Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic p...Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.展开更多
Minimal hepatic encephalopathy(MHE)corresponds to the earliest stage of hepatic encephalopathy(HE).MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptibl...Minimal hepatic encephalopathy(MHE)corresponds to the earliest stage of hepatic encephalopathy(HE).MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests.MHE may affect daily activities and reduce job performance and quality of life.MHE can increase the risk of accidents and may develop into overt encephalopathy,worsening the prognosis of patients with liver cirrhosis.Despite a lack of consensus on the therapeutic indication,interest in finding novel strategies for prevention or reversion has led to numerous clinical trials;their results are the main objective of this review.Many studies address the treatment of MHE,which is mainly based on the strategies and previous management of overt HE.Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia,and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose,antibiotics such as rifaximin,and administration of different probiotics.This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.展开更多
Minimal hepatic encephalopathy(MHE)is a critical neurocognitive complication of decompensated liver cirrhosis and portosystemic shunting,which results in a wide range of cognitive deficits including impairments in wor...Minimal hepatic encephalopathy(MHE)is a critical neurocognitive complication of decompensated liver cirrhosis and portosystemic shunting,which results in a wide range of cognitive deficits including impairments in working attention,psychomotor speed,and executive function.Current guidelines have recommended paper-and-pencil psychometric tests for the diagnosis of MHE.Most high-risk cirrhotic patients are required to be examined;however,paperand-pencil psychometric tests are neither convenient nor rapid to perform in the clinic.Recently,novel computerized psychometric tests,including the inhibitory control test,EncephalApp Stroop App,and critical flicker frequency,have been proven to be rapid,effective,and convenient methods for screening MHE in clinical practice and for identifying high-risk cirrhotic patients for further validation using rigid neuropsychometric examinations.However,diagnostic accuracy of these tests is influenced by educational background,age,and cultural differences.This review summarizes clinical evidence of the application of novel computerized psychometric tests for screening MHE.展开更多
Background and Aims: Psychometric hepatic encephalop-athy score(PHES)is used widely for diagnosis of minimal hepatic encephalopathy(MHE).This prospective study aimed to determine the utility of the inhibitory control ...Background and Aims: Psychometric hepatic encephalop-athy score(PHES)is used widely for diagnosis of minimal hepatic encephalopathy(MHE).This prospective study aimed to determine the utility of the inhibitory control test(ICT)for the diagnosis of MHE.Additionally,the efficacy of rifaximin and lactulose for reversal of MHE was evaluated.Methods:A total of 180 eligible cirrhotic patients underwent testing for MHE.When PHES was ≤ ?5 and ICT lures were ≥ 14,MHE was diagnosed.The 108 patients with MHE were randomized to three groups for treatment with either lactulose,rifaximin,or placebo.Treatment outcomes were measured at the end of 3 months.Results: The 108 patients with MHE diagnosed by PHES and/or ICT accounted for 60%.The diagnosis of MHE was made by both ICT and PHES positivity in 56 patients,by abnormal ICT and normal PHES in 37 patients,and by abnor-mal PHES and normal ICT in 15 patients.For diagnosis of MHE,ICT had sensitivity of 78.87%,specificity of 66.06%with 60.22%positive predictive value and 82.76%negative predictive value.An area under the curve value of 0.724(95%CI: 0.653–0.788)was obtained for diagnosis of MHE.Reversal of MHE was seen in 71.42%,70.27%and 11.11%of patients in the rifaximin,lactulose and placebo arms(p < 0.001).Rifaximin showed better tolerability compared to lactulose.Conclusions: For the diagnosis of MHE,ICT is a simple tool but has lower sensitivity and better specificity than PHES.Rifaximin is as efficacious as lactulose in the treat-ment of MHE and better tolerated.展开更多
Aims:Minimal hepatic encephalopathy(MHE)significantly affects the prognosis of patients with cirrhosis.This study was performed to determine whether there is a difference in the prevalence of MHE among patients with c...Aims:Minimal hepatic encephalopathy(MHE)significantly affects the prognosis of patients with cirrhosis.This study was performed to determine whether there is a difference in the prevalence of MHE among patients with cirrhosis of different etiologies and whether the etiology directly influences the occurrence of MHE.Methods:This multicenter,cross-sectional study enrolled 1879 patients with confirmed cirrhosis at 40 hospitals from October 25,2021,to January 10,2023(Trial registration:https://clinicaltrials.gov/[NCT05140837]).The patients'demographics,etiologies of cirrhosis,and laboratory test results were collected.The psychometric hepatic encephalopathy score(PHES)was determined in all patients to screen for MHE.Multivariate logistic analyses were performed to identify the risk factors for MHE.Results:In total,736 patients with cirrhosis were analyzed.The prevalence of MHE was 42.0%(n=309).The primary etiology among all patients was hepatitis B virus(HBV)-related cirrhosis(71.9%[529/736]).The prevalence of MHE was significantly higher in patients with alcoholic cirrhosis(57.1%[40/70])than in those with HBV-related cirrhosis(40.6%[215/529],p=0.009)or hepatitis C virus(HCV)-related cirrhosis(38.2%[26/68],p=0.026).Age(odds ratio[OR],1.042;95%confidence interval[CI],1.024-1.059;p<0.001),duration of education(OR,0.935;95%CI,0.899-0.971;p=0.001),etiology(OR,1.740;95%CI,1.028-2.945;p=0.039),and high MELD-Na scores(OR,1.038;95%CI,1.009-1.067;p=0.009)were independent risk factors for MHE.When patients with cirrhosis of different etiologies were analyzed separately,the results showed that age(OR,1.035;95%CI,1.014-1.057;p=0.001)and duration of education(OR,0.924;95%CI,0.883-0.966;p=0.001)were risk factors for MHE among patients with HBV-related cirrhosis,whereas age(OR,1.138;95%CI,1.033-1.254;p=0.009)and creatinine concentration(OR,16.487;95%CI,1.113-244.160;p=0.042)were risk factors for MHE in patients with HCV-related cirrhosis.No risk factors for MHE were found in patients with autoimmune cirrhosis.For patients with alcoholic cirrhosis,the platelet count(OR,1.014;95%CI,1.000-1.027;p=0.045)was a risk factor for MHE.The PHES subtest results were inconsistent among patients who had MHE with cirrhosis of different etiologies.Patients with HBV-related cirrhosis performed better on Number Connection Test B and the serial dotting test than those with alcoholic cirrhosis(p=0.007 and p<0.001),better on Number Connection Test B than those with HCV-related cirrhosis(p=0.020),and better on the line tracing test than those with autoimmune cirrhosis(p=0.037).Conclusion:The etiology of cirrhosis affected the prevalence of MHE and risk factors for MHE.The domains of major cognitive impairment varied among patients with cirrhosis of different etiologies.Further studies are required to verify these findings.展开更多
基金Ningxia Natural Science Foundation,No.2020AAC03329the Key Research and Development Projects of Ningxia,No.2022BEG03128.
文摘Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.
基金Supported by the Mexican Institute of Social Security,No.FFIS/IMSS/PROT/G16/1589National Council for Science and Technology(CONACYT),No.SALUD-2014-C01-233823.
文摘Minimal hepatic encephalopathy(MHE)corresponds to the earliest stage of hepatic encephalopathy(HE).MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests.MHE may affect daily activities and reduce job performance and quality of life.MHE can increase the risk of accidents and may develop into overt encephalopathy,worsening the prognosis of patients with liver cirrhosis.Despite a lack of consensus on the therapeutic indication,interest in finding novel strategies for prevention or reversion has led to numerous clinical trials;their results are the main objective of this review.Many studies address the treatment of MHE,which is mainly based on the strategies and previous management of overt HE.Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia,and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose,antibiotics such as rifaximin,and administration of different probiotics.This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.
文摘Minimal hepatic encephalopathy(MHE)is a critical neurocognitive complication of decompensated liver cirrhosis and portosystemic shunting,which results in a wide range of cognitive deficits including impairments in working attention,psychomotor speed,and executive function.Current guidelines have recommended paper-and-pencil psychometric tests for the diagnosis of MHE.Most high-risk cirrhotic patients are required to be examined;however,paperand-pencil psychometric tests are neither convenient nor rapid to perform in the clinic.Recently,novel computerized psychometric tests,including the inhibitory control test,EncephalApp Stroop App,and critical flicker frequency,have been proven to be rapid,effective,and convenient methods for screening MHE in clinical practice and for identifying high-risk cirrhotic patients for further validation using rigid neuropsychometric examinations.However,diagnostic accuracy of these tests is influenced by educational background,age,and cultural differences.This review summarizes clinical evidence of the application of novel computerized psychometric tests for screening MHE.
文摘Background and Aims: Psychometric hepatic encephalop-athy score(PHES)is used widely for diagnosis of minimal hepatic encephalopathy(MHE).This prospective study aimed to determine the utility of the inhibitory control test(ICT)for the diagnosis of MHE.Additionally,the efficacy of rifaximin and lactulose for reversal of MHE was evaluated.Methods:A total of 180 eligible cirrhotic patients underwent testing for MHE.When PHES was ≤ ?5 and ICT lures were ≥ 14,MHE was diagnosed.The 108 patients with MHE were randomized to three groups for treatment with either lactulose,rifaximin,or placebo.Treatment outcomes were measured at the end of 3 months.Results: The 108 patients with MHE diagnosed by PHES and/or ICT accounted for 60%.The diagnosis of MHE was made by both ICT and PHES positivity in 56 patients,by abnormal ICT and normal PHES in 37 patients,and by abnor-mal PHES and normal ICT in 15 patients.For diagnosis of MHE,ICT had sensitivity of 78.87%,specificity of 66.06%with 60.22%positive predictive value and 82.76%negative predictive value.An area under the curve value of 0.724(95%CI: 0.653–0.788)was obtained for diagnosis of MHE.Reversal of MHE was seen in 71.42%,70.27%and 11.11%of patients in the rifaximin,lactulose and placebo arms(p < 0.001).Rifaximin showed better tolerability compared to lactulose.Conclusions: For the diagnosis of MHE,ICT is a simple tool but has lower sensitivity and better specificity than PHES.Rifaximin is as efficacious as lactulose in the treat-ment of MHE and better tolerated.
基金The Innovation Groups of the National Natural Science Foundation of China,Grant/Award Number:81721002Capital Clinical Diagnosis and Treatment Technology Research and Transformation Application Project,Grant/Award Number:Z201100005520046+1 种基金Tianjin Key Medical Specialty Construction Project,Grant/Award Number:TJYXZDXK-034ATianjin Health Science and Technology Project,Grant/Award Number:TJWJ2022XK029。
文摘Aims:Minimal hepatic encephalopathy(MHE)significantly affects the prognosis of patients with cirrhosis.This study was performed to determine whether there is a difference in the prevalence of MHE among patients with cirrhosis of different etiologies and whether the etiology directly influences the occurrence of MHE.Methods:This multicenter,cross-sectional study enrolled 1879 patients with confirmed cirrhosis at 40 hospitals from October 25,2021,to January 10,2023(Trial registration:https://clinicaltrials.gov/[NCT05140837]).The patients'demographics,etiologies of cirrhosis,and laboratory test results were collected.The psychometric hepatic encephalopathy score(PHES)was determined in all patients to screen for MHE.Multivariate logistic analyses were performed to identify the risk factors for MHE.Results:In total,736 patients with cirrhosis were analyzed.The prevalence of MHE was 42.0%(n=309).The primary etiology among all patients was hepatitis B virus(HBV)-related cirrhosis(71.9%[529/736]).The prevalence of MHE was significantly higher in patients with alcoholic cirrhosis(57.1%[40/70])than in those with HBV-related cirrhosis(40.6%[215/529],p=0.009)or hepatitis C virus(HCV)-related cirrhosis(38.2%[26/68],p=0.026).Age(odds ratio[OR],1.042;95%confidence interval[CI],1.024-1.059;p<0.001),duration of education(OR,0.935;95%CI,0.899-0.971;p=0.001),etiology(OR,1.740;95%CI,1.028-2.945;p=0.039),and high MELD-Na scores(OR,1.038;95%CI,1.009-1.067;p=0.009)were independent risk factors for MHE.When patients with cirrhosis of different etiologies were analyzed separately,the results showed that age(OR,1.035;95%CI,1.014-1.057;p=0.001)and duration of education(OR,0.924;95%CI,0.883-0.966;p=0.001)were risk factors for MHE among patients with HBV-related cirrhosis,whereas age(OR,1.138;95%CI,1.033-1.254;p=0.009)and creatinine concentration(OR,16.487;95%CI,1.113-244.160;p=0.042)were risk factors for MHE in patients with HCV-related cirrhosis.No risk factors for MHE were found in patients with autoimmune cirrhosis.For patients with alcoholic cirrhosis,the platelet count(OR,1.014;95%CI,1.000-1.027;p=0.045)was a risk factor for MHE.The PHES subtest results were inconsistent among patients who had MHE with cirrhosis of different etiologies.Patients with HBV-related cirrhosis performed better on Number Connection Test B and the serial dotting test than those with alcoholic cirrhosis(p=0.007 and p<0.001),better on Number Connection Test B than those with HCV-related cirrhosis(p=0.020),and better on the line tracing test than those with autoimmune cirrhosis(p=0.037).Conclusion:The etiology of cirrhosis affected the prevalence of MHE and risk factors for MHE.The domains of major cognitive impairment varied among patients with cirrhosis of different etiologies.Further studies are required to verify these findings.
