Hepatic Encephalopathy In Liver Cirrhosis Research Articles

Role of Branched-Chain Amino Acids and Their Derivative β-Hydroxy-β-Methylbutyrate in Liver Cirrhosis.

Branched-chain amino acids (BCAA) supplementation is used to promote protein synthesis in different clinical conditions in which proteolysis is increased. In addition, lower plasma BCAA levels have been related to an increased risk of hepatic encephalopathy in liver cirrhosis. In this article we will review the role of supplementation with BCAAs and BCAA derivative β-hydroxy-β-methylbutyrate (HMB) in liver cirrhosis, focusing on nutritional and clinical effects. Evidence shows that BCAA supplementation slightly increases muscle mass and body mass index, with an upward trend in muscular strength and no change in fat mass. Moreover, BCAA supplementation improves symptoms of hepatic encephalopathy, and is indicated as second-line therapy. The evidence is more limited for BCAA derivatives. HMB supplementation appears to increase muscle mass in chronic diseases associated with cachexia, although this effect has not yet been clearly demonstrated in liver cirrhosis studies. To date, HMB supplementation has no clinical indication in liver cirrhosis.

Covert hepatic encephalopathy in liver cirrhosis: Risk factors and prognosis

Covert hepatic encephalopathy in liver cirrhosis: Risk factors and prognosis

Hepatic encephalopathy: issues relevant to clinical practice

Hepatic encephalopathy (HE) remains one of the most serious complications of liver cirrhosis. Its clinical spectrum sometimes creates difficulties in the optimal diagnosis at the patient’s bedside and treatment. To present new data on the field of clinical management of cirrhotic patients with hepatic encephalopathy. The role of ammonia in the diagnosis of HE is still under discussion. In clinical practice, in patients with suspected overt HE, normal ammonia concentration can be used to exclude this diagnosis. In contrast, a high concentration of ammonia in the absence of clinical signs of HE should not serve as a criterion for this diagnosis and as a guide for treatment. A separate issue for discussion is the covert HE. The simplest and most affordable test for screening for covert HE and evaluating the effectiveness of therapy is the animal naming test, which can be done on bedside by physician or caregivers. Patients with covert HE need treatment that is similar in approach to overt HE. The diagnosis of overt HE and the methods of its therapy are well known. According to Russian recommendations, depending on the disease course in a certain patient, lactulose, rifaximin, L-ornithine L-aspartate can be used as first-line drugs, which is applicable to the treatment of both overt and latent PE. The main issues on the management of HE in liver cirrhosis relate to the diagnostic role of ammonia, optimal diagnosis and treatment strategy for covert HE, therapy of choice for both overt and latent HE. There are expert opinions and consensus documents on all these issues. Treatment of overt and latent PE is carried out according to the same principles. Drugs of choice: lactulose, rifaximin and L-Ornithine L-Aspartate.

Precipitating Factors and Treatment Outcomes of Hepatic Encephalopathy in Liver Cirrhosis

BackgroundHepatic encephalopathy (HE) is a common cause of hospital admission in patients with liver cirrhosis (LC). The aims of this study were to evaluate the precipitant factors and analyze the treatment outcomes of HE in LC.MethodsAll the LC patients admitted between February 2017 and January 2018 for overt HE were analyzed for precipitating factors and treatment outcomes. Treatments were compared among three treatment groups: receiving lactulose, lactulose plus L-ornithine L-aspartate (LOLA), and lactulose plus rifaximin. The primary endpoints were mortality and hospital stay. The chi-square test was used to compare the different treatment outcomes with hospital stay and mortality with significance at p<0.05.ResultsA total of 132 patients (mean age 49.2 ± 10.2 years; male/female ratio of 103:29) were studied. The most common precipitating factor of HE was infection 65 (49.2%), followed by electrolyte imbalance 54 (41%), constipation 44 (33.33%), and gastrointestinal bleeding 21 (16%) patients. At the time of admission, 29 (22%), 76 (57.5%), 21 (16%), and six (4.5%) patients had grade I, II, III, and IV HE, respectively. The difference in mortality was not statistically significant (p=0.269) in three groups but the hospital stay was shorter among patients in groups B and C than in group A alone (7.36 ± 4.58 and 7 ± 3.69, 9.64 ± 5.28 days, respectively, p=0.015).ConclusionsInfection, especially spontaneous bacterial peritonitis, was the commonest precipitating factor of HE. The combination of lactulose either with LOLA or rifaximin is equally effective in improving HE and reducing the duration of hospital stay than lactulose alone.

Is sarcopenia associated with hepatic encephalopathy in liver cirrhosis? A systematic review and meta-analysis

Hepatic encephalopathy (HE), a major neuropsychiatric complication in advanced liver disease, is associated with poor prognosis. Sarcopenia, characterized by a decline in muscle mass, strength, and physical performance, is prevalent in liver cirrhosis. This study aims to explore whether sarcopenia is associated with HE in cirrhotic patients. PubMed and EMBASE were searched for relevant cohort and case-control studies investigating the association between sarcopenia and HE up to July 2018. Data of patients' characteristics, definition of low muscle mass, and protocols of grading/diagnosing HE were retrieved. The primary outcome was estimated by a pooled odds ratio (OR) and its 95% confidence interval (CI), using a random effect model. The meta-analysis enrolled 6 studies, comprising 1795 patients. Sarcopenia was positively associated with the presence of HE (OR 2.74 with a 95% CI, 1.87 to 4.01). The association was less likely to be influenced by differences in research designs, focused study outcomes, muscle mass measurements, and protocols of grading/diagnosing HE. There was lack of evidence supporting higher serum ammonia levels in patients with sarcopenia. In patients with liver cirrhosis, there is a significant association between sarcopenia and HE. A greater number of prospective studies are necessary to clarify whether the association remains even after adjusting relevant confounders and to suggest effective prevention of HE in patients with coexisting sarcopenia.

2. Treatment outcome of hepatic encephalopathy in liver cirrhosis

Background and Aims: Hepatic encephalopathy (HE) is a common cause of hospital admission in patients with liver cirrhosis (LC). Various precipitating factors are seen in patients with HE. The aims of this study were to evaluate the precipitant factors and to analyze treatment outcome of HE in liver cirrhosis. Methods: A randomized prospective trial was conducted amongst LC patients presenting with HE from August 2016 to July 2017. They were randomized into three groups: group A received lactulose only, group B received lactulose plus L ornithine L asparte (LOLA) and group C received lactulose plus rifaximin. The primary end points were mortality and hospital stay. Results: A total of 132 cases (mean age 49.2 ± 10.2 years; male/ female ratio 103:29) were studied. The most common precipitating factor of HE identified was infection 65 (49.2%), followed by electrolyte imbalance as hyponatremia 54 (41%) and hypokalemia 18 (13.6%), constipation 44 (33.33%) and gastrointestinal bleeding 21 (16%) patients. Thirty eight (28.8%) and 94 (71.2%) patients were in CTP class B and class C respectively. Mean CTP score was 10.24 ± 1.85, MELD score was 22.2 ± 7.54. At the time of admission, 29 (22%), 76 (57.5%), 21 (16%) and 6 (4.5%) patients had grade I, II, III, and IV HE respectively. The difference in mortality was not statistically significant (p = 0.269) in three groups [group B (13.6%) and group C (13.6%) vs. group A 10 (22.7%)] but the hospital stay was shorter among patients in the group B and C than group A patients (7.36 ± 4.58 and 7 ± 3.69, 9.64 ± 5.28 days respectively, p = 0.015). Conclusions: Infection was the commonest precipitating factor of HE. Addition of LOLA or rifaximin was more effective than lactulose alone in the treatment of acute HE but without any difference in mortality. The authors have none to declare.

20. Precipitating factors of hepatic encephalopathy in liver cirrhosis and their impact on hospital stay and mortality—our center experience

20. Precipitating factors of hepatic encephalopathy in liver cirrhosis and their impact on hospital stay and mortality—our center experience

Plasma Nitrotyrosine Level does not Differentiate between Patients with Minimal Hepatic Encephalopathy and without Minimal Hepatic Encephalopathy in Liver Cirrhosis

Plasma Nitrotyrosine Level does not Differentiate between Patients with Minimal Hepatic Encephalopathy and without Minimal Hepatic Encephalopathy in Liver Cirrhosis

Impact of diabetes mellitus on frequency and severity of hepatic encephalopathy in liver cirrhosis

Impact of diabetes mellitus on frequency and severity of hepatic encephalopathy in liver cirrhosis

Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis.

Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.

The Effect of Branched Chain Amino Acids and L-Ornithine L-Aspartate Combination as The Late Evening Snacks on Nutritional Status and Minimal Hepatic Encephalopathy in Liver Cirrhosis

ABSTRACT Background: xe hepatic encephalopathy (MHE) Minimal hepatic encephalopathy (MHE) in liver cirrhotic patients is critical manifestation of low grade hepatic encephalopaty (HE), is caused quality of life decrease and risk of deteriorating into distinct HE. The study was conducted to asses the effect of combination of xe branched-chain amino branched-chain amino acids (BCAA) and xe L-aspartate (LOLA) L-ornithine L-aspartate (LOLA), which was given late evening, on nutritional status and degree of HE. Method: This single-blind randomized study was conducted on liver cirrhotic outpatients in hepatology clinic of Cipto Mangunkusumo Hospital period June 2011-June 2012. The study subjects were divided into two groups, group of late evening snack (LS) and day snack (DS). Each group was supplemented with combination of milk of BCAAs and LOLA (3.7 g/serving). Evaluation based on history, physical examination, laboratory tests and critical flicker frequency (CFF) was performed one month after the intervention. Data were statistically analyzed with SPSS 15. Results: Thirty-two patients whose the inclusion criteria were divided into 16 subjects for each group, LS and DS. After one month of the intervention, the average level of prealbumin for DS group was increased statistically significant (p < 0.001), but not significant for LS group (p = 0.259). The increase of average body weight,mid-arm muscle circumference (MAMC) and CFF test result in both groups. There was no improvement on subject global assessment (SGA) score after one month intervention in both groups. Conclusion: This study proved that giving combination of BCAAs and LOLA may improve the condition of MHE, however for nutritional status can not be assessed. Keywords: minimal hepatic encephalopathy, BCAAs, LOLA, prealbumin, SGA score, nutritional status

Precipitating factors and the outcome of hepatic encephalopathy in liver cirrhosis.

To determine precipitants of hepatic encephalopathy (HE) and their impact on hospital stay and mortality. Cross-sectional, analytical study. The Aga Khan University Hospital, from January 2005 to December 2007. Consecutive patients admitted with different grades of HE were evaluated between January 2005 and December 2007. The precipitants of HE were correlated with the different grades of HE, and length of hospital stay and mortality. Chi-square test was used to compare the proportion of precipitating factors versus hospital stay and grade with significance at p<0.05. Of the 404 patients 252 (62%) were males. Hepatitis C virus was the cause of cirrhosis in 283 (70%); Child Turcotte Pugh (CTP) class C was present in 317 (78%) patients. On presentation, 17% patients had grade 1 HE while 44%, 29% and 10% had grades 2, 3 and 4 respectively. The most common precipitant of HE was spontaneous bacterial peritonitis in 83 (20.5%), constipation in 74 (18.3%) and urinary tract infection in 62 (15.3%). One hundred and forty (35%) patients had (3) 2 precipitating factors while no precipitant was noted in 50 (12%) patients. Mean hospital stay was 4+/-3 days. The lesser the number of precipitants, shorter was the length of stay (p<0.01) and lesser was the grade of HE (p=0.025). Complete reversal of HE was noted in 366 patients (91%) while the remaining had grade 1 HE on discharge. Nine (2.2%) patients died during the hospital stay. No mortality was noted in patients without precipitants. Patients presenting with (3) 2 precipitating factors and advanced grade of HE had a prolonged hospital stay. Moreover, patients without precipitants had better outcomes.

654 SPECTRAL ANALYSIS OF ELECTROENCEPHALOGRAPHY IN PATIENTS WITH LIVER CIRRHOSIS

Background and Aims: Hepatic encephalopathy (HE) is a serious complication of cirrhosis. Electroencephalography (EEG) has been used in detection of HE but because of the subjective nature of the visual analysis its diagnostic value is questioned. Recently, a spectral analysis of EEG was proposed as a more accurate tool in evaluation of HE. We investigated the usefulness of spectral-EEG in detection of HE in patients with cirrhosis. Methods: Eighty two patients: 54 males and 28 females, aged 55±12 years (range 18–87) underwent neurological examination and closed-eye EEG, performed by one experienced neurologist. In 8 patients who underwent liver transplantation reevaluation was repeated in 5–24 posttransplant weeks. Spectral-EEGs was done on the transverse derivation P3-Pz/P4-Pz in the frequency range of 0.5–30Hz. Preselected 80–100s periods of artifact-free recording, split into 5s epochs were analyzed with Fast Fourier Transformation. Mean dominant frequency (MDF) was calculated and relative power of delta (0.5–4.0Hz), theta (4.0–8.0Hz), and alpha (8.0–13.0Hz) and beta (13.0–30.0Hz) rhythms were calculated. EEG results were then graded using the thresholds proposed by Amodio et al (J Hepatol 2008; 346–353). Results: Neurological examination identified 43 (52%) patients with overt HE: 22 (27%) in grade 1, 15 (18%) in grade 2 and 6 (7%) in grade 3 according to West-Haven criteria. We showed strong correlation between MDF and severity of liver disease in ChildPugh classification (p < 0.001) and ammonia levels (p = 0.02). EEG frequency showed no correlation with alcoholic etiology of liver disease. Patients with overt HE had significantly reduced MDF when compared with patients with unaltered neurological status (6.4±2.0Hz vs 8.0±2.3Hz, p = 0.001). We observed a reduction of MDF in patients with more severe HE. Seventeen (21%) patients without overt HE showed abnormal MDF and could be considered as having minimal HE. We observed a normalization of EEG frequency after transplantation (6.6±1.6Hz vs 9.1±2.1Hz, p = 0.02). Conclusions: In patients with cirrhosis, alterations in EEG were associated with the severity of liver disease, HE but not with the etiology of cirrhosis. They reversed after liver transplantation. Spectral analysis of EEG may offer an objective and valuable method in detecting, grading and monitoring of HE in liver cirrhosis. 655 REPRODUCIBILITY OF LIVER STIFFNESS IN CIRRHOSIS CAN AFFECT ITS ACCURACY FOR CLINICALLY SIGNIFICANT PORTAL HYPERTENSION DIAGNOSIS I. Yepes, D. Rincon, C. Ripoll, A. Fernandez, A. Matilla, M.V. Catalina, M. Salcedo, J. Miranda, G. Clemente, R. Banares. Liver Section, Hospital General Universitario Gregorio Maranon, CIBERehd-Hospital General Universitario Gregorio Maranon, Hospital General Universitario Gregorio Maranon, Madrid, Spain E-mail: ismayep@yahoo.com

RNA oxidation and zinc in hepatic encephalopathy and hyperammonemia

Hepatic encephalopathy is a neuropsychiatric manifestation of acute and chronic liver failure. Ammonia plays a key role in the pathogenesis of hepatic encephalopathy by inducing astrocyte swelling and/or sensitizing astrocytes to swelling by a heterogeneous panel of precipitating factors and conditions. Whereas astrocyte swelling in acute liver failure contributes to a clinically overt brain edema, a low grade glial edema without clinically overt brain edema is observed in hepatic encephalopathy in liver cirrhosis. Astrocyte swelling produces reactive oxygen and nitrogen oxide species (ROS/RNOS), which again increase astrocyte swelling, thereby creating a self-amplifying signaling loop. Astroglial swelling and ROS/RNOS increase protein tyrosine nitration and may account for neurotoxic effects of ammonia and other precipitants of hepatic encephalopathy. Recently, RNA oxidation and an increase of free intracellular zinc ([Zn(2+)](i)) were identified as further consequences of astrocyte swelling and ROS/RNOS production. An elevation of [Zn(2+)](i) mediates mRNA expression of metallothionein and the peripheral benzodiazepine receptor (PBR) induced by hypoosmotic astrocyte swelling. Further, Zn(2+) mediates RNA oxidation in ammonia-treated astrocytes. In the brain of hyperammonemic rats oxidized RNA localizes in part to perivascular astrocyte processes and to postsynaptic dendritic spines. RNA oxidation may impair postsynaptic protein synthesis, which is critically involved in learning and memory consolidation. RNA oxidation offers a novel explanation for multiple disturbances of neurotransmitter systems and gene expression and the cognitive deficits observed in hepatic encephalopathy.

Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis

Studies of the pathogenesis of hepatic encephalopathy are hampered by the lack of a satisfactory animal model. We examined the neurological features of rats after bile duct ligation fed a hyperammonemic diet (BDL+HD). Six groups were studied: sham, sham pair-fed, hyperammonemic, bile duct ligation (BDL), BDL pair fed, and BDL+HD. The BDL+HD rats were made hyperammonemic via an ammonia-containing diet that began 2 weeks after operation. One week later, the animals were sacrificed. BDL+HD rats displayed an increased level of cerebral ammonia and neuroanatomical characteristics of hepatic encephalopathy (HE), including the presence of type II Alzheimer astrocytes. Both BDL and BDL+HD rats showed activation of the inflammatory system. BDL+HD rats showed an increased amount of brain glutamine, a decreased amount of brain myo-inositol, and a significant increase in the level of brain water. In coordination tests, BDL+HD rats showed severe impairment of motor activity and performance as opposed to BDL rats, whose results seemed only mildly affected. In conclusion, the BDL+HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances.