胆碱酯酶在乙肝肝硬化患者肝脏储备功能的评估应用

目的:研究胆碱酯酶(CHE)在评估乙肝肝硬化患者肝脏储备功能中的应用价值。方法:收集501例肝硬化患者病例,并根据肝脏功能进行Child分级。应用全动自动生化分析仪,以酶速率比色法检测胆碱酯酶(CHE),溴甲酚绿法检测白蛋白(ALB),凝固法检测凝血酶原时间(PTs)。应用方差分析,研究胆碱酯酶(CHE)在不同CHILD分级组别中的肝功能评价意义。应用相关分析方法,比较胆碱酯酶(CHE)与其他肝脏合成指标白蛋白(ALB)、凝血酶原时间(PTs)的相关性。结果:肝硬化患者在严格Child-Pugh分级标准划分而成的ABC三级中,各级胆碱酯酶(CHE)活性逐级明显下降,分别为5469.04±1777.31 U/L(Child A),2935.08±1206.95 U/L(Child B),1810.40±724.72 U/L(Child C),且结果差异有显著意义(F=261.114,P=0.000)。在肝硬化患者中,胆碱酯酶(CHE)与白蛋白(ALB)总体正相关、与凝血酶原时间(PTs)总体负相关。其中Child A级患者中,CHE与ALB成正相关,与PTs负相关。Child B级患者中,CHE与PTs负相关,但与ALB无显著相关性。Child C级患者中,CHE与ALB正相关,但与PTs无显著相关性。结论:胆碱酯酶(CHE)与肝硬化患者肝细胞损害的严重程度相关,可反映肝脏的储备功能,与白蛋白(ALB)、凝血酶原时间(PTs)有同样重要的价值。     

首届国际精准肝脏外科研讨会在京举行

由解放军总医院主办的＂首届国际精准肝脏外科研讨会暨2011中国国际肝胆外科论坛＂于2011年8月19-21日在京举行。来自美国、法国、日本以及中国大陆和香港、台湾地区的著名肝胆外科专家、知名学者200余名代表参加了会议。     

肝脏类器官的研究及应用进展

肝脏疾病易感性差异大且个体间的肝脏细胞存在明显的异质性,因此开发体外能够长期存活并具有代谢功能的人体类肝组织细胞模型,对治疗终末期肝病、开展肝脏致病机理研究及药物筛选具有重要意义。过去十年中,体外三维类器官模型发展迅猛,为疾病模拟、精准化治疗领域的研究提供了新的工具,显示出巨大潜力。肝脏类器官具有患者的基因表达与突变特征,在体外能够较长时间地保持肝脏细胞功能,已被应用于疾病模拟及药物有效性研究,并具有进行原位或异位移植发挥治疗作用的应用潜能。就干细胞、肝脏原代细胞等不同来源的肝脏类器官的发展及近年的研究进展作了综述,以期为肝脏类器官在疾病建模、药物发现和器官移植领域的研究和应用提供新的思路。     

吲哚氰绿排泄试验评价肝储备功能与拔管时问的研究

目的：术前评估肝硬化患者肝脏储备功能,及其与患者拔管时间及改良OAA/S评分的关系。方法：对60例肝硬化失代偿患者术前行吲哚氰绿排泄试验。将患者分为三组：按吲哚氰绿15min储留率（ICGR15）将患者分为两组I1组,I2组,另30例肝功能正常患者为对照组（C组）。观测ICGR15与患者拔管时间及改良OAA/S评分的关系。结果：拔管时间I1组与I2组均明显长于C组（P〈0.05或P〈0.01）;发生呕吐,烦躁者I1组与I2组均明显多于C组（P〈0.05或P〈0.01）,OAA/S评分〉3分者I1组与I2组均多于C组,但无统计学意义。结论：ICGR15对于判断肝硬化患者围术期拔管的时间具有一定的参考价值。     

吲哚氰绿排泄试验评价肝储备功能与拔管时间的研究

目的:术前评估肝硬化患者肝脏储备功能,及其与患者拔管时间及改良OAA/S评分的关系.方法:对60例肝硬化失代偿患者术前行吲哚氰绿排泄试验.将患者分为三组:按吲哚氰绿15 min储留率(ICGR15)将患者分为两组I1组,I2组,另30例肝功能正常患者为对照组(C组).观测ICGR15与患者拔管时间及改良OAA/S评分的关系.结果:拔管时间I1组与I2组均明显长于C组(P＜0.05或P＜0.01);发生呕吐,烦躁者I1组与I2组均明显多于C组(P＜0.05或P＜0.01),OAA/S评分＞3分者I1组与I2组均多于C组,但无统计学意义.结论:ICGR15对于判断肝硬化患者围术期拔管的时间具有一定的参考价值.     

生物人工肝研究和应用进展

人工肝支持系统是用来为肝衰竭患者提供体外肝脏功能支持的技术方法.非生物人工肝在已经广泛应用肝衰竭患者的临床治疗,生物人工肝(BAL)以分离的哺乳动物肝细胞构成的生物反应器为解毒系统,可有效替代肝脏的解毒功能和合成功能,并可预防肝性脑病、肝昏迷和脑水肿.可作为肝移植前的过渡辅助,同时改善患者自身肝脏的功能以利于其功能的恢复.本文主要对生物人工肝的研究及应用进展进行综述.生物人工肝研究虽然取得了重大进展,但仍然面临寻找理想肝细胞来源,长期维持肝细胞的活性和功能,进一步优化反应器设计等问题.     

面向精准医学时代的胆总管结石影像学及内镜诊断

胆总管结石是胆道外科一种常见病、多发病。随着"精准医学"时代的到来,因人因病而异的胆总管结石精准诊断及精准的个体化治疗意义重大。影像医学作为胆总管结石精准治疗的"导航"手段,其检查方法种类多样且各种方法有着各自的优点及局限性,对于满足精准治疗需要有特殊的要求。因此,本文对胆总管结石的各种影像学及内镜检查方法的优点及局限性进行综述并提出精准医学时代影像学诊断策略,以期能为胆总管结石精准诊断的提供一定的参考。     

Cox回归模型在肝癌病人生存分析中应用的研究

生存时间是癌症患者和临床医师共同关心的焦点,也是临床癌症诊治工作的重要指标之一．生存分析是研究多种因素与生存时间的关系以及关系程度的大小．Cox回归模型是生存分析中常用的方法之一．本文利用Cox回归模型对786名肝癌患者进行生存分析,确定影响肝癌患者预后的主要因素是癌栓、肝癌部位、治疗方式、肝脏储备功能、端粒酶活性、细胞增殖活性、γ-GT(γ-谷氮酰转肽酶)、术后复发等．为临床研究延长肝癌病人的生存期,提高其生存率提供了有力的依据．     

补肾滋阴汤配合人工周期对卵巢早衰患者卵巢储备功能的影响

目的探讨补肾滋阴汤配合人工周期对卵巢早衰患者卵巢储备功能的影响。方法选取2016年4月～2017年10月我院收治的卵巢早衰患者96例,按抽签方法进行分组各48例。对照组采用人工周期治疗,观察组在对照组基础上加服补肾滋阴汤治疗,两组均治疗2个疗程后比较临床疗效、卵巢储备功能及不良反应情况。结果观察组的治疗总有效率、E2水平均较对照组高,LH、FSH水平较对照组低,差异均有统计学意义(P0.05);两组不良反应发生率比较,差异无统计学意义(P0.05)。结论补肾滋阴汤配合人工周期治疗可提升卵巢早衰的临床疗效,调节性激素水平,改善卵巢储备功能,安全性高。     

阿霉素载药微球在免疫缺陷大鼠肝脏原位肿瘤组织内缓释作用与长效抗肿瘤活性研究

目的:建立免疫缺陷大鼠肝脏原位肿瘤模型,以阿霉素为模型药物,在肿瘤组织注射吸附有阿霉素的载药微球,建立肿瘤组织内抗肿瘤药物缓释与长效作用的研究方法。方法:利用MHCC-97H高侵袭肝细胞癌细胞系在免疫缺陷裸鼠皮下成瘤后,解剖瘤块并切割,种植于免疫缺陷大鼠肝脏原位;进行开腹给药,将阿霉素载药微球精准注射进大鼠肝脏原位肿瘤组织中;收集大鼠血液、肿瘤组织标本等,检测药物在大鼠体内特别是肿瘤组织内的留存情况,最后进行PET/CT小动物活体成像,确定阿霉素载药微球在免疫缺陷大鼠肝脏原位肿瘤组织内缓释作用与长效抗肿瘤活性。结果:通过大鼠肝脏原位接种肝细胞癌瘤块可建立免疫缺陷大鼠肝脏原位肿瘤模型;使用阿霉素载药微球对病灶进行精准给药可实现阿霉素载药微球在体内的缓释作用;索拉非尼(Sorafenib)联用阿霉素载药微球可更显著地抑制大鼠肝脏原位肿瘤的生长。结论:建立了免疫缺陷大鼠肝脏原位肿瘤模型,建立了肿瘤组织内抗肿瘤药物缓释与长效作用的研究方法。     

Computer-aided hepatic tumour ablation: requirements and preliminary results

Surgical resection of hepatic tumours is not always possible, since it depends on different factors, among which their location inside the liver functional segments. Alternative techniques consist in local use of chemical or physical agents to destroy the tumour. Radio frequency and cryosurgical ablations are examples of such alternative techniques that may be performed percutaneously. This requires a precise localisation of the tumour placement during ablation. Computer-assisted surgery tools may be used in conjunction with these new ablation techniques to improve the therapeutic efficiency, whilst they benefit from minimal invasiveness. This paper introduces the principles of a system for computer-assisted hepatic tumour ablation and describes preliminary experiments focusing on data registration evaluation. To keep close to conventional protocols, we consider registration of pre-operative CT or MRI data to intra-operative echographic data.     

High-content imaging of human hepatic spheroids for researching the mechanism of duloxetine-induced hepatotoxicity

Duloxetine (DLX) has been approved for the successful treatment of psychiatric diseases, including major depressive disorder, diabetic neuropathy, fibromyalgia and generalized anxiety disorder. However, since the usage of DLX carries a manufacturer warning of hepatotoxicity given its implication in numerous cases of drug-induced liver injuries (DILI), it is not recommended for patients with chronic liver diseases. In our previous study, we developed an enhanced human-simulated hepatic spheroid (EHS) imaging model system for performing drug hepatotoxicity evaluation using the human hepatoma cell line HepaRG and the support of a pulverized liver biomatrix scaffold, which demonstrated much improved hepatic-specific functions. In the current study, we were able to use this robust model to demonstrate that the DLX-DILI is a human CYP450 specific, metabolism-dependent, oxidative stress triggered complex hepatic injury. High-content imaging analysis (HCA) of organoids exposed to DLX showed that the potential toxicophore, naphthyl ring in DLX initiated oxidative stress which ultimately led to mitochondrial dysfunction in the hepatic organoids, and vice versa. Furthermore, DLX-induced hepatic steatosis and cholestasis was also detected in the exposed EHSs. We also discovered that a novel compound S-071031B, which replaced DLX’s naphthyl ring with benzodioxole, showed dramatically lower hepatotoxicities through reducing oxidative stress. Thus, we conclusively present the human-relevant EHS model as an ideal, highly competent system for evaluating DLX induced hepatotoxicity and exploring related mechanisms in vitro. Moreover, HCA use on functional hepatic organoids has promising application prospects for guiding compound structural modifications and optimization in order to improve drug development by reducing hepatotoxicity.Subject terms: Drug safety, Translational research, Toxicology     

Incidence and detection of occult hepatic metastases in colorectal carcinoma.

Isotope liver scan, ultrasonography, and computed tomography of the liver were performed during the postoperative period in 43 consecutive patients undergoing laparotomy for colorectal carcinoma. Obvious hepatic metastases were detected in six patients at the time of surgery. Eleven patients considered to have a disease-free liver at laparotomy developed hepatic metastases during the two-year follow-up period. These patients were considered to have had occult hepatic metastases at the time of surgery. Postoperative isotope liver scan, ultrasonography, and computed tomography detected the presence of overt metastases in four, five, and six patients respectively. Of the 11 patients with occult metastases, isotope liver scan, ultrasonography, and computed tomography detected one, three, and nine respectively. These observations suggest that 29% of patients undergoing apparently curative resection for colorectal carcinoma possess occult hepatic metastases and that computed tomography is superior to ultrasonography and isotope liver scan in detecting them.     

NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir

Liver steatosis was once believed to be a benign condition, with rare progression to chronic liver disease. Thus, in both clinical and experimental practice, it is fundamental to have a reliable and objective method for its precise quantification. An image analysis algorithm was developed and validated for automatically and rapidly quantifying hepatic fat microvesicles. The image processing algorithms automatically segmented interstitial steatosis areas and analyzed the threshold region. Automatic quantifications did not significantly differ from manual evaluations of means of the same areas. Comparison of our image analysis quantifications with staging of histologic evaluations of liver steatosis presented significant correlations that are based on the distribution patterns and on the area quantity of steatosis, respectively. The use of algorithms for analysis and image processing is a sensitive, precise, objective and reproducible method of quantifying hepatic fat microvesicles, which complements semi-quantitative histologic evaluation systems.     

Some functional consequences of partial hepatectomy in rainbow trout (Salmo gairdnerii)

A partial hepatectomy (an average of 36% of hepatic mass removed) was performed in rainbow trout. Thirty days after this partial hepatic removal, the liver had recovered its initial weight. During regeneration the remaining liver was unable to maintain normal blood levels of protein, cholesterol and, partially, lipids which decrease after surgery. The results obtained show that functional and liver weight regeneration proceed at different rates throughout a given time course, weight recovering faster than complete functional restoration.     

Evaluation of serum uric acid changes in different forms of hepatic vascular inflow occlusion in human liver surgeries

Uric acid values in serum have been analyzed as one of the markers to predict cellular damage due to ischemia reperfusion injury in the field of organ transplantation. The present study was conducted to confirm that uric acid values in serum could be an efficient marker of ischemic injury of liver parenchyma following hepatic vascular occlusion in human liver surgery. The changes in serum uric acid values were analyzed at fixed intervals during different liver surgeries. Significant increases in serum uric acid values were observed in patients who received the Pringle's maneuver in which hepatic vascular inflow was manipulated with a repetition of 15 min occlusion and 5 min perfusion, whereas almost no changes in uric acid values were found in both groups of patients who received the hemilobal occlusion of the Glisson's triad in which the right or left vessels were manipulated with a repetition of 30 min occlusion and 5 min perfusion and the "control method" in which the hepatic vessels of the lesion side were previously cut before liver resection. Uric acid values in serum increased in patients of Pringle's maneuver compared to those of the hemilobal occlusion of the Glisson's triad and the control method though these procedures were used in larger hepatectomies rather than Pringle's maneuver. The results indicated that serum uric acid values do not always reflect the severity of ischemia of the liver parenchyma but reflect intestinal congestion because marked intestinal congestion was observed in patients of Pringle's maneuver but not in patients of the hemilobal occlusion of the Glisson's triad and the control method. The evaluation of the severity of the ischemic injury of the liver should be done with caution when uric acid is used as a marker in human liver surgery.     

Generation,characterization and potential therapeutic applications of mature and functional hepatocytes from stem cells

Liver cancer is the sixth most common tumor in the world and the majority of patients with this disease usually die within 1 year. The effective treatment for end‐stage liver disease (also known as liver failure), including liver cancer or cirrhosis, is liver transplantation. However, there is a severe shortage of liver donors worldwide, which is the major handicap for the treatment of patients with liver failure. Scarcity of liver donors underscores the urgent need of using stem cell therapy to the end‐stage liver disease. Notably, hepatocytes have recently been generated from hepatic and extra‐hepatic stem cells. We have obtained mature and functional hepatocytes from rat hepatic stem cells. Here, we review the advancements on hepatic differentiation from various stem cells, including hepatic stem cells, embryonic stem cells, the induced pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, and probably spermatogonial stem cells. The advantages, disadvantages, and concerns on differentiation of these stem cells into hepatic cells are highlighted. We further address the methodologies, phenotypes, and functional characterization on the differentiation of numerous stem cells into hepatic cells. Differentiation of stem cells into mature and functional hepatocytes, especially from an extra‐hepatic stem cell source, would circumvent the scarcity of liver donors and human hepatocytes, and most importantly it would offer an ideal and promising source of hepatocytes for cell therapy and tissue engineering in treating liver disease. J. Cell. Physiol. 228: 298–305, 2013. © 2012 Wiley Periodicals, Inc.     

巨大右半肝肿瘤切除术时的出血控制

巨大右半肝肿瘤切除过程中的出血量是决定手术能否成功的关键因素,控制手术过程中出血的技术也是右半肝切除术中的最重要的技术,有效控制术中出血的方法贯穿于整个手术过程中：良好的术前评估,术中于第一肝门处选择性阻断支配右半肝的入肝血流,于第二肝门处切断肝右静脉,于第三肝门处切断肝短静脉,在无血条件下用超声吸引刀切除预定的右半肝以及肝断面的处理等。此方法能有效控制手术过程中出血,保证左半肝血液供应,减轻肝脏缺血/再灌注损伤,减少术后肝功能不全的发生,保证了胃肠道血流的通畅,避免了黏膜屏障受损,全身血流动力学平稳,对其他脏器功能影响小,缩短了手术时间,极大地提高了手术的安全性。     

Effect of major liver resection on hepatic ureagenesis in humans

Changes in hepatic ureagenesis following major hepatectomy are not well characterized. We studied the relation between urea synthesis and liver mass before and after major hepatectomy in humans. Fifteen patients scheduled for resection of malignancies in otherwise healthy livers were studied. Pre- and postoperative liver volume was assessed by computerized tomography-volumetry. During surgery, a primed, continuous infusion of [(13)C]urea was administered intravenously, and arterial blood samples were obtained hourly. Indocyanine green clearance was determined before and after resection. Seven patients underwent major hepatectomy, and eight patients underwent minor [<5% functional liver volume (total volume -- tumor volume)] or no resection, serving as controls. Resected functional liver volume in the major hepatectomy group averaged 60%. Urea synthesis per gram of functional liver tissue increased 2.6-fold following major hepatectomy, maintaining whole body urea synthesis. Arterial ammonia remained unchanged throughout the study, whereas following hepatectomy a hyperaminoacidemia occurred. In conclusion, immediately following major hepatectomy, urea synthesis per gram of functional liver tissue increases rapidly and proportionately to the amount of liver tissue resected, maintaining whole body urea synthesis at preoperative levels. This rapid and complete adaptation suggests that the capacity of urea synthesis is not limiting the maximum resectable volume in otherwise healthy livers.     

Bleeding varices: 2. Elective management.

Patients who have previously bled from esophageal varices should have their hepatic function, neurologic status and nutritional status evaluated and should be examined for ascites before elective variceal decompression is done to prevent recurrent variceal hemorrhage. The two most important procedures used for this evaluation are liver biopsy and visceral angiography. If the liver biopsy reveals little or no necroinflammatory activity, shunt surgery is indicated. For patients with moderate or severe necroinflammatory activity, surgery is delayed until the inflammation subsides. The central aim of visceral angiography is to determine whether the patient has hepatopetal or hepatofugal portal venous flow. Patients with hepatopetal flow are treated with a selective distal splenorenal shunt. Those with hepatofugal flow are managed with a total shunt, such as an interposition H-graft portacaval or mesocaval shunt.