Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical guidelines.However,with recent evidence arguing against antibiotic prophylaxis,t...Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical guidelines.However,with recent evidence arguing against antibiotic prophylaxis,the role of this intervention has become less clear.展开更多
BACKGROUND Esophageal variceal bleeding is a severe complication associated with liver cirrhosis and typically necessitates endoscopic hemostasis.The current standard treatment is endoscopic variceal ligation(EVL),and...BACKGROUND Esophageal variceal bleeding is a severe complication associated with liver cirrhosis and typically necessitates endoscopic hemostasis.The current standard treatment is endoscopic variceal ligation(EVL),and Western guidelines recom-mend antibiotic prophylaxis following hemostasis.However,given the impro-vements in prognosis for variceal bleeding due to advancements in the management of bleeding and treatments of liver cirrhosis and the global concerns regarding the emergence of multidrug-resistant bacteria,there is a need to reassess the use of routine antibiotic prophylaxis after hemostasis.AIM To evaluate the effectiveness of antibiotic prophylaxis in patients treated for EVL.METHODS We conducted a 13-year observational study using the Tokushukai medical database across 46 hospitals.Patients were divided into the prophylaxis group(received antibiotics on admission or the next day)and the non-prophylaxis group(did not receive antibiotics within one day of admission).The primary outcome was composed of 6-wk mortality,4-wk rebleeding,and 4-wk spontaneous bacterial peritonitis(SBP).The secondary outcomes were each individual result and in-hospital mortality.A logistic regression with inverse probability of treatment weighting was used.A subgroup analysis was conducted based on the Child-Pugh classification to determine its influence on the primary outcome measures,while sensitivity analyses for antibiotic type and duration were also performed.RESULTS Among 980 patients,790 were included(prophylaxis:232,non-prophylaxis:558).Most patients were males under the age of 65 years with a median Child-Pugh score of 8.The composite primary outcomes occurred in 11.2%of patients in the prophylaxis group and 9.5%in the non-prophylaxis group.No significant differences in outcomes were observed between the groups(adjusted odds ratio,1.11;95%confidence interval,0.61-1.99;P=0.74).Individual outcomes such as 6-wk mortality,4-wk rebleeding,4-wk onset of SBP,and in-hospital mortality were not significantly different between the groups.The primary outcome did not differ between the Child-Pugh subgroups.Similar results were observed in the sensitivity analyses.CONCLUSION No significant benefit to antibiotic prophylaxis for esophageal variceal bleeding treated with EVL was detected in this study.Global reassessment of routine antibiotic prophylaxis is imperative.展开更多
Bacterial infections are highly prevalent and a frequent cause of hospitalization and short-term mortality in patients with cirrhosis. Due to their negative impact on survival, antibiotic prophylaxis for bacterial inf...Bacterial infections are highly prevalent and a frequent cause of hospitalization and short-term mortality in patients with cirrhosis. Due to their negative impact on survival, antibiotic prophylaxis for bacterial infections in high-risk subgroups of patients with cirrhosis has been the standard of care for decades. Patients with prophylaxis indications include those at risk for a first episode of spontaneous bacterial peritonitis(SBP) due to a low ascitic fluid protein count and impaired liver and kidney function, patients with a prior episode of SBP and those with an episode of gastrointestinal bleeding. Only prophylaxis due to gastrointestinal bleeding has a known and short-time duration. All other indications imply longlasting exposure to antibiotics-once the threshold requirement for initiating prophylaxis is met-without standardized criteria for re-assessing antibiotic interruption. Despite the fact that the benefit of antibiotic prophylaxis in reducing bacterial infections episodes and mortality has been thoroughly reported, the extended use of antibiotics in patients with cirrhosis has also had negative consequences, including the emergence of multi-drug resistant bacteria.Currently, it is not clear whether restricting the use of broad and fixed antibiotic regimens, tailoring the choice of antibiotics to local bacterial epidemiology or selecting non-antibiotic strategies will be the preferred antibiotic prophylaxis strategy for patients with cirrhosis in the future.展开更多
There is abundant evidence that bacterial infections are severe complications in patients with cirrhosis,being the most frequent trigger of acute-on-chronic liver failure and causing death in one of every four patient...There is abundant evidence that bacterial infections are severe complications in patients with cirrhosis,being the most frequent trigger of acute-on-chronic liver failure and causing death in one of every four patients during hospitalization.For these reasons,early diagnosis and effective treatment of infections are mandatory to improve patient outcomes.However,treating physicians are challenged in daily practice since diagnosing bacterial infections is not always straightforward.This situation might lead to delayed antibiotic initiation or prescription of ineffective regimens,which are associated with poor outcomes.On the other hand,prescribing broad-spectrum antibiotics to all patients suspected of bacterial infections might favor bacterial resistance development.This is a significant concern given the alarming number of infections caused by multidrug-resistant microorganisms worldwide.Therefore,it is paramount to know the local epidemiology to propose tailored guidelines for empirical antibiotic selection in patients with cirrhosis in whom bacterial infections are suspected or confirmed.In this article,we will revise current knowledge in this area and highlight the importance of surveillance programs.展开更多
Bacterial infections are common in cirrhotic patients with acute variceal bleeding,occurring in 20%within48 h.Outcomes including early rebleeding and failure to control bleeding are strongly associated with bacterial ...Bacterial infections are common in cirrhotic patients with acute variceal bleeding,occurring in 20%within48 h.Outcomes including early rebleeding and failure to control bleeding are strongly associated with bacterial infection.However,mortality from variceal bleeding is largely determined by the severity of liver disease.Besides a higher Child-Pugh score,patients with hepatocellular carcinoma are particularly susceptible to infections.Despite several hypotheses that include increased use of instruments,greater risk of aspiration pneumonia and higher bacterial translocation,it remains debatable whether variceal bleeding results in infection or vice versa but studies suggest that antibiotic prophylaxis prior to endoscopy and up to 8 h is useful in reducing bacteremia and spontaneous bacterial peritonitis.Aerobic gram negative bacilli of enteric origin are most commonly isolated from cultures,but more recently,gram positives and quinolone-resistant organisms are increasingly seen,even though their clinical significance is unclear.Fluoroquinolones(including ciprofloxacin and norfloxacin)used for short term(7 d)have the most robust evidence and are recommended in most expert guidelines.Short term intravenous cephalosporin(especially ceftriaxone),given in a hospital setting with prevalent quinolone-resistant organisms,has been shown in studies to be beneficial,particularly in high risk patients with advanced cirrhosis.展开更多
AIM To summarize and critically examine the role of band ligation in secondary prophylaxis of variceal bleeding in patients with cirrhosis. METHODS A literature review was performed using the MEDLINE and PubM ed datab...AIM To summarize and critically examine the role of band ligation in secondary prophylaxis of variceal bleeding in patients with cirrhosis. METHODS A literature review was performed using the MEDLINE and PubM ed databases. The search terms consisted of the words "endoscopic band ligation" OR "variceal band ligation" OR "ligation" AND "secondary prophylaxis" OR "secondary prevention" AND "variceal bleeding" OR "variceal hemorrhage" AND "liver cirrhosis". The data collected from relevant meta-analyses and from the most recent randomized studies that were not included in these meta-analyses were used to evaluate the role of endoscopic band ligation in an effort to demonstrate the most recent advances in the treatment of esophageal varices. RESULTS This study included 11 meta-analyses published from 2002 to 2017 and 10 randomized trials published from 2010 to 2017 that evaluated the efficacy of band ligation in the secondary prophylaxis of variceal bleeding. Overall, the results proved that band ligation was superior to endoscopic sclerotherapy. Moreover, the use of β-blockers in combination with band ligation increased the treatment effectiveness, supporting the current recommendations for secondary prophylaxis of variceal bleeding. The use of transjugular intrahepatic portosystemic shunt was superior to combination therapy regarding rebleeding prophylaxis, with no difference in the survival rates; however, the results concerning the hepatic encephalopathy incidence were conflicting. Recent advances in the management of secondary prophylaxis of variceal bleeding have targeted a decrease in portal pressure based on the pathophysiological mechanisms of portal hypertension.CONCLUSION This review suggests that future research should be conducted to enhance current interventions and/or to develop innovative treatment options with improved clinical endpoints.展开更多
Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Patients with medium- or largesized varices can be treated for primary prophylaxis of va...Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Patients with medium- or largesized varices can be treated for primary prophylaxis of variceal bleeding using two strategies: non-selective beta-blockers(NSBBs) or endoscopic variceal ligation(EVL). Both treatments are equally effective. Patients with acute variceal bleeding are critically ill patients. The available data suggest that vasoactive drugs, combined with endoscopic therapy and antibiotics, are the best treatment strategy with EVL being the endoscopic procedure of choice. In cases of uncontrolled bleeding, transjugular intrahepatic portosystemic shunt(TIPS) with polytetrafluoroethylene(PTFE)-covered stents are recommended. Approximately 60% of the patients experience rebleeding, with a mortality rate of 30%. Secondary prophylaxis should start on day six following the initial bleeding episode. The combination of NSBBs and EVL is the recommended management, whereas TIPS with PTFE-covered stents are the preferred option in patients who fail endoscopic and pharmacologic treatment. Apart from injection sclerotherapy and EVL, other endoscopic procedures, including tissue adhesives, endoloops, endoscopic clipping and argon plasma coagulation, have been used in the management of esophageal varices. However, their efficacy and safety, compared to standard endoscopic treatment, remain to be further elucidated. There are safety issues accompanying endoscopic techniques with aspiration pneumonia occurring at a rate of approximately 2.5%. In conclusion, future research is needed to improve treatment strategies, including novel endoscopic techniques with better efficacy, lower cost, and fewer adverse events.展开更多
AIM:To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.METHODS:A stochastic analysis based on decision trees was perfor...AIM:To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.METHODS:A stochastic analysis based on decision trees was performed to compare the cost-effectiveness of beta-blockers therapy starting from a diagnosis of small varices(Strategy 1)with that of endoscopic surveillance followed by beta-blockers treatment when large varices are demonstrated(Strategy 2),for preventing variceal growth,bleeding and death in patients with cirrhosis and small esophageal varices.The basic nodes of the tree were gastrointestinal endoscopy,inpatient admission and treatment for bleeding,as required.All estimates were performed using a Monte Carlo microsimulation technique,consisting in simulating observations from known probability distributions depicted in the model.Eight-hundred-thousand simulations were performed to obtain the final estimates.All estimates were then subjected to Monte Carlo Probabilistic sensitivity analysis,to assess the impact of the variability of such estimates on the outcome distributions.RESULTS:The event rate(considered as progression of varices or bleeding or death)in Strategy 1[24.09%(95%CI:14.89%-33.29%)]was significantly lower than in Strategy 2[60.00%(95%CI:48.91%-71.08%)].The mean cost(up to the first event)associated with Strategy 1[823£(95%CI:106£-2036£)]was not significantly different from that of Strategy 2[799£(95%CI:0£-3498£)].The cost-effectiveness ratio with respect to this endpoint was equal to 50.26£(95%CI:-504.37£-604.89£)per event avoided over the four-year follow-up.When bleeding episodes/deaths in subjects whose varices had grown were included,the mean cost associated with Strategy 1 was 1028£(95%CI:122£-2581£),while 1699£(95%CI:171£-4674£)in Strategy 2.CONCLUSION:Beta-blocker therapy turn out to be more effective and less expensive than endoscopic surveillance for primary prophylaxis of bleeding in patients with cirrhosis and small varices.展开更多
文摘Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical guidelines.However,with recent evidence arguing against antibiotic prophylaxis,the role of this intervention has become less clear.
基金approved by the Institutional Review Board of the Future Medical Research Centre Ethical Committee(Approval No.TGE02100-02).
文摘BACKGROUND Esophageal variceal bleeding is a severe complication associated with liver cirrhosis and typically necessitates endoscopic hemostasis.The current standard treatment is endoscopic variceal ligation(EVL),and Western guidelines recom-mend antibiotic prophylaxis following hemostasis.However,given the impro-vements in prognosis for variceal bleeding due to advancements in the management of bleeding and treatments of liver cirrhosis and the global concerns regarding the emergence of multidrug-resistant bacteria,there is a need to reassess the use of routine antibiotic prophylaxis after hemostasis.AIM To evaluate the effectiveness of antibiotic prophylaxis in patients treated for EVL.METHODS We conducted a 13-year observational study using the Tokushukai medical database across 46 hospitals.Patients were divided into the prophylaxis group(received antibiotics on admission or the next day)and the non-prophylaxis group(did not receive antibiotics within one day of admission).The primary outcome was composed of 6-wk mortality,4-wk rebleeding,and 4-wk spontaneous bacterial peritonitis(SBP).The secondary outcomes were each individual result and in-hospital mortality.A logistic regression with inverse probability of treatment weighting was used.A subgroup analysis was conducted based on the Child-Pugh classification to determine its influence on the primary outcome measures,while sensitivity analyses for antibiotic type and duration were also performed.RESULTS Among 980 patients,790 were included(prophylaxis:232,non-prophylaxis:558).Most patients were males under the age of 65 years with a median Child-Pugh score of 8.The composite primary outcomes occurred in 11.2%of patients in the prophylaxis group and 9.5%in the non-prophylaxis group.No significant differences in outcomes were observed between the groups(adjusted odds ratio,1.11;95%confidence interval,0.61-1.99;P=0.74).Individual outcomes such as 6-wk mortality,4-wk rebleeding,4-wk onset of SBP,and in-hospital mortality were not significantly different between the groups.The primary outcome did not differ between the Child-Pugh subgroups.Similar results were observed in the sensitivity analyses.CONCLUSION No significant benefit to antibiotic prophylaxis for esophageal variceal bleeding treated with EVL was detected in this study.Global reassessment of routine antibiotic prophylaxis is imperative.
文摘Bacterial infections are highly prevalent and a frequent cause of hospitalization and short-term mortality in patients with cirrhosis. Due to their negative impact on survival, antibiotic prophylaxis for bacterial infections in high-risk subgroups of patients with cirrhosis has been the standard of care for decades. Patients with prophylaxis indications include those at risk for a first episode of spontaneous bacterial peritonitis(SBP) due to a low ascitic fluid protein count and impaired liver and kidney function, patients with a prior episode of SBP and those with an episode of gastrointestinal bleeding. Only prophylaxis due to gastrointestinal bleeding has a known and short-time duration. All other indications imply longlasting exposure to antibiotics-once the threshold requirement for initiating prophylaxis is met-without standardized criteria for re-assessing antibiotic interruption. Despite the fact that the benefit of antibiotic prophylaxis in reducing bacterial infections episodes and mortality has been thoroughly reported, the extended use of antibiotics in patients with cirrhosis has also had negative consequences, including the emergence of multi-drug resistant bacteria.Currently, it is not clear whether restricting the use of broad and fixed antibiotic regimens, tailoring the choice of antibiotics to local bacterial epidemiology or selecting non-antibiotic strategies will be the preferred antibiotic prophylaxis strategy for patients with cirrhosis in the future.
文摘There is abundant evidence that bacterial infections are severe complications in patients with cirrhosis,being the most frequent trigger of acute-on-chronic liver failure and causing death in one of every four patients during hospitalization.For these reasons,early diagnosis and effective treatment of infections are mandatory to improve patient outcomes.However,treating physicians are challenged in daily practice since diagnosing bacterial infections is not always straightforward.This situation might lead to delayed antibiotic initiation or prescription of ineffective regimens,which are associated with poor outcomes.On the other hand,prescribing broad-spectrum antibiotics to all patients suspected of bacterial infections might favor bacterial resistance development.This is a significant concern given the alarming number of infections caused by multidrug-resistant microorganisms worldwide.Therefore,it is paramount to know the local epidemiology to propose tailored guidelines for empirical antibiotic selection in patients with cirrhosis in whom bacterial infections are suspected or confirmed.In this article,we will revise current knowledge in this area and highlight the importance of surveillance programs.
文摘Bacterial infections are common in cirrhotic patients with acute variceal bleeding,occurring in 20%within48 h.Outcomes including early rebleeding and failure to control bleeding are strongly associated with bacterial infection.However,mortality from variceal bleeding is largely determined by the severity of liver disease.Besides a higher Child-Pugh score,patients with hepatocellular carcinoma are particularly susceptible to infections.Despite several hypotheses that include increased use of instruments,greater risk of aspiration pneumonia and higher bacterial translocation,it remains debatable whether variceal bleeding results in infection or vice versa but studies suggest that antibiotic prophylaxis prior to endoscopy and up to 8 h is useful in reducing bacteremia and spontaneous bacterial peritonitis.Aerobic gram negative bacilli of enteric origin are most commonly isolated from cultures,but more recently,gram positives and quinolone-resistant organisms are increasingly seen,even though their clinical significance is unclear.Fluoroquinolones(including ciprofloxacin and norfloxacin)used for short term(7 d)have the most robust evidence and are recommended in most expert guidelines.Short term intravenous cephalosporin(especially ceftriaxone),given in a hospital setting with prevalent quinolone-resistant organisms,has been shown in studies to be beneficial,particularly in high risk patients with advanced cirrhosis.
文摘AIM To summarize and critically examine the role of band ligation in secondary prophylaxis of variceal bleeding in patients with cirrhosis. METHODS A literature review was performed using the MEDLINE and PubM ed databases. The search terms consisted of the words "endoscopic band ligation" OR "variceal band ligation" OR "ligation" AND "secondary prophylaxis" OR "secondary prevention" AND "variceal bleeding" OR "variceal hemorrhage" AND "liver cirrhosis". The data collected from relevant meta-analyses and from the most recent randomized studies that were not included in these meta-analyses were used to evaluate the role of endoscopic band ligation in an effort to demonstrate the most recent advances in the treatment of esophageal varices. RESULTS This study included 11 meta-analyses published from 2002 to 2017 and 10 randomized trials published from 2010 to 2017 that evaluated the efficacy of band ligation in the secondary prophylaxis of variceal bleeding. Overall, the results proved that band ligation was superior to endoscopic sclerotherapy. Moreover, the use of β-blockers in combination with band ligation increased the treatment effectiveness, supporting the current recommendations for secondary prophylaxis of variceal bleeding. The use of transjugular intrahepatic portosystemic shunt was superior to combination therapy regarding rebleeding prophylaxis, with no difference in the survival rates; however, the results concerning the hepatic encephalopathy incidence were conflicting. Recent advances in the management of secondary prophylaxis of variceal bleeding have targeted a decrease in portal pressure based on the pathophysiological mechanisms of portal hypertension.CONCLUSION This review suggests that future research should be conducted to enhance current interventions and/or to develop innovative treatment options with improved clinical endpoints.
文摘Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Patients with medium- or largesized varices can be treated for primary prophylaxis of variceal bleeding using two strategies: non-selective beta-blockers(NSBBs) or endoscopic variceal ligation(EVL). Both treatments are equally effective. Patients with acute variceal bleeding are critically ill patients. The available data suggest that vasoactive drugs, combined with endoscopic therapy and antibiotics, are the best treatment strategy with EVL being the endoscopic procedure of choice. In cases of uncontrolled bleeding, transjugular intrahepatic portosystemic shunt(TIPS) with polytetrafluoroethylene(PTFE)-covered stents are recommended. Approximately 60% of the patients experience rebleeding, with a mortality rate of 30%. Secondary prophylaxis should start on day six following the initial bleeding episode. The combination of NSBBs and EVL is the recommended management, whereas TIPS with PTFE-covered stents are the preferred option in patients who fail endoscopic and pharmacologic treatment. Apart from injection sclerotherapy and EVL, other endoscopic procedures, including tissue adhesives, endoloops, endoscopic clipping and argon plasma coagulation, have been used in the management of esophageal varices. However, their efficacy and safety, compared to standard endoscopic treatment, remain to be further elucidated. There are safety issues accompanying endoscopic techniques with aspiration pneumonia occurring at a rate of approximately 2.5%. In conclusion, future research is needed to improve treatment strategies, including novel endoscopic techniques with better efficacy, lower cost, and fewer adverse events.
文摘AIM:To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.METHODS:A stochastic analysis based on decision trees was performed to compare the cost-effectiveness of beta-blockers therapy starting from a diagnosis of small varices(Strategy 1)with that of endoscopic surveillance followed by beta-blockers treatment when large varices are demonstrated(Strategy 2),for preventing variceal growth,bleeding and death in patients with cirrhosis and small esophageal varices.The basic nodes of the tree were gastrointestinal endoscopy,inpatient admission and treatment for bleeding,as required.All estimates were performed using a Monte Carlo microsimulation technique,consisting in simulating observations from known probability distributions depicted in the model.Eight-hundred-thousand simulations were performed to obtain the final estimates.All estimates were then subjected to Monte Carlo Probabilistic sensitivity analysis,to assess the impact of the variability of such estimates on the outcome distributions.RESULTS:The event rate(considered as progression of varices or bleeding or death)in Strategy 1[24.09%(95%CI:14.89%-33.29%)]was significantly lower than in Strategy 2[60.00%(95%CI:48.91%-71.08%)].The mean cost(up to the first event)associated with Strategy 1[823£(95%CI:106£-2036£)]was not significantly different from that of Strategy 2[799£(95%CI:0£-3498£)].The cost-effectiveness ratio with respect to this endpoint was equal to 50.26£(95%CI:-504.37£-604.89£)per event avoided over the four-year follow-up.When bleeding episodes/deaths in subjects whose varices had grown were included,the mean cost associated with Strategy 1 was 1028£(95%CI:122£-2581£),while 1699£(95%CI:171£-4674£)in Strategy 2.CONCLUSION:Beta-blocker therapy turn out to be more effective and less expensive than endoscopic surveillance for primary prophylaxis of bleeding in patients with cirrhosis and small varices.