Neuroinflammatory Signals during Acute and Chronic Liver Diseases

A spectrum of neurological complications can result from acute and chronic liver diseases and is termed hepatic encephalopathy. The precise pathogenic mechanisms by which hepatic encephalopathy occurs is unclear. However, it is commonly accepted that the development of hepatic encephalopathy shares a long-standing relationship with neuroinflammation. This chapter will outline the evidence for a role of neuroinflammation and proinflammatory cytokines in the pathogenesis of hepatic encephalopathy. Furthermore, we will identify the possible circulating factors, released from the liver after damage, that may contribute to the neurological complications of hepatic encephalopathy, including neuroinflammation. Lastly, we discuss the current and experimental treatment options aimed at reducing neuroinflammation for the management of hepatic encephalopathy

Rifaximin Treatment in Hepatic Encephalopathy

Background Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. Methods In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. Results Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P Conclusions Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.

Association Of Electroencephalogram Patterns With Ammonia Levels In Hepatic Encephalopathy Patients

Objective: To find out the association between electroencephalogram (EEG) and hepatic encephalopathy. Methodology: This cross-sectional study included 100 patients (with the age of52.5±6.09years for males and 51.7 ± 6.10 years for females) of reported hepatic encephalopathy, visiting the medical department (indoor and OPD) at Federal Government Polyclinic Hospital, Islamabad. The study was conducted from January 2020 to May 2021. Patients who had known epileptic and structural brain lesions or strokes were excluded from the study. Statistical analysis was done using GraphPad Prism software. The significance of data (p-value or R2 value) was calculated through a two-tailed test or correlation coefficient. Results: All the patients in hepatic encephalopathy grade IV reported abnormal EEG representing triphasic waves and flattening of EEG pattern. There was no correlation observed between age, gender and hepatic encephalopathy grades. However, a significant correlation (R2= 0.9032) was observed between serum ammonia levels and hepatic encephalopathy grades. Elevated serum ammonia levels depicted the severity of hepatic encephalopathy. Overall, the percentage of patients with abnormal EEG increased with increasing grade of hepatic encephalopathy. It was quite intriguing to note that EEG, being the common method to diagnose hepatic encephalopathy grades, is not dependent on patients’ socio-economic status. Conclusion: Data concluded that serum ammonia levels are well associated with the progression of hepatic encephalopathy. Moreover, the EEG patter provides the appropriate information about the neurological abnormalities associated with the severity of hepatic encephalopathy. Hence, serum ammonia levels and EEG both should accurately be used as indicators for diagnosis and monitoring the response to the treatment of various grades of hepatic encephalopathy. Data warrant further investigations to get a better insight into hepatic encephalopathy's relationship with EEG patterns through the inclusion of molecular parameters

Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a complex neurological syndrome, characteristic of patients with liver disease, that causes a wide and complex spectrum of nonspecific neurological and psychiatric manifestations, ranging from a subclinical entity such as minimal or covert hepatic encephalopathy to a deep form in which a complete alteration of consciousness can be observed: overt hepatic encephalopathy. Both minimal and overt hepatic encephalopathy have a high impact on patients, caregivers, and national health services, driving substantial consumption of economic resources. In this Special Issue, we discussed the current state-of-the-art research, address ongoing knowledge gaps, and ongoing controversies related to the pathogenesis, diagnosis, and therapeutic management of hepatic encephalopathy

Incisional hernia as an unusual cause of hepatic encephalopathy in a 62-year-old man with cirrhosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hepatic encephalopathy may be initiated by many factors such as gastrointestinal bleeding, infections, fluid and electrolyte disturbances. Hypokalemia is one of the most commonly encountered electrolyte abnormalities causing hepatic encephalopathy in patients with cirrhosis.</p> <p>Case presentation</p> <p>We present the case of a 62-year-old Caucasian man with decompensated liver cirrhosis having multiple episodes of hepatic encephalopathy precipitated by vomiting. He had an incisional hernia at the right lumbar region. A barium contrast study of the small intestine and magnetic resonance imaging showed that the hernial sac included gastric antrum and bowel. We observed that hepatic encephalopathy coincided with hypokalemia as a result of a large volume of vomiting triggered by the collapsed hernial sac. Hepatic encephalopathy was resolved by administration of intravenous potassium.</p> <p>Conclusion</p> <p>This case illustrates that a hernia causing a large volume of vomiting may be a precipitant factor in the development of hepatic encephalopathy.</p

Current Management of Hepatic Encephalopathy: A Review Article

Hepatic encephalopathy, a neuropsychiatric syndrome stemming from liver failure, manifests in acute and chronic cases. The prevailing cause behind its development involves the neurotoxicity resulting from elevated ammonia levels in the brain, which can occur due to increased ammonia production or impaired ammonia excretion. The main objective in treating hepatic encephalopathy is to decrease ammonia levels. The detoxification of ammonia in this condition is regulated by two enzymes: glutaminase and glutamine synthetase. Numerous drugs, such as lactulose, rifaximin, BCAA, LOLA, glycerol phenylbutyrate, and zinc, have been utilized to treat hepatic encephalopathy. In terms of future research, experimental treatment options like fecal microbiota transplant, probiotics, bromocriptine, minocycline, indomethacin, ibuprofen, and flumazenil warrant investigation. Furthermore, albumin infusions have been shown to enhance cognitive function and improve the psychosocial quality of life, possibly by alleviating endothelial dysfunction in patients with minimal hepatic encephalopathy or previous episodes of hepatic encephalopathy. This review article offers a comprehensive overview of the current management strategies for hepatic encephalopathy

Therapeutic efficacy of l-ornithine l-aspartate in patients with hepatic encephalopathy

To determine the efficacy of ornithine-aspartate in reducing blood ammonia levels and clinical improvement, as a part of treatment in hepatic encephalopathy. Material & method: A randomized placebo controlled trial was conducted in 2013 in Jinnah medical and dental college hospital Korangi Karachi. One hundred patients with hepatic encephalopathy due to underlying chronic liver disease were randomly assigned into two groups with 50 patients each. One group received three days of ornithine-aspartate infusions (trial-treatment group) and the other group received three days of infusion of placebo (placebo group). Serum ammonia was measured in both groups on day 1 and day 3. Clinical improvement was assessed by West Haven’s grading of hepatic encephalopathy. Result: The patients in trial group showed statistically significant improvement in serum ammonia levels and grading of hepatic encephalopathy as compared to placebo. Conclusion: L -Ornithinie L-Aspartate (LOLA) is effective in decreasing serum ammonia as well as results in clinical improvement in patients with hepatic encephalopathy and may be recommended for use in hepatic encephalopathy

The bile duct ligated rat : a relevant model to study muscle mass loss in cirrhosis

Muscle mass loss and hepatic encephalopathy (complex neuropsychiatric disorder) are serious complications of chronic liver disease (cirrhosis) which impact negatively on clinical outcome and quality of life and increase mortality. Liver disease leads to hyperammonemia and ammonia toxicity is believed to play a major role in the pathogenesis of hepatic encephalopathy. However, the effects of ammonia are not brain-specific and therefore may also affect other organs and tissues including muscle. The precise pathophysiological mechanisms underlying muscle wasting in chronic liver disease remains to be elucidated. In the present study, we characterized body composition as well as muscle protein synthesis in cirrhotic rats with hepatic encephalopathy using the 6-week bile duct ligation (BDL) model which recapitulates the main features of cirrhosis. Compared to sham-operated control animals, BDL rats display significant decreased gain in body weight, altered body composition, decreased gastrocnemius muscle mass and circumference as well as altered muscle morphology. Muscle protein synthesis was also significantly reduced in BDL rats compared to control animals. These findings demonstrate that the 6-week BDL experimental rat is a relevant model to study liver disease-induced muscle mass loss

Prevalence of minimal hepatic encephalopathy among patients with chronic liver disease in Ilorin, Nigeria

Background: Minimal Hepatic encephalopathy is the mildest form of Hepatic Encephalopathy which presents with significant cognitive impairment and affectation of activities of daily living. The literature is scanty on the prevalence of minimal hepatic encephalopathy in Nigerians with chronic liver disease.Aim: This study aimed at determining the prevalence of minimal hepatic encephalopathy among patients with chronicliver disease using neuro-psychometric tests.Methods: The study was a hospital-based cross-sectional study carried out at the University of Ilorin Teaching Hospital, Ilorin from February 2015 to February 2016. Chronic liver disease was diagnosed with the presence of peripheral stigmata of liver disease, liver biochemistry, prothrombin time, and sonographic findings in keeping with liver disease. Minimal hepatic encephalopathy was diagnosed using number connection tests-A and B for patients who were educated while Line tracing test and constructional dyspraxia were used for patients without any formal education. Data obtained were analysed using Statistical Package for the Social Sciences (SPSS) version 20 computer software package.Results: Sixty-four patients with chronic liver disease were recruited. The mean age (SD) of the patients was 47.1±14.6 yrs, and the 30-39 and 40-49 yrs age groups each had the highest frequency of 21(32.8%). There were 54(84.4%) males and 10 (15.6%) females. The prevalence of Minimal Hepatic Encephalopathy was 43.8%.Conclusion: The prevalence of Minimal Hepatic Encephalopathy in this study was similar to previous studies. Significant number of patients with minimal HE were in Child-Pugh class B and C.Keywords: Minimal, Hepatic Encephalopathy, Liver Disease, Neuro-psychometric testFunding: Non

Hepatic encephalopathy: a neurochemical, neuroanatomical, and neuropsychological study.

Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests, which are not very specific and do not reveal the underlying pathology. Magnetic resonance imaging (MRI) and spectroscopy (MRS) of the brain offer alternative and possibly more specific markers for HE. These methods were applied in conjunction with NP testing in order to determine their usefulness in the identification of HE and to understand the pathogenesis of HE more clearly. MR imaging and spectroscopy examinations, in addition to a battery of 15 NP tests, were administered to investigate 31 patients awaiting liver transplantation and 23 healthy controls. MR image intensities from the globus pallidus region were calculated and normalized to those of the thalamus. Absolute concentrations and ratios with respect to creatine (Cr) of several metabolites were computed from MR spectra. The MR data were correlated with the results of NP tests. The patients showed impairment in NP tests of attention and visuospatial and verbal fluency. In T1-weighted MRI, the relative intensity of the globus pallidus with respect to that of the thalamus region was significantly elevated in patients and correlated(negatively) with three NP tests (Hooper, FAS, and Trails B). The absolute concentrations of myo-inositol (mI) and choline (Ch) were significantly reduced in three brain regions. In addition, the absolute concentrations of glutamine (Gln) and combined glutamate and glutamine (Glx) were increased in all three locations, with Gln increase being significant in all areas while that of Glx only in the occipital white matter. In summary, this study partially confirms a hypothesized mechanism of HE pathogenesis, an increased synthesis of glutamine by brain glutamate in astrocytes due to excessive blood ammonia, followed by a compensatory loss of myo-inositol to maintain astrocyte volume homeostasis. It also indicates that the hyperintensity observed in globus pallidus could be used as complementary to the NP test scores in evaluating the mental health of HE patients