reperfusion injury was also rare in machine perfused DCD livers.     

Diagnostic value of transjugular liver biopsy in liver transplant recipients

Liver biopsy after hepatic transplantation essential for the correct diagnosis of grant dysfunction. However, seriously imparied coagulation or massive ascites contraindicate percutaneous liver biopsy. In these cases transjugular liver biopsy may be valid alternative. in this study the efficacy, feasibility and safety of 69 transjugular biopsies carried out in 56 liver transplant recipients are evaluated. The suprahepatic veins were catheterized in 100% of the patients and histological samples were obtained in 63 (91.3%). The number of portal tracts was greater than six in 20.6% of the samples, lower than three in 35% and oscillated between four and six in 44%. The specimens obtained were sufficient for diagnosis in 82.5% of the patients, the overall diagnostic efficacy being 75.4%. The most common histological diagnosis (28.8%) was graft damage, while rejection represented 7.7%. Only one patient (1.18%) suffered a serious complication after transjugular biopsy. Transjugular biopsy is feasible and effective in liver transplant recipients with severely imparied coagulation.     

Invasive fungal infection before and after liver transplantation

Invasive infections are a major complication before liver transplantation (LT) and in the early phase after surgery. There has been an increasing prevalence of invasive fungal disease (IFD), especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure, who suffer from a profound state of immune dysfunction and receive intensive care management. In such patients, who are listed for LT, development of an IFD often worsens hepatic and extra-hepatic organ dysfunction, requiring a careful evaluation before surgery. In the post-transplant setting, the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis, even if several major issues still remain, such as duration, target population and drug type(s). Nevertheless, the development of IFD in the early phase after surgery significantly impairs graft and patient survival. This review outlines presentation, prophylactic and therapeutic strategies, and outcomes of IFD in LT candidates and recipients, providing specific considerations for clinical practice.     

Elevated levels of interleukin-8 in donor lungs is associated with early graft failure after lung transplantation

Increased levels of the neutrophil chemokine interleukin (IL)-8 in the lungs of severe trauma patients can predict subsequent development of acute respiratory distress syndrome. Because the lungs of brain-dead organ donors can contain high levels of IL-8, we hypothesized that this may predispose to early graft failure in the recipient after lung transplantation. Twenty-six organ donors prospectively satisfying clinical criteria for lung donation underwent bronchoalveolar lavage and lung biopsy to determine the effect of neutrophil infiltration and IL-8 expression in the donor lung on graft function and survival in 26 respective recipients after lung transplantation. Nine recipients developed severe graft dysfunction, of whom six subsequently died (median survival: 24 d [range: 5 to 39 d]); all others survived beyond 6 mo. The IL-8 signal in the donor lung correlated with the percent neutrophils in bronchoalveolar lavage fluid (BALF) before implantation (42.4 +/- 7.24 [mean +/- SE]%, p = 0.03) and with the degree of impairment in graft oxygenation after implantation (p = 0.01). An increased level of IL-8 in the donor BALF was associated with the development of severe early graft dysfunction (p = 0.027) and with early recipient mortality (p = 0.0034). Use of donor lungs with high IL-8 levels is associated with a poor prognosis after lung transplantation. Attenuating the donor's inflammatory response before organ retrieval may improve early outcome after lung transplantation, and help maximize lung use from the existing donor pool.     

Vascular complications after adult living donor liver transplantation:Evaluation with ultrasonography

Living donor liver transplantation(LDLT) has beenwidely used to treat end-stage liver disease with improvement in surgical technology and the application of new immunosuppressants. Vascular complications after liver transplantation remain a major threat to the survival of recipients. LDLT recipients are more likely to develop vascular complications because of their complex vascular reconstruction and the slender vessels. Early diagnosis and treatment are critical for the survival of graft and recipients. As a non-invasive, cost-effective and non-radioactive method with bedside availability, conventional gray-scale and Doppler ultrasonography play important roles in identifying vascular complications in the early postoperative period and during the follow-up. Recently, with the detailed vascular tracing and perfusion visualization, contrastenhanced ultrasound(CEUS) has significantly improved the diagnosis of postoperative vascular complications. This review focuses on the role of conventional grayscale ultrasound, Doppler ultrasound and CEUS for early diagnosis of vascular complications after adult LDLT.     

Donation after cardio-circulatory death liver transplantation

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.     

Cytomegalovirus infections in patients after liver transplantation: determination of risk groups]

The goal of this study was to identify high-risk groups for cytomegalovirus infection after liver transplantation. Sixty-one patients were evaluated. Twenty-five patients (41 percent) had infection. Among the 16 patients who were seronegative for the virus before transplantation, 11 received a liver graft and blood products from seronegative donors and none of them developed infection. All seronegative recipients of a liver from seropositive donors (5/5) developed primary infection. Among the 45 patients seropositive before transplantation, 20 developed a cytomegalovirus infection, whatever the donor serologic status. The incidence of symptomatic reactivation or reinfection was high (14/20), and, for 12/14 of them, associated with early acute rejection. Two high-risk groups of patients, eligible for cytomegalovirus prophylaxis, were identified: seronegative recipients of seropositive donors and seropositive recipients with early acute rejection.     

The histological assessment of liver fibrosis in grafts from extended criteria donors predicts the outcome after liver transplantation: A retrospective study

BackgroundThe use of extended criteria donors (ECD) in liver transplantation is increasing due to the organ shortage. Histological evaluation of the liver graft in the context of procurement is an important tool for extending the donor pool without affecting the quality of the transplanted organs. Macrovesicular steatosis is widely accepted as predictor of early allograft dysfunction (EAD), while other features, such as portal fibrosis, are poorly studied.AimTo identify morphological features, other than macrovesicular steatosis, that may affect recipients’ outcome.MethodsBetween 2014 and 2016, 132 donors with extended criteria underwent pre-transplant liver biopsy during procurement. Histological variables of the graft, donors’/recipients’ clinical data, EAD and patient/graft survival were registered.ResultsThe recipients who received a graft with histological-proven portal fibrosis had a significant lower patient and graft survival in comparison to patients without fibrosis (P = 0.044 and P = 0.039, respectively). Donors’ dyslipidemia was significantly associated with the occurrence of EAD (P = 0.021). When dyslipidemia was combined with histological liver fibrosis a 54.5% incidence of EAD was observed (P = 0.012).ConclusionsThe histological assessment of liver fibrosis in pre-transplant biopsy of ECD grafts, together with donor’s clinical data, provides important information on recipients’ outcome.     

Critical care issues following orthotopic liver transplantation

Orthotopic liver transplantation (OLT) remains a formidable undertaking. A multidisciplinary approach to pre-operative optimization and intra- and postoperative care of patients undergoing OLT increases the chance of a successful outcome. Although there have been moves towards avoidance of Intensive Care Unit (ICU) admission for "routine" OLT recipients, critical care practitioners continue to play a key role in liver transplant programs in the MELD era. Use of protocolized care delivery and innovative ICU therapeutic interventions have streamlined the pre-operative optimization and perioperative care of OLT recipients. The postoperative course is significantly influenced by the patient's pre-operative status, the intraoperative course and the function of the liver graft. In addition to discussion of general ICU concepts such as the use of prognostic scoring systems and protocolization of care, this review will use an organ-system based approach to describe the postoperative ICU care of OLT recipients. We discuss hemodynamic management, ventilator weaning, optimization of sedation and analgesia, and the investigation and management of renal and metabolic abnormalities. In addition, we examine postoperative complications including hemorrhage, central nervous system pathology and graft dysfunction. The review concludes with a discussion of the additional challenges practitioners face when dealing with living donor liver transplantation and donation after cardiac death.