Nutritional assessment in cirrhotic patients with hepatic encephalopathy

Hepatic encephalopathy(HE) is one of the worst complications of liver disease and can be greatly influenced by nutritional status. Ammonia metabolism, inflammation and muscle wasting are relevant processes in HE pathophysiology. Malnutrition worsens the prognosis in HE, requiring early assessment of nutritional status of these patients. Body composition changes induced by liver disease and limitations superimposed by HE hamper the proper accomplishment of exams in this population, but evidence is growing that assessment of muscle mass and muscle function is mandatory due to the role of skeletal muscles in ammonia metabolism. In this review, we present the pathophysiological aspects involved in HE to support further discussion about advantages and drawbacks of some methods for evaluating the nutritional status of cirrhotic patients with HE, focusing on body composition.     

Rifaximin for the treatment of hepatic encephalopathy

Hepatic encephalopathy (HE) is a complication of cirrhosis, the severity of which can range from subtle, neurocognitive dysfunction (minimal HE) to more apparent and severe cognitive and motor manifestations with increasing grades of the condition (overt HE). Current treatment options are targeted at reducing the levels of ammonia and other gut-derived toxins, the purported culprits behind the pathogenesis of HE. One of these therapeutic options, the nonsystemic antibiotic rifaximin, is efficacious for the treatment of minimal and overt HE. However, HE may be a cyclic condition in which patients with overt HE enter remission following treatment and then relapse. Thus, safe, effective and well-tolerated treatments are needed to maintain HE remission. Rifaximin maintained HE remission more effectively than placebo in a large, randomized controlled trial. Rifaximin is safe and well-tolerated for the treatment of minimal and overt HE and for the maintenance of HE remission.     

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.     

Improvement of hepatic encephalopathy using a modified high-calorie high-protein diet

BACKGROUND AND AIM: Protein-calorie malnutrition (PCM) occurs in 20-60% of patients with hepatic cirrhosis and is associated with the development of life-threatening complications. We evaluated the effect of a modified, casein-vegetable-based, high-protein high-calorie (HPHC) diet on the outcome of cirrhotic patients with hepatic encephalopathy (HE). METHODS: One hundred and fifty three consecutive cirrhotic patients with overt HE were included in this study. An HPHC diet based on better-tolerated vegetable and milk-derived proteins was initiated in order to ensure the adequate protein-energy requirements of 30 kcal/kg/day and 1.2g proteins/kg/day. Serial (daily) assessments were done, including mental status, asterixis, a conventional Number Connection Test (NCT), bowel movements and blood ammonia level. The assessment of the mental status was performed using the West Haven scale. Favorable evolution or response to HPHC diet was defined as an improvement in HE stage with 1 or more (Delta > or =1 stage) after 14 days of diet. RESULTS: During the HPHC diet, 122 patients (79.7%) improved in terms of response definition. A significant decrease in blood ammonia level was observed after 14 days (p<0.0001) in all patients, whatever the improvement of the mental status. A significant improvement in the NCT scores was also noted (p<0.0001). More patients with advanced HE (West Haven stage 3) precipitated by various factors showed a Delta = -2 improvement of their mental status during the modified HPHC diet compared with patients in lower initial stages (50% vs 18.9%, p=0.002). More patients in Child-Pugh B class had a Delta = -2 decrease in the grade of HE compared with patients in Child-Pugh C class (61.7% vs. 14%, p=0.001). CONCLUSIONS: Almost 80% of patients in our study improved their mental status during the casein-vegetable-based HPHC diet, showing that dietary protein restriction is not required for the improvement of HE. A higher rate of improvement was noted in patients with severe impairment of mental status related to precipitating factors and in patients with well preserved liver function. The daily eating pattern consisting of 4 snack-meals and a late evening meal may contribute to HE improvement by equal protein distribution during the day.     

L-Carnitine in the treatment of mild or moderate hepatic encephalopathy

Hepatic encephalopathy (HE) is one of the major complications of cirrhosis. Experimental and clinical findings observed in liver, muscle and brain have provided new insights into the ammonia mechanism of action. L-Carnitine (LC), inducing ureagenesis, may decrease blood and brain ammonia levels. 120 patients meeting inclusion criteria were randomized either to a treatment for 60 days with LC or placebo (2 g twice a day). Previous studies have reported a significant protective effect of LC in mice and rats, which is associated with a significant reduction of blood and brain ammonia concentration, suggesting an action of LC either at peripheral or central sites. Results of our study show a protective effect of LC in ammonia-precipitated encephalopathy in cirrhotic patients. Either in subjects with HE 1 or 2 we observed a significant reduction at day 30 and more markedly at day 60 of treatment. A significant therapeutic effect of LC was also observed in the NCT-A, which is an accepted and reliable psychometric test for the assessment of mental function in cirrhotic patients with HE.     

Minimal hepatic encephalopathy: time to recognise and treat

Minimal hepatic encephalopathy represents a part of the spectrum of hepatic encephalopathy and is the mildest form. While patients with hepatic encephalopathy have impaired intellectual functioning, personality changes, altered levels of consciousness, and neuromuscular dysfunction, patients with minimal hepatic encephalopathy have no recognisable clinical symptoms of hepatic encephalopathy but have mild cognitive and psychomotor deficits. The prevalence of minimal hepatic encephalopathy has been reported to vary between 30% and 84% in patients with liver cirrhosis and is higher in patients with poor liver function. The diagnosis is usually made by neuropsychological and/or neurophysiological testing in cirrhotic patients who are otherwise normal on neurological examination. Minimal hepatic encephalopathy is a clinically significant disorder that impairs the health-related quality of life, predicts the development of overt encephalopathy and is probably associated with a poor prognosis. Thus screening all patients with cirrhosis for minimal hepatic encephalopathy using psychometric testing is recommended. Pharmacologic therapy is recommended for patients diagnosed with minimal hepatic encephalopathy. The pathogenesis of minimal hepatic encephalopathy is considered similar to that of overt hepatic encephalopathy and ammonia plays a key role. Thus ammonia lowering agents such as lactulose, L-ornithine and L-aspartate that have good safety profiles are recommended. Future studies will better define the role of probiotics, levocarnitine and sodium benzoate.     

Does malnutrition affect survival in cirrhosis?

A total of 1,053 cirrhotic patients were included in a prospective study to determine whether malnutrition is a risk factor for mortality in cirrhotic patients. Child-Pugh classification as well as clinical and biochemical variables were used to assess the severity of cirrhosis. Nutritional status was evaluated both by anthropometric and clinical measurements. Patients were defined as malnourished when midarm muscle area (MAMA) and/or midarm fat area (MAFA) were below the 5th percentile of an age- and sex-matched population. During follow-up, 419 patients died. The estimated survival rate was 82.7% at 1 year, 65.1% at 3 years, and 50.7% at 5 years. The presence of muscle depletion and/or of a steep reduction in fat deposits was associated with a higher risk of mortality (midarm muscle area, < 5th percentile, relative risk = 1.79; midarm fat area, < 5th percentile, relative risk = 1.35). When patients were stratified according to the Child-Pugh classification, cumulative survival was lower in patients with a reduction in muscle mass in Child-Pugh classes A and B (log rank: P = .027; P = .022, respectively) but not in class C. Conversely, a significant reduction in adipose tissue deposits appeared to have no independent impact on survival in any Child-Pugh class. When examined using a multivariate Cox proportional hazard analysis, age, sex, bilirubin, cholinesterase, ascites, and esophageal varices were selected, whereas the parameters of nutritional status were not. This suggests that malnutrition, while strongly associated with the deterioration of liver function, cannot be considered an independent risk factor for mortality in a general population of cirrhotic patients. (Hepatology 1996 May;23(5):1041-6)     

幽门螺杆菌感染对高氨血症和肝性脑病发病的影响

目的了解幽门螺杆菌(Hp)感染和血氨水平、肝性脑病(HE)发病的关系,并探讨根除Hp对血氨水平和HE发生的影响。方法2003年7月-2005年1月在浙江省5个地区收集肝硬化住院患者,记录患者的一般资料、数字连接试验结果、Hp感染情况、肝功能Child-Pugh分级、血氨水平和HE情况。Hp(+)患者予“奥美拉唑+克拉霉素+替硝唑”1周根除治疗,1个月后查~(14)C尿素呼气试验,并记录患者的神经精神症状和血氨水平。结果(1)共收集肝硬化住院患者457例,Hp感染率60．6%,HE发生率47．5%。检出亚临床肝性脑病(SHE)患者55例,SHE占未发生HE肝硬化患者的47．0%(55/117)。(2)Hp(+)和Hp(-)肝硬化患者血氨浓度分别为(78．4±63．6)μmoL/L和(53．8±51．4)μmol/L(P＜0．01);根除Hp后血氨显著下降至(53．5±37．7)μmol/L(P＜0．01)。Hp(+)和Hp(-)肝硬化患者HE发生率差异有统计学意义(58．5%比30．6%,P＜0．01);根除Hp后HE发生率下降至34．1%(P＜0．01)。(3)HE、SHE和肝硬化患者的Hp感染率分别为74．4%、69．1%和53．2%(P＜0．05)。三组患者的血氨水平分别为(94．5±75．6)μmol/L、(59．9±49．2)μmol/L和(47．3±33．5)μmol/L(P＜0．05)。结论Hp感染是引起肝硬化高氨血症和并发HE的重要因素,根除Hp有利于治疗和预防HE的发生。     

Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients

AIM: To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of H pylori eradication in cirrhotic patients.METHODS: From July 2003 to January 2005, 457 cirrhotic patients in five regions of Zhejiang Province were enrolled. Patients were evaluated for demographics, number connection test, H pylori infection, liver impairment, blood ammonia concentration and HE. Patients with H pylori infection were given 1 wk therapy with omeprazole plus clarithromycin and tinidazole. 14C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after bacterium eradication.RESULTS: Overall H pylori infection rate was 60.6%, and HE occurred in 47.5% of cirrhotic patients. Subclinical HE (SHE) was detected in 55 of 117 cirrhotic patients. Blood ammonia concentration in H pylori negative (n = 180) and positive (n = 277) cirrhotic patients was 53.8 ± 51.4 and 78.4 ± 63.6 nmol/L, respectively (P < 0.01), which was significantly reduced to 53.5 ± 37.7 nmol/L after bacterium eradication (n = 126) (P < 0.01). Blood ammonia was 97.5 ± 81.0 nmol/L in H py/ori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after H pylori eradication (n = 11). HE was more frequently observed in patients with H pylori infection than in those without (58.5% vs 30.6%, P < 0.01). HE rate significantly dropped to 34.1% after H pylori eradiation (P < 0.01). H pylori prevalence significantly differed among cirrhotic patients with HE (74.4%), SHE (69.1%), and those without HE (53.2%) (P < 0.05). Blood ammonia level was significantly different among cirrhotic patients with HE (94.5 ± 75.6 nmol/L), SHE (59.9 ± 49.2 nmol/L), and without HE (47.3 ± 33.5 nmol/L) (P < 0.05). Logistic regression analysis showed that blood ammonia concentration, Child-Pugh stage, upper gastrointestinal bleeding, electrolyte disturbance, and urea nitrogen were risk factors for HE.CONCLUSION: H pylori infection is an important factor for inducing high blood ammonia concentration and HE in cirrhotic patients. H pylori eradication may be helpful for treatment and prevention of HE.     

Nutritional risk and malnutrition determination by anthropometry in cirrhotic children and adolescents

BACKGROUND: The malnutrition is a frequent finding in adults with cirrhosis, but the prevalence of nutritional risk and malnutrition is little known in pediatric patients. AIM: To evaluate through anthropometry the presence of nutritional risk and malnutrition in cirrhotic pediatric patients regularly attended at the Pediatric Gastroenterology Service of "Hospital de Clínicas" of Porto Alegre, RS, Brazil. METHODS: Cross-sectional study with 42 cirrhotic children and adolescents aged between 3 months and 18 years. The nutritional evaluation was made by the determination of the weight/age, height/age, body mass index and triceps skinfold thickness and arm muscle circumference measurements. Patients considered in nutritional risk were < or = -1,28 Z score which corresponds to < or = 10th percentile, and those under -2,0 Z and < or = 3th percentile were in malnutrition status. According to Child-Pugh criteria, 22 patients were classified as A (mild severity), 15 (moderate) B and 5 C (intense). RESULTS: The mean weight/age, height/age and body mass index Z scores were, respectively, - 0,38 +/- 1,4 SD, - 0,83 +/- 1,16 SD and 0,17 +/- 1,3 SD. Patients in nutritional risk were 3/42 (weight/age), 8/42 (height/age), 12/37 (triceps skinfold thickness), 9/37 (arm muscle circumference), 2/38 (body mass index); in malnutrition status were 6/42 (weight/age), 7/42 (height/age), 4/37 (triceps skinfold thickness) and 4/37 (arm muscle circumference) and 3/38 (body mass index). CONCLUSION: The prevalence of nutritional risk was 32.4% and chronic malnutrition was 16.7%. The index which better reflected the nutritional risk in these patients was triceps skinfold thickness. Chronic malnutrition status occurrence was greater in the height/age index.     

Neurological and neuropsychiatric syndromes associated with liver disease

The clinical presentation of acute liver failure and hepatic encephalopathy (HE) in patients with cirrhosis differs significantly. The most serious neurological complication of acute liver failure is the development of devastating brain oedema. Therefore, intracranial pressure monitoring is urgently needed in these patients. Brain oedema is amplified by hypoglycemia, hypoxia and seizures, which are also frequent complications of acute liver failure. Therefore, these parameters must also be monitored. In contrast to acute liver failure in which cerebral dysfunction progresses rapidly, cognitive decline may be clinically undetectable for a long time in cirrhotic patients, until clinically overt symptoms such as psychomotor slowing, disorientation, confusion, extrapyramidal and cerebellar symptoms or a decrease in consciousness occur. Clinically, overt HE is preceded by minimal alterations of cerebral function that can only be detected by neuropsychological or neurophysiological measures, but which nevertheless interfere with the patient's daily living. Rapidly progressing spastic paraparesis (hepatic myelopathy) is a rare complication of cirrhosis. In contrast to HE, it does not respond to blood ammonia lowering therapies but must be considered as an indication for urgent liver transplantation. Cognitive dysfunction has recently been detected in hepatitis C virus (HCV)-infected patients with normal liver function. The patients presented with severe fatigue, cognitive dysfunction and mood disorders. Alterations in brain metabolites, as detected by magnetic resonance spectroscopy, indicated central nervous system alteration in these patients. In contrast to patients with HE, HCV-infected patients did not show motor symptoms or deficits in visual perception, but considerable deficits in attention and concentration ability.     

Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients

AIM： To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy （HE）, and the effect of Hpylori eradication in cirrhotic patients. METHODS： From July 2003 to January 2005, 457 cirrhotic patients in five regions of Zhejiang Province were enrolled. Patients were evaluated for demographics, number connection test, Hpylori infection, liver impairment, blood ammonia concentration and HE. Patients with Hpylori infection were given I wk therapy with omeprazole plus clarithromycin and tinidazole. ^14C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after RESULTS： Overall H pylori infection rate was 60.6%, and HE occurred in 47.5% of cirrhotic patients. Subclinical HE （SHE） was detected in 55 of 117 cirrhotic patients. Blood ammonia concentration in H pylori negative （n = 180） and positive （n = 277） cirrhotic patients was 53.8 ± 51.4 and 78.4 ± 63.6 μmol/L, respectively （P 〈 0.01）, which was significantly reduced to 53.5 ± 37.7 μmol/L after bacterium eradication （n = 126） （P 〈 0.01）. Blood ammonia was 97.5 ± 81.0 μmol/L in H pylori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after Hpylori eradication （n = 11）. HE was more frequently observed in patients with H pylori infection than in those without （58.5% vs 30.6%, P 〈 0.01）. HE rate significantly dropped to 34.1% after H pylori eradiation （P 〈 0.01）. H pylori prevalence significantly differed among cirrhotic patients with HE （74.4%）, SHE （69.1%）, and those without HE （53.2%） （P 〈 0.05）. Blood ammonia level was significantly different among cirrhotic patients with HE （94.5 ± 75.6 μmol/L）, SHE （59.9 ± 49.2 μmol/L）, and without HE （47.3 ± 33.5 μmol/L） （P 〈 0.05）. Logistic regression analysis showed that blood ammonia concentration, Child-Pugh stage, upper gastrointestinal bleeding, electrolyte disturbance, and urea nit     

Branched-chain amino acids and muscle ammonia detoxification in cirrhosis

Branched-chain amino acids (BCAA) are used as a therapeutic nutritional supplement in patients with cirrhosis and hepatic encephalopathy (HE). During liver disease, the decreased capacity for urea synthesis and porto-systemic shunting reduce the hepatic clearance of ammonia and skeletal muscle may become the main alternative organ for ammonia detoxification. We here summarize current knowledge of muscle BCAA and ammonia metabolism with a focus on liver cirrhosis and HE. Plasma levels of BCAA are lower and muscle uptake of BCAA seems to be higher in patients with cirrhosis and hyperammonemia. BCAA metabolism may improve muscle net ammonia removal by supplying carbon skeletons for formation of alfa-ketoglutarate that combines with two ammonia molecules to become glutamine. An oral dose of BCAA enhances muscle ammonia metabolism but also transiently increases the arterial ammonia concentration, likely due to extramuscular metabolism of glutamine. We, therefore, speculate that the beneficial effect of long term intake of BCAA on HE demonstrated in clinical studies may be related to an improved muscle mass and nutritional status rather than to an ammonia lowering effect of BCAA themselves.     

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.     

Blood methanethiol in alcoholic liver disease with and without hepatic encephalopathy.

Blood methanethiol and ammonia concentrations were measured in 16 healty volunteers, 52 consecutive alcoholic cirrhotics without overt hepatic encephalopathy (HE), and 42 consecutive patients with alcoholic liver disease and overt HE. The mean concentration of blood methanethiol was significantly greater than normal in the cirrhotics without overt HE, and the means of both methanethiol and ammonia were significantly greater in the patients with than in those without overt HE. Only one patient with overt HE had both normal ammonia and methanethiol blood concentrations. Twenty of the patients with HE were followed serially. The directions of change in methanethiol and ammonia were consistent with the direction of change in mental status in 85% adn 60% respectively. All of the patients who deteriorated and died had changes in blood methanethiol that correlated with the change in mental status. We conclude that blood methanethiol is a valuable adjunct to the ammonia determination in the evaluation of the patient with possible HE. It is especially helpful in following the course of a patient with hepatic encephalopathy, both as to prognosis and as an indicator of response to therapy.     

Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients

BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy. The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE). Well established triggers for HE include infection, gastrointestinal bleeding, constipation, and medications. Alterations to the gut microbiome is one of the leading ammonia producers in the body, and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center, retrospective analysis. Patients were included in the study with an admitting diagnosis of HE. The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria. The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course. Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo, mean ammonia level, and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P = 0.001). The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P =0.046). Twenty-seven(31.8%) patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P = 0.138). Finally, 10(11.8%) patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P = 0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.     

Lower values of handgrip strength and adductor pollicis muscle thickness are associated with hepatic encephalopathy manifestations in cirrhotic patients

Hepatic encephalopathy (HE) is a late complication of liver cirrhosis and is clearly associated with poor outcomes. Chronic liver insufficiency leads to progressive muscle wasting, impairing ammonia metabolism and thus increasing the risk for HE. Given the association between lean mass and adductor pollicis muscle thickness (APMT), it has been used to predict outcome and complications in many conditions, but not yet in cirrhotic patients. Therefore, this article aimed to study the association between HE manifestations and measures related to muscle mass and strength. This cross-sectional study included 54 cirrhotic outpatients with HE varying from subclinical to grade II according to the West-Haven criteria, who were submitted to neuropsychometric tests, electroencephalogram, brain Single Photon Emission Computed Tomography (SPECT), anthropometric measurements, handgrip strength (HGS) and dual energy X-ray absorptiometry exam (DXA). Multiple logistic regression analysis was performed to investigate the association between body composition measures and HE grade. Analysis of the area under the receiver operator characteristic (AUROC) curve revealed the values related to neurological manifestations (HE grades I and II). Reductions in APMT and HGS were associated with higher HE grades, suggesting a big impact caused by the loss of muscle mass and function on HE severity. The link between HE manifestations and anthropometric measures, namely APMT and HGS, point to a significant relation concerning skeletal muscles and the neurological impairment in this population.     

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.     

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。     

Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis

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.