自制铐式可调型肝钳在肝段切除中的应用

背景：研制自制铐式可调型肝钳以半肝血流阻断及肝局部血流阻断法行半肝、肝段及肝部分切除可减少肝功能损伤及胆瘘的发生。 目的：探讨自制铐式可调型肝钳以半肝血流阻断及肝局部血流阻断法行半肝、肝段及肝部分切除对血流变、肝肾功能的影响,评价其手术安全性。 方法：对85例半肝、肝段及肝部分切除的患者,应用自制铐式可调型肝钳以半肝血流阻断及肝局部血流阻断法行半肝、肝段及肝部分切除患者31例设为实验组,同期54例行不阻断肝门血流半肝、肝段及肝部分切除,比较术中出血量、术后胆瘘例数以及血流变学、肝肾功能的改变。 结果与结论：实验组31例患者术中出血量少、肝切除后无胆瘘、对血流变学、肝肾功能影响小。说明应用自制铐式可调型肝钳以半肝血流阻断及肝局部血流阻断法行半肝、肝段及肝部分切除,术式安全有效。     

Comparison of blood parameters in degenerative liver disease and liver neoplasia in dogs

The evaluation of blood parameters is the first step in the diagnosis of liver disease. In many cases the blood parameters indicate only cell destruction or disturbances of liver cell synthesis. It is impossible for one to make a diagnosis by blood parameters only. In our investigation we compared the liver parameters ALT, ALP, GLDH, albumin, bile acid and total bilirubin in dogs with severe degenerative liver disease and in dogs with malignant liver tumours. The aim of our investigation was to find differences between the blood parameters in both liver diseases. We found no significant difference in parameters between degenerative liver disease and liver neoplasia. However, in our investigation, compared with other reports, the mean levels of ALT, ALP, albumin and bilirubin were more often altered in liver neoplasia than in degenerative liver disease. Thus, we conclude that disturbances of liver cell integrity and function occur more often in liver tumours than in severe degenerative liver disease.     

活体肝移植中轻度脂肪变性供肝的应用

背景：在活体肝移植中使用脂肪变性供肝不但影响供者的安全,同时也影响受者的生存。 目的：评价活体肝移植中使用轻度脂肪变性供肝时供者的安全性及受者预后情况。 方法：回顾性分析104例成人间右半肝活体肝移植的资料,根据移植过程中供肝活检病理标本的脂肪变性程度将所有病例分成4个组。比较各组移植供受者移植后2周的肝体积增生率,分析104例成人间活体右半肝肝移植受者移植后死亡情况及原因。 结果与结论：4组病例在供受者移植后肝功能的恢复和受者后移植预后无明显差别,没有肝功能延迟恢复和原发无功发生。轻度大泡性脂肪肝者只要残肝足够可以成为合适的活体肝移植供者。使用轻度大泡性脂肪肝并不增加受者病死率和移植物失功。     

Endotheliopathy of liver sinusoidal endothelial cells in liver disease

Liver is the largest solid organ in the abdominal cavity, with sinusoid occupying about half of its volume. Under liver disease, hemodynamics in the liver tissue dynamically change, resulting in injury to liver sinusoidal endothelial cells (LSECs). We discuss the injury of LSECs in liver diseases in this article. Generally, in noninflamed tissues, vascular endothelial cells maintain quiescence of circulating leukocytes, and unnecessary blood clotting is inhibited by multiple antithrombotic factors produced by the endothelial cells. In the setting of inflammation, injured endothelial cells lose these functions, defined as inflammatory endotheliopathy. In chronic hepatitis C, inflammatory endotheliopathy in LSECs contributes to platelet accumulation in the liver tissue, and the improvement of thrombocytopenia by splenectomy is attenuated in cases with severe hepatic inflammation. In COVID-19, LSEC endotheliopathy induced by interleukin (IL)-6 trans-signaling promotes neutrophil accumulation and platelet microthrombosis in the liver sinusoids, resulting in liver injury. IL-6 trans-signaling promotes the expression of intercellular adhesion molecule-1, chemokine (C-X-C motif) ligand (CXCL1), and CXCL2, which are the neutrophil chemotactic mediators, and P-selectin, E-selectin, and von Willebrand factor, which are involved in platelet adhesion to endothelial cells, in LSECs. Restoring LSECs function is important for ameliorating liver injury. Prevention of endotheliopathy is a potential therapeutic strategy in liver disease.     

Distribution of plasminogen activator inhibitor in normal liver, cirrhotic liver, and liver with metastases.

AIMS--To examine the distribution of PAI-1 antigen in normal and cirrhotic liver and liver with metastases. METHODS--Sections of normal and cirrhotic liver and liver with metastases were stained using the alkaline phosphatase antialkaline phosphatase (APAAP) technique and monoclonal antibody specific for plasminogen activator inhibitor (PAI-1). RESULTS--PAI-1 antigen was identified as discrete granules in the cytoplasm of hepatocytes in normal liver, particularly around portal tracts and central veins of the liver lobule. In cirrhotic liver a striking reduction of PAI-1 antigen was noted. In liver with metastases increased amounts of PAI-1 antigen were concentrated in hepatocytes around the margins of malignant deposits. CONCLUSIONS--Cirrhotic liver contains considerably less PAI-1 antigen than does normal liver, despite raised plasma concentrations of PAI-1. This may reflect release of hepatic PAI-1 into the circulation or decreased clearance of PAI-1 from the plasma. Secondary malignant deposits in the liver seem to stimulate production of PAI-1 in adjacent hepatocytes. This may influence the invasive process and may contribute to the thrombotic tendency associated with malignancy.     

慢性肝病肝剪切波速与血清肝纤维化标志物在肝纤维化诊断中的对比研究

目的 探讨慢性肝病肝剪切波速及血清肝纤维化标志物在肝纤维化分级诊断中的临床应用价值.方法 选择235例慢性肝病患者(肝纤维化组),其中男性179例,女性56例;年龄17～64岁,平均年龄36.3岁.40例健康对照者,其中男性25例,女性15例;年龄25～62岁,平均年龄43.2岁.先进行肝剪切波速和抽血实验室检查,然后在超声引导下穿刺活组织检查,以病理结果为标准,分析剪切波速及血清肝纤维化标志物在评价肝纤维化分级之间的关系.并将检查结果与健康对照者进行比较.结果 235例慢性肝病患者有215例进行肝穿刺活组织检查,除F0级肝病患者与健康对照组F0级之间剪切波速比较差异无统计学意义(P＞0.05)外,其余肝病各分组剪切波速随肝纤维化程度的增高而波速增快;且血清肝纤维化标志物含量亦随肝纤维化病理分期的增高而增高.结论 肝剪切波速及血清肝纤维化标志物对肝纤维化患者的病理分期有良好相关性,对肝纤维化的诊断及疗效观察有重要的临床应用价值.     

肝移植后肝功能的异常

背景：肝移植后导致肝功能异常原因复杂,早期弄清引起肝功能异常的原因对治疗至关重要。 目的：较全面的了解肝移植后可以导致肝功能异常的原因,以便应用于临床诊治。 方法：应用计算机检索CNKI和FMJS数据库,采用医学主题词检索,检索词为“肝移植;肝功能异常;转氨酶异常;胆红素升高;原因”或“liver transplantation; abnormal liver function; transaminase abnormalities; bilirubin increased, and causes”,时间范围为1991年1月至2012年7月,共检索到98篇文章,选择文章主要内容与肝移植后肝功能异常直接相关的、发表在权威杂志上的文章共35篇进行综述。 结果与结论：肝移植后导致肝功能异常的原因众多,临床表现复杂。最常见的原因依次是急性排斥反应、胆道并发症及病毒感染。肝移植后早期,尤其是1个月内出现肝功能异常,需警惕小体积综合征和原发性移植物无功的发生。各种原因引起的肝功能异常,转氨酶及胆红素升高的程度不尽相同。急性排斥反应、自身免疫性肝炎、病毒感染、门静脉及肝静脉狭窄、缺血-再灌注损伤等转氨酶升高较胆红素升高显著;慢性排斥反应、胆道并发症、肝动脉狭窄、原发性胆汁性肝硬化、原发性硬化性胆管炎等早期以梗阻酶碱性磷酸酶、谷氨酰转移酶、总胆红素、直接胆红素升高为主;肿瘤导致的肝功能异常视肿瘤大小、压迫部位不同,可表现出以转氨酶升高为主或以胆红素升高为主。此外,各种原因多有其特殊病史,仔细询问病史有助于早期诊断。临床工作中,应重视尽量详尽的采集病史,根据转氨酶和胆红素升高的具体情况,首先考虑引起肝功能异常的常见原因,经临床证实排除后再考虑其他相对不常见原因,并结合实验室检查、影像学检查及肝脏穿刺病理活检,尽早明确病因及治疗。     

Postoperative liver regeneration and complication in live liver donor after partial hepatectomy for living donor liver transplantation

The safety of donor is the first priority during whole procedure in living donor liver transplantation. We evaluated the short-term results of partial living donor liver transplantation in the view of donor safety. We prospectively evaluated the extent of liver regeneration, the recovery of liver function, and the perioperative complications in 41 live liver donors for partial liver transplantation at our institution. We developed novel personal computer volumetry program for the evaluation of liver regeneration. Serial CAT scan was performed preoperatively, at postoperative day (POD) #7 and POD #30 and liver volume was measure by using volumetry program. The serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (T.bil.) was serially monitored. There were 34 males and 7 females. The mean preoperative liver volume was 1320.6 cm3. The remained mean liver volume was 687.8 cm3 after harvest, and increased to 954.4 cm3 (144.6%) at POD #7, and 1169.5 cm3 (81.4%) at POD #30, which was 88.5% of preoperative total liver volume. The serum level of ALT/ AST and T.bil. peaked at POD #1 and declined thereafter, and finally returned to preoperative level at POD #30. The regeneration rate was significantly different by age, type and size of graft according to the donors. Six donors experienced postoperative complications and they were four pleural effusions, one wound infection and one case of bile duct stenosis that was treated by endoscopic nasal biliary drainage. All of them were right lobe donors. In conclusion, the donor liver regenerated up to 88.5% of preoperative volume with full recovery of liver function at POD #30. Right lobe donors suffered more complications and need more meticulous operative and postoperative care than left lobe or left lateral segment donors.     

Evaluation of a hybrid artificial liver module with liver lobule-like structure in rats with liver failure

We studied the recovery of rats with fulminant hepatic failure (FHF) by treating them with our original hybrid artificial liver support system (HALSS). We developed an original artificial liver module having a liver lobule-like structure (LLS). This module consists of many hollow fibers regularly arranged in close proximity and hepatocyte aggregates (organoids) induced into the extra capillary space of the module by centrifugal force. The LLS module can express some liver specific functions at high levels and maintain them for several months in vitro. In this study, we evaluated the efficacy of our LLS-HALSS by using rats with FHF induced by a method that combined partial hepatectomy with hepatic ischemia. In the animal experiments, blood ammonia levels rapidly increased in the control group (sham-HALSS group). These rats died during or immediately after application of the sham-HALLS. On the other hand, in the LLS module application group (LLS-control group), the increase in blood ammonia was completely suppressed and all rats recovered. Blood constituents at 4 weeks after application were at normal levels, and the weight of the liver was the same as that of a normal rat. These results indicate that HALSS may be useful for treating liver failure patients until liver transplantation can be performed or until regeneration of the native liver occurs.     

The stimulation of regenerative processes in the liver in acute liver failure

The efficiency of the newborn allogenic hepatocytes (NAH) in the treatment of the acute liver failure (ALF) in dogs is studied histologically, histochemically and ultrastructurally. The administration of NAH prevents, in part, the ischemic cell death and is efficient in the stimulation of the liver regeneration in ALF. NAH enhance hepatocyte and Kupffer cell proliferation, reduce the number of degenerative and necrotic foci, increase the number of cell organelles, their volume, compensate the function of the damaged liver, facilitate the morpho-functional restoration of the recipient ischemically damaged liver.     

Morphometric analysis of liver macrophages in patients with colorectal liver metastasis

Kupffer cells, residential liver macrophages, have binding sites for carcinoembryonic antigen (CEA), but their role in metastatic liver tumor progression has not been well addressed clinically. Liver macrophages were analyzed morphometrically and their relationship with CEA and tumor microvessel density (MVD) was examined in 71 patients who underwent macroscopic curative hepatectomy for metastatic liver tumors from colorectal cancer. In paraffin-embedded sections, MVD was evaluated by CD34-positive cell counts, liver macrophages visualized using anti PG-M1 (CD68) antibody were analyzed, and membrane-bound CEA was assessed by immunoreactivity of tumor cells for CEA. The area of liver macrophages in peritumoral regions (43.0±11.6 μm²) was significantly larger than that in non-tumor regions (25.2±24.2 μm²) (P<0.0001). The liver macrophage density in peritumoral regions was 154±49 per field, and was significantly higher than in non-tumor regions (74±24 per field) (P<0.001). The density and the area of liver macrophages had no correlation with serum CEA levels and the degree of tumor CEA expression. A weak positive correlation was observed between MVD and liver macrophage density (P=0.0104, Spearman rank correlation coefficient = 0.31). Cox multivariate regression analysis showed that MVD greater than 50 (P=0.0233, hazard ratio = 2.463), and the area of liver macrophages larger than 40.9 μm² (P=0.0485, hazard ratio = 2.127), were significant independent prognostic factors. The present morphometric analysis suggests that the liver macrophages are accumulated and activated in peritumoral regions in patients with colorectal liver metastasis and this accumulation and activation of liver macrophages, with which soluble or membrane-bound CEA might not be associated, are related with patients' poor prognosis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Cell-mediated immunity to liver antigen in toxic liver injury. II. Role in pathogenesis of liver damage.

The possible pathogenetic role of lymphocytes sensitized to liver antigens was investigated in CBA mice in which sublethal hepatic necrosis had been induced by carbon tetrachloride (CCl4). Sensitized lymphocytes from CCl4-treated mice were administered to syngeneic recipients. The recipients developed sensitivity to liver antigens but showed no evidence of liver damage. The cell mediating the immune response both in the donor and the recipient was a T cell. This was demonstrated further by studies involving mice rendered T cell deficient. These mice did not develop sensitized lymphocytes when they were treated with CCl4 but the extent of liver damage was similar in both T cell-depleted and intact animals. These findings suggest that T cell sensitization to liver antigens occurs as a result of toxic liver damage and does not play a role in the pathogenesis of the hepatic necrosis.     

Thrombocytopenia in liver cirrhosis

To examine the pathogenesis of thrombocytopenia associated with liver cirrhosis, the platelet count, spleen size and serum cholinesterase levels were measured together with plasma concentration of beta-thromboglobulin, fibrinopeptide A and serum albumin in 38 patients with histologically proven, severe but stable liver cirrhosis. The spleen size contributed most significantly to thrombocytopenia in this disorder and the serum cholinesterase level also correlated with the platelet count, both in decompensated and compensated liver cirrhosis. Plasma beta-thromboglobulin, serum fibrinopeptide A levels and serum albumin did not correlate with the platelet count. These findings indicate that disseminated intravascular coagulation is not likely to be the cause of thrombocytopenia in liver cirrhosis. Splenomegaly as well as the diminished protein synthetic activity of the liver participates in the pathogenesis of the thrombocytopenia in this disease.     

腹腔镜下改制电凝刀肝肿瘤切除术

目的探讨运用一种新的电凝刀行腹腔镜肝肿瘤切除术的可行性。方法将骨科用的克氏针改制为适合腹腔镜手术的电凝刀头，2002年2月至2003年12月间在腹腔镜下用改制的电凝刀行4例肝肿瘤腹腔镜肝切除术。结果4例肝肿瘤腹腔镜肝切除术成功，手术操作简便，未使用超声波刀等昂贵的器械。平均手术时间130min，平均术中出血约50ml．平均术后住院天数5．5d。术中及术后无并发症发生。结论用改制的电凝刀行腹腔镜肝肿瘤切除术是一种简易可行并易于推广应用的方法。     

肝衰竭肝脏的组织病理学变化及其干细胞活化情况

目的探讨肝移植病例中重型肝炎肝衰竭的病理组织学变化与其肝脏干细胞活化状态的关系。方法收集肝移植病例中重型肝炎肝衰竭33例,以相应供肝组织作为正常对照,以免疫组织化学EnVision法检测肝组织中c-kit、Ki-67、HBsAg及HBcAg表达情况,并选择10例c-kit明显阳性病例进行了甲苯胺蓝组织化学染色做为对比染色,分析肝衰竭病例肝脏病理组织学、病毒抗原表达、有无人工肝治疗史,c—kit阳性肝脏干细胞活化数量。结果33例中男性25例,女性8例,年龄分布为21～64岁。符合急性肝衰竭6例,其中2例与乙型肝炎病毒感染有关,3例为药物中毒所致,1例为急性妊娠脂肪肝;亚急性肝衰竭5例,均为乙型肝炎病毒感染所致;慢性急性发作性肝衰竭22例,均为乙型肝炎病毒感染所致。肝移植手术前有人工肝治疗史13例。肝脏活化的干细胞被c-kit单克隆抗体所标记,但不能被甲苯胺蓝染料染色。正常供肝内无或偶见c-kit阳性细胞;急性肝衰竭组c-kit阳性细胞为3．50±2．66（0～8）个／mm^2。;亚急性肝衰竭组为11．47±8．85（3～30）个／mm^2;慢性急性发作性重型肝炎组为15．50±10．95（5～45）个／mm^2,各组之间c-kit阳性细胞数差异有统计学意义。有无人工肝治疗史对c-kit阳性细胞计数无明显影响。供体肝脏组织Ki-67染色阴性,而肝衰竭病例在汇管区或旁汇管区可以检测到数量不等的Ki-67阳性细胞,但并不与c-kil阳性前体细胞呈平行关系。结论急性肝衰竭时肝细胞大片坏死但内源性干细胞活化不足是预后差的原因之一。而病程迁延较长的亚急性或慢性肝衰竭,肝脏干细胞活化水平逐渐升高,提示积极治疗肝衰竭使其设法渡过急性期,可以不同程度调动肝脏自身再生重建机制。     

Heterotopic erythropoiesis in liver transplantation

Various conditions may restore hematopoietic activity in the adult liver. Of them, liver transplantation is of most interest. The causes and the mechanism of hematopoiesis restoral in liver grafts is not yet fully clarified. The Authors analyze the incidence of immature erythroid cells in a series of hepatic fine-needle aspiration biopsies performed in 28 patients with orthotopic liver transplant and in two clusters. The post-mortem liver examination, available in the two clusters, confirmed the ungoing hematopoietic activity.     

IgA deposition in liver in alcoholic liver disease. An index of progressive injury

A retrospective study was done to evaluate the prognostic importance of the patterns of IgA deposition in the liver in alcoholic liver disease. The patterns of IgA deposition in the liver were determined by direct immunofluorescence with fluorescein conjugated rabbit antihuman IgA. Twenty of 40 patients showed a characteristic continuous pattern, and 20 patients showed the nonspecific discontinuous pattern of IgA deposition in the liver. Alcoholic liver disease progressed considerably in 14 (70%) of the 20 patients with an initial continuous pattern and in three (15%) of the 20 patients with an initial discontinuous pattern. Alcoholic liver disease did not progress in six (30%) of 20 patients with an initial continuous pattern and in 17 (85%) of the 20 patients with an initial discontinuous pattern of IgA deposition in the liver.     

中国人肝细胞系1运用于生物人工肝的生物代谢功能

背景：前期研究发现,中国人肝细胞系1细胞分化程度高且生物代谢功能良好, 并且中国人肝细胞系1细胞组织学上来源于正常肝组织,较其他来源于肿瘤源性的肝细胞系更为安全。 目的：探讨中国人肝细胞系中国人肝细胞系1细胞在混合型生物人工肝中的生物代谢功能。 方法：15只食蟹猴随机分成对照组(n=5)和治疗组(n=10),均建立急性肝功能衰竭模型,治疗组接受以全接触灌流型生物反应器接种微载体微重力中国人肝细胞系1细胞建立的人源细胞混合型生物人工肝进行治疗。 结果与结论：急性肝功能衰竭食蟹猴血清谷氨酸转氨酶、总胆红素、总胆汁酸、尿素氮、肌酐、血氨均明显上升,而白蛋白、Fischer指数则显著下降;人源细胞混合型生物人工肝治疗后,急性肝功能衰竭食蟹猴血清谷氨酸转氨酶、总胆红素、总胆汁酸、尿素氮、肌酐、血氨和白蛋白均恢复。提示中国人肝细胞系1细胞在混合型生物人工肝中生物代谢功能良好,表现出良好的肝特异性生物合成及生物代谢功能。     

Copper-binding protein in liver cells

The patterns and incidences of orcein-positive granules of copper-binding protein (CBP) in 2,531 liver biopsy specimens from children and adults with a large variety of liver diseases are reported. Fetal and neonatal livers have high physiologic levels of copper and CBP, which fall to within the adult range by the third to the sixth month of life. Therefore, in liver specimens from children less than 6 months of age, it was not possible to determine whether the orcein-positive granules present represented physiologic or pathologic deposits of CBP. In adults and in children older than 6 months of age, CBP granules were found almost exclusively in association with four main groups of liver diseases: Wilson's disease, chronic biliary disorders, cirrhosis/extensive fibrosis, and primary liver tumors. Orcein-positive granules were never found in patients with acute liver disease. The granules were extremely helpful in distinguishing chronic biliary diseases from acute cholestatic and hepatic disorders, primary biliary cirrhosis from chronic active hepatitis, and primary liver tumors from metastatic tumor deposits.