BACKGROUND Fas ligand(FasL)is one ligand that activates extrinsic apoptosis pathway.High expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation(LT).No high blood co...BACKGROUND Fas ligand(FasL)is one ligand that activates extrinsic apoptosis pathway.High expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation(LT).No high blood concentrations of soluble FasL(sFasL)have been found in patients with acute LT rejection;however,the samples size of those studies was small.AIM To determine whether patients with hepatocellular carcinoma(HCC)that dead during the first year of LT have higher blood sFasL concentrations previously to LT that those who that remain alive in a study of higher sample size.METHODS Patients underwent LT due to HCC were included in this retrospective study.Serum sFasL levels prior to LT were measured and one-year LT mortality was registered.RESULTS Non-surviving patients(n=14)showed higher serum sFasL levels[477(269-496)vs 85(44-382)pg/mL;P<0.001]than surviving patients(n=113).Serum sFasL levels(pg/mL)were associated with mortality(OR=1.006;95%CI=1.003-1.010;P=0.001)independently of age of LT donor in the logistic regression analysis.CONCLUSION We report for the first time that HCC patients who die within the first year of HT have higher blood sFasL concentrations prior to HT than those who remain alive.展开更多
Management of acute variceal bleeding has greatly improved over recent years. Available data indicates that general management of the bleeding cirrhotic patient by an experienced multidisciplinary team plays a major r...Management of acute variceal bleeding has greatly improved over recent years. Available data indicates that general management of the bleeding cirrhotic patient by an experienced multidisciplinary team plays a major role in the f inal outcome of this complication. It is currently recommended to combine pharmacological and endoscopic therapies for the initial treatment of the acute bleeding. Vasoactive drugs (preferable somatostatin or terlipressin) should be started as soon as a variceal bleeding is suspected (ideally during transfer to hospital) and maintained afterwards for 2-5 d. After stabilizing the patient with cautious fluid and blood support, an emergency diagnostic endoscopy should be done and, as soon as a skilled endoscopist is available, an endoscopic variceal treatment (ligation as f irst choice, sclerotherapy if endoscopic variceal ligation not feasible) should be performed. Antibiotic prophylaxis must be regarded as an integral part of the treatment of acute variceal bleeding and should be started at admission and maintained for at least 7 d. In case of failure to control the acute bleeding, rescue therapies should be immediately started. Shunt therapies (especially tran sjugular intrahepatic portosystemic shunt) are very effective at controlling treatment failures after an acute variceal bleeding. Therapeutic developments and increasing knowledge in the prognosis of this complication may allow optimization of the management strategy by adapting the different treatments to the expected risk of complications for each patient in the near future. Theoretically, this approach would allow the initiation of early aggressive treatments in high-risk patients and spare low-risk individuals unnecessary proce dures. Current research efforts will hopefully clarify this hypothesis and help to further improve the outcomes of the severe complication of cirrhosis.展开更多
Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and f ibrosis). Pancreatic acinar cells can metabolize ethanol via the o...Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and f ibrosis). Pancreatic acinar cells can metabolize ethanol via the oxidative pathway, which generates acetaldehyde and involves the enzymes alcohol dehydrogenase and possibly cytochrome P4502E1. Additionally, ethanol can be metabolized via a nonoxidative pathway involving fatty acid ethyl ester synthases. Metabolism of ethanol by acinar and other pancreatic cells and the consequent generation of toxic metabolites, are postulated to play an important role in the development of alcohol-related acute and chronic pancreatic injury. This current work will review some recent advances in the knowledge about ethanol actions on the exocrine pancreas and its relationship to inflammatory disease and cancer.展开更多
BACKGROUND Oxidative damage of DNA and RNA has been associated with mortality of patients with different diseases.However,there is no published data on the potential use of DNA and RNA oxidative damage to predict the ...BACKGROUND Oxidative damage of DNA and RNA has been associated with mortality of patients with different diseases.However,there is no published data on the potential use of DNA and RNA oxidative damage to predict the prognosis of patients with hepatocellular carcinoma(HCC)undergoing liver transplantation(LT).AIM To determine whether patients with increased DNA and RNA oxidative damage prior to LT for HCC have a poor LT prognosis.METHODS Patients with HCC who underwent LT were included in this observational and retrospective study.Serum levels of all three oxidized guanine species(OGS)were measured prior to LT since guanine is the nucleobase that forms DNA and RNA most prone to oxidation.LT mortality at 1 year was the end-point study.RESULTS Surviving patients(n=101)showed lower serum OGS levels(P=0.01)and lower age of the liver donor(P=0.03)than non-surviving patients(n=13).An association between serum OGS levels prior to LT and 1-year LT(odds ratio=2.079;95%confidence interval=1.356-3.189;P=0.001)was found in the logistic regression analysis.CONCLUSION The main new finding was that high serum OGS concentration prior to LT was associated with the mortality 1 year after LT in HCC patients.展开更多
文摘BACKGROUND Fas ligand(FasL)is one ligand that activates extrinsic apoptosis pathway.High expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation(LT).No high blood concentrations of soluble FasL(sFasL)have been found in patients with acute LT rejection;however,the samples size of those studies was small.AIM To determine whether patients with hepatocellular carcinoma(HCC)that dead during the first year of LT have higher blood sFasL concentrations previously to LT that those who that remain alive in a study of higher sample size.METHODS Patients underwent LT due to HCC were included in this retrospective study.Serum sFasL levels prior to LT were measured and one-year LT mortality was registered.RESULTS Non-surviving patients(n=14)showed higher serum sFasL levels[477(269-496)vs 85(44-382)pg/mL;P<0.001]than surviving patients(n=113).Serum sFasL levels(pg/mL)were associated with mortality(OR=1.006;95%CI=1.003-1.010;P=0.001)independently of age of LT donor in the logistic regression analysis.CONCLUSION We report for the first time that HCC patients who die within the first year of HT have higher blood sFasL concentrations prior to HT than those who remain alive.
基金Supported partially by a Grant from Ministerio de Ciencia e Innovación SAF2009-08354Salvador Augustin is a recipient of a Río Hortega’ Fellowship Grant from the Instituto de Salud Carlos Ⅲ and is enrolled in the postgraduate programme of the Universitat Autònoma de Barcelona
文摘Management of acute variceal bleeding has greatly improved over recent years. Available data indicates that general management of the bleeding cirrhotic patient by an experienced multidisciplinary team plays a major role in the f inal outcome of this complication. It is currently recommended to combine pharmacological and endoscopic therapies for the initial treatment of the acute bleeding. Vasoactive drugs (preferable somatostatin or terlipressin) should be started as soon as a variceal bleeding is suspected (ideally during transfer to hospital) and maintained afterwards for 2-5 d. After stabilizing the patient with cautious fluid and blood support, an emergency diagnostic endoscopy should be done and, as soon as a skilled endoscopist is available, an endoscopic variceal treatment (ligation as f irst choice, sclerotherapy if endoscopic variceal ligation not feasible) should be performed. Antibiotic prophylaxis must be regarded as an integral part of the treatment of acute variceal bleeding and should be started at admission and maintained for at least 7 d. In case of failure to control the acute bleeding, rescue therapies should be immediately started. Shunt therapies (especially tran sjugular intrahepatic portosystemic shunt) are very effective at controlling treatment failures after an acute variceal bleeding. Therapeutic developments and increasing knowledge in the prognosis of this complication may allow optimization of the management strategy by adapting the different treatments to the expected risk of complications for each patient in the near future. Theoretically, this approach would allow the initiation of early aggressive treatments in high-risk patients and spare low-risk individuals unnecessary proce dures. Current research efforts will hopefully clarify this hypothesis and help to further improve the outcomes of the severe complication of cirrhosis.
基金Supported by Junta de Extremadura-FEDER, PRI08A018
文摘Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and f ibrosis). Pancreatic acinar cells can metabolize ethanol via the oxidative pathway, which generates acetaldehyde and involves the enzymes alcohol dehydrogenase and possibly cytochrome P4502E1. Additionally, ethanol can be metabolized via a nonoxidative pathway involving fatty acid ethyl ester synthases. Metabolism of ethanol by acinar and other pancreatic cells and the consequent generation of toxic metabolites, are postulated to play an important role in the development of alcohol-related acute and chronic pancreatic injury. This current work will review some recent advances in the knowledge about ethanol actions on the exocrine pancreas and its relationship to inflammatory disease and cancer.
文摘BACKGROUND Oxidative damage of DNA and RNA has been associated with mortality of patients with different diseases.However,there is no published data on the potential use of DNA and RNA oxidative damage to predict the prognosis of patients with hepatocellular carcinoma(HCC)undergoing liver transplantation(LT).AIM To determine whether patients with increased DNA and RNA oxidative damage prior to LT for HCC have a poor LT prognosis.METHODS Patients with HCC who underwent LT were included in this observational and retrospective study.Serum levels of all three oxidized guanine species(OGS)were measured prior to LT since guanine is the nucleobase that forms DNA and RNA most prone to oxidation.LT mortality at 1 year was the end-point study.RESULTS Surviving patients(n=101)showed lower serum OGS levels(P=0.01)and lower age of the liver donor(P=0.03)than non-surviving patients(n=13).An association between serum OGS levels prior to LT and 1-year LT(odds ratio=2.079;95%confidence interval=1.356-3.189;P=0.001)was found in the logistic regression analysis.CONCLUSION The main new finding was that high serum OGS concentration prior to LT was associated with the mortality 1 year after LT in HCC patients.
