Pub Date : 2017-01-01Epub Date: 2017-09-26DOI: 10.1155/2017/8462756
Sameh Abdelkhalik Ahmed, Amal Selim, Nehad Hawash, Ahmed Khaled Tawfik, Mohamed Yousef, Abdelrahman Kobtan, Rehab Badawi, Sally Elnawasany, Reham Abdelkader Elkhouly, Amr Shaaban Hanafy, Fatma H Rizk, Loai Mansour, Sherief Abd-Elsalam
Objectives: We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy.
Methods: A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopist rating, and hemodynamic parameters including oxygen saturation, heart rate, mean arterial pressure, incidence of side effect as (bradycardia, hypotension, hypoxia, nausea and vomiting, cough, shivering, or diplopia), time needed for complete recovery, and time needed for discharge.
Results: There was no statistical significant difference between the studied groups regarding age, sex, weight, Child-Pugh classification score, type and duration of endoscopic intervention, time needed for complete recovery, or time needed for discharge. Complication rates were similar in both groups except for mean arterial blood pressure which was significantly lower in group of patients receiving propofol and fentanyl (P = 0.001).
Conclusion: The use of either propofol or midazolam in combination to fentanyl is effective in sedation of patients with advanced liver diseases presented for upper GIT endoscope. The trial is registered with ClinicalTrials.gov Identifier: NCT03063866.
{"title":"Randomized Controlled Study Comparing Use of Propofol Plus Fentanyl versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients with Advanced Liver Disease.","authors":"Sameh Abdelkhalik Ahmed, Amal Selim, Nehad Hawash, Ahmed Khaled Tawfik, Mohamed Yousef, Abdelrahman Kobtan, Rehab Badawi, Sally Elnawasany, Reham Abdelkader Elkhouly, Amr Shaaban Hanafy, Fatma H Rizk, Loai Mansour, Sherief Abd-Elsalam","doi":"10.1155/2017/8462756","DOIUrl":"https://doi.org/10.1155/2017/8462756","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy.</p><p><strong>Methods: </strong>A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopist rating, and hemodynamic parameters including oxygen saturation, heart rate, mean arterial pressure, incidence of side effect as (bradycardia, hypotension, hypoxia, nausea and vomiting, cough, shivering, or diplopia), time needed for complete recovery, and time needed for discharge.</p><p><strong>Results: </strong>There was no statistical significant difference between the studied groups regarding age, sex, weight, Child-Pugh classification score, type and duration of endoscopic intervention, time needed for complete recovery, or time needed for discharge. Complication rates were similar in both groups except for mean arterial blood pressure which was significantly lower in group of patients receiving propofol and fentanyl (<i>P</i> = 0.001).</p><p><strong>Conclusion: </strong>The use of either propofol or midazolam in combination to fentanyl is effective in sedation of patients with advanced liver diseases presented for upper GIT endoscope. The trial is registered with ClinicalTrials.gov Identifier: NCT03063866.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2017 ","pages":"8462756"},"PeriodicalIF":1.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/8462756","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35718393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-01-29DOI: 10.1155/2017/5128760
C D Gillespie, M K O'Reilly, G N Allen, S McDermott, V O Chan, C A Ridge
Cystic fibrosis (CF) is a multisystem disease with a range of abdominal manifestations including those involving the liver, pancreas, and kidneys. Recent advances in management of the respiratory complications of the disease has led to a greater life expectancy in patients with CF. Subsequently, there is increasing focus on the impact of abdominal disease on quality of life and survival. Liver cirrhosis is the most important extrapulmonary cause of death in CF, yet significant challenges remain in the diagnosis of CF related liver disease. The capacity to predict those patients at risk of developing cirrhosis remains a significant challenge. We review representative abdominal imaging findings in patients with CF selected from the records of two academic health centres, with a view to increasing familiarity with the abdominal manifestations of the disease. We review their presentation and expected imaging findings, with a focus on the challenges facing diagnosis of the hepatic manifestations of the disease. An increased familiarity with these abdominal manifestations will facilitate timely diagnosis and management, which is paramount to further improving outcomes for patients with cystic fibrosis.
{"title":"Imaging the Abdominal Manifestations of Cystic Fibrosis.","authors":"C D Gillespie, M K O'Reilly, G N Allen, S McDermott, V O Chan, C A Ridge","doi":"10.1155/2017/5128760","DOIUrl":"https://doi.org/10.1155/2017/5128760","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a multisystem disease with a range of abdominal manifestations including those involving the liver, pancreas, and kidneys. Recent advances in management of the respiratory complications of the disease has led to a greater life expectancy in patients with CF. Subsequently, there is increasing focus on the impact of abdominal disease on quality of life and survival. Liver cirrhosis is the most important extrapulmonary cause of death in CF, yet significant challenges remain in the diagnosis of CF related liver disease. The capacity to predict those patients at risk of developing cirrhosis remains a significant challenge. We review representative abdominal imaging findings in patients with CF selected from the records of two academic health centres, with a view to increasing familiarity with the abdominal manifestations of the disease. We review their presentation and expected imaging findings, with a focus on the challenges facing diagnosis of the hepatic manifestations of the disease. An increased familiarity with these abdominal manifestations will facilitate timely diagnosis and management, which is paramount to further improving outcomes for patients with cystic fibrosis.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2017 ","pages":"5128760"},"PeriodicalIF":1.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/5128760","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34775870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Kumar, Akanksha Singh, A. Jaryal, P. Ranjan, K. Deepak, Sanjay Sharma, R. Lakshmy, R. Pandey, N. Vikram
Aim. The present study was designed to evaluate the heart rate variability (HRV) in nonalcoholic fatty liver disease (NAFLD) and to assess the effect of grade of NAFLD and diabetic status on HRV. Methods. This cross-sectional study included 75 subjects (25 NAFLD without diabetes, 25 NAFLD with diabetes, and 25 controls). Measurements included anthropometry, body composition analysis, estimation of plasma glucose, serum lipids, hsCRP, and serum insulin. HRV analysis was performed in both time and frequency domains. Results. The time and frequency domain indices of overall variability (SDNN, total power) were significantly lower in NAFLD with diabetes as compared to the controls. However, the LF : HF ratio did not differ among the three groups. The variables related to obesity, lipid profile, and glucose metabolism were also higher in NAFLD with diabetes and those with Grade II NAFLD without diabetes, as compared to controls. Multivariate stepwise regression analysis showed a negative correlation between HRV and total cholesterol and fat percentage. Conclusion. The grade of NAFLD as well as diabetic status contributes to the decrease in the cardiovascular autonomic function, with diabetic status rather than grade of NAFLD playing a critical role. Serum lipids and adiposity may also contribute to cardiac autonomic dysfunction.
{"title":"Cardiovascular Autonomic Dysfunction in Patients of Nonalcoholic Fatty Liver Disease","authors":"M. Kumar, Akanksha Singh, A. Jaryal, P. Ranjan, K. Deepak, Sanjay Sharma, R. Lakshmy, R. Pandey, N. Vikram","doi":"10.1155/2016/5160754","DOIUrl":"https://doi.org/10.1155/2016/5160754","url":null,"abstract":"Aim. The present study was designed to evaluate the heart rate variability (HRV) in nonalcoholic fatty liver disease (NAFLD) and to assess the effect of grade of NAFLD and diabetic status on HRV. Methods. This cross-sectional study included 75 subjects (25 NAFLD without diabetes, 25 NAFLD with diabetes, and 25 controls). Measurements included anthropometry, body composition analysis, estimation of plasma glucose, serum lipids, hsCRP, and serum insulin. HRV analysis was performed in both time and frequency domains. Results. The time and frequency domain indices of overall variability (SDNN, total power) were significantly lower in NAFLD with diabetes as compared to the controls. However, the LF : HF ratio did not differ among the three groups. The variables related to obesity, lipid profile, and glucose metabolism were also higher in NAFLD with diabetes and those with Grade II NAFLD without diabetes, as compared to controls. Multivariate stepwise regression analysis showed a negative correlation between HRV and total cholesterol and fat percentage. Conclusion. The grade of NAFLD as well as diabetic status contributes to the decrease in the cardiovascular autonomic function, with diabetic status rather than grade of NAFLD playing a critical role. Serum lipids and adiposity may also contribute to cardiac autonomic dysfunction.","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"31 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2016-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84487945","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}
Antje Bruckbauer, J. Banerjee, Lizhi Fu, Fenfen Li, Q. Cao, Xin Cui, R. Wu, Hang Shi, B. Xue, M. Zemel
Sirt1, AMPK, and eNOS modulate hepatic energy metabolism and inflammation and are key players in the development of NASH. L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Here we tested a possible multicomponent synergy to yield greater therapeutic efficacy in NAFLD/NASH. Liver cells and macrophages or an atherogenic diet induced NASH mouse model was treated with two-way and three-way combinations. The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker in vitro. In mice, Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects. Therefore, these data provide preclinical evidence for therapeutic efficacy of Sild-Met-Leu in the treatment of NAFLD and NASH.
{"title":"A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice","authors":"Antje Bruckbauer, J. Banerjee, Lizhi Fu, Fenfen Li, Q. Cao, Xin Cui, R. Wu, Hang Shi, B. Xue, M. Zemel","doi":"10.1155/2016/9185987","DOIUrl":"https://doi.org/10.1155/2016/9185987","url":null,"abstract":"Sirt1, AMPK, and eNOS modulate hepatic energy metabolism and inflammation and are key players in the development of NASH. L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Here we tested a possible multicomponent synergy to yield greater therapeutic efficacy in NAFLD/NASH. Liver cells and macrophages or an atherogenic diet induced NASH mouse model was treated with two-way and three-way combinations. The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker in vitro. In mice, Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects. Therefore, these data provide preclinical evidence for therapeutic efficacy of Sild-Met-Leu in the treatment of NAFLD and NASH.","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"21 3 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2016-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90695073","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. Hyperammonemia resulting from chronic liver disease (CLD) can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was 42.33 ± 7.60. The mean duration (years) of CLD was 10.15 ± 3.53 while the mean Child-Pugh (CP) score was 8.84 ± 3.30. Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE). The frequency of hyperammonemia was 67.3%, more frequent in males (N = 81, z-score = 2.4, and P < 0.05) than in females (N = 34, z-score = 2.4, and P < 0.05), and had a statistically significant relationship with increasing CP grade of cirrhosis (χ 2(2) = 27.46, P < 0.001, Phi = 0.40, and P < 0.001). Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; P < 0.001. Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy.
背景。慢性肝病(CLD)引起的高氨血症可以潜在地挑战和损害身体的任何器官系统,特别是大脑。然而,关于血清氨在肝性脑病患者的诊断或预后价值,特别是在急性慢性或慢性肝衰竭的情况下,仍然存在一些争议。此外,血清氨与Child-Pugh肝硬化分级恶化的关系尚未得到研究。目标。本研究旨在解决关于高氨血症与肝硬化,特别是慢性肝功能衰竭患者肝性脑病之间关系的争议。材料和方法。本研究对171例肝硬化患者的血清氨进行了测量,并使用SPSS version 16进行了分析。采用卡方检验和单因素方差分析。结果。这项研究有110名男性和61名女性参与者。所有参与者的平均年龄为42.33±7.60岁。CLD平均病程(年)为10.15±3.53,Child-Pugh (CP)平均评分为8.84±3.30。慢性病毒性肝炎占71.3%。此外,86.5%的参与者患有肝性脑病(HE)。高氨血症发生率为67.3%,男性(N = 81, z-score = 2.4, P < 0.05)高于女性(N = 34, z-score = 2.4, P < 0.05),且与肝硬化CP分级的升高有统计学意义(χ 2(2) = 27.46, P < 0.001, Phi = 0.40, P < 0.001)。肝性脑病患者血清氨水平高于无肝性脑病患者;P < 0.001。结论。高氨血症与肝硬化Child-Pugh分级增加和肝性脑病相关。
{"title":"Hyperammonemia Is Associated with Increasing Severity of Both Liver Cirrhosis and Hepatic Encephalopathy","authors":"Abidullah Khan, M. Ayub, Wazir Mohammad Khan","doi":"10.1155/2016/6741754","DOIUrl":"https://doi.org/10.1155/2016/6741754","url":null,"abstract":"Background. Hyperammonemia resulting from chronic liver disease (CLD) can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was 42.33 ± 7.60. The mean duration (years) of CLD was 10.15 ± 3.53 while the mean Child-Pugh (CP) score was 8.84 ± 3.30. Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE). The frequency of hyperammonemia was 67.3%, more frequent in males (N = 81, z-score = 2.4, and P < 0.05) than in females (N = 34, z-score = 2.4, and P < 0.05), and had a statistically significant relationship with increasing CP grade of cirrhosis (χ 2(2) = 27.46, P < 0.001, Phi = 0.40, and P < 0.001). Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; P < 0.001. Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy.","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"48 11 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2016-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88923391","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}
Patients with chronic liver diseases (CLD) undergo a range of invasive procedures during their clinical lifetime. Various hemostatic abnormalities are frequently identified during the periprocedural work-up; including thrombocytopenia. Thrombocytopenia of cirrhosis is multifactorial in origin, and decreased activity of thrombopoietin has been identified to be a major cause. Liver is an important site of thrombopoietin production and its levels are decreased in patients with cirrhosis. Severe thrombocytopenia (platelet counts < 60–75,000/µL) is associated with increased risk of bleeding with invasive procedures. In recent years, compounds with thrombopoietin receptor agonist activity have been studied as therapeutic options to raise platelet counts in CLD. We reviewed the use of Eltrombopag, Romiplostim, and Avatrombopag prior to various invasive procedures in patients with CLD. These agents seem promising in raising platelet counts before elective procedures resulting in reduction in platelet transfusions, and they also enabled more patients to undergo the procedures. However, these studies were not primarily aimed at comparing bleeding episodes among groups. Use of these agents had some adverse consequences, importantly being the occurrence of portal vein thrombosis. This review highlights the need of further studies to identify reliable methods of safely reducing the provoked bleeding risk linked to thrombocytopenia in CLD.
{"title":"The Use of Thrombopoietin Receptor Agonists for Correction of Thrombocytopenia prior to Elective Procedures in Chronic Liver Diseases: Review of Current Evidence","authors":"K. Qureshi, Shyam Patel, A. Meillier","doi":"10.1155/2016/1802932","DOIUrl":"https://doi.org/10.1155/2016/1802932","url":null,"abstract":"Patients with chronic liver diseases (CLD) undergo a range of invasive procedures during their clinical lifetime. Various hemostatic abnormalities are frequently identified during the periprocedural work-up; including thrombocytopenia. Thrombocytopenia of cirrhosis is multifactorial in origin, and decreased activity of thrombopoietin has been identified to be a major cause. Liver is an important site of thrombopoietin production and its levels are decreased in patients with cirrhosis. Severe thrombocytopenia (platelet counts < 60–75,000/µL) is associated with increased risk of bleeding with invasive procedures. In recent years, compounds with thrombopoietin receptor agonist activity have been studied as therapeutic options to raise platelet counts in CLD. We reviewed the use of Eltrombopag, Romiplostim, and Avatrombopag prior to various invasive procedures in patients with CLD. These agents seem promising in raising platelet counts before elective procedures resulting in reduction in platelet transfusions, and they also enabled more patients to undergo the procedures. However, these studies were not primarily aimed at comparing bleeding episodes among groups. Use of these agents had some adverse consequences, importantly being the occurrence of portal vein thrombosis. This review highlights the need of further studies to identify reliable methods of safely reducing the provoked bleeding risk linked to thrombocytopenia in CLD.","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"30 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2016-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82121090","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}
Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are particularly attractive cells for cellular and gene therapy in acute liver failure (ALF). However, the efficacy of this cell therapy in animal studies needs to be significantly improved before it can be translated into clinics. In this study, we investigated the therapeutic potential of UCMSCs that overexpress hepatocyte growth factor (HGF) in an acetaminophen-induced acute liver failure mouse model. We found that the HGF-UCMSC cell therapy protected animals from acute liver failure by reducing liver damage and prolonging animal survival. The therapeutic effect of HGF-UCMSCs was associated with the increment in serum glutathione (GSH) and hepatic enzymes that maintain redox homeostasis, including γ-glutamylcysteine synthetase (γ-GCS), superoxide dismutase (SOD), and catalase (CAT). Immunohistochemical staining confirmed that HGF-UCMSCs were mobilized to the injured areas of the liver. Additionally, HGF-UCMSCs modulated apoptosis by upregulating the antiapoptotic Bcl2 and downregulating proapoptotic genes, including Bax and TNFα. Taken together, these data suggest that ectopic expression of HGF in UCMSCs protects animals from acetaminophen-induced acute liver failure through antiapoptosis and antioxidation mechanisms.
{"title":"Therapeutic Potential of HGF-Expressing Human Umbilical Cord Mesenchymal Stem Cells in Mice with Acute Liver Failure","authors":"Yunxia Tang, Qiongshu Li, Fanwei Meng, Xingyu Huang, Chan Li, Xin Zhou, Xiaoping Zeng, Yixin He, Jia Liu, Xiang Hu, Ji-fan Hu, Tao Li","doi":"10.1155/2016/5452487","DOIUrl":"https://doi.org/10.1155/2016/5452487","url":null,"abstract":"Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are particularly attractive cells for cellular and gene therapy in acute liver failure (ALF). However, the efficacy of this cell therapy in animal studies needs to be significantly improved before it can be translated into clinics. In this study, we investigated the therapeutic potential of UCMSCs that overexpress hepatocyte growth factor (HGF) in an acetaminophen-induced acute liver failure mouse model. We found that the HGF-UCMSC cell therapy protected animals from acute liver failure by reducing liver damage and prolonging animal survival. The therapeutic effect of HGF-UCMSCs was associated with the increment in serum glutathione (GSH) and hepatic enzymes that maintain redox homeostasis, including γ-glutamylcysteine synthetase (γ-GCS), superoxide dismutase (SOD), and catalase (CAT). Immunohistochemical staining confirmed that HGF-UCMSCs were mobilized to the injured areas of the liver. Additionally, HGF-UCMSCs modulated apoptosis by upregulating the antiapoptotic Bcl2 and downregulating proapoptotic genes, including Bax and TNFα. Taken together, these data suggest that ectopic expression of HGF in UCMSCs protects animals from acetaminophen-induced acute liver failure through antiapoptosis and antioxidation mechanisms.","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"32 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2016-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79176754","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}
Pub Date : 2016-01-01Epub Date: 2016-06-15DOI: 10.1155/2016/3852126
Allison M Bell, Jamie L Wagner, Katie E Barber, Kayla R Stover
Hepatitis C virus (HCV) is estimated to affect up to 150 million people worldwide. Despite worldwide prevalence, treatment modalities prior to 2011 remained suboptimal, with low virologic response rates and intolerable side effect profiles. Fortunately, the landscape of treatment for chronic hepatitis C has rapidly evolved since the introduction of HCV NS3/4 protease inhibitors in 2011. Elbasvir, a NS5A inhibitor, combined with grazoprevir, a NS3/4A protease inhibitor, is the latest FDA-approved therapy for patients with genotype 1 or 4 chronic hepatitis C, with or without compensated cirrhosis. This review will focus on the current literature and clinical evidence supporting elbasvir/grazoprevir as first-line therapy in patients with genotypes 1 and 4 chronic hepatitis C.
{"title":"Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C.","authors":"Allison M Bell, Jamie L Wagner, Katie E Barber, Kayla R Stover","doi":"10.1155/2016/3852126","DOIUrl":"10.1155/2016/3852126","url":null,"abstract":"<p><p>Hepatitis C virus (HCV) is estimated to affect up to 150 million people worldwide. Despite worldwide prevalence, treatment modalities prior to 2011 remained suboptimal, with low virologic response rates and intolerable side effect profiles. Fortunately, the landscape of treatment for chronic hepatitis C has rapidly evolved since the introduction of HCV NS3/4 protease inhibitors in 2011. Elbasvir, a NS5A inhibitor, combined with grazoprevir, a NS3/4A protease inhibitor, is the latest FDA-approved therapy for patients with genotype 1 or 4 chronic hepatitis C, with or without compensated cirrhosis. This review will focus on the current literature and clinical evidence supporting elbasvir/grazoprevir as first-line therapy in patients with genotypes 1 and 4 chronic hepatitis C. </p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2016 ","pages":"3852126"},"PeriodicalIF":1.8,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/3852126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34659634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background. Based on recent basic and clinical investigations, the extract of artichoke (Cynara scolymus) leaf has been revealed to be used for hepatoprotective and cholesterol reducing purposes. We aimed to assess the therapeutic effects of artichoke on biochemical and liver biomarkers in patients with nonalcoholic steatohepatitis (NASH). Methods. In a randomized double blind clinical trial, 60 consecutive patients suffering NASH were randomly assigned to receive Cynara scolymus extract (as 6 tablets per day consisting of 2700 mg extract of the herb) as the intervention group or placebo as the control group for two months. Results. Comparing changes in study markers following interventions showed improvement in liver enzymes. The levels of triglycerides and cholesterol were significantly reduced in the group treated with Cynara scolymus when compared to placebo group. To compare the role of Cynara scolymus use with placebo in changes in study parameters, multivariate linear regression models were employed indicating higher improvement in liver enzymes and also lipid profile particularly triglycerides and total cholesterol following administration of Cynara scolymus in comparison with placebo use. Conclusion. This study sheds light on the potential hepatoprotective activity and hypolipidemic effect of Cynara scolymus in management of NASH. This clinical trial is registered in the IRCT, Iranian Registry of Clinical Trials, by number IRCT2014070218321N1.
{"title":"The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis.","authors":"Vajiheh Rangboo, Mostafa Noroozi, Roza Zavoshy, Seyed Amirmansoor Rezadoost, Asghar Mohammadpoorasl","doi":"10.1155/2016/4030476","DOIUrl":"10.1155/2016/4030476","url":null,"abstract":"<p><p>Background. Based on recent basic and clinical investigations, the extract of artichoke (Cynara scolymus) leaf has been revealed to be used for hepatoprotective and cholesterol reducing purposes. We aimed to assess the therapeutic effects of artichoke on biochemical and liver biomarkers in patients with nonalcoholic steatohepatitis (NASH). Methods. In a randomized double blind clinical trial, 60 consecutive patients suffering NASH were randomly assigned to receive Cynara scolymus extract (as 6 tablets per day consisting of 2700 mg extract of the herb) as the intervention group or placebo as the control group for two months. Results. Comparing changes in study markers following interventions showed improvement in liver enzymes. The levels of triglycerides and cholesterol were significantly reduced in the group treated with Cynara scolymus when compared to placebo group. To compare the role of Cynara scolymus use with placebo in changes in study parameters, multivariate linear regression models were employed indicating higher improvement in liver enzymes and also lipid profile particularly triglycerides and total cholesterol following administration of Cynara scolymus in comparison with placebo use. Conclusion. This study sheds light on the potential hepatoprotective activity and hypolipidemic effect of Cynara scolymus in management of NASH. This clinical trial is registered in the IRCT, Iranian Registry of Clinical Trials, by number IRCT2014070218321N1. </p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2016 ","pages":"4030476"},"PeriodicalIF":1.8,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34636611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-01Epub Date: 2016-07-20DOI: 10.1155/2016/2647130
Abu Bakar Hafeez Bhatti, Faisal Saud Dar, Haseeb Zia, Muhammad Salman Rafique, Nusrat Yar Khan, Mohammad Salih, Najmul Hassan Shah
Background. Concomitant vascular injury might adversely impact outcomes after iatrogenic bile duct injury (IBDI). Whether a new HPB center should embark upon repair of complex biliary injuries with associated vascular injuries during learning curve is unknown. The objective of this study was to determine outcome of surgical management of IBDI with and without vascular injuries in a new HPB center during its learning curve. Methods. We retrospectively reviewed patients who underwent surgical management of IBDI at our center. A total of 39 patients were included. Patients without (Group 1) and with vascular injuries (Group 2) were compared. Outcome was defined as 90-day morbidity and mortality. Results. Median age was 39 (20-80) years. There were 10 (25.6%) vascular injuries. E2 injuries were associated significantly with high frequency of vascular injuries (66% versus 15.1%) (P = 0.01). Right hepatectomy was performed in three patients. Out of these, two had a right hepatic duct stricture and one patient had combined right arterial and portal venous injury. The number of patients who developed postoperative complications was not significantly different between the two groups (11.1% versus 23.4%) (P = 0.6). Conclusion. Learning curve is not a negative prognostic variable in the surgical management of iatrogenic vasculobiliary injuries after cholecystectomy.
背景。合并血管损伤可能对医源性胆管损伤(IBDI)后的预后产生不利影响。一个新的HPB中心是否应该在学习曲线中着手修复复杂的胆道损伤和相关的血管损伤是未知的。本研究的目的是确定一个新的HPB中心在其学习曲线期间有和没有血管损伤的IBDI手术治疗的结果。方法。我们回顾性地回顾了在本中心接受手术治疗的IBDI患者。共纳入39例患者。无血管损伤组(1组)与血管损伤组(2组)进行比较。结果定义为90天的发病率和死亡率。结果。中位年龄39岁(20-80岁)。血管损伤10例(25.6%)。E2损伤与高血管性损伤发生率显著相关(66%比15.1%)(P = 0.01)。3例患者行右肝切除术。其中2例为右肝管狭窄,1例为右动脉和门静脉合并损伤。两组术后并发症发生率无显著差异(11.1% vs 23.4%) (P = 0.6)。结论。在胆囊切除术后医源性血管损伤的外科治疗中,学习曲线并不是一个负面的预后变量。
{"title":"Prognostication of Learning Curve on Surgical Management of Vasculobiliary Injuries after Cholecystectomy.","authors":"Abu Bakar Hafeez Bhatti, Faisal Saud Dar, Haseeb Zia, Muhammad Salman Rafique, Nusrat Yar Khan, Mohammad Salih, Najmul Hassan Shah","doi":"10.1155/2016/2647130","DOIUrl":"https://doi.org/10.1155/2016/2647130","url":null,"abstract":"<p><p>Background. Concomitant vascular injury might adversely impact outcomes after iatrogenic bile duct injury (IBDI). Whether a new HPB center should embark upon repair of complex biliary injuries with associated vascular injuries during learning curve is unknown. The objective of this study was to determine outcome of surgical management of IBDI with and without vascular injuries in a new HPB center during its learning curve. Methods. We retrospectively reviewed patients who underwent surgical management of IBDI at our center. A total of 39 patients were included. Patients without (Group 1) and with vascular injuries (Group 2) were compared. Outcome was defined as 90-day morbidity and mortality. Results. Median age was 39 (20-80) years. There were 10 (25.6%) vascular injuries. E2 injuries were associated significantly with high frequency of vascular injuries (66% versus 15.1%) (P = 0.01). Right hepatectomy was performed in three patients. Out of these, two had a right hepatic duct stricture and one patient had combined right arterial and portal venous injury. The number of patients who developed postoperative complications was not significantly different between the two groups (11.1% versus 23.4%) (P = 0.6). Conclusion. Learning curve is not a negative prognostic variable in the surgical management of iatrogenic vasculobiliary injuries after cholecystectomy. </p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2016 ","pages":"2647130"},"PeriodicalIF":1.8,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/2647130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34307412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}