肝硬化患者血清IGF-Ⅰ、IGFBP-3检测的临床意义

目的：探讨肝硬化患者血清胰岛素样生长因子（IGF—Ⅰ）及其结合蛋白（IGFBP-3）检测的临床意义。方法：应用免疫放射分析测定35例肝硬化患者（肝硬化组）,25例急性肝炎患者（肝炎组）,35例健康人（对照组）血清IGF—Ⅰ、IGFBP-3水平,比较两者在3组中的浓度不同及在肝硬化不同Child—Pugh级别者中的变化。结果：血清IGF—Ⅰ、IGFBP-3水平肝硬化组显著低于急性肝炎组和正常对照组（P〈0．01）,且在肝硬化组不同Child—Pugh分级中呈逐渐下降。而急性肝炎组与正常对照组之间无显著差异（P〉0．05）。结论：IGF—Ⅰ、IGFBP～3水平下降是发生肝硬化的重要指标之一。联合检测IGF—Ⅰ、IGFBP-3水平可用来综合评估肝硬化患者的肝功能状态。     

乙肝肝硬化患者血清HBV DNA与透明质酸的关系

目的研究乙肝肝硬化患者血清HBV DNA水平和血清透明质酸的关系。方法临床确诊为乙肝肝硬化的62例患者,采用荧光定量PCR检测血清HBV DNA水平,放射免疫法检测血清透明质酸,对血清HBV DNA水平和透明质酸的关系进行研究分析。结果乙肝肝硬化患者的血清透明质酸水平显著升高,随Child分级的加重血清透明质酸也呈增高趋势(P<0.05),但与血清HBV DNA水平差异无统计学意义(P>0.05)。结论乙肝肝硬化患者的血清HBV DNA和肝硬化的程度及血清透明质酸水平无显著相关性。     

肝硬化患者血清毒素与肝纤维化标志物的相关性的临床研究

目的 探讨不同Child-pugh分级肝硬化患者血清内毒素与肝纤维化标志物的相关性。方法 对101例不同Child-pugh分级肝硬化患者采用偶氮基质显色法检测血清内毒素，放免和固相酶免疫法测定肝纤维化标志物HA、PCⅢ、LN、IV-C水平。结果 肝硬化患者血清HA、PCⅢ、LN、IV-C水平明显高于健康对照组（P〈0．05或P〈0．01）。不同Child．pugh分级肝硬化患者均存在不同程度的内毒素血症，内毒素水平随着Child．pugh分级的逐渐升高明显递增，血清HA、PCⅢ、LN、IV-C水平也显著增加，二者呈明显正相关。结论 肝硬化患者血清内毒素水平与肝纤维化标志物水平呈正相关，防治内毒素血症有利于缓减肝纤维化进程及改善预后。     

肝硬化患者外周血单个核细胞TLR4表达及其基因多态性的研究

目的：检测肝硬化及其不同Child分级患者外周血单个核细胞(PBMCs)Toll样受体4（TLR4）表达，分析TLR4基因Asp299Gly、Thr399Ile的多态性及其与肝硬化疾病发生的相关性。方法:分离110例汉族乙肝后肝硬化患者与健康对照者静脉抗凝血的PBMCs，流式细胞、实时荧光定量PCR及PCR-限制性片段长度多态性分别检测PBMCs TLR4蛋白、 mRNA及Asp299Gly、Thr399Ile基因多态性，分析TLR4基因多态性与肝硬化发生的相关性。结果:肝硬化组PBMCs TLR4阳性细胞率与mRNA表达正相关，均显著高于对照组(P<0.01)，且随着Child评分的升高而升高(P<0.01)；但220例受试对象均未检测到TLR4基因Asp299Gly、Thr399Ile的突变型。结论:乙肝后肝硬化患者PBMCs TLR4表达水平明显增高，与肝硬化损伤的严重程度相关；TLR4基因Asp299Gly、Thr399Ile多态性在中国汉族人群中出现频率低，且与肝硬化疾病的易感性可能无关。     

肝硬化肝门静脉血流超声测定与肝纤维化指标的比较

目的：探讨肝门静脉血流和肝纤维化指标对诊断肝硬化的诊断价值。方法：50例肝硬化患者和20例正常对照组用肝门静脉超声和放免法分别测定肝门静脉血流和肝纤维化指标。结果：肝硬化肝门静脉血流动力学指标均高于正常对照组（P〈0．05），并随着肝功能Child Puph分级程度严重而下降；活动性肝纤维化指标明显高于静止性肝硬化（P〈0．05～0．01）；超声与血清判断肝硬化的符合率比较大致相同。结论：肝门静脉超声和肝纤维化指标能判断肝硬化损害的程度。     

16层螺旋CT灌注成像在肝硬化中的临床应用研究

目的：探讨16层螺旋CT灌注成像在肝硬化中的临床应用研究价值。方法：2009年3月至2010年3月我院接受16层螺旋CT肝脏灌注扫描肝硬化患者5l例,男性39例,女12例,年龄26～79岁,平均年龄51．6岁。根据肝脏功能分级标准进行Child．Pugh分级将肝硬化病人进行分级：其中Child．PughA级33例;Child-PughB级9例;Child—PughC级9例。采用的设备为德国西门子公司Sensation16MSCT扫描系统;将重建后的原始数据采用仪器自带功能软件DynEva进行数据后处理,分别测得并计算出肝脏灌注参数：BV、BF、HAP、PVP、HPI,对所得结果采用SPSSl3．0统计学软件包对不同级别肝硬化之间的各个量化指标进行差异性比较,两组间比较采用t检验法（配对t检验）;多组间比较采用单因素方差分析的方法。结果：（1）主动脉时间．密度曲线（TDC）可分为基线、升段、降段、水平段。肝硬化患者Child-pughA、B、C三级曲线形式大致相似。（2）HAP值从Child—PughA级的（O．2482±0．0401）mL（Inin．mL）增加到C级的（0．3078±0．0326）mL／（min．mL）,HPI值从Child—PughA级的（0．2482±0．0401）mL（min．mL）增加到C级的（0．3078±0．0326）mL／（min．mL）。HPP值从Child．PughA级的（0．2641±0．0410）mL／（min．mL）减少到C级的（0．2144±0．0963）mL／（min．mL）。HBF值从Child—PughA级的（0．2974±0．1232）mL／（min．mL）减少到C级的（0．1856±0．1022）mL／（min．mL）。BV值从Child-PughA级的（0．9575±0．1283）mL／（min．mL）减少到C级的（0．6302±0．1033）mL／（min．mL）。结论：（1）MSCT灌注成像可对肝脏血流灌注参数定量监测。（2）肝脏血流灌注参数能够反映肝硬化的程度。     

组织因子在肝细胞癌的发生及侵袭转移中的研究

目的：检测组织因子（TF）在肝细胞癌患者中的表达并探讨其意义。方法:采用酶联免疫法检测肝细胞癌患者50例及对照组30例的血浆TF水平，采用RT-PCR法检测其中27例肝癌、癌旁、正常肝组织TF mRNA表达。结果:①肝细胞癌患者血浆TF显著高于对照组（P<0.05）。血浆TF在分化高低、肿瘤大小及是否合并肝硬化组间表达有显著差异（P<0.05），在有淋巴转移、肝外脏器转移及门脉癌栓组高于无转移及癌栓组(P<0.05)，而在不同癌灶数目及包膜情况组间无显著差异（P＞0.05）。②TF mRNA在肝癌组织中阳性率及相对表达强度分别为62.96%（17/27）、0.567±0.268，均显著高于癌旁组织及正常组织。阳性患者相对表达强度在肿瘤大小及部分侵袭转移指标中表达有显著差异（P<0.05） 。结论：TF在肝癌患者血浆及组织中升高且与部分侵袭转移指标相关，提示其TF可能促进了肝癌的发生与侵袭转移。     

上转发光免疫层析法检测乙肝病毒外膜大蛋白在不同类型慢性肝病中的临床意义

目的 探讨上转发光免疫层析法检测的乙肝病毒外膜大蛋白（HBV-LP）在慢性乙型肝炎（CHB）、乙肝后肝硬化（LC）、乙肝原发性肝癌（PHCC）患者血清中水平变化及临床意义.方法 利用一种新的基于上转发光法的免疫层析检测技术（UPT）检测260例慢性乙型肝炎、190例乙肝肝硬化及45例乙肝原发性肝癌患者血清中乙肝病毒外膜大蛋白（HBV-LP）的含量,化学发光法检测乙肝E抗原（HBeAg）含量,实时荧光定量PCR法检测乙肝病毒核酸（HBV DNA）.结果 HBV-LP阳性结果浓度水平CHB组主要以＞40 U/ml的高浓度为主,LC组和PHCC组主要集中在＜10 U/ml的低浓度范围内;HBeAg、HBV DNA和HBV-LP的阳性率均表现为CHB组＞LC组＞PHCC组,HBeAg和HBV DNA在LC和PHCC患者中的阳性率均明显低于CHB患者,差异有统计学意义（P＜0.01）;HBV-LP在LC和PHCC患者中的阳性率明显高于HBV DNA和HBeAg,差异有统计学意义（P＜0.05）.结论 上转发光免疫层析法检测HBV-LP水平快捷可靠并且对慢性肝病进展的诊断以及疗效监测有重要的价值.     

肝硬化患者血清TGF-β1水平和肝功能损伤的相关性探讨

目的：探讨了肝硬化患者血清转化生长因子（TGF—β1）水平的变化与肝功能损伤的关系。方法：应用酶联法（ELISA）测定了63例肝硬化患者血清中TGF—β1水平的变化，生化法测定谷丙转氨酶（ALT）和总胆红素（TBIL）水平，并与35名正常健康人作比较。结果：肝硬化患者血清中TGF—β1水平非常显著地高于正常人组（P〈0．01），且与ALT、TBIL呈明显正相关（r=0．4185、0．5937，P〈0．01）。结论：检测血清TGF—β1水平是反映肝硬化患者肝功能损害程度指标之一，可用于判断肝硬化患者肝功能损害程度及评价预后。     

乙肝肝硬化患者血清HA、ⅣC及IL-6检测的临床意义

本文对83例乙肝肝硬化患者血清分别进行了透明质酸（HA）、Ⅳ型胶原（ⅣC）及白细胞介素-6（IL-6）等三项指标检测，了解不同Child-Pugh改良肝功能分级的乙肝肝硬化患者血清中HA、ⅣC及IL-6变化情况，以期探讨HA、ⅣC及IL-6与乙肝肝硬化预后的关系。     

肝硬化患者血清TNF-α和IL-8变化及其临床意义

为研究肝硬化患者血清肿瘤坏死因子（TNF-α）、白介素-8（IL-8）变化与肝功能Child-pugh分级的关系及临床意义,本文对46例肝硬化患者按Child-pugh肝功能分级标准分为A、B、C三组,并设正常对照组30名,采用放射免疫分析法（RIA）分别测定他们的血清TNF-α、IL-8值,同时测定血清总胆红素（TBiL）、谷丙转氨酶（ALT）、白蛋白（ALB）、透明质酸（HA）、层粘蛋白（LN）和III型前胶原（PCIII）。结果显示,肝硬化患者TNF-α、IL-8值较正常组明显升高（P〈0.01）,且A、B、C三组TNF-α、IL-8水平依次递增,各组间比较差异显著（P〈0.01或P〈0.05）。以上数据表明,肝硬化患者血清TNF-α及IL-8水平是反映肝功能损害程度及病情预测的重要指标。     

Effects of hemochromatosis and transferrin gene mutations on iron dyshomeostasis, liver dysfunction and on the risk of Alzheimer's disease

It is now accepted that transition metals, such as iron and copper, are involved in the pathogenesis of the Alzheimer's disease (AD) through their participation in toxic oxidative phenomena. In this context, hemochromatosis (Hfe) and transferrin (Tf) genes are of particular importance, since they play a key role in iron homeostasis. Also, signs of liver distress which accompany metal dysmetabolisms have been shown to be linked to AD. In order to investigate whether and how all these factors are interconnected, in this study we have explored the relationship of the gene variants of Hfe H63D and C282Y and of Tf C2 with serum markers of iron status (iron, ferritin, TF, TF-saturation, ceruloplasmin -CP-, CP and TF serum concentrations (CP/TF) ratio), and of liver function (albumin, transaminases, prothrombin time-prothrombin time (PT)) in a sample of 160 AD patients and 79 healthy elderly controls. Albumin resulted in lower, PT longer and AST/ALT higher ratios in AD patients than in controls, indicating a distress of the liver. Also TF was lower and ferritin higher in AD. Multiple logistic regression backward analyses, performed to evaluate the effects of our biochemical variables upon the probability of developing AD, revealed that a one-unit TF serum-decrease increases the probability of AD by 80%, a one-unit albumin serum-decrease reduces this probability by 20%, and a one-unit increase of AST/ALT ratio generates a 4-fold probability increase. Patients who were carriers of the H63D mutation showed higher levels of iron, lower levels of TF and CP and higher CP/TF ratios, a panel resembling hemochromatosis. This picture was found neither in H63D non-carrier patients, nor in healthy controls. Our results suggest the existence of a link between Hfe mutations and iron abnormalities that increases the probability of developing AD when accompanied by a distress of the liver.     

Iron overload and HFE gene mutations in Czech patients with chronic liver diseases

The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {\it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.     

Effects of chronic aluminum administration on blood and liver iron-related parameters in mice

In this study, the effects of chronically administered aluminum on iron metabolism-related parameters of liver and blood of mice were investigated. An additional purpose to determine how chronic aluminum administration together with vitamin E as an antioxidant to mice changed the parameters related to iron metabolism. For these purposes, we used 21 adult female Balb-c mice in this study. The animals were divided into three groups: one group with aluminum administered chronically, another group with aluminum plus vitamin E administered chronically, and the control group. Serum levels of hemoglobin, ferritin, iron, transferrin, hematocrit, total iron binding capacity (TIBC), as well as percentage of transferrin saturation were determined in all groups. In addition, the liver tissue levels of ferritin and iron were analyzed. Hemoglobin and hematocrit levels of the aluminum group and aluminum plus vitamin E group were significantly decreased compared to the control. In conclusion, no changes occurred in the serum iron related parameters although Al induced anemia in mice when Al administered chronically. There was an increase in the levels of liver iron and ferritin with Al, but Vit E had no effect on the changes of all blood and liver parameters caused by Al.     

Serum transferrin as a liver fibrosis biomarker in patients with chronic hepatitis B

Background/Aims

Transferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B.

Methods

The study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared.

Results

Univariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B.

Conclusions

Serum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.     

CSF iron, ferritin and transferrin levels in restless legs syndrome

The aim of this study is evaluating iron, ferritin, and transferrin in both serum and CSF in patients of restless legs syndrome (RLS), based on the hypothesis that iron deficiency in the central nervous system (CNS) causes the symptoms as a result of the dysfunction of dopaminergic systems. These parameters, polysomnographic sleep measures, and subjective evaluation of the sleep quality were compared in 10 patients of idiopathic RLS (RLS group) and 10 age-matched patients of psychophysiological insomnia without RLS symptoms (non-RLS group). With sleep patterns, sleep latency was longer and sleep efficiency was lower in the RLS group than those in the non-RLS group. Periodic leg movement index in the RLS group was higher than that of the non-RLS group. With serum examination, there were no significant differences for the iron, ferritin, and transferrin values between the both groups. With CSF examination, the iron and ferritin values were lower and the transferrin values were higher in the RLS group than those in the non-RLS group. There was positive correlation between the serum and CSF ferritin levels in the both groups, but the slope of the regression lines for the RLS group was lower than that for the non-RLS group. These results indicate low brain iron concentration caused by the dysfunction of iron transportation from serum to CNS in patients with idiopathic RLS.     

Is there any connection between angiotensin converting enzyme activity and liver cirrhosis of alcoholic genesis?

The objective of this study was to assess the serum angiotensin converting enzyme (ACE) activity in patients with liver cirrhosis caused by chronic alcohol consumption, in order to get better insight into the function of the renin-angiotensin system. PATIENTS AND METHODS: Serum level of ACE activity was measured by Neels spectrophotometry in 35 alcoholic liver cirrhosis patients classified according to Child-Pugh-Turcotte criteria and 35 dyspeptic patients with any liver disease excluded (control group). RESULTS: Serum values of ACE were statistically significantly higher (p < 0.00001) in the group of liver cirrhosis patients (x = 250.16 +/- 85.5 nmol) than in the control group (x = 115.88 +/- 58.19 nmol). The highest levels of ACE were measured in class B group of liver cirrhosis patients vs. class A and class B groups (p < 0.013). CONCLUSION: It is concluded that liver cirrhosis patients have elevated ACE levels, which coud be useful in the diagnosis and follow up of these patients.     

A population-based study of the clinical expression of the hemochromatosis gene.

BACKGROUND AND METHODS: Hereditary hemochromatosis is associated with homozygosity for the C282Y mutation in the hemochromatosis (HFE) gene on chromosome 6, elevated serum transferrin saturation, and excess iron deposits throughout the body. To assess the prevalence and clinical expression of the HFE gene, we conducted a population-based study in Busselton, Australia. In 1994, we obtained blood samples for the determination of serum transferrin saturation and ferritin levels and the presence or absence of the C282Y mutation and the H63D mutation (which may contribute to increased hepatic iron levels) in 3011 unrelated white adults. We evaluated all subjects who had persistently elevated transferrin-saturation values (45 percent or higher) or were homozygous for the C282Y mutation. We recommended liver biopsy for subjects with serum ferritin levels of 300 ng per milliliter or higher. The subjects were followed for up to four years. RESULTS: Sixteen of the subjects (0.5 percent) were homozygous for the C282Y mutation, and 424 (14.1 percent) were heterozygous. The serum transferrin saturation was 45 percent or higher in 15 of the 16 who were homozygous; in 1 subject it was 43 percent. Four of the homozygous subjects had previously been given a diagnosis of hemochromatosis, and 12 had not. Seven of these 12 patients had elevated serum ferritin levels in 1994; 6 of the 7 had further increases in 1998, and 1 had a decrease, although the value remained elevated. The serum ferritin levels in the four other homozygous patients remained in the normal range. Eleven of the 16 homozygous subjects underwent liver biopsy; 3 had hepatic fibrosis, and 1, who had a history of excessive alcohol consumption, had cirrhosis and mild microvesicular steatosis. Eight of the 16 homozygous subjects had clinical findings that were consistent with the presence of hereditary hemochromatosis, such as hepatomegaly, skin pigmentation, and arthritis. CONCLUSIONS: In a population of white adults of northern European ancestry, 0.5 percent were homozygous for the C282Y mutation in the HFE gene. However, only half of those who were homozygous had clinical features of hemochromatosis, and one quarter had serum ferritin levels that remained normal over a four-year period.