Establishing Region-specific Testing Strategies for Minimal Hepatic Encephalopathy: Lessons and Future Perspectives from a Young, Literate Indian Cohort.

Changing Epidemiology of Cirrhosis and Hepatic Encephalopathy

Objective To investigate the metabolites of serum samples from liver cirrhotic patients with or without minimal hepatic encephalopathy, and even overt hepatic encephalopathy, then to find out diagnostic markers for minimal hepatic encephalopathy. Methods High performance liquid chromatography-orbit trap mass spectrometry (UPLC/LTQ-Orbit trap MS) technology was applied to analyze the serum metabolites from 38 patients of liver cirrhosiswith hepatitis B and 33 healthy volunteers. Results The serum metabolites of patients with simple liver cirrhosis were different from those of patients with minimal or overt hepatic encephalopathy. The serum metabolites of patients with minimal hepatic encephalopathy was mostly similar with those of overt hepatic encephalopathy patients. Arginase, L-tyrosine, glutamic acid, two L-phenylalanine peptide, homovanillic acid, ornithine, L-serine were increased in patients with minimal or overt hepatic encephalopathy, and hypoxanthine decreased in patients with minimal or overt hepatic encephalopathy patients. Conclusions The serum metabolites of patients with minimal hepatic encephalopathy are mostly similar to those of patients with overt hepatic encephalopathy. Arginase, L-tyrosine, glutamic acid, two L-phenylalanine peptide, homovanillic acid, ornithine, L-serine maybe the early metabolites biomarkers to diagnose minimal hepatic encephalopathy. Hypoxanthine is likely to be an effective complement to treat patients with hepatic encephalopathy. Key words: Liver cirrhosis; Hepatic encephalopathy; Minimal hepatic encephalopathy; Metabonomics

Covert Hepatic Encephalopathy: Not as Minimal as You Might Think

Value of Critical Flicker Frequency and Psychometric Hepatic Encephalopathy Score in Diagnosis of Low-Grade Hepatic Encephalopathy

Deciphering the Spectrum of Low-Grade Hepatic Encephalopathy in Clinical Practice

Can we ignore minimal hepatic encephalopathy any longer?

Muscle Alterations Are Associated With Minimal and Overt Hepatic Encephalopathy in Patients With Liver Cirrhosis.

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

Introduction Hepatic encephalopathy (HE) is a neurological manifestation of decompensated liver disease which develops in approximately 50% of patients with cirrhosis. The current diagnostic challenge presented by Hepatic encephalopathy is the detection of minimal HE, as opposed to the more clinically apparent overt HE. Rifaximin, licensed for overt HE, is an effective therapy for these patients, but earlier identification and treatment of HE could prevent liver disease progression and hospitalisation. We conducted a pilot study to analyse the breath samples of patients with different HE grades, alongside the breath of healthy controls, using a portable type electronic nose (uvFAIMS). Method 42 patients were enrolled; 22 with HE and 20 healthy controls. Breath samples were captured at the bedside using a Warwick designed breath capture device. The samples were then analysed using an ultra violet FAIMS machine. This uses ultra violet light to energise electrons rather than ionising radiation in the traditional FAIMS devices. West Haven criteria were applied and MELD scores calculated. Data was analysed using a previously developed pipeline based on a 2D wavelet transform and threshold, removing background noise. Sensitivity, specificity, and Area Under Receiver Operator Curve (AUROC) were calculated in 10-fold cross validation and reported using sparse logistic regression. Results 12 patients had minimal HE and 10 had covert/overt HE. Classification of HE vs controls showed a sensitivity of 0.88 (0.73 – 0.95) and specificity of 0.68 (0.51 – 0.81), AUROC 0.84 (0.75–0.93). Minimal HE was distinguished from covert/overt HE with a sensitivity of 0.79 (0.49 – 0.95) and specificity of 0.50 (0.37 – 0.63), AUROC 0.71 (0.57–0.84). There was no statistically significant differences between differing HE grades; AUROC 0.61 (0.43 – 0.79). Conclusion This pilot study has confirmed the potential of detection and diagnosis of HE via breath analysis identification of VOCs signatures. Importantly this was performed utilising a non-invasive, portable bedside device and holds potential for future early diagnosis of minimal or covert HE. Disclosure of interest None Declared.

A Clinical and Microbiological Study on Spontaneous Bacterial Peritonitis in Patients of Cirrhosis of Liver with Ascites Due to Portal Hypertension

Proton Pump Inhibitors Are Associated With Minimal and Overt Hepatic Encephalopathy and Increased Mortality in Patients With Cirrhosis.

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 to 80% 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.

Liver cirrhosis is associated with latent systemic inflammatory response syndrome as evidenced by elevated levels of proinflammatory cytokines. It has been proposed that inflammatory mediators play a role in the pathogenesis of minimal and overt hepatic encephalopathy (HE); hence, they may also have an effect on health-related quality of life (HRQL). The aim of this study was to investigate the relationship between serum levels of interleukin-1β (IL-1β), IL-6, and IL-18 and the occurrence of minimal HE and HRQL. Forty-two consecutive patients with liver cirrhosis were prospectively enrolled to the study. Minimal HE was detected by the Psychometric Hepatic Encephalopathy Score (PHES) and critical flicker frequency. HRQL was assessed with Chronic Liver Disease Questionnaire and 36-Item Short Form Health Survey (SF-36) questionnaires. The interleukins studied were determined using colorimetric sandwich enzyme-linked immunosorbent assay. Serum levels of interleukins correlated with liver dysfunction, but did not discriminate patients with minimal HE from those with overt or absent HE. IL-1β and IL-6 showed significant correlations with PHES, but showed no relationship with critical flicker frequency. Serum IL-6 and IL-18 correlated with both physical-related general health and mental component summary evaluated by the SF-36 questionnaire. This study shows that chronic inflammation plays a role in impaired HRQL in patients with cirrhosis irrespective of minimal HE.

What Is Driving the Legal Interest in Hepatic Encephalopathy?

BACKGROUND: Muscle alterations (myosteatosis and sarcopenia) are frequent in cirrhosis and related to some complications included overt hepatic encephalopathy. The aim of our study was to investigate the relationship between muscle alterations and minimal hepatic encephalopathy (MHE) and their role on the risk of overt HE. METHODS: 64 cirrhotics were submitted to Psychometric Hepatic Encephalopathy Score (PHES) and to Animal Naming Test (ANT) to detect MHE. CT scan was used to analyse the skeletal muscle index (SMI) and attenuation. The incidence of the first episode of HE, taking into account the competing risk nature of the data, was estimated. RESULTS: Myosteatosis was observed in 24 patients (37.5%), sarcopenia in 37 (58%) and MHE in 32 (50%). Both myosteatosis (62.5 vs 12.5%; P < 0.001) and sarcopenia (84 vs 31%; P < 0.001) were more frequent in patients with MHE. The variables independently associated to the presence of MHE were: sarcopenia, previous overt HE and myosteatosis. Thirty-one (48%) patients developed overt HE during 16.1 ± 13 months; myosteatosis was detected in 68% and sarcopenia in 84% of them. Sarcopenia and myosteatosis were also independently associated to the development of overt HE. Venous ammonia was significantly higher in sarcopenic patients (62.6 ± 17.7 vs 41.4 ± 16.1 μg/dl; P < 0.001) and in myosteatosic patients (65.2 ± 19.2 vs 46.7 ± 17.1 μg/dl; P < 0.001) and inversely correlated to both parameters. Survival was significantly lower in malnourished patients compared with patients without myosteatosis or sarcopenia (P < 0.001). CONCLUSIONS: Myosteatosis and sarcopenia, probably by reducing the handling of ammonia in the muscle, are independently associated to MHE and to the risk of overt HE in cirrhotics. In malnourished patients, the amelioration of nutritional status may be a possible goal to decrease both the prevalence oh MHE and the incidence of overt HE.