Amal Shawky, Ayman M. Abdel Aziz, Christina Alphonse, Zakaria Mahmoud
Introduction: Patients with liver cirrhosis have high incidence of oesophageal varices with high morbidity and mortality due to bleeding; active surveillance via upper gastrointestinal endoscopic examination may be unnecessary for patients, therefore, the increasing number of non-invasive predictors of oesophageal varices has gained wide attention. Nevertheless, few Meta analyses have involved predicting oesophageal varices using Liver Stiffness measured using fibroscan. Aim of the work: To compare between predictive values of spleen stiffness and liver stiffness as non-invasive predictors of oesophageal varices in patients with liver cirrhosis. Patients and methods: After taking consent, 61 patients with liver cirrhosis attending outpatient clinic at Theodor Biharz Research Institute were assessed by history taking, clinical examination, Complete blood count, serum alanine aminotransferase, serum aspartate aminotransferase, bilirubin, serum albumin, prothrombin concentration, Alpha fetoprotein, abdominal ultrasound, upper gastrointestinal endoscopy and fibroscan. Data was collected and analysed. Results: This study included 61 patients with liver cirrhosis, 38 of them were males, with mean age 58.28 ± 1.18 years. All patients had post hepatitis C cirrhosis, and 6 of them had history of bilharziasis in addition. Using U/S there were 12 patients (19.67%) with mild ascites, 13 patients (21.31%) with moderate ascites and 7patients (11.48%) with marked ascites 53 patients (86.90%) had enlarged spleen, 8 patients (13.10%) showed average spleen with Splenic longitudinal diameter mean (16.08 ± 2.81) cm by U/S, 47 patients (77%) had shrunken liver, 12 patients (19.7 %) showed average liver, 2 patients (3.30%) had enlarged liver with portal vein diameter mean (13.70 ± 2.26) by U/S. Splenic stiffness mean was (59.66 ± 15.15) KPa & liver stiffness mean was (29.46 ± 12.11) KPa by fibroscan. Conclusion: Spleen stiffness is superior to Liver stiffness in predicting oesophageal varices in patients with liver cirrhosis and combination of spleen stiffness and liver stiffness is better than spleen stiffness and/or liver stiffness alone with sensitivity 95% and specificity 40%. *Correspondence to: Zakaria Mahmoud, Theodor Bilharz Research Institute, Mahad Al Abhas Al Bahari, Warraq Al Arab, El Warraq, Giza Governorate, Egypt, Tel: +20-235-401-019; E-mail: ibrahimshalash@yahoo.com key words: oesophageal varices, liver, fibroscan, ultrasound Received: December 05, 2019; Accepted: December 20, 2019; Published: December 23, 2019 Introduction Acute variceal bleeding is the major cause (70%) of upper gastrointestinal bleeding in cirrhotic patients with first episode mortality rate up to 15–20%, The main predictors of bleeding in clinical practice are: large versus small varices, red wale marks, Child Pugh C versus Child Pugh A-B [1]. The gold standard for the diagnosis of oesophageal varices is EGD which must be performed at the time of cirrhosis diagnosis, in absence of
简介:肝硬化患者食道静脉曲张发生率高，因出血导致的发病率和死亡率高;对于患者来说，通过上消化道内镜检查进行主动监测可能是不必要的，因此，越来越多的食管静脉曲张的非侵入性预测因素得到了广泛的关注。然而，很少有Meta分析涉及使用纤维扫描测量肝脏硬度来预测食管静脉曲张。研究目的:比较脾脏僵硬度和肝脏僵硬度作为肝硬化患者食管静脉曲张无创预测指标的预测价值。患者与方法:经同意后，对61例在Theodor Biharz研究所门诊就诊的肝硬化患者进行病史调查、临床检查、全血细胞计数、血清丙氨酸转氨酶、血清天冬氨酸转氨酶、胆红素、血清白蛋白、凝血酶原浓度、甲胎蛋白、腹部超声、上消化道内镜、纤维扫描等评估。收集并分析了数据。结果:本研究纳入肝硬化患者61例，其中男性38例，平均年龄58.28±1.18岁。所有患者均为丙型肝炎后肝硬化，其中6例有血吸虫病病史。用U/S计算，轻度腹水12例(19.67%)，中度腹水13例(21.31%)，明显腹水7例(11.48%)，脾肿大53例(86.90%)，脾平均8例(13.10%)，脾纵径平均(16.08±2.81)cm，肝萎缩47例(77%)，肝平均12例(19.7%)，肝肿大2例(3.30%)，门静脉直径平均(13.70±2.26)cm。脾脏硬度平均值为(59.66±15.15)KPa，肝脏硬度平均值为(29.46±12.11)KPa。结论:脾僵硬度预测肝硬化患者食管静脉曲张优于肝僵硬度，脾僵硬度和肝僵硬度联合预测肝硬化患者食管静脉曲张的敏感性为95%，特异性为40%。*通讯:Zakaria Mahmoud, Theodor Bilharz研究所，Mahad Al Abhas Al Bahari, Warraq Al Arab, El Warraq，吉萨省，埃及，电话:+20-235-401-019;E-mail: ibrahimshalash@yahoo.com关键词:食管静脉曲张，肝脏，纤维扫描，超声录用日期:2019年12月20日;急性静脉曲张出血是肝硬化患者上消化道出血的主要原因(70%)，首发死亡率高达15-20%，临床实践中出血的主要预测因素是:大静脉曲张vs小静脉曲张，红色纹痕，Child Pugh C vs Child Pugh A-B[1]。食管静脉曲张诊断的金标准是EGD，必须在肝硬化诊断时进行，如果基线内镜检查没有静脉曲张，则应每2-3年重复一次EGD，而小静脉曲张患者则每1-2年重复一次。在失代偿(大静脉曲张)的情况下，EGD应每年进行一次[2]。内镜检查是有创的，对一些患者来说可能是不必要的负担，因此，出血的预测指标应该有助于识别食管静脉曲张患病率最高的患者，提高内镜筛查的成功率和成本效益[3]。研究目的:比较脾脏僵硬度与肝脏僵硬度作为肝硬化患者食管静脉曲张无创预测指标的预测价值。患者和方法患者本研究对61例经病史、临床、实验室和放射学资料诊断为肝硬化的患者进行研究。排除有内镜介入下消化道上段出血史、肝细胞癌、门静脉血栓形成史、接受降低门静脉高压症药物治疗或直接使用抗病毒药物的患者、有肝移植或经颈静脉肝内门静脉全身分流术史的患者。Shawky A .(2019)肝硬化患者食管静脉曲张的非侵入性预测指标与脾脏僵硬度的比较(埃及研究)vol . 4: 2-5 .国际胃肠病学杂志，2019 doi: 10.15761/ geh .1000192将患者分为三组:•第一组:肝硬化合并食管小静脉曲张患者20例。•第二组:21例肝硬化伴中、大食管静脉曲张患者。•第三组:20例肝硬化伴食管静脉曲张患者。方法在获得伦理委员会批准和所有患者的书面同意后，进行以下检查:•全部病史记录:特别强调可能的原因(血吸虫病，乙型肝炎，丙型肝炎等....)
{"title":"Evaluation of spleen stiffness compared to liver stiffness as non-invasive predictors for esophageal varices in patient with liver cirrhosis (Egyptian study)","authors":"Amal Shawky, Ayman M. Abdel Aziz, Christina Alphonse, Zakaria Mahmoud","doi":"10.15761/ghe.1000192","DOIUrl":"https://doi.org/10.15761/ghe.1000192","url":null,"abstract":"Introduction: Patients with liver cirrhosis have high incidence of oesophageal varices with high morbidity and mortality due to bleeding; active surveillance via upper gastrointestinal endoscopic examination may be unnecessary for patients, therefore, the increasing number of non-invasive predictors of oesophageal varices has gained wide attention. Nevertheless, few Meta analyses have involved predicting oesophageal varices using Liver Stiffness measured using fibroscan. Aim of the work: To compare between predictive values of spleen stiffness and liver stiffness as non-invasive predictors of oesophageal varices in patients with liver cirrhosis. Patients and methods: After taking consent, 61 patients with liver cirrhosis attending outpatient clinic at Theodor Biharz Research Institute were assessed by history taking, clinical examination, Complete blood count, serum alanine aminotransferase, serum aspartate aminotransferase, bilirubin, serum albumin, prothrombin concentration, Alpha fetoprotein, abdominal ultrasound, upper gastrointestinal endoscopy and fibroscan. Data was collected and analysed. Results: This study included 61 patients with liver cirrhosis, 38 of them were males, with mean age 58.28 ± 1.18 years. All patients had post hepatitis C cirrhosis, and 6 of them had history of bilharziasis in addition. Using U/S there were 12 patients (19.67%) with mild ascites, 13 patients (21.31%) with moderate ascites and 7patients (11.48%) with marked ascites 53 patients (86.90%) had enlarged spleen, 8 patients (13.10%) showed average spleen with Splenic longitudinal diameter mean (16.08 ± 2.81) cm by U/S, 47 patients (77%) had shrunken liver, 12 patients (19.7 %) showed average liver, 2 patients (3.30%) had enlarged liver with portal vein diameter mean (13.70 ± 2.26) by U/S. Splenic stiffness mean was (59.66 ± 15.15) KPa & liver stiffness mean was (29.46 ± 12.11) KPa by fibroscan. Conclusion: Spleen stiffness is superior to Liver stiffness in predicting oesophageal varices in patients with liver cirrhosis and combination of spleen stiffness and liver stiffness is better than spleen stiffness and/or liver stiffness alone with sensitivity 95% and specificity 40%. *Correspondence to: Zakaria Mahmoud, Theodor Bilharz Research Institute, Mahad Al Abhas Al Bahari, Warraq Al Arab, El Warraq, Giza Governorate, Egypt, Tel: +20-235-401-019; E-mail: ibrahimshalash@yahoo.com key words: oesophageal varices, liver, fibroscan, ultrasound Received: December 05, 2019; Accepted: December 20, 2019; Published: December 23, 2019 Introduction Acute variceal bleeding is the major cause (70%) of upper gastrointestinal bleeding in cirrhotic patients with first episode mortality rate up to 15–20%, The main predictors of bleeding in clinical practice are: large versus small varices, red wale marks, Child Pugh C versus Child Pugh A-B [1]. The gold standard for the diagnosis of oesophageal varices is EGD which must be performed at the time of cirrhosis diagnosis, in absence of","PeriodicalId":93828,"journal":{"name":"World journal of gastroenterology, hepatology and endoscopy","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83783420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shulman Lm, Parizade M, K. Z., Anis E, Perry Markovich M, Bassal R, M. E, Grotto I, Kopel E
{"title":"Combining syndrome and laboratory surveillance with genetic analysis to monitor for emergence of vaccine escape mutants after identification of a rapid rise in rotavirus acute gastroenteritis (RAGE) among children visiting HMOs, Israel, January 2014","authors":"Shulman Lm, Parizade M, K. Z., Anis E, Perry Markovich M, Bassal R, M. E, Grotto I, Kopel E","doi":"10.15761/ghe.1000177","DOIUrl":"https://doi.org/10.15761/ghe.1000177","url":null,"abstract":"","PeriodicalId":93828,"journal":{"name":"World journal of gastroenterology, hepatology and endoscopy","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74027626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background and aim: The mechanism of secretion of plasma proteins into bile has been shown for rats but not for higher animals and for humans. Since dogs are a much better model for human beings, the experiments were performed in dogs. Methods: The radioactive precursor amino acid leucine was injected into the dog vein and the increase of free radioactivity and of the protein bound radioactivity in serum and in bile was followed. Results: The secretion time for plasma proteins in the dog was 8-20 minutes. The secretion of radioactive proteins into bile showed a smaller peak after 20 minutes and a steep increase after 45 minutes. Conclusion: The biphasic appearance of radioactive proteins in bile indicates that the majority of bile proteins are derived from serum, a small amount, however, is secreted by hepatocytes directly into the bile. *Correspondence to: Kurt Weigand, Department of Medicine, Stauferklinik, Mutlangen, Teaching Hospital of the University of Ulm, Germany, Tel: 0049717163723; E-mail: k-weigand@t-online.de key words: dog bile, bile proteins, protein secretion Received: September 30, 2019; Accepted: October 14, 2019; Published: October 18, 2019 Introduction It has been demonstrated that the quantitatively most important proteins in bile, albumin and IgA [1], are transferred from plasma into bile [2]. However, it is unknown whether hepatocytes can secrete these proteins also directly into bile. If proteins are exclusively transferred from plasma into bile, radioactive proteins should not be detectible in bile earlier than in plasma after IV injection of a radioactive precursor amino acid. To determine if hepatocytes secrete newly synthesized proteins into bile directly, we studied the secretion of radioactively labeled proteins into bile and into plasma in the dog. The experiments were performed with dogs since it has been shown that for the study of the transport of IgA from plasma to bile dogs are a suitable model for humans in contrast to rats or rabbits [3]. Methods The experiments were performed in two not anesthetized female boxer dogs, weighing 20 (24) kg. Both dogs were equipped with a permanent Thomas cannula. A bile duct catheter was placed through the Thomas cannula and bile was collected at two minutes intervals. Bile flow was kept constant by infusion of 20 μmol taurocholate per minute. After i.v. injection of 250 μCi 1-14-C-leucine (59 mCi/mmol) plasma samples were drawn every 2 minutes. Protein radioactivity was measured according to Mans and Novelli [4]. Protein was measured by the method of Lowry [5]. Bile acids were measured enzymatically [6]. Dogs were kept and treated strictly according to the guidelines of the health department of the city of Berne, Switzerland. Results After injection of 250 μCi 1-14-C-leucine (59 mCi/mmol) it decreased rapidly in serum (Figure 1 and 2). Radioactively labeled proteins in serum were detectable after 10 to 14 minutes and increased exponentially. In bile non protein bound radioacti
{"title":"Early appearance of serum proteins in dog bile","authors":"K. Weigand","doi":"10.15761/ghe.1000188","DOIUrl":"https://doi.org/10.15761/ghe.1000188","url":null,"abstract":"Background and aim: The mechanism of secretion of plasma proteins into bile has been shown for rats but not for higher animals and for humans. Since dogs are a much better model for human beings, the experiments were performed in dogs. Methods: The radioactive precursor amino acid leucine was injected into the dog vein and the increase of free radioactivity and of the protein bound radioactivity in serum and in bile was followed. Results: The secretion time for plasma proteins in the dog was 8-20 minutes. The secretion of radioactive proteins into bile showed a smaller peak after 20 minutes and a steep increase after 45 minutes. Conclusion: The biphasic appearance of radioactive proteins in bile indicates that the majority of bile proteins are derived from serum, a small amount, however, is secreted by hepatocytes directly into the bile. *Correspondence to: Kurt Weigand, Department of Medicine, Stauferklinik, Mutlangen, Teaching Hospital of the University of Ulm, Germany, Tel: 0049717163723; E-mail: k-weigand@t-online.de key words: dog bile, bile proteins, protein secretion Received: September 30, 2019; Accepted: October 14, 2019; Published: October 18, 2019 Introduction It has been demonstrated that the quantitatively most important proteins in bile, albumin and IgA [1], are transferred from plasma into bile [2]. However, it is unknown whether hepatocytes can secrete these proteins also directly into bile. If proteins are exclusively transferred from plasma into bile, radioactive proteins should not be detectible in bile earlier than in plasma after IV injection of a radioactive precursor amino acid. To determine if hepatocytes secrete newly synthesized proteins into bile directly, we studied the secretion of radioactively labeled proteins into bile and into plasma in the dog. The experiments were performed with dogs since it has been shown that for the study of the transport of IgA from plasma to bile dogs are a suitable model for humans in contrast to rats or rabbits [3]. Methods The experiments were performed in two not anesthetized female boxer dogs, weighing 20 (24) kg. Both dogs were equipped with a permanent Thomas cannula. A bile duct catheter was placed through the Thomas cannula and bile was collected at two minutes intervals. Bile flow was kept constant by infusion of 20 μmol taurocholate per minute. After i.v. injection of 250 μCi 1-14-C-leucine (59 mCi/mmol) plasma samples were drawn every 2 minutes. Protein radioactivity was measured according to Mans and Novelli [4]. Protein was measured by the method of Lowry [5]. Bile acids were measured enzymatically [6]. Dogs were kept and treated strictly according to the guidelines of the health department of the city of Berne, Switzerland. Results After injection of 250 μCi 1-14-C-leucine (59 mCi/mmol) it decreased rapidly in serum (Figure 1 and 2). Radioactively labeled proteins in serum were detectable after 10 to 14 minutes and increased exponentially. In bile non protein bound radioacti","PeriodicalId":93828,"journal":{"name":"World journal of gastroenterology, hepatology and endoscopy","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78859424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ido Zambreg, Benjamin Assouline, C. Housset, E. Schiffer
Transforming growth factor alpha (TGF-α) is a mitogenic factor for hepatocyte and a ligand of the epithelial growth factor receptor (EGFR). TGF-α promotes liver carcinogenesis. TGF-α is also overexpressed in regenerative nodules of the cirrhotic liver but the mechanism of this expression is poorly known. Because hypoxia is a feature of cirrhotic livers and hypoxia may induce TGF-α and EGFR expressions, the aim of this study was to determine whether the TGF-α/EGFR pathway is affected by hypoxia in liver cells. Cell isolates were prepared from normal Wistar rats. Liver myofibroblasts were obtained in culture by activation of hepatic stellate cells (HSC), and by outgrowth of portal myofibroblasts from bile duct segments. Hepatocytes, Kupffer cells and liver myofibroblasts in culture were submitted to hypoxia for 4-24 hours. Hypoxia was achieved using a catalytic system, which reduces oxygen concentration to less than 1% within 30 minutes. The absence of toxicity was verified by lactate dehydrogenase dosing in cell supernatant. Vascular endothelial growth factor (VEGF) served as a hypoxia-inducible control gene. Gene expression was assessed by real-time reverse transcription polymerase chain reaction (RT-PCR). Under normoxia, the expression of TGF-α was significantly higher in hepatocytes than in non-parenchymal liver cells (~1.7-fold). EGFR transcripts were also more abundant in Hepatocytes than in myofibroblasts (~3-fold) or in Kupffer cells (~22-fold). Hypoxia induced an increase in VEGF mRNA to a similar extent in all cell types. By contrast, hypoxia caused an increase in TGF-α transcripts mainly in Hepatocytes (112 ± 7 vs 32 ± 2 under normoxia), also but to a lesser extent in portal myofibroblasts (35 ± 5 vs 17 ± 4), but not in HSC-derived myofibroblasts nor in Kupffer cells. An increase in EGFR expression was induced by hypoxia also predominantly in Hepatocytes (125 ± 12 vs 44 ± 6), and to a much lesser extent in other cell types. These results demonstrate that hypoxia induces TGFand EGFR overexpression in hepatocytes and, thereby, might act as a promoting event in liver carcinogenesis upon cirrhotic liver. *Correspondence to: Eduardo Schiffer, Department of Anesthesiology, Geneva University Hospitals, Switzerland, Tel: (41) 79 55 32 069, Fax: (41) 22 372 76 90; E-mail: eduardo.schiffer@hcuge.ch key words: TGF-α, EGFR, hypoxia, carcinogenesis Received: July 02, 2019; Accepted: July 16, 2019; Published: July 19, 2019 Introduction TGF-α is a mitogenic factor for hepatocytes and a ligand of the EGF receptor (EGFR). TGF-α can promote liver carcinogenesis, as illustrated in TGF-α transgenic mice, which constantly develop hepatocellular carcinoma [1]. TGFis also overexpressed in regenerative nodules of the cirrhotic liver but the reason for this expression is unknown. Because local hypoxia is a constant feature of cirrhotic livers and hypoxia may induce TGF-α and EGFR expressions, the aim of this study was to determine whether the TGF-α/EGFR pathway
转化生长因子α (TGF-α)是肝细胞的有丝分裂因子，是上皮生长因子受体(EGFR)的配体。TGF-α促进肝癌发生。TGF-α在肝硬化再生结节中也过表达，但其表达机制尚不清楚。由于缺氧是肝硬化肝脏的特征，缺氧可诱导TGF-α和EGFR表达，本研究的目的是确定肝细胞中TGF-α/EGFR通路是否受到缺氧的影响。从正常Wistar大鼠制备细胞分离物。通过激活肝星状细胞(HSC)和从胆管段培养门静脉肌成纤维细胞获得肝肌成纤维细胞。培养的肝细胞、库普弗细胞和肝肌成纤维细胞缺氧4-24小时。使用催化系统实现缺氧，在30分钟内将氧浓度降低到1%以下。通过在细胞上清液中加入乳酸脱氢酶证实其无毒性。血管内皮生长因子(VEGF)作为缺氧诱导的控制基因。实时逆转录聚合酶链反应(RT-PCR)检测基因表达。正常缺氧条件下，肝细胞中TGF-α的表达明显高于非实质肝细胞(约1.7倍)。肝细胞中的EGFR转录物也比肌成纤维细胞丰富(约3倍)或库普弗细胞丰富(约22倍)。在所有细胞类型中，缺氧诱导VEGF mRNA增加的程度相似。相比之下，缺氧导致TGF-α转录物主要在肝细胞中增加(112±7 vs 32±2)，门脉肌成纤维细胞也增加(35±5 vs 17±4)，但在hsc来源的肌成纤维细胞和Kupffer细胞中没有增加。缺氧诱导EGFR表达的增加也主要发生在肝细胞(125±12 vs 44±6)，在其他细胞类型中的表达程度要小得多。这些结果表明，缺氧诱导肝细胞中tgf和EGFR过表达，因此可能在肝硬化肝的肝癌发生中起促进作用。*通讯:Eduardo Schiffer，瑞士日内瓦大学医院麻醉科，电话:(41)79 55 32 069，传真:(41)22 372 76 90;关键词:TGF-α， EGFR，缺氧，致癌作用录用日期:2019年7月16日;TGF-α是肝细胞的有丝分裂因子，也是EGF受体(EGFR)的配体。TGF-α可促进肝癌的发生，TGF-α转基因小鼠不断发展为肝细胞癌[1]。tgfi在肝硬化再生结节中也过表达，但其表达原因尚不清楚。由于局部缺氧是肝硬化肝脏的一个不变特征，缺氧可诱导TGF-α和EGFR表达，因此本研究的目的是确定肝细胞缺氧是否会影响TGF-α/EGFR通路。材料与方法细胞分离与培养采用Seglen的方法从正常Wistar大鼠中分离肝细胞[2]。实验是按照国家关于照顾和使用实验动物的伦理准则进行的。所有实验均经机构动物使用与护理委员会批准。采用氯丙嗪(2mg /kg)和氯胺酮(20mg /kg)皮下注射麻醉。肝脏原位灌注无Ca2+的10 mM Hepes缓冲液15分钟，流速为30 ml.min-1, 0.025%胶原酶B (Boehringer Mannheim, Meylan, France)在含Ca2+的10 mM Hepes缓冲液中灌注15分钟，流速为20 ml.min-1。然后在含有0.2%牛血清白蛋白(BSA, Sigma)的Leibovitz-15 (L15)培养基(Sigma)中轻轻搅拌将肝细胞从结缔组织中分离出来。用纱布过滤细胞悬浮液，在4℃下沉淀20分钟，用含bsa的L15洗涤。根据相差显微镜下的特征细胞大小，肝细胞纯度为80-85%，细胞存活率超过90%。将肝细胞以1.0-1.2 × 105个细胞/cm2的密度，在10 ml William’s medium E (GIBCO BRL, Life Technologies, Cergy-Pontoise)培养皿中，其中含有10%胎牛血清(GIBCO BRL)、5 mm Hepes缓冲液、5 μg/ ml胰岛素(Novo Nordisk, Boulogne Billancourt, France)和10万IU-100 mg/L青霉素-链霉素(GIBCO BRL)。3 h后，将培养基替换为添加1 μM氢化可的松21-半乙酰化(Sigma)的无血清培养基。24 h后换液，缺氧处理肝细胞。
{"title":"Overexpression of TGF-α and EGFR, a key event in liver carcinogenesis, is induced by hypoxia specifically in hepatocytes","authors":"Ido Zambreg, Benjamin Assouline, C. Housset, E. Schiffer","doi":"10.15761/ghe.1000183","DOIUrl":"https://doi.org/10.15761/ghe.1000183","url":null,"abstract":"Transforming growth factor alpha (TGF-α) is a mitogenic factor for hepatocyte and a ligand of the epithelial growth factor receptor (EGFR). TGF-α promotes liver carcinogenesis. TGF-α is also overexpressed in regenerative nodules of the cirrhotic liver but the mechanism of this expression is poorly known. Because hypoxia is a feature of cirrhotic livers and hypoxia may induce TGF-α and EGFR expressions, the aim of this study was to determine whether the TGF-α/EGFR pathway is affected by hypoxia in liver cells. Cell isolates were prepared from normal Wistar rats. Liver myofibroblasts were obtained in culture by activation of hepatic stellate cells (HSC), and by outgrowth of portal myofibroblasts from bile duct segments. Hepatocytes, Kupffer cells and liver myofibroblasts in culture were submitted to hypoxia for 4-24 hours. Hypoxia was achieved using a catalytic system, which reduces oxygen concentration to less than 1% within 30 minutes. The absence of toxicity was verified by lactate dehydrogenase dosing in cell supernatant. Vascular endothelial growth factor (VEGF) served as a hypoxia-inducible control gene. Gene expression was assessed by real-time reverse transcription polymerase chain reaction (RT-PCR). Under normoxia, the expression of TGF-α was significantly higher in hepatocytes than in non-parenchymal liver cells (~1.7-fold). EGFR transcripts were also more abundant in Hepatocytes than in myofibroblasts (~3-fold) or in Kupffer cells (~22-fold). Hypoxia induced an increase in VEGF mRNA to a similar extent in all cell types. By contrast, hypoxia caused an increase in TGF-α transcripts mainly in Hepatocytes (112 ± 7 vs 32 ± 2 under normoxia), also but to a lesser extent in portal myofibroblasts (35 ± 5 vs 17 ± 4), but not in HSC-derived myofibroblasts nor in Kupffer cells. An increase in EGFR expression was induced by hypoxia also predominantly in Hepatocytes (125 ± 12 vs 44 ± 6), and to a much lesser extent in other cell types. These results demonstrate that hypoxia induces TGFand EGFR overexpression in hepatocytes and, thereby, might act as a promoting event in liver carcinogenesis upon cirrhotic liver. *Correspondence to: Eduardo Schiffer, Department of Anesthesiology, Geneva University Hospitals, Switzerland, Tel: (41) 79 55 32 069, Fax: (41) 22 372 76 90; E-mail: eduardo.schiffer@hcuge.ch key words: TGF-α, EGFR, hypoxia, carcinogenesis Received: July 02, 2019; Accepted: July 16, 2019; Published: July 19, 2019 Introduction TGF-α is a mitogenic factor for hepatocytes and a ligand of the EGF receptor (EGFR). TGF-α can promote liver carcinogenesis, as illustrated in TGF-α transgenic mice, which constantly develop hepatocellular carcinoma [1]. TGFis also overexpressed in regenerative nodules of the cirrhotic liver but the reason for this expression is unknown. Because local hypoxia is a constant feature of cirrhotic livers and hypoxia may induce TGF-α and EGFR expressions, the aim of this study was to determine whether the TGF-α/EGFR pathway ","PeriodicalId":93828,"journal":{"name":"World journal of gastroenterology, hepatology and endoscopy","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85411758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Death by cardiovascular events has reduced by statins due to altering atherosclerosis development. As of 2007, no data on the use of statins in patients with decompensated cirrhosis were available. Aims: To evaluate the simvastatin efficacy and safety in patients with decompensated cirrhosis and cardiovascular factors. Methods: We performed a matched cases-series study. The case group included patients who agreed to add simvastatin to the standard therapy. The series group included patients who did not accept to add this drug to the standard of care. Each group had nine patients. Age, gender, cirrhosis etiology, Child-Pugh class, and Model for End-Stage Liver Disease (MELD) score matched case and series group in a ratio 1:1. Results: The intervals between cirrhosis complications in the case and series groups were 33.6 ± 19.9 months and 9.4 ± 8.2 months, respectively, P = 0.0065 . There was a significant deterioration of the liver function, which was evaluated through Child-Pugh and MELD scores in the series group while it was not affected in the case group. Median survival in the case group was 107 months, whereas it was 20 months in the series group (HR = 0.14; P < 0.0001 ). On the other hand, no patient in the case group experienced simvastatin-related adverse events. Furthermore, no patient in the case or series groups developed cardiovascular events. Conclusions: The addition of simvastatin to the standard therapy in patients with decompensated cirrhosis and cardiovascular risk factors was efficient as it decreased the patient’s mortality. Furthermore, the simvastatin was safe as patients showed good tolerance, considering that they did not develop adverse effects or serious adverse effects.
{"title":"Addition of simvastatin to the standard therapy increases survival and is safe in patients with decompensated cirrhosis","authors":"A. Muñoz, Walter Taddey, P. Salgado","doi":"10.15761/ghe.1000189","DOIUrl":"https://doi.org/10.15761/ghe.1000189","url":null,"abstract":"Background: Death by cardiovascular events has reduced by statins due to altering atherosclerosis development. As of 2007, no data on the use of statins in patients with decompensated cirrhosis were available. Aims: To evaluate the simvastatin efficacy and safety in patients with decompensated cirrhosis and cardiovascular factors. Methods: We performed a matched cases-series study. The case group included patients who agreed to add simvastatin to the standard therapy. The series group included patients who did not accept to add this drug to the standard of care. Each group had nine patients. Age, gender, cirrhosis etiology, Child-Pugh class, and Model for End-Stage Liver Disease (MELD) score matched case and series group in a ratio 1:1. Results: The intervals between cirrhosis complications in the case and series groups were 33.6 ± 19.9 months and 9.4 ± 8.2 months, respectively, P = 0.0065 . There was a significant deterioration of the liver function, which was evaluated through Child-Pugh and MELD scores in the series group while it was not affected in the case group. Median survival in the case group was 107 months, whereas it was 20 months in the series group (HR = 0.14; P < 0.0001 ). On the other hand, no patient in the case group experienced simvastatin-related adverse events. Furthermore, no patient in the case or series groups developed cardiovascular events. Conclusions: The addition of simvastatin to the standard therapy in patients with decompensated cirrhosis and cardiovascular risk factors was efficient as it decreased the patient’s mortality. Furthermore, the simvastatin was safe as patients showed good tolerance, considering that they did not develop adverse effects or serious adverse effects.","PeriodicalId":93828,"journal":{"name":"World journal of gastroenterology, hepatology and endoscopy","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85490799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The pancreas, a fleshy retroperitoneal organ with mixed exocrine and endocrine function, is not spared of malignant disorders. Malignancies of the pancreas are generally of acinar, ductal or neuroendocrine origin. Majority of these are pancreatic ductal cancer (PDAC) with head of pancreas as the most common site. In the developed world, PDAC is the fourth deadliest malignancy for men and the fifth for women and is predicted to become the second by 2030 [1]. Periampullary cancer is a complex disease of heterogenous origin. This is cancer arising within 2 cm of the papilla of Vater and include pancreatic, ampullary, biliary and duodenal cancers [2]. Duodenal cancer has the highest estimated 5-year survival (49%), followed by ampullary cancer (45%), distal bile duct cancer (27%), and pancreatic cancer (18%) [3]. There is some variance in the clinical presentation of periampullary cancer and cancer in the head of pancreas, but the main distinction lies in their cell biology and histology which affect prognosis and outcome. In all, surgical resection involving a pancreaticoduodenectomy is the main stay for curative treatment.
{"title":"Periampullary cancer and cancer in head of pancreas: What is the difference?","authors":"E. Ray-Offor","doi":"10.15761/ghe.1000184","DOIUrl":"https://doi.org/10.15761/ghe.1000184","url":null,"abstract":"The pancreas, a fleshy retroperitoneal organ with mixed exocrine and endocrine function, is not spared of malignant disorders. Malignancies of the pancreas are generally of acinar, ductal or neuroendocrine origin. Majority of these are pancreatic ductal cancer (PDAC) with head of pancreas as the most common site. In the developed world, PDAC is the fourth deadliest malignancy for men and the fifth for women and is predicted to become the second by 2030 [1]. Periampullary cancer is a complex disease of heterogenous origin. This is cancer arising within 2 cm of the papilla of Vater and include pancreatic, ampullary, biliary and duodenal cancers [2]. Duodenal cancer has the highest estimated 5-year survival (49%), followed by ampullary cancer (45%), distal bile duct cancer (27%), and pancreatic cancer (18%) [3]. There is some variance in the clinical presentation of periampullary cancer and cancer in the head of pancreas, but the main distinction lies in their cell biology and histology which affect prognosis and outcome. In all, surgical resection involving a pancreaticoduodenectomy is the main stay for curative treatment.","PeriodicalId":93828,"journal":{"name":"World journal of gastroenterology, hepatology and endoscopy","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76851463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Should we always perform bulbar biopsies in celiac disease?","authors":"Aomari A, B. I, Firwana M, Ajana Fz","doi":"10.15761/ghe.1000176","DOIUrl":"https://doi.org/10.15761/ghe.1000176","url":null,"abstract":"","PeriodicalId":93828,"journal":{"name":"World journal of gastroenterology, hepatology and endoscopy","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83219416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quantum microRNA network analysis in gastric and esophageal cancers: Xenotropic plant microRNAs cure from cancerous paradox via Helicobacter pylori infection","authors":"Yoichi R Fujii","doi":"10.15761/ghe.1000187","DOIUrl":"https://doi.org/10.15761/ghe.1000187","url":null,"abstract":"","PeriodicalId":93828,"journal":{"name":"World journal of gastroenterology, hepatology and endoscopy","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81838497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug-induced liver injury (DILI) is a rare adverse reaction to medications or herbal and dietary supplements (HDS). Several studies have shown an increase in incidence over the last decades with a disproportionate higher increase in cases connected to HDS. Even though DILI is very rare, it is one of the leading causes of acute liver failure (ALF). The pathogenesis is not entirely understood, and specific diagnostic markers are not available yet. This together with the vast number of etiologic agents and variable presentations makes diagnosing DILI challenging. The aim of this study was to determine the demographic and clinical features, the most common causal agents in Latvia, the resulting liver injury patterns, and their relationships to its severity, to improve the understanding of the disease. This analysis was a retrospective study on patients diagnosed with DILI at the hepatology department of the Latvian Infectiology Center from 2014 to 2017. Among the 128 included patients 58.6% were women, and the mean age was 54 years. In 52 cases a single drug was implicated (40.6%), in 28 cases HDS (21.9%), and in 48 cases multiple agents were suspected (37.5%). Antimicrobials were the most frequently implicated class of drugs, and the most frequent HDS were multivitamin and herbal combinations. The proportion of HDS-induced injury increased from 17.9% in 2014 to 25% in 2017; these patients had fewer comorbidities ( p = 0.044), men were younger and had even fewer comorbidities than women. These findings call for more regulation and testing of freely available HDS. The main injury pattern was hepatocellular in 78 cases (66.7%), 19 cases showed a mixed pattern (16.25), and 20 cases were cholestatic (17.1%). The liver injury patterns of several etiologic agents differed from those described as their “signature” patterns found in the literature, questioning their validity. Risk factors for severe liver injury were a high number of comorbidities ( p = 0.041), underlying chronic liver disease ( p = 0.028), hypersensitivity reaction ( p = 0.017), male gender ( p = 0.050), and possibly diabetes mellitus ( p = 0.389).
{"title":"Clinical data analysis of patients with drug and dietary supplement induced liver injury in Latvia","authors":"G. Schmidt, I. Tolmane","doi":"10.15761/ghe.1000186","DOIUrl":"https://doi.org/10.15761/ghe.1000186","url":null,"abstract":"Drug-induced liver injury (DILI) is a rare adverse reaction to medications or herbal and dietary supplements (HDS). Several studies have shown an increase in incidence over the last decades with a disproportionate higher increase in cases connected to HDS. Even though DILI is very rare, it is one of the leading causes of acute liver failure (ALF). The pathogenesis is not entirely understood, and specific diagnostic markers are not available yet. This together with the vast number of etiologic agents and variable presentations makes diagnosing DILI challenging. The aim of this study was to determine the demographic and clinical features, the most common causal agents in Latvia, the resulting liver injury patterns, and their relationships to its severity, to improve the understanding of the disease. This analysis was a retrospective study on patients diagnosed with DILI at the hepatology department of the Latvian Infectiology Center from 2014 to 2017. Among the 128 included patients 58.6% were women, and the mean age was 54 years. In 52 cases a single drug was implicated (40.6%), in 28 cases HDS (21.9%), and in 48 cases multiple agents were suspected (37.5%). Antimicrobials were the most frequently implicated class of drugs, and the most frequent HDS were multivitamin and herbal combinations. The proportion of HDS-induced injury increased from 17.9% in 2014 to 25% in 2017; these patients had fewer comorbidities ( p = 0.044), men were younger and had even fewer comorbidities than women. These findings call for more regulation and testing of freely available HDS. The main injury pattern was hepatocellular in 78 cases (66.7%), 19 cases showed a mixed pattern (16.25), and 20 cases were cholestatic (17.1%). The liver injury patterns of several etiologic agents differed from those described as their “signature” patterns found in the literature, questioning their validity. Risk factors for severe liver injury were a high number of comorbidities ( p = 0.041), underlying chronic liver disease ( p = 0.028), hypersensitivity reaction ( p = 0.017), male gender ( p = 0.050), and possibly diabetes mellitus ( p = 0.389).","PeriodicalId":93828,"journal":{"name":"World journal of gastroenterology, hepatology and endoscopy","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82219049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：