国外人工肝治疗的现状与评价

人工肝支持系统简称人工肝，是国外20世纪50年代开始逐渐发展起来的为肝衰竭患者提供体外肝功能支持的一种技术。目前国外人工肝治疗的方法主要是借助体外机械、化学或生物性装置暂时及部分替代肝脏功能，在体外采用某种具有解毒、代谢等作用的装置和方法来代偿肝脏功能，从而辅助治疗肝功能不全、肝衰竭或相关疾病；其作用原理是基于肝损伤具有可逆性和肝细胞有强大的再生能力，通过人工肝辅助治疗在内环境改善的情况下，肝功能能够自发恢复，或为肝脏移植和其他特效治疗进行准备。近年来随着材料学、细胞工程学及临床医学的不断发展，人工肝支持系统已成为肝衰竭治疗不可缺少的有效方法之一。     

人工肝的临床应用研究

人工肝脏简称为人工肝（Artificial liver），是借助体外机械、化学或生物性装置，暂时及部分替代肝脏功能从而协助治疗肝脏功能不全、肝衰竭或相关疾病的方法。国外20世纪50年代就已经歼始逐渐发展起来的为肝衰竭患者提供体外肝功能支持的技术方法．它的出现与发展为肝衰竭的治疗开辟了新途径。人工肝的临床应用为各种重型肝病早期的救治、肝衰竭病人晚期适当延长生命及争取时间进行肝移植手术治疗开辟出了一条很有希望的新的路子。经过50余年不懈努力．人工肝技术己逐步成熟。目前，人工肝按照组成及性质可分为：①非生物型人工肝（Non-bioartificial liver NBAL）：②生物型人工肝（bioartificial liver BAL）：③组合生物型人工肝（hybrid bioartificial liver support system，HBALSS）。     

人工肝技术造福肝病患者

首都医科大学附属北京佑安医院是我国较早涉足人工肝研究的单位之一，早在上世纪七十年代，就开展了肝脏细胞体外分离培养等人工肝相关的基础工作。2000年5月，经北京市人民政府有关部门批准，正式成立了“北京市人工肝治疗培训中心”。该中心是一所集医疗、科研、教学、培训、国际交流与合作为一体的大型综合性人工肝临床治疗和技术服务中心，     

人工肝技术的进展

人工肝的作用原理基于肝脏损伤的可逆性及肝细胞的强大再生能力，即通过人工肝辅助治疗，期望在内环境改善的情况下肝脏能够自发恢复，或为肝脏移植和其它治疗进行准备。具备良好的解毒功能是人工肝最基本和最重要的作用。具有肝脏一种或几种功能的肝脏支持系统，从理论上讲都应称为人工肝脏。现从细胞水平、动物模型和临床研究三个方面来概述人工肝技术的最新进展。     

MARS人工肝治疗重型肝炎26例疗效评价

目的 探讨MARS人工肝对急慢性重型肝炎的疗效。方法 26例急慢性重型肝炎患者，每例患者进行MARS人工肝治疗2～3次，每次治疗时间6小时。在每次MARS人工肝治疗前后检测肝肾功能、电解质、PT、血氨及血常规。结果 治疗后血清总胆红素、总胆汁酸明显下降，肝性脑病清醒率为75％，存活率为62％。结论 MARS人工肝治疗急慢性重型肝炎并发症少，可有效地清除体内胆红素、总胆汁酸、血氨、BUN、Cr等毒性物质，有利于肝细胞再生以及为进行肝移植赢得时间。MARS人工肝治疗慢性重型肝炎效果较好。     

非生物型人工肝治疗肝衰竭的现状

肝衰竭（重型肝炎）的主要治疗目标是通过支持治疗使肝脏再生以达到有效的重建肝脏基本功能,或者等到肝移植。肝移植作为改善肝衰竭患者的生存率最有效治疗手段存在着供肝来源困难的问题。而人工肝支持技术能明显改善肝衰竭患者的临床症状和生化学指标,并为肝移植起到了良好的桥梁作用。人工肝可分为非生物型人工肝和生物型人工肝。非生物型人工肝以去除体内蛋白结合毒素及水溶性毒素、补充一些体内缺乏的但必需的有益物质为目的,通过为肝脏的自我修复创造时间和机会来达到治疗肝衰竭的目的。生物型人工肝可以较好的替代肝脏解毒、生物合成和分泌代谢等功能,是国内外研究的热点。     

人工肝研究进展

人工肝研究进展王宇明，吴易东各种原因所致暴发性肝衰竭（ＦＨＦ）的救治一直是；临床上亟待解决的难题。由于此类患者的大部分肝细胞发生变性、坏死、功能衰竭，依靠多种药物疗法均未获得突破性进展。为此，国外学者一直致力于非内科药物疗法即人工肝及肝移植治疗的研究...     

MARS治疗重型肝损害病人的临床作用

目的：研究MARS人工肝治疗各种原因所致重型肝脏损害病人的临床改善作用。方法：对2002-05～2003-12重型肝损害病人20例进行的42次MARS治疗的有关资料进行分析。结果：MARS人工肝治疗后，病人临床症状明显改善，血清胆碱酯酶、凝血酶原活动度(PTA)上升；总胆红素、间接胆红素、胆质酸和血氨明显降低；肝性脑病和肾功能改善。院内存活率为65％，1年存活率为36．36％，半年存活率为54．55％。结论：MARS人工肝治疗能有效改善重型肝损害病人的多脏器功能，提高抢救存活率，为后续治疗创造条件。     

人工肝支持系统治疗重型肝炎13例报告

人工肝支持系统治疗重型肝炎１３例报告李兰娟黄建荣朱琮陈江华程瑛陈月美冯玉凤干梦九病毒性肝炎尤其是重型病毒性肝炎病死率高，应用人工肝支持系统（ＡＬＳＳ）治疗能清除各种有害物质，补充必须物质，起到治疗期的支持作用，改善环境使病变的肝脏通过再生而修复其原有...     

人工肝治疗重型肝炎的临床研究

探讨人工肝辅助治疗重型肝炎的疗效及其安全性。分析51例102次人工肝治疗前后重肝患者生化，血常规，凝血酶原活动度（PTa)，血氨和症状变化，观察治疗术中，术后出现的不良反应及术后生存率。人工肝术后10－72小时内症状改善显效率为89．5％。治疗前后白蛋白，血氨，血常规水平无显著性变化（P＞0．05），总胆红素，转氨酶，总胆汁酸水平显著下降（P＜0．01，0．005及0．001），胆固醇，PTa显著上升（P＜0．01及0．001）术后96小时胆红素反弹幅度约为前的60％。临床痊愈出院75％。术中及术后总并发症发生率为14．7%，其中最常见为皮肤瘙痒及荨麻疹（10．78％），其次为寒战发热及血压下降（1．96％），未出现致死性并发症。人工肝辅助治疗重型肝炎安全，可靠，疗效。     

活体肝移植的进展与展望

活体肝移植（LDLT）可扩大供肝来源,有效缓解供体紧缺局面,尤其是对儿童、急性肝功能衰竭患者和无,法长期等待的肝癌患者有着十分重要的意义。为尽可能减少LDLT潜在的手术风险,尤其是供者的风险,应由肝病内外科医师共同进行严格的供受体术前评估和准备,选择恰当的手术方案。中闰应稳步开展LDLT,并积极拓展尸体和脑死亡供体肝移植,进一步发展儿童LDLT和劈离式肝移植（SIX）以提高器官利用率。在第六届上海国际胃肠病学会议期间,国内外肝病专家就LDLT的现状作了相关报道,本文就此次会议的有关内容和最新进展作一简要介绍。     

Liver regeneration after liver resection: Clinical aspects and correlation with infective complications

AIM:To investigate whether early liver regeneration after resection in patients with hepatic tumors might be influenced by post-operative infective complications.METHODS:A retrospective analysis of 27 liver resections for tumors performed in a single referral center from November 2004 to January 2010.Regeneration was evaluated by multidetector computed tomographyat a mean follow-up of 43.85 d.The Clavien-Dindo classification was used to evaluate postoperative events in the first 6 mo after transplantation,and Centers for Disease Control and Prevention definitions were used for healthcare associated infections data.Generalized linear regression models with Gaussian family distribution and log link function were used to reveal the principal promoters of early liver regeneration.RESULTS:Ten of the 27 patients(37%)underwent chemotherapy prior to surgery,with a statistically significant prevalence of patients with metastasis(P=0.007).Eight patients(30%)underwent embolization,3 with primary tumors,and 5 with secondary tumors.Twenty patients(74%)experienced complications,with 12(60%)experiencing Clavien-Dindo Grade 3a to 5 complications.Regeneration≥100%occurred in 10(37%)patients.The predictors were smaller future remnant liver volume(-0.002;P<0.001),and a greater spleen volume/future remnant liver volume ratio(0.499;P=0.01).Patients with a resection of≥5 Couinaud segments experienced greater early regeneration(P=0.04).Nine patients experienced surgical site infections,and in 7 cases Clavien-Dindo Grade 3a to 4 complications were detected(P=0.016).There were no significant differences between patients with primary or secondary tumors,and either onset or infections or severity of surgical complications.CONCLUSION:Regardless of the onset of infective complications,future remnant liver and spleen volumes may be reliable predictors of early liver regeneration after hepatic resection on an otherwise healthy liver.     

Current management of liver diseases and the role of multidisciplinary approach

Liver is an organ having extremely diversified functions, ranging from metabolic and synthetic to detoxification of harmful chemicals. The multifunctionality of the liver in principle requires the multidisciplinary and pluralistic interventions for its management. Several studies have investigated liver function, dysfunction and clinic. This editorial work discusses new ideas, challenges and perspectives of current research regarding multidisciplinary and pluralistic management of liver diseases. In one hand the discussions have carried out on the involvement of extracellular vesicles, Na⁺/H⁺ exchangers, severe acute respiratory syndrome coronavirus 2 and Epstein–Barr virus infections, Drug-induced liver injury, sepsis, pregnancy, and food supplements in hepatic disorders. In the other hand this study has discussed hepatocellular carcinoma algorithms and new biochemical and imaging experiments pertaining to liver diseases. Relevant articles with an impact index value "> 0" from reference citation analysis, which is an open multidisciplinary citation analysis database based on artificial intelligence technology, have served for the study’s argumentation. This work may be a useful tool for the clinical practice and research in managing and investigating liver disorders.     

人工肝在肝移植围手术期的应用

目的 探讨人工肝支持系统在肝移植围手术期的应用效果。方法采用非生物人工肝治疗9例等待供肝患者，3例肝移植术后患者(包括1例等待供肝成功过渡到肝移植患者)。9例等待供肝患者中4例成功过渡到肝移植。结果 人工肝支持后患者肝性脑病有所好转，血清胆红素明显下降。4例成功过渡到肝移植的启者中2例痊愈出院，已存活12和14个月。结论 术前使用人工肝支持系统能改善患者一般情况；原位肝移植加人工肝支持系统是治疗慢性肝衰竭的有效方法。     

慢性乙型肝炎患者肝组织病理研究

目的:探讨慢性乙型肝炎(CHB)患者临床表现和病理诊断的相关性.方法:收集30例CHB患者的临床资料,分析临床表现与病理诊断的相关性.结果:肝组织的炎症和纤维化程度的相关性显著(r=0.659,P＜0.01),白蛋白/球蛋白比值(A/G)与肝脏炎症和纤维化分级显著负相关(r=-0.368,P＜0.05;r=-0.401,P＜0.05).年龄、性别及其他化验指标如ALT、AST、TP、ALB、GLO、TBil、PLT、PT、PTA、门静脉宽度、脾脏厚度等与肝组织炎症和纤维化分级无显著相关性(P＞0.05).结论:慢性乙型肝炎肝脏炎症和纤维化的严重程度密切相关,仅根据肝功能判断轻中度的CHB患者的肝脏炎症及纤维化程度有相当的局限性.     

Right hepatic lobe living donation: A 12 years single Italian center experience

Mini invasive techniques are taking over conventional open liver resections in the setting of left lateral segmentectomy for living liver donation,and hydride procedure are being implemented for the living related right hepatectomy.Our center routinely performs laparoscopic left lateral segmentectomy for pediatric recipient and has been the first in the Europe performing an entirely robotic right hepatectomy.Great emphasis is posed on living donor safety which is the first priority during the entire operation,then the most majority of our procedures are still conventional open right hepatectomy(RHLD),defined as removal of a portion of liver corresponding to Couinaud segments 5-8,in order to obtain a graft for adult to adult living related liver transplant.During this 10 years period some changes,herein highlighted,have occurred to our surgical techniques.This study reports the largest Italian experience with RHLD,focused on surgical technique evolution over a 10 years period.Donor safety must be the first priority in right-lobe living-related donation:the categorization of complications of living donors,specially,after this"highly sensitive"procedure,reflects the need for prompt and detailed reports.     

Metrically measuring liver biopsy： A chronic hepatitis B and C computer-aided morphologic description

AIM： To describe a quantitative analysis method for liver biopsy sections with a machine that we have named ＂Dioguardi Histological Metriser＂ which automatically measures the residual hepatocyte mass （including hepatocytes vacuolization）, inflammation, fibrosis and the loss of liver tissue tectonics.METHODS： We analysed digitised images of liver biopsy sections taken from 398 patients, The analysis with Dioguardi Histological Metriser was validated by comparison with semi-quantitative scoring system.RESULTS： The method provides： （1） the metrical extension in two-dimensions （the plane） of the residual hepatocellular set, including the area of vacuoles pertinent to abnormal lipid accumulation; （2） the geo- metric measure of the inflammation basin, which distinguishes intra-basin space and extra-basin dispersed parenchymal leukoo/tes; （3） the magnitude of collagen islets, （which were considered truncated fractals and classified into three degrees of magnitude）; and （4） the tectonic index that quantifies alterations （disorders） in the organization of liver tissue. Dioguardi Histological Metriser machine allows to work at a speed of 0.1 mm^2/s, scanning a whole section in 6-8 min.CONCLUSION： The results are the first standardized metrical evaluation of the geometric properties of the parenchyma, inflammation, fibrosis, and alterations in liver tissue tectonics of the biopsy sections. The present study confirms that biopsies are still valuable, not only for diagnosing chronic hepatitis, but also for quantifying changes in the organization and order of liver tissue structure.     

Introducing an Optimal Liver Allocation System for Liver Cirrhosis Patients

Background

Liver transplantation (LT) is the only treatment option for patients with advanced liver disease. Currently, liver donation to these patients, considering priorities, is based on the Model for End-Stage Liver Disease (MELD). MELD score is a tool for predicting the risk of mortality in patients with advanced liver disease. However, few studies have so far been conducted in Iran on the efficacy of MELD score of these patients.

Objectives

This study reviews the present status of the MELD score and introduces a new model for optimal prediction of the risk of mortality in Iranian patients with advanced liver disease.

Patients and Methods

Data required were collected from 305 patients with advanced liver disease who enrolled in a waiting list (WL) in Imam Khomeini Hospital from May 2008 to May 2009. All of the patients were followed up for at least 3 years until they died or underwent LT. Cox regression analysis was applied to select the factors affecting their mortality. Survival curves were plotted. Wilcoxson test and receiver operating characteristics curves for survival predictive model were used to compare the scores. All calculations were performed with the SPSS (version 13.0) and R softwares.

Results

During the study, 71 (23.3%) patients died due to liver cirrhosis and 43 (14.1%) underwent LT. Viral Hepatitis (43.7%) is the most common cause of end-stage liver disease among Iranian patients. A new model (NMELD) was proposed with the use of the natural logarithms of two blood serum variables (total bilirubin and albumin) and the patients'' age (year) by applying the Cox model:NMELD = 10 × (0.736 × ln (bilirubin) – 1.312 × ln (albumin) + 0.025 × age + 1.776)

Conclusions

The results of the Wilcoxon test showed that there is a significant difference between the usual MELD and our proposed NMELD scores (P < 0.001). Receiver operating characteristics curve for survival predictive model indicated that the NMELD score is more efficient compared with the MELD score in predicting the risk of mortality. Since serum creatinine was not significant in NMELD score, further studies to clarify this issue are suggested.     

肝窦内皮细胞在肝损伤中的功能研究进展

肝窦内皮细胞（liver sinusoidal endothelial cells, LSECs）位于肝血窦表面，是肝脏与血液接触的第一道防线，也是肝脏中含量最多的非实质细胞。在生理情况下，LSECs通过参与物质运输、代谢废物清除而诱导肝脏免疫耐受，从而维持肝脏稳态；在病理情况下，LSECs通过抗原递呈促进肝脏炎症反应。LSECs在维持肝再生和肝纤维化平衡中发挥了重要的调节作用。本文对LSECs功能、LSECs在肝损伤中的变化、调节LSECs功能相关的信号通路以及LSECs与肝内其他细胞的相互作用等四方面研究进展进行综述，从而进一步明确LSECs的功能及在肝损伤中的作用。     

Isolated Tuberculosis of Transplanted Liver,A Case Report and Review of the Literature

Introduction

Recipients of liver transplantation are prone to different types of infections such as tuberculosis (TB).

Case Presentation

Herein we report a 59-year-old man with liver transplantation due to HBV cirrhosis who developed isolated hepatic TB, 18 months after OLT (orthotropic liver transplantation). He has been successfully treated with anti-TB regimen and now after 12 months he is completely symptom-free.

Conclusions

Organ transplantation and treatment of transplanted patients with immunosuppressive drugs would prone them to various unusual infections. One of these is unusual primary involvement of liver by tuberculosis which has been extremely rare in the previous reports.