AIM： To evaluate the influence of Locarnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy （HE）. METHODS： One hundred and fifty patients （10 patients with alcoholism, 41 patien...AIM： To evaluate the influence of Locarnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy （HE）. METHODS： One hundred and fifty patients （10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection, 21 patients with cryptogenetic cirrhosis） meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine （2 g twice a day） or into group B receiving placebo in double blind. RESULTS： At the end of the study period, a significant decrease in NI-14 fasting serum levels was found in patients with hepatic encephalopathy （P〈0.0S） after the treatment with levocarnitine （LC）. Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy （P〈0.0S）. CONCLUSION： Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.展开更多
AIM： To assess the actigraphy, an ambulatory and continuous monitoring of wrist motor activity fitted to study sleep/wake patterns in hepatic encephalopathy （HE）. METHODS： Twenty-five cirrhotic patients （17 M, 8 ...AIM： To assess the actigraphy, an ambulatory and continuous monitoring of wrist motor activity fitted to study sleep/wake patterns in hepatic encephalopathy （HE）. METHODS： Twenty-five cirrhotic patients （17 M, 8 F, mean age 56± 11 years, 24/25 alcoholic, Child-Pugh A, B, C： 2, 6, 17） were included. The patients were classified into 3 groups： stage 0 group （n = 12）, stage 1-2 group （n = 6）, and stage 3-4 group （n = 7） of encephalopathy. Over three consecutive days, patients had clinical evaluation 3 times a day with psychometric test, venous ammoniemia, flash visually evoked potentials （VEP）, electroencephalogram and continuous actigraphic monitoring for 3 d, providing 5 parameters： mesor, amplitude, acrophase, mean duration of activity （MDAI） and inactivity （MDII） intervals. RESULTS： Serum ammonia and VEP did not differ among the 3 groups. Electroencephalography mean dominant frequency （MDF） correlated significantly with clinical stages of HE （r=0.65, P=0.003）. The best correlation with HE stage was provided by actigraphy especially with MDAI （r= 0.7, P〈10^-4） and mesor （r= 0.65, P〈 10^-4）. MDAI correlated significantly with MDF （r= 0.62, 0.004） and was significantly shorter in case of HE compared to patients without HE （stage 0： 5.33± 1.6 min; stage 1-2：3.28±1.4 min; stage 3-4：2.52±1.1 min; P〈0.05）. Using a threshold of MDAI of less than 4.9 min, sensitivity, specificity, positive predictive value, negative predictive value for HE diagnosis were 85%, 67%, 73% and 80%, respectively. CONCLUSION： Actigraphy may be an objective method to identify HE, especially for early HE detection. Motor activity at the wrist correlates well with clinical stages of HE. MDAI and mesor are the most relevant parameters.展开更多
The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic...The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.展开更多
Hepatic encephalopathy(HE) is a common complica-tion in patients with liver cirrhosis but its pathogenesis remains incompletely understood.Malnutrition is com-monly encountered in patients with liver cirrhosis and it ...Hepatic encephalopathy(HE) is a common complica-tion in patients with liver cirrhosis but its pathogenesis remains incompletely understood.Malnutrition is com-monly encountered in patients with liver cirrhosis and it has been reported to affect the quality of life of this group of patients.Experimental studies suggest that low energy intake and poor nutritional status may facil-itate the development of HE but there are scarce data on the potential role of malnutrition in HE in patients with liver cirrhosis.Two recently published studies have evaluated the potential role of malnutrition in the development of HE in cirrhotic patients with conflicting results.In this letter to the editor we briefly present the results of the two studies as well as potential rea-sons for the conflicting results reported.展开更多
Objective To investigate the correlation between plasma fibrinogen level and cerebral infarction (CI) as well as the difference of fibrinogen among subtypes of CI. Methods A case-controlled study was conducted with 13...Objective To investigate the correlation between plasma fibrinogen level and cerebral infarction (CI) as well as the difference of fibrinogen among subtypes of CI. Methods A case-controlled study was conducted with 131 cases of CI and 148 controls. Plasma fibrinogen levels were detected by the Clauss method. Results High fibrinogen level (3.09±0.94 g/L) was correlated with CI (OR=2.47, 95%CI: 1.51-4.04, P<0.005) at the onset stage of the disease. Persistent high fibrinogen level (3.14±0.81 g/L) at 6-month after stroke onset was detected and correlated with CI(OR=4.34,95% CI:1.80-10.51, P=0.001). Higher fibrinogen level was correlated with total anterior circulation infarction (TACI), partial anterior circulation infarction (PACI), and posterior circulation infarction (POCI) (OR=4.008, P<0.001). Higher fibrinogen level was correlated with extracranial atherosclerosis (OR=3.220, P<0.05), but not with intracranial atherosclerosis.Conclusion Fibrinogen level may be a risk factor of CI and probably correlates with subtypes of CI and distributions of atherosclerosis.展开更多
AIM： To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 dafer ligation when portal pressure is spontaneously normalized. METHODS： ...AIM： To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 dafer ligation when portal pressure is spontaneously normalized. METHODS： Adult male Wistar rats were divided into four groups： Group Ⅰ： Sham14d, sham operated; Group Ⅱ： PHil, portal vein stenosis, （both groups were used 14 days after surgery）; Group Ⅲ： Sham4od, Sham operated and Group Ⅳ： PH4od Portal vein stenosis （Groups Ⅱ and Ⅳ used 40 d afer surgery）. Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS： Forty days afer stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION： The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment.展开更多
AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other ora...AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identifi ed through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics[odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profi le (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical signifi cance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any signifi cant difference in the above fi ndings. CONCLUSION: Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profi le.展开更多
Although the pathogenesis of cardio-cerebrovascular disease （CCVD） is multifactorial, an increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase （HDAC）-mediate...Although the pathogenesis of cardio-cerebrovascular disease （CCVD） is multifactorial, an increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase （HDAC）-mediated epigenetic processes in the development of cardio-cerebrovascular injury. HDACs are a family of enzymes to balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. To date, 18 mammalian HDACs are identified and grouped into four classes based on similarity to yeast orthologs. The zinc-dependent HDAC family currently consists of 11 members divided into three classes （class I, II, and IV） on the basis of structure, sequence homology, and domain organization. In comparison, class III HDACs （also known as the sirtuins） are composed of a family of NAD＋-dependent protein-modifying enzymes related to the Sir2 gene. HDAC inhibitors are a group of compounds that block HDAC activities typically by binding to the zinc-containing catalytic domain of HDACs and have displayed an- ti-inflammatory and antifibrotic effects in the cardio-cerebrovascular system. In this review, we summarize the current knowledge about classifications, functions of HDACs and their roles and regulatory mechanisms in the cardio-cerebrovascular system. Pharmacological tar- geting of HDAC-mediated epigenetic processes may open new therapeutic avenues for the treatment of CCVD.展开更多
文摘AIM： To evaluate the influence of Locarnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy （HE）. METHODS： One hundred and fifty patients （10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection, 21 patients with cryptogenetic cirrhosis） meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine （2 g twice a day） or into group B receiving placebo in double blind. RESULTS： At the end of the study period, a significant decrease in NI-14 fasting serum levels was found in patients with hepatic encephalopathy （P〈0.0S） after the treatment with levocarnitine （LC）. Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy （P〈0.0S）. CONCLUSION： Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.
文摘AIM： To assess the actigraphy, an ambulatory and continuous monitoring of wrist motor activity fitted to study sleep/wake patterns in hepatic encephalopathy （HE）. METHODS： Twenty-five cirrhotic patients （17 M, 8 F, mean age 56± 11 years, 24/25 alcoholic, Child-Pugh A, B, C： 2, 6, 17） were included. The patients were classified into 3 groups： stage 0 group （n = 12）, stage 1-2 group （n = 6）, and stage 3-4 group （n = 7） of encephalopathy. Over three consecutive days, patients had clinical evaluation 3 times a day with psychometric test, venous ammoniemia, flash visually evoked potentials （VEP）, electroencephalogram and continuous actigraphic monitoring for 3 d, providing 5 parameters： mesor, amplitude, acrophase, mean duration of activity （MDAI） and inactivity （MDII） intervals. RESULTS： Serum ammonia and VEP did not differ among the 3 groups. Electroencephalography mean dominant frequency （MDF） correlated significantly with clinical stages of HE （r=0.65, P=0.003）. The best correlation with HE stage was provided by actigraphy especially with MDAI （r= 0.7, P〈10^-4） and mesor （r= 0.65, P〈 10^-4）. MDAI correlated significantly with MDF （r= 0.62, 0.004） and was significantly shorter in case of HE compared to patients without HE （stage 0： 5.33± 1.6 min; stage 1-2：3.28±1.4 min; stage 3-4：2.52±1.1 min; P〈0.05）. Using a threshold of MDAI of less than 4.9 min, sensitivity, specificity, positive predictive value, negative predictive value for HE diagnosis were 85%, 67%, 73% and 80%, respectively. CONCLUSION： Actigraphy may be an objective method to identify HE, especially for early HE detection. Motor activity at the wrist correlates well with clinical stages of HE. MDAI and mesor are the most relevant parameters.
文摘The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.
文摘Hepatic encephalopathy(HE) is a common complica-tion in patients with liver cirrhosis but its pathogenesis remains incompletely understood.Malnutrition is com-monly encountered in patients with liver cirrhosis and it has been reported to affect the quality of life of this group of patients.Experimental studies suggest that low energy intake and poor nutritional status may facil-itate the development of HE but there are scarce data on the potential role of malnutrition in HE in patients with liver cirrhosis.Two recently published studies have evaluated the potential role of malnutrition in the development of HE in cirrhotic patients with conflicting results.In this letter to the editor we briefly present the results of the two studies as well as potential rea-sons for the conflicting results reported.
文摘Objective To investigate the correlation between plasma fibrinogen level and cerebral infarction (CI) as well as the difference of fibrinogen among subtypes of CI. Methods A case-controlled study was conducted with 131 cases of CI and 148 controls. Plasma fibrinogen levels were detected by the Clauss method. Results High fibrinogen level (3.09±0.94 g/L) was correlated with CI (OR=2.47, 95%CI: 1.51-4.04, P<0.005) at the onset stage of the disease. Persistent high fibrinogen level (3.14±0.81 g/L) at 6-month after stroke onset was detected and correlated with CI(OR=4.34,95% CI:1.80-10.51, P=0.001). Higher fibrinogen level was correlated with total anterior circulation infarction (TACI), partial anterior circulation infarction (PACI), and posterior circulation infarction (POCI) (OR=4.008, P<0.001). Higher fibrinogen level was correlated with extracranial atherosclerosis (OR=3.220, P<0.05), but not with intracranial atherosclerosis.Conclusion Fibrinogen level may be a risk factor of CI and probably correlates with subtypes of CI and distributions of atherosclerosis.
基金Supported by Grant TB 56 from the University of Buenos Aires, Buenos Aires, Argentina
文摘AIM： To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 dafer ligation when portal pressure is spontaneously normalized. METHODS： Adult male Wistar rats were divided into four groups： Group Ⅰ： Sham14d, sham operated; Group Ⅱ： PHil, portal vein stenosis, （both groups were used 14 days after surgery）; Group Ⅲ： Sham4od, Sham operated and Group Ⅳ： PH4od Portal vein stenosis （Groups Ⅱ and Ⅳ used 40 d afer surgery）. Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS： Forty days afer stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION： The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment.
文摘AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identifi ed through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics[odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profi le (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical signifi cance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any signifi cant difference in the above fi ndings. CONCLUSION: Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profi le.
基金This study was supported by grants from the National 973 Basic Research Program of China，the National Nature Science Foundation of China，Foundation of Program for New Century Excellent Talents in University (NCET-11-0311) to Yi F，Program for Changjiang Scholars and Innovative Research Team in University，the Special Financial Grant from the China Postdoctoral Science Foundation，the China Postdoctoral Science Foundation，the Shandong Province Post-doctoral Innovation Foundation
文摘Although the pathogenesis of cardio-cerebrovascular disease （CCVD） is multifactorial, an increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase （HDAC）-mediated epigenetic processes in the development of cardio-cerebrovascular injury. HDACs are a family of enzymes to balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. To date, 18 mammalian HDACs are identified and grouped into four classes based on similarity to yeast orthologs. The zinc-dependent HDAC family currently consists of 11 members divided into three classes （class I, II, and IV） on the basis of structure, sequence homology, and domain organization. In comparison, class III HDACs （also known as the sirtuins） are composed of a family of NAD＋-dependent protein-modifying enzymes related to the Sir2 gene. HDAC inhibitors are a group of compounds that block HDAC activities typically by binding to the zinc-containing catalytic domain of HDACs and have displayed an- ti-inflammatory and antifibrotic effects in the cardio-cerebrovascular system. In this review, we summarize the current knowledge about classifications, functions of HDACs and their roles and regulatory mechanisms in the cardio-cerebrovascular system. Pharmacological tar- geting of HDAC-mediated epigenetic processes may open new therapeutic avenues for the treatment of CCVD.
