Cirrhosis is a leading cause of morbidity and mortality,impacting more than 120 million people worldwide.Although geographic differences exist,etiologic factors such as alcohol use disorder,chronic viral hepatitis inf...Cirrhosis is a leading cause of morbidity and mortality,impacting more than 120 million people worldwide.Although geographic differences exist,etiologic factors such as alcohol use disorder,chronic viral hepatitis infections,and non-alcoholic fatty liver disease are prevalent in nearly every region.Historically,significant effort has been devoted to modifying these risks to prevent disease progression.Nevertheless,more than 11%of patients with compensated cirrhosis experience hepatic decompensation each year.This transition signifies the most important prognostic factor in the natural history of the disease,corresponding to a decline in median survival to below 2 years.Over the past decade,the need for pharmacotherapies aimed at reducing the risk for hepatic decompensation has been emphasized,and non-selective beta-blockers have emerged as the most effective option to date.However,a critical therapeutic gap still exists,and additional therapies have been proposed,including statins,rifaximin,and sodium-glucose cotransporter-2 inhibitors.Based on the results of innovative retrospective analyses and small-scale prospective trials,these pharmacotherapies represent promising options,but further studies,including randomized controlled trials,are necessary before they can be incorporated into clinical use.This report highlights the potential impact of these agents and others in preventing hepatic decompensation and discusses how this paradigm shift may pave the way for guideline-directed medical therapy in cirrhosis.展开更多
Septic shock impacts approximately 6% of hospitalized patients with cirrhosis and is associated with high rates of morbidity and mortality. Although a number of landmark clinical trials have paved the way for incremen...Septic shock impacts approximately 6% of hospitalized patients with cirrhosis and is associated with high rates of morbidity and mortality. Although a number of landmark clinical trials have paved the way for incremental improvements in the diagnosis and management of septic shock in the general population, patients with cirrhosis have largely been excluded from these studies and critical knowledge gaps continue to impact the care of these individuals. In this review,we discuss nuances in the care of patients with cirrhosis and septic shock using a pathophysiology-based approach. We illustrate that septic shock may be challenging to diagnose in this population in the context of factors such as chronic hypotension, impaired lactate metabolism, and concomitant hepatic encephalopathy. Furthermore, we demonstrate that the application of routine interventions such as intravenous fluids, vasopressors, antibiotics, and steroids should be carefully considered among those with decompensated cirrhosis in light of hemodynamic, metabolic, hormonal, and immunologic disturbances. We propose that future research should include and characterize patients with cirrhosis in a systematic manner, and clinical practice guidelines may need to be refined accordingly.展开更多
BACKGROUND In monotherapy studies for bleeding peptic ulcers,large volumes of epinephrine were associated with a reduction in rebleeding.However,the impact of epinephrine volume in patients treated with combination en...BACKGROUND In monotherapy studies for bleeding peptic ulcers,large volumes of epinephrine were associated with a reduction in rebleeding.However,the impact of epinephrine volume in patients treated with combination endoscopic therapy remains unclear.AIM To assess whether epinephrine volume was associated with bleeding outcomes in individuals who also received endoscopic thermal therapy and/or clipping.METHODS Data from 132 patients with Forrest class Ia,Ib,and IIa peptic ulcers were reviewed.The primary outcome was further bleeding at 7 d;secondary outcomes included further bleeding at 30 d,need for additional therapeutic interventions,post-endoscopy blood transfusions,and 30-day mortality.Logistic and linear regression and Cox proportional hazards analyses were performed.RESULTS There was no association between epinephrine volume and all primary and secondary outcomes in multivariable analyses.Increased odds for further bleeding at 7 d occurred in patients with elevated creatinine values(aOR 1.96,95%CI 1.30-3.20;P<0.01)or hypotension requiring vasopressors(aOR 6.34,95%CI 1.87-25.52;P<0.01).Both factors were also associated with all secondary outcomes.CONCLUSION Epinephrine maintains an important role in the management of bleeding ulcers,but large volumes up to a range of 10-20 mL are not associated with improved bleeding outcomes among individuals receiving combination endoscopic therapy.Further bleeding is primarily associated with patient factors that likely cannot be overcome by increased volumes of epinephrine.However,in carefully-selected cases where ulcer location or size pose therapeutic challenges or when additional modalities are unavailable,it is conceivable that increased volumes of epinephrine may still be beneficial.展开更多
文摘Cirrhosis is a leading cause of morbidity and mortality,impacting more than 120 million people worldwide.Although geographic differences exist,etiologic factors such as alcohol use disorder,chronic viral hepatitis infections,and non-alcoholic fatty liver disease are prevalent in nearly every region.Historically,significant effort has been devoted to modifying these risks to prevent disease progression.Nevertheless,more than 11%of patients with compensated cirrhosis experience hepatic decompensation each year.This transition signifies the most important prognostic factor in the natural history of the disease,corresponding to a decline in median survival to below 2 years.Over the past decade,the need for pharmacotherapies aimed at reducing the risk for hepatic decompensation has been emphasized,and non-selective beta-blockers have emerged as the most effective option to date.However,a critical therapeutic gap still exists,and additional therapies have been proposed,including statins,rifaximin,and sodium-glucose cotransporter-2 inhibitors.Based on the results of innovative retrospective analyses and small-scale prospective trials,these pharmacotherapies represent promising options,but further studies,including randomized controlled trials,are necessary before they can be incorporated into clinical use.This report highlights the potential impact of these agents and others in preventing hepatic decompensation and discusses how this paradigm shift may pave the way for guideline-directed medical therapy in cirrhosis.
文摘Septic shock impacts approximately 6% of hospitalized patients with cirrhosis and is associated with high rates of morbidity and mortality. Although a number of landmark clinical trials have paved the way for incremental improvements in the diagnosis and management of septic shock in the general population, patients with cirrhosis have largely been excluded from these studies and critical knowledge gaps continue to impact the care of these individuals. In this review,we discuss nuances in the care of patients with cirrhosis and septic shock using a pathophysiology-based approach. We illustrate that septic shock may be challenging to diagnose in this population in the context of factors such as chronic hypotension, impaired lactate metabolism, and concomitant hepatic encephalopathy. Furthermore, we demonstrate that the application of routine interventions such as intravenous fluids, vasopressors, antibiotics, and steroids should be carefully considered among those with decompensated cirrhosis in light of hemodynamic, metabolic, hormonal, and immunologic disturbances. We propose that future research should include and characterize patients with cirrhosis in a systematic manner, and clinical practice guidelines may need to be refined accordingly.
基金Supported by the National Institutes of Health,No. T32 2T32DK007356-42
文摘BACKGROUND In monotherapy studies for bleeding peptic ulcers,large volumes of epinephrine were associated with a reduction in rebleeding.However,the impact of epinephrine volume in patients treated with combination endoscopic therapy remains unclear.AIM To assess whether epinephrine volume was associated with bleeding outcomes in individuals who also received endoscopic thermal therapy and/or clipping.METHODS Data from 132 patients with Forrest class Ia,Ib,and IIa peptic ulcers were reviewed.The primary outcome was further bleeding at 7 d;secondary outcomes included further bleeding at 30 d,need for additional therapeutic interventions,post-endoscopy blood transfusions,and 30-day mortality.Logistic and linear regression and Cox proportional hazards analyses were performed.RESULTS There was no association between epinephrine volume and all primary and secondary outcomes in multivariable analyses.Increased odds for further bleeding at 7 d occurred in patients with elevated creatinine values(aOR 1.96,95%CI 1.30-3.20;P<0.01)or hypotension requiring vasopressors(aOR 6.34,95%CI 1.87-25.52;P<0.01).Both factors were also associated with all secondary outcomes.CONCLUSION Epinephrine maintains an important role in the management of bleeding ulcers,but large volumes up to a range of 10-20 mL are not associated with improved bleeding outcomes among individuals receiving combination endoscopic therapy.Further bleeding is primarily associated with patient factors that likely cannot be overcome by increased volumes of epinephrine.However,in carefully-selected cases where ulcer location or size pose therapeutic challenges or when additional modalities are unavailable,it is conceivable that increased volumes of epinephrine may still be beneficial.
