Angiopoietin-2 levels are elevated in exudative pleural effusions

OBJECTIVE: To examine the pleural fluid (PF) and serum levels of angiopoietin (Ang)-1, Ang-2, and vascular endothelial growth factor (VEGF) in patients with pleural effusions (PEs). METHODS: One hundred fifteen patients, 16 with transudative PEs due to heart failure and 99 with exudative PEs (malignant, 40; para-pneumonic, 24; tuberculous, 13; miscellaneous etiologies, 22) were included in the study. PF and serum levels of the growth factors were measured using enzyme-linked immunosorbent assay. RESULTS: PF Ang-2 and VEGF levels but not Ang-1 levels were higher (p < 0.001) in exudates than in transudates. PF Ang-2 levels were higher in tuberculous PEs than in PEs of any other etiology and were lower in heart failure PEs than in PEs of any other etiology. The highest PF VEGF levels were observed in patients with malignant and parapneumonic PEs. The lowest PF VEGF levels were observed in patients with transudates. In PEs, Ang-2 levels correlate with VEGF levels (p < 0.001), RBC count (p = 0.002), nucleated cell count (p < 0.001), total protein levels (p < 0.001), and lactate dehydrogenase levels (p < 0.001). PF Ang-1 levels were lower than serum Ang-1 levels both in patients with exudates (p < 0.001) and in those with transudates (p = 0.001). PF Ang-2 levels were higher than serum Ang-2 levels both in patients with exudates (p < 0.001) and in those with transudates (p = 0.045). PF VEGF levels were higher than serum VEGF levels in patients with malignant PEs (p < 0.001) and parapneumonic PEs (p = 0.003), but lower than serum VEGF levels in heart failure PEs (p < 0.001). In patients with tuberculous PEs and exudative PEs of miscellaneous etiology, PF and serum VEGF levels did not differ significantly. CONCLUSION: Ang-2 levels but not Ang-1 levels are elevated in exudative PEs, and they correlate with levels of VEGF and markers of pleural inflammation. It is thus possible that Ang-2 along with VEGF participate in pleural inflammation and the pathogenesis of exudative PEs.     

Increased serum reverse triiodothyronine levels at diagnosis of hepatocellular carcinoma in patients with compensated HCV-related liver cirrhosis

OBJECTIVE: The aim of this study was to investigate changes in thyroid hormone metabolism in relation to the development of hepatocellular carcinoma (HCC) in patients with HCV-related liver cirrhosis. MATERIALS AND METHODS: The study group (Group A) comprised 31 patients (25 M, 6 F; median age 62.1 years, range 54.0-81.5 years) affected by HCV-related liver cirrhosis with superimposed HCC. Acute and chronic systemic disease, other than cirrhosis, inducing 'euthyroid sick syndrome' was excluded in all patients. Serum TSH, FT4, FT3, rT3, and thyroxine-binding globulin (TBG) levels were retrospectively evaluated in frozen aliquots drawn at the time of tumour diagnosis and every 6 months for 3-7 years before HCC diagnosis. The control group (Group B) comprised 29 patients affected by HCV-related liver cirrhosis without HCC, matched for sex, age and grade of liver dysfunction. RESULTS: At the time of HCC diagnosis, all patients in Group A were euthyroid with serum TSH, FT4, FT3 and TBG values not significantly different from those of cirrhotic patients of Group B. However, at diagnosis Group A patients had serum rT3 values that were significantly higher than those in Group B (35.0 ng/dl, range 12.0-162.0 vs. 19.0 ng/dl, range 10.0-51.0; Group A vs. Group B; P < 0.001). Serum rT3 values above the normal range were found in 12 patients in Group A (38.7%) but in only one of the patients from Group B (3.4%) (chi2 10.2; P = 0.001). The serum rT3 levels were not significantly correlated to the Child grade of liver cirrhosis (rho 0.1; P = 0.5). The intrasubject analysis demonstrated that a significant increase in serum rT3 levels occurred at the time of HCC diagnosis but serum FT4, FT3 and TSH values did not change significantly. A receiver operating curve (ROC) demonstrated that a 6-monthly increase in serum rT3 levels of at least +22.5% identified patients with HCC with a diagnostic accuracy of 81.7%. CONCLUSIONS: Our study has demonstrated that development of hepatocellular carcinoma is accompanied by a significant increase in serum rT3 levels in patients with low-grade HCV-related liver cirrhosis who had no other illness causing the 'euthyroid sick syndrome'.     

Des-gamma-carboxyprothrombin in patients with hepatocellular carcinoma and liver cirrhosis

OBJECTIVES: To ascertain serum and tissue expression of des‐gamma‐carboxyprothrombin (DCP) in patients with hepatocellular carcinoma (HCC) and liver cirrhosis and clarify the relationship between DCP expression and prognosis. METHODS: Expression of DCP in tissues was evaluated with immunohistochemical staining using anti‐DCP antibody in 74 patients with a single primary HCC nodule and liver cirrhosis. Their serum DCP levels were determined using an enzyme immunoassay with a double antibody sandwich system. RESULTS: Positive DCP expression in cancerous and non‐cancerous tissues was related to a worse prognosis for patients with HCC and liver cirrhosis. The combined evaluation of tissue DCP expression and serum DCP level showed that prognosis was the worst for patients with positive tissue DCP expression and a high serum DCP level. Univariate analysis indicated that a lower 5‐year survival rate was significantly correlated with positive tissue DCP expression, a high serum DCP level and the combined factor of positive tissue DCP expression and a high serum DCP level. Multivariate analysis indicated that the combined factor of positive tissue DCP expression and a high serum DCP level was a significant prognostic factor. CONCLUSION: The combined evaluation of tissue DCP expression and serum DCP level is more useful than either factor alone in predicting prognosis for patients with HCC and liver cirrhosis.     

Plasma amino acid levels in patients with colorectal cancers and liver cirrhosis with hepatocellular carcinoma

BACKGROUND/AIMS: A variety of cancer-bearing patients have been shown to have disturbances in carbohydrate, lipid and protein metabolism. The complex of metabolic derangements of protein in cancer patients may be reflected by alteration in the plasma free amino acid profile. In this study, we try to investigate the plasma free amino acid profile in patients with colorectal cancer and liver cirrhosis with hepatocellular carcinoma, which are the most common cancers in Taiwan. METHODOLOGY: Fasting venous blood samples were drawn from sixteen control volunteers and 42 cancer-bearing patients including 14 early stage colorectal cancer patients (Duke A and B), 18 late stage ones (Duke C and D) and 10 liver cirrhotic patients with hepatocellular carcinoma. Seventeen amino acid levels were measured using a Beckman amino acid analyzer. RESULTS: About one third of early or late colorectal cancer patients had body weight loss more than 10% in half a year and were defined as malnourished. For individual amino acids, in early colorectal cancer patients, the plasma level of most essential amino acids and non-essential amino acids decreased (significantly in Tyr, Ala, Met, Phe and Thr). In late stage colorectal cancer patients and patients with liver cirrhosis with hepatocellular carcinoma, plasma levels of most essential amino acids and non-essential amino acids decreased more obviously. For group amino acids, the plasma levels of essential amino acids, non-essential amino acids, gluconeogenic amino acids and branched-chain amino acids were also lower in the cancer patients than those in control volunteers. The difference was also noticeably significant in patients with late stage colorectal cancer and liver cirrhosis with hepatocellular carcinoma. The plasma free amino acid patterns in colorectal cancer patients are quite different from those in patients with non-gastrointestinal cancer and weight loss. The plasma level of essential amino acids and branched-chain amino acids was not kept within normal range in colorectal cancer patients. Elevation of plasma aromatic amino acids and methionine levels usually observed in liver cirrhotic patients without hepatocellular carcinoma was not apparent in our cirrhotic patients with hepatocellular carcinoma. CONCLUSIONS: The plasma free amino acid patterns in our colorectal cancer patients and cirrhotic patients with hepatocellular carcinoma were rather characteristic. The results will offer useful tools for improving diagnosis and therapy.     

肝硬化患者血清CA50水平升高的原因及临床意义的探讨

研究肝硬化患者血清CA50水平与肝功能指标的关系,探讨肝硬化患者血清CA50升高的原因。选取肝硬化患者53例为研究对象,抽取静脉血检查生化肝功、CA50。结果表明22例(41.50%)血清CA50升高显著。血清CA50与丙氨酸转移酶(ALT)、天冬氨酸转移酶(AST)、直接胆红素(DB il)、Ch ild-Pugh评分存在明显正相关性,与总胆红素(TB il)、血清白蛋白(ALB)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)无相关性。在已除外并发恶性肿瘤的情况下,肝硬化患者血清CA50水平升高的主要原因是肝功损害及胆汁淤积,测定CA50水平有助于判断病情的严重程度及预后。     

血清可溶性Endogin对肝硬化和肝细胞癌的诊断和鉴别诊断价值研究

目的 探讨肝硬化和肝细胞癌（HCC）患者血清可溶性Endogin（sEng）水平差异及其对鉴别诊断的临床意义。方法 2009年6月至2014年6月在我院就诊的乙型肝炎肝硬化患者77例、HCC患者54例和健康人36例,采用化学发光法检测血清甲胎蛋白（AFP）水平;采用ELISA法检测血清sEng;sEng与临床指标的相关性检验采用Pearson或Spearman相关分析;采用受试者工作特征曲线下面积（AUC）评价sEng及其联合AFP检测诊断HCC的价值;观察不同sEng水平的HCC患者3 a生存率的差异。结果 HCC患者血清sEng水平为19.71（15.16～23.56） ng/L,显著高于肝硬化患者[6.42（4.23～9.89） ng/L]和健康人[2.83（2.28～3.30） ng/L,P<0.05];HCC患者sEng与AFP水平呈正相关（r=0.660,P＜0.001）;sEng或sEng联合AFP鉴别HCC与健康人的AUC分别为0.912（95%CI：0.851～0.973）和0.951（95%CI：0.911～0.992）;sEng或sEng联合AFP鉴别HCC与肝硬化的AUC分别为0.849（95%CI：0.778～0.920）和0.920（95%CI：0.867～0.972）;高血清sEng水平（≥20.0ng/L）的HCC患者3 a生存率（24.0%）显著低于低血清sEng水平（<20.0 ng/L）者（41.4%,P<0.05）。结论 肝硬化与HCC患者血清sEng水平存在差异,可作为HCC患者诊断的参考指标。     

肝硬变和原发性肝癌患者HCV与HBV标志物分析

目的探讨肝硬变（ＬＣ），原发性肝癌（ＨＣＣ）发生和发展与ＨＣＶ及ＨＢＶ感染的关系．方法ＨＣＣ２８例，ＬＣ４８例和对照组５０例，用ＥＬＩＳＡ法同步检测ＨＢＶ及ＨＣＶ的６项血清标志物（Ｍ）．结果ＨＣＣ，ＬＣ及对照组ＨＢＶ＿Ｍ的阳性率分别为７５０％，８１３％和４００％；ＨＣＶ＿Ｍ的阳性率分别为７１％，２０８％和２０％．ＨＣＣ，ＬＣ中ＨＢＶ＿Ｍ阴性患者ＨＣＶ＿Ｍ阳性率为１２５％．ＨＣＶ与ＨＢＶ重叠感染者占ＨＣＣ和ＬＣ全部患者的１３２％．结论ＨＣＣ，ＬＣ发生和发展与ＨＢＶ及ＨＣＶ病毒感染密切相关，重叠感染者肝功能损害及临床失代偿程度更严重．     

The Bcl-2 and TGF-beta1 levels in patients with chronic hepatitis C, liver cirrhosis and hepatocellular carcinoma

Relatively little is known about the biochemical mechanisms controlling proliferation and neoplastic transformation of Hepatocellular carcinoma (HCC). The aim of study was to determine the level of the oncoproteins Bcl-2, transforming growth factor-beta1 (TGF-beta1) and alpha fetoprotein (AFP) in serum of patients with chronic hepatitis C (CHC), and liver cirrhosis (LC) as compared to HCC as a biomarkers of malignant transformation and early detection of suspected patients. A total of forty-three patients were included, 30 of them were males and 13 females, their ages ranged from 29-66 years (49.37 +/- 8.35). Increased levels of Bcl-2 were found in liver cirrhosis and HCC groups as compared to CHC and control groups (P < 0.001). The level of Bcl-2 was higher in CHC than control but the difference was insignificant (P > 0.05). Serum TGF-beta1 was significantly increased in CHC and liver cirrhosis groups as compared to HCC and control groups (p < 0.001). However, there was no significant difference between TGF-beta1 in HCC and control group (P > 0.05). The AFP level was significantly increased in HCC than CHC and liver cirrhosis. No significant difference was detected in AFP between CHC and LC patients (P > 0.05) or between CHC and healthy control (P > 0.05). A positive correlation was found between Bcl-2, and AFP in LC and HCC groups. It is concluded that the increased level of Bcl-2 in HCC may be involved in hepatocacingenesis. TGF-beta1 may be the primary marker to start the process of carcinogenesis, however, low level of TGF-beta1 may be needed to the progress of malignancy.     

High circulating D-dimers are associated with ascites and hepatocellular carcinoma in liver cirrhosis

AIM： To measure plasma D-dimer levels in cirrhotic patients with and without ascites, assessing the effect of ascites resolution in D-dimer concentration. METHODS： Seventy consecutive cirrhotic patients （M = 44, F = 26, mean age 65 years, SD ± 13）, observed from October 2005 to March 2006 were enrolled. Circulating D-dimer levels were measured using a latex-enhanced, immunoturbidimetric test. In patients with ascites （n = 42） the test was repeated after ascites resolution. RESULTS： Ascites was present in 42 patients （group A） and absent in 28 （group B）. Group A patients had more advanced liver disease. Hepatocellular carcinoma （HCC） was diagnosed in 14 patients and was more frequent in group B. Above normal range D-dimers were found in 45/70 patients. High D-dimers were more frequent in group A than in group B （P = 0.001）. High D-dimers were associated with presence of HCC （P = 0.048） only in group B. After ascites resolution, obtained in all patients, mean D-dimer values decreased in those 34 patients with high basal levels （P = 0.007）, returning to normal in 17. CONCLUSION： In patients with liver cirrhosis, ascites and HCC are the main factors associated with increased fibrinolytic activity.     

Risk factors for hepatocellular carcinoma in patients with liver cirrhosis.

OBJECTIVE: Although cirrhosis is known to predispose toward hepatocellular carcinoma (HCC), there is no agreement on the factors that can influence the risk for HCC in patients with cirrhosis. This study was designed to identify differences in cirrhosis-related risk factors for developing HCC in relation to epidemiological characteristics, stage of the disease and etiology. METHODS: 512 patients from southwestern Spain with Child-Pugh stage A or B cirrhosis were examined periodically by ultrasonography, and alpha-fetoprotein (AFP) concentration was measured. RESULTS: The average length of follow-up was 37 months. A total of 52 cases of HCC were detected, which represented a risk of 17% after 5 years of follow-up. The Cox model showed that the risk of HCC increased by 8% per year of increasing age. Male sex (relative risk: 3.4), hepatitis C virus infection (relative risk: 4.6), hepatitis B virus infection (relative risk: 2.9) and AFP levels higher than 15 ng/ml (relative risk: 2.5) were also shown to be risk factors. Among alcoholic patients, only age (risk increased by 15% per year), and hepatitis C virus infection (relative risk: 5.4) were risk factors for HCC. However, in patients infected by hepatitis C virus, the main risk factors were age (relative risk increased by 8% per year), male sex (relative risk: 3.9), co-infection with hepatitis B virus (relative risk: 4.9), and increased AFP (relative risk: 2.8). Of the patients with HCC, 71% were infected with hepatitis C virus. Alcoholism, Child-Pugh stage and duration of cirrhosis did not increase the risk of the appearance of HCC. CONCLUSIONS: The risk of HCC increased to 17% after 5 years of follow-up in patients with Child-Pugh stage A or B cirrhosis. Hepatitis C virus infection was the main risk factor in patients with cirrhosis. Other risk factors were age, male sex, hepatitis B virus infection and altered AFP level.     

Normal serum gastrin levels in patients with liver cirrhosis.

In 28 patients with cirrhosis of the liver, histologically confirmed by liver biopsy, serum gastrin concentrations were determined radioimmunologically afer an overnight fast. Mean value and standard deviation in the patients with cirrhosis (30.1 +/- 19.3 pg/ml) was not found to be significantly different from the mean value established in 275 normal subjects (39.7 +/- 21.3 pg/ml).     

Endoscopic variceal ligation of patients with liver cirrhosis and cirrhosis accompanied by hepatocellular carcinoma

Background: Rupture of esophageal varices with severe gastrointestinal hemorrhage is one of the most serious complications of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) complicating LC. The present study looks at the success of hemostasis in LC and LC accompanied by HCC, the success of breaking the varices cluster and the rate of rebleeding in patients of LC subject to emergency ligation and prophylactic ligation. Methods: Seventy‐five patients were divided into three groups. Group 1: 30 patients with LC accompanied by HCC with digestive bleeding; group 2: 30 patients with LC with digestive bleeding; and group 3: 15 patients with LC with high risk of digestive bleeding from esophageal varices (with no medical history of digestive bleeding). Success of hemostasis 72 h after endoscopic variceal ligation (EVL) was that patients did not vomit blood nor produce black feces. The effectiveness of EVL for iradication of the variceal cluster was classified into three levels: good, fairly good and poor. Results: The hemostasis success in group 1 (LC accompanied by HCC) and group 2 (LC with digestive bleeding due to esophageal varices) was 73.3% and 93.4%, respectively. The success of breaking the varix cluster in group 2 (LC) and group 3 (LC with high risk of digestive bleeding and treated by prophylactic ligation) was 73.3% and 80%, respectively. The rate of rebleeding in group 2 and group 3 after 1 year was 20% and 13.3%, respectively. Conclusion: Endoscopic variceal ligation is a good technique for variceal hemostasis and eradication of the esophageal varices cluster.     

Juvenile hepatocellular carcinoma with congestive liver cirrhosis

A case of juvenile hepatocellular carcinoma (HCC) with congestive liver cirrhosis is reported. The patient was a 21-year-old woman. She had been diagnosed as having transposition of the great arteries, type 2, in 1978. She underwent the Mustard operation, but suffered from chronic heart failure. In 1995, she experienced abdominal pain and underwent examination. The laboratory data were normal, except for elevated total bilirubin (5.2mg/dl). Blood examinations were performed at frequent intervals, and the total bilirubin level fluctuated between 0.9 and 8.1mg/dl over the next 4 years, but the transaminase level remained normal. In 1999, she experienced abdominal pain again and was admitted to our hospital. Computed tomography showed four space-occupying lesions in the liver; 45mm, 20mm, 12mm, and 10mm in size. She was diagnosed as having HCC, and transcatheter arterial chemoembolization and percutaneous ethanol injection therapy were performed. Histology of the cancerous and the noncancerous liver tissue revealed HCC, moderately differentiated type, in cirrhotic liver with congestion. This patient had no background factors of liver disease, except for liver congestion, associated with the chronic heart failure. Because most patients with cardiac cirrhosis die of cardiac disease, only a small number of these patients develop liver failure. However, the incidence of HCC in patients with congestive liver disease is likely to increase in the future, as survival time is prolonged with the advances in treatment for chronic heart failure. Therefore, patients with congestive liver disease should be followed, taking into account the possibility of HCC.     

肝细胞癌患者血清DcR3水平与临床意义

目的:探讨血清DcR3水平对HCC的诊断价值及临床意义.方法:采用ELISA检测67例HCC、8例肝硬化、17例胆囊炎患者和28例正常人血清DcR3水平; 化学发光法测定血清AFP水平; 免疫组织化学二步法检测HCC癌组织中DcR3蛋白的表达.结果:HCC组和肝硬化组血清DcR3水平均明显高于正常对照组( P<0.01), HCC血清DcR3水平与伴有肝硬化、包膜浸润和复发转移有关( P<0.05). DcR3蛋白在HCC癌组织中的表达与血清水平呈正相关( r = 0.395, P<0.01), 但DcR3血清阳性率明显高于癌组织IHC( P<0.05). AFP与DcR3联合检测对HCC的诊断灵敏度可由单项检测的82%和76%提高到93%.结论:血清DcR3升高在HCC的发生发展及浸润转移中起重要作用, 通过监测高危人群以及肝癌患者血清中的DcR3水平, 同时联合检测AFP, 可能对HCC的筛查、诊断和判断预后有一定意义.     

单核细胞趋化蛋白-1及其受体在肝癌和肝硬化患者中的表达

近期研究表明单核细胞趋化蛋白-1(MCP-1)及受体CC族趋化因子受体2(CCR2)和肿瘤的血管牛成有关[1].但在肝癌中的表达及其意义少见报道.     

肝癌、肝硬化患者淋巴细胞染色体着丝粒点结构的变化

目的 探讨染色体着丝粒点结构（Ｃｄ）的变化在肝癌发生过程的意义。方法 采用染色体Ｃｄ带技术检测２８例肝癌、２５例肝硬化及２６例正常人染色体Ｃｄ结构丢 失频率。结果 肝癌组Ｃｄ结构在总消失率、Ａ和Ｃ组染色体中明显高于肝硬化和正常对组（Ｐ〈０．０１）,在Ｄ、Ｅ组染色体中亦高于正常组（Ｐ〈０．０５）。结论 肝癌患者外周血细胞染色体Ｃｄ结构丢失在增高趋势,提示Ｃｄ结构消失率增加是引起肝癌细胞染色体非整倍性     

Plasma P-selectin levels are elevated in patients with chronic liver disease.

P-selectin is a leukocyte receptor and platelet activation marker that has been shown to be involved in thrombogenesis as well as bleeding disorders and may represent a possible link between inflammation and thrombosis. In animal models, high plasma levels correlated with a procoagulant tendency. In acute liver damage models such as hepatic ischaemia-reperfusion-injury, P-selectin was found to be a key mediator of liver injury. In order to investigate the clinical and pathogenetic role of P-selectin in chronic liver diseases, plasma P-selectin levels were measured in 111 patients with chronic liver diseases. P-Selectin was significantly elevated in patients (median 56 ng/ml, range 0-180) compared with controls (n = 38, median 20 ng/ml, range 3.3-42, P < 0.001). Current clinical bleeding symptoms were common, whereas thrombotic events occurred rarely. P-selectin levels were not associated with haemorrhagic or thromboembolic complications. P-selectin correlated with platelet and white-blood-cell counts, but not with endothelial injury markers thrombomodulin and tissue factor or coagulation factors. Interestingly, P-selectin levels were not associated with Child's stage of cirrhosis or disease aetiology, but were generally elevated in chronic liver diseases. Severe hepatic leukocyte infiltration in liver histology was associated with a tendency towards higher P-selectin levels. In line with its role in acute liver damage, P-selectin elevation in chronic liver disease may suggest a possible pathogenetic role in the course of liver cirrhosis.     

Elevated neopterin levels are associated with acute-on-chronic liver failure and mortality in patients with liver cirrhosis

BackgroundMacrophage activation plays a central role in hepatic and systemic inflammation and is involved in the pathogenesis of acute-on-chronic liver failure (ACLF).AimsThis study aimed to investigate neopterin levels in patients admitted for acute decompensation (AD) of cirrhosis, evaluating its relationship with ACLF and prognosis.MethodsThis prospective cohort study included 205 adult subjects hospitalized for AD of cirrhosis. Twenty-one healthy subjects and 89 patients with stable cirrhosis were evaluated as controls.ResultsCirculating neopterin was higher in AD as compared to stable cirrhosis and healthy controls (p<0.001). ACLF was independently associated with higher neopterin levels (OR 1.015, 95% CI 1.002–1.028, p = 0.025). In the multivariate Cox regression analysis, neopterin levels (HR = 1.002, IC 95% 1.000–1.004, p = 0.041), Child–Pugh class C, and ACLF were predictors of 30-day survival. Among patients with ACLF, the Kaplan–Meier survival probability was 71.4% in those with neopterin levels < 25 nmol/L and 31.0% if neopterin ≥ 25 nmol/L (p<0.001).ConclusionsHigher circulating neopterin was associated with ACLF in patients hospitalized for AD of cirrhosis. Neopterin levels were also independently predictors of high short-term mortality, especially among patients with ACLF, and could represent a useful biomarker of macrophage activation in clinical practice.