Development Of Overt Hepatic Encephalopathy Research Articles

Diagnosis of Minimal Hepatic Encephalopathy Using Stroop EncephalApp: A Multicenter US-Based, Norm-Based Study.

Diagnosing minimal hepatic encephalopathy (MHE) is challenging, and point-of-care tests are needed. Stroop EncephalApp has been validated for MHE diagnosis in single-center studies. The objective of the study was to validate EncephalApp for MHE diagnosis in a multicenter study. Outpatient cirrhotics (with/without prior overt hepatic encephalopathy (OHE)) and controls from three sites (Virginia (VA), Ohio (OH), and Arkansas (AR)) underwent EncephalApp and two gold standards, psychometric hepatic encephalopathy score (PHES) and inhibitory control test (ICT). Age-/gender-/education-adjusted values for EncephalApp based on direct norms, and based on ICT and PHES, were defined. Patients were followed, and EncephalApp cutoff points were used to determine OHE prediction. These cutoff points were then used in a separate VA-based validation cohort. A total of 437 cirrhotics (230 VA, 107 OH, 100 AR, 36% OHE, model for end-stage liver disease (MELD) score 11) and 308 controls (103 VA, 100 OH, 105 AR) were included. Using adjusted variables, MHE was present using EncephalApp based on norms in 51%, EncephalApp based on PHES in 37% (sensitivity 80%), and EncephalApp based on ICT in 54% of patients (sensitivity 70%). There was modest/good agreement between sites on EncephalApp MHE diagnosis using the three methods. OHE developed in 13% of patients, which was predicted by EncephalApp independent of the MELD score. In the validation cohort of 121 VA cirrhotics, EncephalApp directly and based on gold standards remained consistent for MHE diagnosis with >70% sensitivity. In this multicenter study, EncephalApp, using adjusted population norms or in the context of existing gold standard tests, had good sensitivity for MHE diagnosis and predictive capability for OHE development.

Differences in cognitive function between patients with viral and alcoholic compensated liver cirrhosis.

As alcohol induces change in frontal cortex primarily involved in cognition, cognitive function may be different between viral and alcoholic liver cirrhosis (LC). This study aimed to determine the differences of cognitive function between viral and alcoholic compensated LC. From October 2011 to March 2013, 80 patients (viral: 37; alcohol: 43) with compensated LC were prospectively enrolled. Neuropsychological functions including attention, language, visuospatial, verbal memory, visual memory, and frontal/executive function were evaluated between two groups and compared with age-matched normal group (n = 1000). Cumulative incidence rate of overt hepatic encephalopathy (HE) was calculated. In the comparison with normal group, both two groups showed decreased memory function, frontal/executive function, and Korea-Mini Mental Status Examination. In the analysis of two groups, memory function by Verbal Learning Test (recognition: 20.1 ± 3.6 and 17.8 ± 4.8, p = 0.022), visuospatial function by Ray-Complex Figure Copy Test (recognition: 19.0 ± 2.6 and 17.3 ± 4.0, p = 0.043), frontal/executive function by Controlled Oral Ward Association (semantic: 17.1 ± 6.9 and 12.7 ± 6.9, p = 0.004), and the Korea-Mini Mental Status Examination (27.5 ± 1.9 and 26.2 ± 3.1, p = 0.03) showed low scores in alcoholic compensated LC patients. The 1-, 2-, and 3-year cumulative incidence rates of overt HE were 23%, 26%, and 26% and 33%, 43%, and 49% in the viral and alcoholic compensated LC group, respectively (p = 0.033). Impaired memory and frontal lobe executive functions and early development of overt HE were more common in patients with alcoholic LC. For patients with alcoholic LC, more integrated tests for early detection of minimal HE and intensive treatment should be considered to prevent overt HE.

P0126 : The stroop App can predict the development of overt hepatic encephalopathy in a multi-center study

P0126 : The stroop App can predict the development of overt hepatic encephalopathy in a multi-center study

A Model for Predicting Development of Overt Hepatic Encephalopathy in Patients With Cirrhosis

Overt hepatic encephalopathy (HE) affects patients' quantity and quality of life and places a burden on families. There is evidence that overt HE might be prevented pharmacologically, but prophylaxis would be justified and cost effective only for patients at risk. We aimed to identify patients with cirrhosis at risk for overt HE. We collected data from October 2009 through December 2012 for 216 consecutive patients with cirrhosis (based on liver biopsy, 96 patients with minimal HE), admitted to the Gastroenterology Unit at the University of Rome. Patients were followed up and evaluated for an average of 14.7 ± 11.6 months; development of overt HE was recorded. We analyzed end-stage liver disease scores, shunt placement, previous overt or minimal HE, psychometric hepatic encephalopathy score (PHES), and levels of albumin, bilirubin, creatinine, and sodium to develop a prediction model. We validated the model in 112 patients with cirrhosis seen at the University of Padua and followed up for 12 ± 9.5 months. During the follow-up period, 68 patients (32%) developed at least 1 episode of overt HE. Based on multivariate analysis, the development of overt HE was associated with previous HE, minimal HE (based on PHES), and level of albumin less than 3.5 g/dL (area under curve [AUC], 0.74). A model that excluded minimal HE but included albumin level and previous HE also identified patients who would develop overt HE (AUC, 0.71); this difference in AUC values was not statistically significant (P = .104). Both models were validated in the independent group of patients (3 variables: AUC, 0.74; 95% confidence interval, 0.66-0.83; and 2 variables: AUC, 0.71; 95% confidence interval, 0.63-0.78). We developed and validated a model to identify patients with cirrhosis at risk for overt HE based on previous HE, albumin levels, and PHES. If PHES was not available, previous HE and albumin levels still can identify patients at risk. Psychometric evaluation is essential for patients with no history of HE. These findings should aid in planning studies of pharmacologic prevention of overt HE.

Effects of probiotic therapy on hepatic encephalopathy in patients with liver cirrhosis: an updated meta-analysis of six randomized controlled trials

Liver cirrhotic patients with hepatic encephalopathy have poor prognosis. Probiotics alter the intestinal microbiota and reduce the production of ammonia. We conducted a meta-analysis about the role of probiotics on liver cirrhotic patients with hepatic encephalopathy. We collected the relevant literatures up to February 21, 2014 from databases of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. A statistical analysis was conducted by RevMan 5.2 and STATA 12.0 software. Six randomized controlled trials involving 496 liver cirrhotic patients were included. The results showed that probiotic therapy significantly reduced the development of overt hepatic encephalopathy (OR [95% CI]: 0.42 [0.26, 0.70], P=0.0007). However, probiotics did not affect mortality, levels of serum ammonia and constipation (mortality: OR [95% CI]: 0.73 [0.38, 1.41], P=0.35; serum ammonia: WMD [95% CI]: -3.67 [-15.71, 8.37], P=0.55; constipation: OR [95% CI]: 0.67 [0.29, 1.56], P=0.35). Probiotics decrease overt hepatic encephalopathy in patients with liver cirrhosis.

Issue Highlights

Issue Highlights

Hyponatremia: A Risk Factor for Early Overt Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation.

Hepatic encephalopathy (HE) is a frequent complication in cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). Hyponatremia (HN) is a known contributing risk factor for the development of HE. Predictive factors, especially the effect of HN, for the development of overt HE within one week of TIPS placement were assessed. A single-center, retrospective chart review of 71 patients with cirrhosis who underwent TIPS creation from 2006–2011 for non-variceal bleeding indications was conducted. Baseline clinical and laboratory characteristics were collected. Factors associated with overt HE within one week were identified, and a multivariate model was constructed. Seventy one patients who underwent 81 TIPS procedures were evaluated. Fifteen patients developed overt HE within one week. Factors predictive of overt HE within one week included pre-TIPS Na, total bilirubin and Model for End-stage Liver Disease (MELD)-Na. The odds ratio for developing HE with pre-TIPS Na <135 mEq/L was 8.6. Among patients with pre-TIPS Na <125 mEq/L, 125–129.9 mEq/L, 130–134.9 mEq/L and ≥135 mEq/L, the incidence of HE within one week was 37.5%, 25%, 25% and 3.4%, respectively. Lower pre-TIPS Na, higher total bilirubin and higher MELD-Na values were associated with the development of overt HE post-TIPS within one week. TIPS in hyponatremic patients should be undertaken with caution.

Encéphalopathie hépatique minime : un diagnostic précoce pour améliorer le pronostic

Minimal hepatic encephalopathy (MHE) is the mildest form of the spectrum of hepatic encephalopathy that impairs health-related quality of life. The aim of this study is to evaluate the prevalence of MHE in patients with liver cirrhosis and analyze risk factors. Between September 2011 and December 2012, consecutive cirrhotic patients seen in our department were evaluated. Patients included were screened by the psychometric hepatic encephalopathy score (PHES) battery comprising 5 tests: number connection test A and B, line tracing test, serial dotting test and digit symbol test. Patients included were regularly followed-up for the development of overt hepatic encephalopathy, driving accidents, falls and death. We included 45 cirrhotic patients. Etiology of cirrhosis was viral in half of cases. Child-Pugh score was A in 55.6 %, B in 26.7 % and C in 17.8 %. Median Meld score was 14. According to the PHES score, MHE was detected in 44.4 % of patients. Univariate analysis identified 4 variables significantly associated with the presence of MHE: age ≥ 55 years (P=0.031), poor educational status with years of study< 9 years (P=0.007), MELD score ≥ 15 (P=0.002) and Child-Pugh ≥ 7 (P=0.001). At multivariate analysis, the only independent risk factor of MHE was a MELD score≥15 (OR=15.4; P<0.001). During the follow-up, patients with MHE developed more often overt encephalopathy, falls and driving accidents, and had a lower survival, although the difference was not statically significant. In this preliminary small series, prevalence of MHE in Tunisian cirrhotic patient was 44.4 %. A MELD score ≥ 15 was the only independent risk factor. MHE had a negative impact on the outcome, justifying an early diagnostic. Adequate therapy may improve cognitive function.

203 ORAL GLUTAMINE CHALLENGE – DOES IT IMPROVE REVEALING MINIMAL HEPATIC ENCEPHALOPATHY IN CIRRHOSIS?

Background and Aims: Minimal hepatic encephalopathy (MHE) is a prevalent asymptomatic condition, whose diagnosis is difficult due to the lack of a gold standard test. Oral glutamine challenge (OGC) has been found to increase blood ammonia in patients with cirrhosis which could lead to significant cognitive impairment. The aim of our study was to evaluate the value of OGC in improving the performance of psychometric tests and arterial blood ammonia for the diagnosis of MHE. Secondary we followed the risk for development of overt hepatic encephalopathy (OHE). Methods: Fifty-four patients (male/female: 34/20; mean age 59.5yrs) with cirrhosis and 13 healthy controls matched by sex and age were included. Follow-up lasted 12 months. MHE was assessed using the psychometric hepatic encephalopathy score (PHES). Arterial ammonia blood concentrations and PHES were evaluated preand post-60 minutes of a 20 g oral glutamine load. Statistical analysis used paired t-test, relative operating characteristics (ROC) and multivariate logistic regression analysis. Results: At baseline, 29 (53.7%) out of 54 patients met the criteria for MHE, while post glutamine challenge, 43 patients (79.63%) had MHE (p < 0.0001). Arterial blood ammonia levels had significantly raised after glutamine challenge in the cirrhotic patients (baseline vs post glutamine: 85.2±20.8mg/dL vs 159.82±66.01mg/dL, p < 0.0001) as compared to controls values which remained unchanged. ROC analysis showed a pathological glutamine tolerance cut-off value of 124mg/dl. For baseline arterial blood ammonia the AUROC was 0.54 (CI: 0.402–0.680, p = 0.58), with no significant change post glutamine challenge (AUROC = 0.53, CI: 0.389–0.667, p = 0.77). In the follow-up 16 patients (29.62%) developed OHE. In multivariate model, MELD score (OR = 1.5187, 95%CI: 1.0690–2.1574, P = 0.0197), but not Child Pugh class, arterial blood ammonia, esophageal varices grading, was a strong independent predictor of OHE. Conclusions: In cirrhotic patients, OGC appears to improve the performance of psychometric tests, but not arterial blood ammonia for the diagnosis of MHE. MELD score has proven to be independently related with OHE in the follow up. Acknowledgements: This work was made possible by the project ‘Doctoral Scholarships for increasing competitiveness in the medical and pharmaceutical field’ POSDRU/88/1.5/S/58965.

A Randomised Double Blind Controlled Trial Comparing Rifaximin Plus Lactulose with Lactulose Alone in Treatment of Overt Hepatic Encephalopathy

Background: Hepatic encephalopathy (HE) is associated with poor prognosis. Probiotics alter gut flora with nonurease producing organism with decrease ammonia production. Present study assessed efficacy of probiotics for primary prophylaxis of HE. Methods: In prospective randomised controlled trial, patients with no history of overt HE were randomised into: group 1 [Probiotics, n=86, one capsule (110 billion CFU) TDS] and group 2 [control, n = 74]. All patients underwent psychometric tests, critical flicker frequency (CFF), glucose hydrogen breath test (GHBT) for small intestinal bacterial overgrowth (SIBO) and lactulose hydrogen breath test (LHBT) for oro-cecal transit time (OCTT). Primary end point was development of overt HE. Results: One hundred and sixty patients (age 48.6 11.1 years, M:F 96:64) were included. 25 (15.6%), 51 (31.9%) and 82 (52.5%) patients were in CTP class A, B and C respectively. Baseline laboratory parameters, CTP score, MELD score, CFF, psychometric hepatic encephalopathy score (PHES) and OCTT were comparable. Forty two patients (48.8%) in group 1 and 33 (44.6%) in group 2 had minimal HE (P=0.88). Mean follow up of Group 1 and Group 2 patients was 38.6 8.80 vs. 40.3 9.8 weeks (P =0.67). Eleven patients (6.9%) were lost during follow up. Six patients (7.5%) in group 1 and 7 (10.1%) in group 2 died (P =0.81). There was significant improvement in arterial ammonia levels, SIBO, OCTT, PHES, CFF andMHE after 3 months of treatment with probiotics. Seven (8.8%) patients in Group 1 and 14 (20.3%) patients in Group 2 developed overt HE (P <0.05, hazard ratio 2.1, 95% CI, 1.31-6.53). MHE, CTP score and SIBO correlated with development of overt HE. Conclusion: Probiotics are effective in primary prophylaxis of HE.

A look at the hepatic encephalopathy in cirrhosis

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome complicating acute and chronic liver failure and characterized by a wide range of manifestations, in absence of other brain disease. HE is very frequent in course of cirrhosis and even mild forms involve a great additional burden on patients, their families and health-care resources. Its onset affects subsequent survival of patients. Historically, pathophysiology of HE was connected to several substances (mostly ammonia) produced in the gut and normally metabolized by the liver, but more recently other factors such as inflammation, bacterial translocation and oxidative stress have shown a crucial role. Symptoms are often overt (confusion, asterixis, disorientation, ataxia or coma) but can also be subtle (sleep disturbances, cognitive impairment, mood alterations, impairment of executive decision-making, and psychomotor speed – Minimal HE); the West Haven Criteria are most often used to grade Overt HE (OHE), with grade ranging from 0 to 4 (4 corresponding to coma). Since both Minimal HE and grade 1 HE cannot be diagnosed by clinical examination and need for specific tests, it results practical to combine these entities and name them "Covert" HE (CHE) to aid clinical use. Diagnosis is based on evidence of neurological impairment in presence of liver cirrhosis, only after the exclusion of other brain diseases. Measurement of serum ammonia and electroencephalography are little specific, while brain magnetic resonance and search for portosystemic shunts are important in complex cases. Diagnosis of OHE is often just clinical, while that of CHE requires dedicated psychometric and neurophysiological tests. Although these tests are difficult to be performed in the clinical practice, detection and treatment of CHE are cost-effective and important; indeed, CHE affects patients’ quality of life, socioeconomic status and driving skills, and increases the risk for falls, car accidents, development of OHE, and death. Management of HE includes early diagnosis and prompt treatment of precipitating factors (infection, gastrointestinal bleeding, electrolyte disturbances, dehydration, hypotension, use of benzodiazepines, psychoactive drugs, and/or alcohol). Current treatment is based principally on reducing intestinal ammonia with nonabsorbable disaccharides (lactulose or lactitol); rifaximin, used solely or in addition, is also becoming a first-line treatment.

A look at the hepatic encephalopathy in cirrhosis

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome complicating acute and chronic liver failure and characterized by a wide range of manifestations, in absence of other brain disease. HE is very frequent in course of cirrhosis and even mild forms involve a great additional burden on patients, their families and health-care resources. Its onset affects subsequent survival of patients. Historically, pathophysiology of HE was connected to several substances (mostly ammonia) produced in the gut and normally metabolized by the liver, but more recently other factors such as inflammation, bacterial translocation and oxidative stress have shown a crucial role. Symptoms are often overt (confusion, asterixis, disorientation, ataxia or coma) but can also be subtle (sleep disturbances, cognitive impairment, mood alterations, impairment of executive decision-making, and psychomotor speed – Minimal HE); the West Haven Criteria are most often used to grade Overt HE (OHE), with grade ranging from 0 to 4 (4 corresponding to coma). Since both Minimal HE and grade 1 HE cannot be diagnosed by clinical examination and need for specific tests, it results practical to combine these entities and name them "Covert" HE (CHE) to aid clinical use. Diagnosis is based on evidence of neurological impairment in presence of liver cirrhosis, only after the exclusion of other brain diseases. Measurement of serum ammonia and electroencephalography are little specific, while brain magnetic resonance and search for portosystemic shunts are important in complex cases. Diagnosis of OHE is often just clinical, while that of CHE requires dedicated psychometric and neurophysiological tests. Although these tests are difficult to be performed in the clinical practice, detection and treatment of CHE are cost-effective and important; indeed, CHE affects patients’ quality of life, socioeconomic status and driving skills, and increases the risk for falls, car accidents, development of OHE, and death. Management of HE includes early diagnosis and prompt treatment of precipitating factors (infection, gastrointestinal bleeding, electrolyte disturbances, dehydration, hypotension, use of benzodiazepines, psychoactive drugs, and/or alcohol). Current treatment is based principally on reducing intestinal ammonia with nonabsorbable disaccharides (lactulose or lactitol); rifaximin, used solely or in addition, is also becoming a first-line treatment.

Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis: An open labeled randomized controlled trial of lactulose versus no lactulose

Development of overt hepatic encephalopathy (HE) is associated with poor prognosis in patients with cirrhosis. Lactulose is used for the treatment of HE. There is no study on the prevention of overt HE using lactulose in patients who never had HE earlier. Consecutive cirrhotic patients who never had an episode of overt HE were randomized to receive lactulose (Gp-L) or no lactulose (Gp-NL). All patients were assessed by psychometry (number connection test [NCT-A and B], figure connection test if illiterate [FCT-A and B], digit symbol test [DST], serial dot test [SDT], line tracing test [LTT]) and critical flicker frequency test (CFF) at inclusion and after 3 months. These patients were followed every month for 12 months for development of overt HE. Of 250 patients screened, 120 (48%) meeting the inclusion criteria were randomized to Gp-L (n = 60) and Gp-NL (n = 60). Twenty (19%) of 105 patients followed for 12 months developed an episode of overt HE. Six (11%) of 55 in the lactulose (Gp-L) group and 14 (28%) of 50 in the Gp-NL (P = 0.02) developed overt HE. Ten (20%) of 50 patients in Gp-NL and five (9%) of 55 patients in the Gp-L group died, P = 0.16. Number of patients with minimal hepatic encephalopathy (MHE) were comparable in two groups at baseline (Gp-L vs Gp-NL, 32:36, P = 0.29). Lactulose improved MHE in 66% of patients in Gp-L. Taking a cutoff < 38 Hz sensitivity and specificity of CFF in predicting HE were 52% and 77% at baseline and 52% and 82% at 3 months of treatment. On multivariate analysis, Child's score and presence of MHE at baseline were significantly associated with development of overt HE. Lactulose is effective for primary prevention of overt hepatic encephalopathy in patients with cirrhosis.

Changes in cerebral blood flow after transjugular intrahepatic portosystemic shunt can help predict the development of hepatic encephalopathy: An arterial spin labeling MR study

Background and purposeCerebral blood flow (CBF) changes after transjugular intrahepatic portosystemic shunt (TIPS) are still unclear. Our aim is to assess the TIPS-induced CBF changes and their potential clinical significance using the arterial spin labeling (ASL) perfusion magnetic resonance imaging. Materials and methodsNine cirrhotic patients underwent ASL 1–8 days before and 4–7 days after TIPS. CBF was calculated at each voxel and mean CBF values were computed in the whole brain, gray matter and white matter. Changes of CBFs before and after TIPS were compared by paired t-test. ResultsVoxel-wise results showed CBF diffusely increased in patients after TIPS, but no region with significant decrease in CBF was found, nor was any significant mean CBF difference detected in the whole brain, gray matter and white matter. Six patients out of nine showed a global CBF increase of 9–39%; one patient presented a global CBF decrease of 6%; another two showed a global CBF decrease of 16% and 31% respectively. Follow-up studies showed that the two patients with greatly decreased global CBF suffered from multiple episodes of overt hepatic encephalopathy (OHE) after TIPS and one died of OHE. ConclusionsCBF derived from noninvasive ASL MRI could be used as a useful biomarker to predict the development of OHE through consecutively tracking CBF changes in patients with inserted TIPS. Increased CBFs in many cortical regions could be common effects of the TIPS procedure, while decreased global CBF following TIPS might indicate the development of OHE.

Lactulose in the treatment of hepatic encephalopathy: New evidence for an old modality

See article in J. Gastroenterol. Hepatol. 2012; 27: 1329–1335.

Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis: An Open-Label, Randomized Controlled Trial of Lactulose, Probiotics, and No Therapy

Lactulose is effective in secondary prophylaxis of hepatic encephalopathy (HE). Probiotics improves minimal hepatic encephalopathy (MHE), which predisposes to HE. No study has been conducted on the secondary prophylaxis of HE using probiotics. Our objective was to study the effects of lactulose and probiotics for secondary prophylaxis of HE. Consecutive cirrhotic patients who had recovered from HE were randomized to receive lactulose (Gp-L, 30 ml three times per day), three capsules of probiotics (Gp-P) per day containing 112.5 billion viable lyophilized bacteria per capsule, or no therapy (Gp-N). All patients were assessed by psychometry (number connection test (NCT-A, B), figure connection test if illiterate (FCT-A, B), digit symbol test (DST), and block design test (BDT)), critical flicker frequency (CFF) test, and arterial ammonia at inclusion. The patients were followed up monthly. The primary end point was development of overt HE according to West Haven criteria or a follow-up of 12 months. Of 360 patients who recovered, 235 (65.2%) met the inclusion criteria (Gp-L, n=80; Gp-P, n=77; and Gp-N, n=78). In all, 38 patients (16.1%) were lost to follow-up and 77 patients developed HE (Gp-L, n=18; Gp-P, n=22; and Gp-N, n=37). There was a significant difference between Gp-L and Gp-N (P=0.001) and between Gp-P and Gp-N (P=0.02) but no difference between the Gp-L and Gp-P groups (P=0.349). The rate of readmission for causes other than HE (Gp-L, Gp-P, and Gp-N, 19:21:28; P=0.134) and deaths (Gp-L:Gp-P:Gp-N=13:11:16; P=0.56) in all three groups were similar. There was a high prevalence of abnormal psychometry test results (NCT-A, 71.5%; NCT-B, 69.2%; DST, 76.9%; and BDT, 85.2%), and FCT-A and -B were abnormal in 35 of 48 patients (72.7%). CFF was <38 Hz in 118 patients (50.2%). Upon multivariate analysis, recurrence of overt HE was significantly associated with two or more abnormal psychometric tests and arterial ammonia after the recovery of an episode of HE. Lactulose and probiotics are effective for secondary prophylaxis of HE in patients with cirrhosis.

Prophylaxis of hepatic encephalopathy in acute variceal bleed: A randomized controlled trial of lactulose versus no lactulose

Acute variceal bleed (AVB) is an important precipitating factor for development of hepatic encephalopathy (HE). However, there is paucity of data on the role of lactulose for prevention of HE after AVB. We evaluated the role of lactulose for prophylaxis of HE after AVB. Consecutive patients of cirrhosis with AVB enrolled. Patients included if >18 years old and had no HE at the time of presentation. Patients were randomized to receive lactulose (Group-L) or no lactulose (Group-P) along with standard treatment of AVB as per Baveno 4 guidelines. Primary endpoint was development of overt HE as per West Haven criteria within 120 h of randomization. Seventy patients were randomized into group-L (Gp-L, n = 35) and group-P (Gp-P, n = 35). There was no significant difference in baseline characteristics between the two groups. Characteristics of variceal bleed were also similar (Gp-L vs Gp-P [mean arterial pressure 81.0 ± 10.5 vs 79.5 ± 9.9 mmHg], Hb [8.4 ± 1.5 vs 9.3 ± 2.3 g/dL], blood transfusion requirement [1.6 ± 1.1 vs 1.3 ± 0.9 units], time to endoscopy [6.3 ± 2.8 vs 7.0 ± 3.1 h], and esophageal source of bleed [92% vs 88%]). Nineteen (27%) patients developed HE; five patients (14%) in Gp-L and 14 patients (40%) in Gp-P, P = 0.03. The median grade of HE was 2 (range 2-4) and median time interval of development of HE after randomization was 2 days (range 1-4). Nine patients (13%) died; three (8.5%) patients in Gp-L and six (17%) patients in Gp-P, P = 0.23. Patients who developed HE had significantly higher baseline Child-Turcotte-Pugh score score (10.2 ± 1.2 vs 9.4 ± 1.4 P = 0.04), model for end stage liver disease score (18.2 ± 3.9 vs 15.4 ± 4.5 P = 0.02), arterial ammonia level (112.2 ± 22.7 vs 94.8 ± 17.6 umol/L, P = 0.001), baseline total leukocyte count (10,505.2 ± 8911.9 vs 5784.3 ± 3387.0 P = 0.002), total bilirubin (3.4 ± 1.3 vs 2.1 ± 1.8 mg%, P = 0.008) as compared to patients who did not develop HE. On multivariate analysis only baseline arterial ammonia, blood requirement during hospital stay and lactulose therapy were predictors of development of HE. Lactulose is effective in prevention of HE in patients with cirrhosis and acute variceal bleed.

Lactulose a day keeps encephalopathy at bay

Lactulose a day keeps encephalopathy at bay

A Simplified Psychometric Evaluation for the Diagnosis of Minimal Hepatic Encephalopathy

The psychometric hepatic encephalopathy score (PHES), which includes 5 psychometric tests, is a standard for the diagnosis of minimal hepatic encephalopathy (HE). We investigated whether a simplified PHES (SPHES) is as useful as the whole PHES. The PHES was determined for 79 cirrhotic patients (the training group), who were followed up for the development of overt HE. Backward logistic regression was performed by eliminating stepwise variables--removal did not impair regression. A separate series of 65 patients was used as a validation group. The PHES was abnormal in 45 patients. The SPHES, determined from the digit symbol, serial dotting, and line tracing tests, did not differ significantly from the full PHES; 24 of the 79 patients developed overt HE. The likelihood of developing overt HE was higher among patients with an abnormal PHES (log-rank P = .003) or SPHES (P = .004). By using Cox regression and model for end-stage liver disease scores to analyze data from patients with previous HE and transjugular intrahepatic portosystemic shunts, PHES (relative risk, 4.16; P = .003) and SPHES (relative risk, 3.70; P = .004) were the only variables associated with the development of overt HE. The accuracy of the SPHES was confirmed in the validation group. A simplified PHES is as good as the PHES in diagnosing minimal HE and in predicting the occurrence of overt HE.

Advances in the Evaluation and Management of Minimal Hepatic Encephalopathy

Minimal hepatic encephalopathy (MHE) is a neurocognitive disorder that affects up to 80% of cirrhotic patients. Similar to overt hepatic encephalopathy, ammonia and oxidative stress play key roles in the pathogenesis of MHE. However, MHE is characterized by subtle deficits and psychomotor abnormalities that can only be elicited by specialized psychometric tests. Although no gold standard exists for the diagnosis, MHE remains an important entity for clinicians to recognize because of its negative impact on a patient's health-related quality of life and association with driving impairment and vehicle accidents. MHE has also been associated with an increased rate in the development of overt hepatic encephalopathy and increased mortality; therefore, identification and treatment should not be delayed. Treatment to date has been focused on reducing serum ammonia levels with agents such as lactulose, probiotics, and synbiotics. MHE is a real and growing problem that is epidemic in cirrhosis, and increasing awareness of this condition is necessary for adequate management of these patients.