Critical flicker frequency for diagnosis and assessment of recovery from minimal hepatic encephalopathy in patients with cirrhosis

BACKGROUND:Minimal hepatic encephalopathy (MHE) impairs quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients.Diagnosis of MHE requires cumbersome tests.Lactulose is effective in the treatment of MHE.This study aimed to evaluate the use of critical flicker frequency (CFF) for the diagnosis of MHE in cirrhotic patients after treatment.METHODS:One hundred and ten patients were evaluated by psychometry (number connection tests A,B or figure connection tests A,B),P300 auditory eve...     

Is it a medical error if we do not screen cirrhotic patients for minimal hepatic encephalopathy?

Minimal hepatic encephalopathy (MHE) refers to subtle neurocognitive and neurophysiological defects in patients with liver cirrhosis without clinical signs of hepatic encephalopathy. Using appropriate diagnostic methods the prevalence of MHE is approximately 25-30%. MHE has clinical significance as it results in a diminished daily functioning, precedes overt hepatic encephalopathy and is associated with a poor prognosis. Treatment with non-absorbable disaccharides can reverse the neurocognitive and neurophysiological defects found in MHE. The failure to diagnose MHE in apparently normal cirrhotic patients could, therefore, be considered a medical error. However, whether treatment also improves patients' quality of life and prognosis remains to be determined.     

Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy

BACKGROUND/AIMS: We assessed the usefulness of oral glutamine challenge (OGC) and minimal hepatic encephalopathy in evaluating risk of overt hepatic encephalopathy in cirrhotic patients.METHODS: Minimal hepatic encephalopathy (MHE) was inferred using neuro-psychological tests. Venous ammonia concentrations were measured pre- and post-60 min (NH(3)-60m) of a 10 g oral glutamine load. Receiver-operating-characteristic curve analysis indicated a pathological glutamine tolerance cut-off value of NH(3)-60m >128 microg/dl. RESULTS: In healthy control subjects (n=10) ammonia concentrations remained unchanged but increased significantly in cirrhotic patients (from 70.41+/-45.2 to 127.43+/-78.6; P<0.001). In multiple logistic regression analysis, altered OGC was related to Child-Pugh (odds ratio, OR=7.69; 95% confidence interval, CI=1.72-33.3; P<0.01) and MHE (OR=5.45; 95% CI=1.17-25.4; P<0.05). In the follow-up 11 patients (15%) developed overt hepatic encephalopathy (HE). In multivariate analysis OGC (OR=14.5; 95% CI=1.26-126.3) and MHE (OR=1.56; 95% CI=1.02-21.9) were independently related with HE in the follow-up. Patients with MHE and altered OGC showed significantly higher risk of overt HE in the follow-up (60%) than patients without MHE and normal OGC (2.8%) (Log rank test=21.60; P<0.0001). CONCLUSIONS: A pathological OGC in patients with MHE appears to be a prognostic factor for the development of overt hepatic encephalopathy, whereas a normal OGC in patients without MHE could exclude risk of overt HE.     

Altered Motor Cortex Excitability to Magnetic Stimulation in Alcohol Withdrawal Syndrome

Background: Alcohol addiction is a complex brain disease caused by alterations in crucial neurotransmitter systems, including gamma‐aminobutyric acid (GABA) and glutamate. These disturbances could be revealed by changes in cortical excitability parameters, as assessed by transcranial magnetic stimulation (TMS). This study was aimed to further investigate the complex pathophysiology of alcohol withdrawal syndrome (AWS). Methods: Motor cortex excitability was examined in 13 subjects with AWS in a mild predelirial state, in 12 chronic alcoholics and in 15 age‐matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, short latency intracortical inhibition (SICI), and intracortical facilitation (ICF) to paired TMS were examined. Results: Intracortical facilitation was significantly increased in the AWS patients when compared with the chronic alcoholics and the control subjects. The other TMS parameters did not differ significantly from the controls. Administration of a single oral dose of the glutamatergic antagonist riluzole in a subgroup of 8 patients significantly reduced ICF; motor threshold and SICI were not affected by riluzole. Conclusion: Transcranial magnetic stimulation shows a selective increase in intracortical facilitation after ethanol withdrawal. Our findings support the theory that altered glutamatergic receptor function plays an important role in the pathogenesis of human alcohol withdrawal. This study provides further physiological evidence that antiglutamatergic approaches represent an efficacious alternative for treating alcohol withdrawal symptoms.     

Minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is the mildest form of spectrum of hepatic encephalopathy (HE). Patients with MHE have no recognizable clinical symptoms of HE but have mild cognitive and psychomotor deficits. The prevalence of MHE is high in patients with cirrhosis of liver and varies between 30% and 84%; it is higher in patients with poor liver function. The diagnostic criteria for MHE have not been standardized but rest on careful patient history and physical examination, normal mental status examination, demonstration of abnormalities in cognition and/or neurophysiological function, and exclusion of concomitant neurological disorders. MHE is associated with impaired health-related quality of life, predicts the development of overt HE and is associated with poor survival. Hence, screening all patients with cirrhosis for MHE using psychometric tests, and treatment of those patients diagnosed to have MHE has been recommended. Ammonia plays a key role in the pathogenesis of MHE, which is thought to be similar to that of overt HE. Thus, ammonia-lowering agents such as lactulose and probiotics have been tried. These agents have been shown to improve cognitive and psychometric deficits, and have good safety profile. Future studies will better define the role of other drugs, such as rifaximin, acetyl L-carnitine and L-ornithine L-aspartate.     

Impairment of Response Inhibition Precedes Motor Alteration in the Early Stage of Liver Cirrhosis: A Behavioral and Electrophysiological Study

Abnormality in movement initiation may partially explain psychomotor delay of cirrhotic patients, even in the absence of overt hepatic encephalopathy (HE). Therefore, the aim of this study was to determine the mechanisms of psychomotor delay observed in patients with cirrhosis in the absence of overt HE. Fourteen patients with nonalcoholic cirrhosis and 12 healthy matched control subjects underwent the lateralized readiness potential (LRP) measurement elicited by a visuospatial compatibility task (Simon task). Stimulus-triggered LRPonset reflects the time in which response is selected, while response-triggered LRP onset reflects motor execution. Cirrhotic patients showed delayed reaction times (RTs) compared to controls, particularly those with trial-making test A (TMT-A) or electroencephalogram (EEG) alterations. Stimulus-triggered LRP onset was found to be delayedin cirrhotic patients compared to controls, with a significant Group-versus-Condition interaction, showing a reduced cognitive ability to cope with interfering codes, even in patients without minimal HE (MHE). Response-triggered LRP was found to be delayed only in the patients with TMT-A or EEG alterations. In conclusion, cirrhotic patients without overt HE display a psychomotor slowing, depending firstlyon response inhibition and only later accompanied by impaired motor execution.     

Minimal hepatic encephalopathy: Consensus statement of a working party of the Indian National Association for Study of the Liver

Hepatic encephalopathy (HE) is a major complication that develops in some form and at some stage in a majority of patients with liver cirrhosis. Overt HE occurs in approximately 30–45% of cirrhotic patients. Minimal HE (MHE), the mildest form of HE, is characterized by subtle motor and cognitive deficits and impairs health‐related quality of life. The Indian National Association for Study of the Liver (INASL) set up a Working Party on MHE in 2008 with a mandate to develop consensus guidelines on various aspects of MHE relevant to clinical practice. Questions related to the definition of MHE, its prevalence, diagnosis, clinical characteristics, pathogenesis, natural history and treatment were addressed by the members of the Working Party.     

Chinese guidelines on management of hepatic encephalopathy in cirrhosis

The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists' consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy(HE) including minimal hepatic encephalopathy(MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.     

Sarcopenia and cognitive impairment in liver cirrhosis: A viewpoint on the clinical impact of minimal hepatic encephalopathy

Minimal hepatic encephalopathy(MHE) represents the mildest type of hepatic encephalopathy(HE). MHE is considered as a preclinical stage of HE and is part of a wide spectrum of typical neurocognitive alterations characteristic of patients with liver cirrhosis, particularly involving the areas of attention, alertness,response inhibition, and executive functions. MHE can be detected by testing the patients' psychometric performance, attention, working memory, psychomotor speed, and visuospatial ability, as well as by means of electrophysiological and other functional brain measures. MHE is very frequent, affecting from 20% up to80% of patients tested, depending of the diagnostic tools used. Although subclinical, MHE is considered to be clinically relevant. In fact, MHE has been related to the patients' falls, fitness to drive, and working ability. As a consequence, MHE affects the patients and caregivers lives by altering their quality of life and even their socioeconomic status. Recently sarcopenia, a very common condition in patients with advanced liver disease, has been shown to be strictly related to both minimal and overt HE. Aim of this review is to summarize the most recently published evidences about the emerging relationship between sarcopenia and cognitive impairment in cirrhotic patients and provide suggestions for future research.     

Small intestinal bacterial overgrowth and delayed orocecal transit time in patients with cirrhosis and low-grade hepatic encephalopathy

Background

Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Gut-derived nitrogenous substances play a role in pathogenesis of HE. The present study was conducted to assess small intestinal bacterial overgrowth (SIBO) and prolonged orocecal transit time (OCTT) in cirrhosis and low-grade HE.

Methods

In cross-sectional prospective study, 75 patients were divided into 3 groups: group 1 (no HE, n = 31), group 2 (minimal HE, n = 29), and group 3 (early/grade 1 HE, n = 15). Minimal HE (MHE) was diagnosed when psychometric hepatic encephalopathy score (PHES) was ≤5. Early HE was diagnosed, according to West Haven criteria. All patients underwent glucose hydrogen breath test (GHBT) for SIBO and lactulose hydrogen breath test (LHBT) for OCTT.

Results

A total of 29 patients (38.67 %) had MHE and 15 (20 %) had early HE. Prevalence of MHE in Child–Turcotte–Pugh (CTP) class A, B, and C was 33.3, 38.71, and 45 %, respectively, while SIBO was detected in 26 (34.67 %). Prevalence of SIBO was 12.5 % in CTP class A, 41.94 % in CTP class B, and 50 % in CTP class C. Five (16.13 %) patients in no HE group had SIBO as compared to 14 (48.28 %) in MHE group and 7 (46.67 %) in early HE group (p = 0.018). OCTT was 111.13 ± 13.95 min in patients with no HE as compared to 137.59 ± 14.80 min in patients with MHE and 150 ± 15.12 min in patients with early HE (p < 0.001). OCTT was significantly prolonged in patients with SIBO (145 ± 17.49 min) than in those without SIBO (120.71 ± 18.3 min) (p < 0.001).

Conclusion

SIBO and delayed OCTT are more common with MHE and early HE in patients with cirrhosis.     

Risk factors for hepatic encephalopathy and mortality in cirrhosis: The role of cognitive impairment,muscle alterations and shunts

Introduction/AimMuscle alterations, portosystemic shunts (SPSS) and minimal hepatic encephalopathy (MHE) are related to hepatic encephalopathy (HE), however no studies have investigated the relative role of all these risk factors detected in the same patients. The aim of the study was to assess the prognostic impact of muscle alterations, MHE and SPSS on hepatic encephalopathy and transplant free survival.Patients/Methods114 cirrhotics were submitted to Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT) to detect MHE. CT scan was used to analyze the skeletal muscle index (SMI), muscle attenuation and SPSS. The incidence of the first episode of HE and survival were estimated.ResultsPrevious HE was present in 47 patients (41%). The variables independently associated to previous HE were: sarcopenia, MHE and SPSS. 44 patients (39%) developed overt HE during 14±11 months; MHE and SPSS were the only variables significantly asociated to overt HE. During the same follow-up, 42 patients died (37%); MELD and sarcopenia were the only variables significantly asociated to transplant free survival.ConclusionsMHE, sarcopenia and SPSS are clinically relevant and should be sought for in cirrhotics. In particular, MHE and SPSS are the only risk factors significantly associated to the development of HE while MELD and sarcopenia are independently associated to overall mortality.     

Quality of life in patients with minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) represents the mildest type of hepatic encephalopathy (HE). This condition alters the performance of psychometric tests by impairing attention, working memory, psychomotor speed, and visuospatial ability, as well as electrophysiological and other functional brain measures. MHE is a frequent complication of liver disease, affecting up to 80% of tested patients, depending of the diagnostic tools used for the diagnosis. MHE is related to falls, to an impairment in fitness to drive and the development of overt HE, MHE severely affects the lives of patients and caregivers by altering their quality of life (QoL) and their socioeconomic status. MHE is detected in clinically asymptomatic patients through appropriate psychometric tests and neurophysiological methods which highlight neuropsychological alterations such as video-spatial orientation deficits, attention disorders, memory, reaction times, electroencephalogram slowing, prolongation of latency evoked cognitive potentials and reduction in the critical flicker frequency. Several treatments have been proposed for MHE treatment such as non-absorbable disaccharides, poorly absorbable antibiotics such rifaximin, probiotics and branched chain amino acids. However, because of the multiple diagnosis methods, the various endpoints of treatment trials and the variety of agents used in trials, to date the treatment of MHE is not routinely recommended apart from on a case-by-case basis. Aim of this review is analyze the burden of MHE on QoL of patients and provide a brief summary of therapeutic approaches.     

Default Mode Network Functional Connectivity: A Promising Biomarker for Diagnosing Minimal Hepatic Encephalopathy: CONSORT-Compliant Article

To investigate the contribution of brain default mode network (DMN) in the early diagnosis of the minimal hepatic encephalopathy (MHE), the mildest form of HE from cirrhotic patients by using resting-state functional magnetic resonance imaging (rs-fMRI).This study was approved by the local ethical committee, and a written informed consent was obtained from each participant. A total of 103 cirrhotic patients (34 MHE, 69 non-HE) and 103 matched healthy controls underwent rs-fMRI scanning. The DMN correlation map was acquired by using unbiased seed-based functional connectivity analysis and compared among MHE patients, non-HE patients, and healthy controls with analysis of variance tests. Pearson correlation analysis was performed between the abnormal DMN connectivity and neuropsychological performances. Receiver operator characteristic (ROC) analysis was used to evaluate the contribution of DMN connectivity strength in the differential diagnosis between MHE and non-HE.Compared with the healthy controls, MHE and non-HE patients showed decreased DMN connectivity in medial prefrontal cortex (MPFC), left superior frontal gyrus (SFG), left temporal lobe, and bilateral middle temporal gyri (MTG). The MHE patients showed even more decreased connectivity in MPFC, left SFG, and right MTG when compared with non-HE patients. Pearson correlation analyses revealed that the decreased connectivity strength of some DMN regions correlated with patients’ neuropsychological tests scores. Connectivity strength of the MPFC, right MTG, and left SFG could differentiate MHE from non-HE, of which the MPFC had the highest effectiveness (sensitivity = 81.5%, specificity = 70.4%).Cirrhotic patients had gradually reduced DMN functional connectivty from non-HE patients to MHE patients. DMN function, especially the MPFC, might be a useful imaging marker for differentiating MHE from cirrhotic patients.     

Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China

AIM:To construct normal values for the tests of the psychometric hepatic encephalopathy score(PHES)and to evaluate its usefulness in the diagnosis of minimal hepatic encephalopathy(MHE)among Chinese individuals with cirrhosis.METHODS:The five tests of PHES,number connection test-A(NCT-A),number connection test-B,serial dotting test,line tracing test and digit symbol test(DST),were administered to all enrolled subjects in a quiet room with sufficient light.Cirrhotic subjects with overt HE were excluded by the West-Haven criteria and a detailed neurological examination.Based on the nomograms of healthy volunteers,the patients were classified as having MHE when their PHES was less than-4.RESULTS:In total,146 healthy volunteers completed all the PHES tests.Age and education years were confirmed to be predictors of all five tests.In total,53patients with liver cirrhosis completed the PHES.Of the patients with liver cirrhosis,24(45.3%),22(41.5%)and 7(13.2%)had Child-Pugh grades A,B and C,respectively.MHE was diagnosed in 26 patients(49.1%).Compared with compensated cirrhotic patients(Child A),decompensated cirrhotic patients(Child B and C)had a higher proportion of MHE(65.5%vs 29.2%).No differences in age and education years were found between the MHE and non-MHE groups.NCT-A and DST were able to diagnose MHE with a sensitivity of 76.9%and a specificity of 96.3%(AUC=0.866,K=0.735).CONCLUSION:The proportion of MHE is associated with liver function.NCT-A and DST are simple tools that can be used for the diagnosis of MHE in China.     

Intestinal glutaminase activity is increased in liver cirrhosis and correlates with minimal hepatic encephalopathy

BACKGROUND/AIMS: We performed the current study to assess the intestinal activity of enterocyte phosphate-activated glutaminase (PAG) in cirrhosis. METHODS: Forty-nine cirrhotic patients and 36 control subjects underwent endoscopic duodenal biopsies. Minimal hepatic encephalopathy (MHE) was evaluated using three psychometric tests. Oral glutamine challenge (OGC) was performed and MELD, Child-Pugh and the presence of esophageal varices were recorded. PAG was measured by enzymatic methods. Cerebral magnetic resonance spectroscopy was performed in 10 cirrhotics. RESULTS: PAG was found to be higher in cirrhotics than control subjects 2.4+/-1.51 vs. 0.68+/-0.57IU/mg protein (P<0.001). PAG was also increased in patients with MHE and correlated with MELD, INR, esophageal varices and serum bile acids. A negative correlation was observed between PAG activity and intra-cerebral choline/creatine ratio (r=-0.67; P=0.035) and a positive correlation with glutamine plus glutamate/creatine ratio (r=0.78; P=0.007). In multivariate analysis using backward logistic regression, presence of MHE was the only variable independently related to altered enterocyte PAG. CONCLUSIONS: Enterocyte PAG is increased in cirrhotic patients and correlates with MHE. These data support a possible role for intestinal glutaminase in the pathogenesis of hepatic encephalopathy (HE) and could be a new target for future therapies.     

小肠细菌过度生长相关性轻微肝性脑病患者的血浆内毒素水平

目的观察肝硬化患者小肠细菌过度生长相关性轻微肝性脑病患者的内毒素水平,探讨内毒素与轻微肝性脑病的关系。方法对90例肝硬化患者及20例健康志愿者进行内毒素水平、葡萄糖氢呼气试验（GHBT）、数字连接试验（NCT—A和NCT—BC）和数字符号试验（DST）检测,观察小肠细菌过度乍长相关性轻微肝性脑病患者的内毒素水平变化。结果肝硬化组小肠细菌过度生长（36．7％,33／90）明显高于健康对照组（5％,1／20）。20名健康志愿者未检出轻微肝性脑病（MHE）;90例肝硬化患者轻微肝性脑病37例（41．1％）,其中伴小肠细菌过度生长肝硬化患者轻微肝性脑病发生率高于不伴小肠细菌过度生长患者。肝硬化组内毒素水平（69．6±21．3）pg／mL高于健康对照组（18．7±8．6）pg／mL;肝硬化小肠细菌过度生长组内毒素水平（89．5±17．6）pg／mL高于无小肠细菌过度生长组（57．3±15．8）pg／mL（P〈0．05）。应用抗生素抑制小肠细菌过度生长及乳果糖治疗1周后GHBT、内毒素水平、NCT—A、NCT-BC及DST检查结果改善。结论内毒素与伴小肠细菌过度生长的轻微肝性脑病的发生及进展可能有一定的关系。     

轻微肝性脑病患病情况调查及相关危险因素分析

目的本研究应用简易智能量表(MMSE)及数字连接试验-A(NCT-A)筛查住院肝硬化患者轻微肝性脑病(MHE)的患病情况,同时进行营养风险筛查2002(NRS 2002)筛查工作,纳入MHE危险因素分析。方法连续调查239例肝硬化患者,对91例符合入选标准的患者进行MMSE、NCT-A检测,并进行NRS 2002筛查。排除显性肝性脑病(OHE)后,如MMSE或NCT-A任何一项检测阳性或两项均阳性,则诊断为MHE。NRS 2002≥3分,判定为存在营养风险。结果检测91例肝硬化患者,排除显性肝性脑病12例,余79例中,NCT-A阳性31例(39.2%),MMSE阳性6例(7.6%),两者均阳性2例(2.5%),诊断MHE 35例(44.3%)。肝功能Child B/C组MHE患者明显多于Child A组(P=0.023),与<50岁(13/46)的肝硬化患者相比,≥50岁(22/33)的MHE更多见(P=0.001)。未发现营养风险等因素对MHE有影响(P>0.05)。结论住院肝硬化患者中存在相当高比例的MHE(44.3%),NCT-A检测MHE敏感性明显高于MMSE,但MMSE有利于发现早期OHE。住院肝硬化患者年龄越大、肝功能Child分级越差,MHE越多。     

Serotonin Brain Circuits with a Focus on Hepatic Encephalopathy

Despite enormous strides in our understanding of human disease, the precise mechanisms of hepatic encephalopathy (HE), a potential long-term complication of liver failure, are still unclear. Brain serotonin, a neurotransmitter with widespread distribution in the CNS, plays a role in the regulation of a wide range of physiological behaviors and functions. In addition, it has been implicated in the pathogenesis of several pathological processes, including HE. This work reviews the relationship between brain serotonergic dysfunction and hepatic encephalopathy in cirrhotic patients and experimental animals. The existing changes in the synthesis, metabolism, storage, and release of neuronal serotonin in HE point to a serotonergic synaptic deficit in this condition. Given the established role of the brain serotonergic system in the regulation of sleep, circadian rhythmicity, and locomotion, selective alterations of this system could be an important part of the neurophysiological background responsible for the behavioral changes in rats with portacaval anastomosis and may contribute to the pathogenesis of HE in cirrhotic patients. The findings that serotoninergic turnover is exquisitely and selectively sensitive to the degree of porto-systemic shunting and hyperammonemia suggest a role for serotonin in early neuropsychiatric symptoms of HE. Pharmacological manipulation of the brain serotonergic system may be beneficial in the prevention and treatment of HE in cirrhotic patients.     

Memory function in early hepatic encephalopathy

BACKGROUND: Early hepatic encephalopathy (HE) is characterized by deficits in motor performance, visual perception, visuo-constructive abilities and attention. Whether defective memory is a feature of early HE is controversial. AIMS: To analyze memory function in patients with early HE. METHODS: Memory tests were applied to cirrhotic patients with grade 0 HE, minimal HE and grade I HE (n=45) and controls (n=52). The battery included short and long term memory tests requiring free recall or recognition. Minimal HE was diagnosed by assessing the psychometric hepatic encephalopathy score using the PSE-Syndrom-Test and by carrying out a neurological examination. Group differences of the test results were analyzed using analysis of covariance. RESULTS: HE 0 patients achieved test results similar to the controls in all but two tests. Patients with early HE (minimal and grade I HE) scored lower than the controls in all tests applied. A detailed analysis of test performance showed that the patients' deficits were in attention and visual perception, rather than memory. CONCLUSIONS: Patients with early HE score lower than controls in memory tasks predominantly because of deficits in attention and visual perception.     

Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity

It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n?=?16; without MHE [NHE], n?=?20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients.