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  1. Hepatic Encephalopathy due to Congenital Multiple Intrahepatic Portosystemic Venous Shunts Successfully Treated by Percutaneous Transhepatic Obliteration

    PubMed Central

    Takenaga, Shinsuke; Narita, Kenichi; Matsui, Yo; Fukuda, Kunihiko

    2016-01-01

    Hepatic encephalopathy due to intrahepatic portosystemic venous shunts (IPSVS) in a non-cirrhotic condition is rare. Here we report a rare case of a patient with congenital multiple IPSVS successfully treated by percutaneous transhepatic obliteration. The patient was a 67-year-old woman who presented to our hospital with progressive episodes of consciousness disorder and vomiting. Laboratory tests revealed hyperammonemia (192.0 μg/dL), and computed tomography revealed multiple IPSVS in both lobes. There was no evidence of underlying liver disease or hepatic trauma. Transcatheter embolization for IPSVS was performed because conservative therapy was not sufficiently effective. After endovascular shunt closure, hepatic encephalopathy improved. The serum ammonia level normalized during the 5-year follow-up period. Thus, transcatheter embolization may be an effective therapy for patients with symptomatic and refractory IPSVS. Careful follow-up is necessary for portal hypertension-related complications after transcatheter embolization for IPSVS. PMID:27990104

  2. Pathogenesis of Hepatic Encephalopathy

    PubMed Central

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

    Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

  3. Combination therapy using PSE and TIO ameliorates hepatic encephalopathy due to intrahepatic portosystemic venous shunt in idiopathic portal hypertension

    PubMed Central

    Kojima, Seiichiro; Ito, Hiroyuki; Takashimizu, Shinji; Ichikawa, Hitoshi; Matsumoto, Tomohiro; Hasebe, Terumitsu

    2016-01-01

    A 64-year-old woman treated for anemia and ascites exhibited hepatic encephalopathy. Abdominal ultrasonography and computed tomography (CT) showed communication between the portal vein and the middle hepatic vein, indicating an intrahepatic portosystemic venous shunt (PSS). Since hepatic encephalopathy of the patient was resistant to medical treatment, interventional radiology was performed for the treatment of shunt obliteration. Hepatic venography showed anastomosis between the hepatic vein branches, supporting the diagnosis of idiopathic portal hypertension (IPH). To minimize the increase in portal vein pressure after shunt obliteration, partial splenic artery embolization (PSE) was first performed to reduce portal vein blood flow. Transileocolic venous obliteration (TIO) was then performed, and intrahepatic PSS was successfully obliterated using coils with n-butyl-2-cyanoacrylate (NBCA). In the present case, hepatic encephalopathy due to intrahepatic PSS in the patient with IPH was successfully treated by combination therapy using PSE and TIO. PMID:27651930

  4. Hepatic Encephalopathy

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    ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ... travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic ...

  5. Minimal hepatic encephalopathy.

    PubMed

    Zamora Nava, Luis Eduardo; Torre Delgadillo, Aldo

    2011-06-01

    The term minimal hepatic encephalopathy (MHE) refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy; the prevalence is as high as 84% in patients with hepatic cirrhosis. Physician does generally not perceive cirrhosis complications, and neuropsychological tests and another especial measurement like evoked potentials and image studies like positron emission tomography can only make diagnosis. Diagnosis of minimal hepatic encephalopathy may have prognostic and therapeutic implications in cirrhotic patients. The present review pretends to explore the clinic, therapeutic, diagnosis and prognostic aspects of this complication.

  6. Management of Hepatic Encephalopathy

    PubMed Central

    Wright, G.; Chattree, A.; Jalan, R.

    2011-01-01

    Hepatic encephalopathy (HE), the neuropsychiatric presentation of liver disease, is associated with high morbidity and mortality. Reduction of plasma ammonia remains the central therapeutic strategy, but there is a need for newer novel therapies. We discuss current evidence supporting the use of interventions for both the general management of chronic HE and that necessary for more acute and advanced disease. PMID:21994873

  7. Management of covert hepatic encephalopathy.

    PubMed

    Waghray, Abhijeet; Waghray, Nisheet; Mullen, Kevin

    2015-03-01

    Hepatic encephalopathy is a reversible progressive neuropsychiatric disorder that encompasses a wide clinical spectrum. Covert hepatic encephalopathy is defined as patients with minimal hepatic encephalopathy and Grade I encephalopathy by West-Haven Criteria. Terminology such as "sub-clinical", "latent", and "minimal" appear to trivialize the disease and have been replaced by the term covert. The lack of clinical signs means that covert hepatic encephalopathy is rarely recognized or treated outside of clinical trials with options for therapy based on patients with episodic hepatic encephalopathy. This review discusses the current available options for therapy in covert hepatic encephalopathy and focuses on non-absorbable disacharides (lactulose or lactitol), antibiotics (rifaximin), probiotics/synbiotics and l-ornithine-l-aspartate.

  8. Pharmacoeconomics of hepatic encephalopathy.

    PubMed

    Neff, Guy

    2010-05-01

    Understanding and appreciating the science of pharmacoeconomics have become even more important for health care providers and insurers during the recent economic downturn. Evaluating the true costs of any disease is complex; both direct costs, such as costs of drug therapy and the provision of care, and indirect costs, such as lost earnings and reduced quality of life, must be taken into account. With chronic liver disease, the most recent data indicate that direct costs were more than $2 billion whereas indirect costs were more than $450 million. Hepatic encephalopathy, a common complication of chronic liver disease, contributes to this economic burden. Although patients' length of stay during hospitalization for hepatic encephalopathy decreased from almost 9 days to 6 days (and has remained stable over the past few years) from 1993 to 2007, hospitalization costs rose from $13,000 to $30,000/hospital stay. In addition, 22% of patients were discharged directly to nursing homes or rehabilitation centers, which increases total costs. When assessing therapy for hepatic encephalopathy, it is important to consider the total costs of the disease, not just treatment costs. Although more expensive on a daily basis than lactulose, rifaximin has been shown to reduce hospitalization rates, has a better adverse-effect profile, and increases patient compliance. One study found that rifaximin produced a cost savings/patient/year of more than $3000 over lactulose therapy.

  9. An outbreak of acute hepatic encephalopathy due to severe aflatoxicosis in Malaysia.

    PubMed

    Lye, M S; Ghazali, A A; Mohan, J; Alwin, N; Nair, R C

    1995-07-01

    In October 1988, 13 Chinese children died of acute hepatic encephalopathy in the northwestern state of Perak in peninsular Malaysia. The acuteness of the illness differed from previously reported outbreaks described in Kenya, India, and Thailand. Epidemiologic investigations determined that the children had eaten a Chinese noodle, loh see fun, hours before they died. The attack rates among those who had eaten the noodles were significantly higher than those who had not (P < 0.0001). The cases were geographically scattered in six towns in two districts along the route of distribution of the noodle supplied by one factory in Kampar town. Aflatoxins were confirmed in postmortem samples from patients. This outbreak has important public health implications for many developing countries.

  10. Correlation between interleukin-6 and ammonia in patients with overt hepatic encephalopathy due to cirrhosis.

    PubMed

    Luo, Ming; Li, Lei; Yang, Er-Na; Dai, Chen-Yang; Liang, Shu-Ren; Cao, Wu-Kui

    2013-09-01

    Previous studies have shown that elevated serum levels of interleukin-6 (IL-6) correlate with the severity of overt hepatic encephalopathy (OHE) in cirrhotic patients. However, the correlation between serum IL-6 levels and plasma ammonia levels in these patients remains unclear. Therefore, the present study investigated this correlation between both variables in cirrhotic patients with OHE. Fifty-five cirrhotic patients with various grades of OHE, 29 cirrhotic patients without OHE, and 30 healthy controls were recruited. Concentrations of plasma ammonia and serum IL-6 were simultaneously measured. In cirrhotic patients with OHE, the severity of OHE, represented by the West Haven criteria, correlated with serum IL-6 levels (r=0.43, P<0.05) and plasma ammonia levels (r=0.59, P<0.05). IL-6 and ammonia were found to be significant independent predictors of OHE severity (P<0.05 for both variables). Furthermore, the severity of liver cirrhosis, determined by Child-Pugh scores, correlated with serum IL-6 levels (r=0.45, P<0.05) and plasma ammonia levels (r=0.68, P<0.05) in these patients. Moreover, there was a significant positive correlation between serum IL-6 levels and plasma ammonia levels (r=0.58, P<0.05) in cirrhotic patients with OHE, but not in patients without OHE (r=0.42, P>0.05) or healthy controls (r=0.27, P>0.05). The correlation between IL-6 and ammonia was independent of infectious precipitating factors. The results of the present study suggest that IL-6 might be involved in the mechanism by which ammonia contributes to the pathogenesis of OHE. There is also evidence of a potential synergistic interaction between proinflammatory cytokines and ammonia in the pathogenesis of OHE. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  11. [Prevention of hepatic encephalopathy].

    PubMed

    Morillas, Rosa M; Sala, Marga; Planas, Ramon

    2014-06-06

    Hepatic encephalopathy (HE) is a frequent complication of cirrhosis which, in addition to producing a great social impact, deteriorates the quality of life of patients and is considered a sign of advanced liver disease and therefore a clinical indication for liver transplant evaluation. Patients who have had episodes of HE have a high risk of recurrence. Thus, after the HE episode resolves, it is recommended: control and prevention of precipitating factors (gastrointestinal bleeding, spontaneous bacterial peritonitis, use of diuretics with caution, avoid nervous system depressant medications), continued administration of non-absorbable disaccharides such as lactulose or lactitol, few or non-absorbable antibiotics such as rifaximin and assess the need for a liver transplant as the presence of a HE episode carries a poor prognosis in cirrhosis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  12. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy.

    PubMed

    Cichoż-Lach, Halina; Michalak, Agata

    2013-01-07

    Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause neurological death with brain edema and intracranial hypertension. It is assumed that approximately 60%-80% of patients with liver cirrhosis develop hepatic encephalopathy. This review explores the complex mechanisms that lead to hepatic encephalopathy. However, noncirrhotic hyperammonemic encephalopathy is not associated with hepatic diseases and has a completely different etiology. Noncirrhotic hyperammonemic encephalopathy is a severe occurrence that is connected with multiple pathogeneses.

  13. Challenges in diagnosing hepatic encephalopathy.

    PubMed

    Weissenborn, K

    2015-02-01

    The term "hepatic encephalopathy" (HE) covers the neuropsychiatric syndrome associated with acute, chronic and acute-on-chronic liver disease (CLD). This paper deals with clinical features and diagnosis of HE in patients with liver cirrhosis and portal hypertension or porto-systemic shunts. The possible impact of concomitant disorders and the cirrhosis underlying liver disease upon brain function is described emphasizing the need of a detailed diagnostic work up of every individual case before diagnosing HE. Currently used methods for diagnosing minimal or covert hepatic encephalopathy are compared with regard to their sensitivity and specificity for diagnosing HE against the background of a multitude of concomitant disorders and diseases that could contribute to brain dysfunction.

  14. GABAergic transmission in hepatic encephalopathy.

    PubMed

    Sergeeva, Olga A

    2013-08-15

    Hepatic encephalopathy (HE)(1) is a neuropsychiatric disorder caused by chronic or acute liver failure. Nearly thirty years ago a hypothesis was formulated explaining the neuropathology of HE by increased GABAergic tone. Recent progress in the GABAA-receptor (GABAAR) molecular pharmacology and biochemistry as well as the physiology of GABAergic transmission provided better understanding of GABA's role in health and disease. A detailed analysis of neuronal populations and their GABAergic afferents affected in HE is still missing. The slow progress in understanding the pathology of GABAergic transmission in HE is due to the high complexity of brain circuitries controlled by multiple types of GABAergic interneurons and the large variety of GABAAR, which are differently affected by pathological conditions and not yet fully identified. The mechanisms of action of the GABAAR agonist taurine, allosteric positive modulators (inhibitory neurosteroids, anaesthetics, benzodiazepines and histamine) and inhibitors of the GABAAR (excitatory neurosteroids, Ro15-4513) are discussed with respect to HE pathophysiology. Perspectives for GABAergic drugs in the symptomatic treatment of HE are suggested.

  15. Nutritional support in hepatic encephalopathy.

    PubMed

    Mizock, B A

    1999-03-01

    Hepatic encephalopathy (HE) is a syndrome of global cerebral dysfunction resulting from underlying liver disease or portal-systemic shunting. HE can present as one of four syndromes, depending on the rapidity of onset of hepatic failure and the presence or absence of preexisting liver disease. The precise pathogenesis is unknown but likely involves impaired hepatic detoxification of ammonia as well as alterations in brain transport and metabolism of amino acids and amines. The etiology of malnutrition in hepatic failure is multifactorial. Nutritional deficits may be clinically manifest as marasmus or kwashiorkor, or both. Nutritional support in HE is directed toward reducing morbidity related to underlying malnutrition and concurrent disease. However, reaching nutritional goals is often complicated by protein and carbohydrate intolerance. The use of protein restriction in HE is controversial. Modified formulas that are supplemented in branched chain amino acids may be of value in patients who exhibit protein intolerance with standard feeding solutions or in patients who present with advanced degrees of encephalopathy.

  16. Rifaximin in the treatment of hepatic encephalopathy

    PubMed Central

    Iadevaia, Maddalena Diana; Prete, Anna Del; Cesaro, Claudia; Gaeta, Laura; Zulli, Claudio; Loguercio, Carmelina

    2011-01-01

    Hepatic encephalopathy is a challenging complication in patients with advanced liver disease. It can be defined as a neuropsychiatric syndrome caused by portosystemic venous shunting, ranging from minimal to overt hepatic encephalopathy or coma. Its pathophysiology is still unclear, although increased levels of ammonia play a key role. Diagnosis of hepatic encephalopathy is currently based on specific tests evaluating the neuropsychiatric state of patients and their quality of life; the severity of hepatic encephalopathy is measured by the West Haven criteria. Treatment of hepatic encephalopathy consists of pharmacological and corrective measures, as well as nutritional interventions. Rifaximin received approval for the treatment of hepatic encephalopathy in 2010 because of its few side effects and pharmacological benefits. The aim of this work is to review the use and efficacy of rifaximin both in acute and long-term management of hepatic encephalopathy. Treatment of overt hepatic encephalopathy involves management of the acute episode as well as maintenance of remission in those patients who have previously experienced an episode, in order to improve their quality of life. The positive effect of rifaximin in reducing health care costs is also discussed. PMID:24367227

  17. Management of Hepatic Encephalopathy in the Hospital

    PubMed Central

    Leise, Michael D.; Poterucha, John J.; Kamath, Patrick S.; Kim, W. Ray

    2014-01-01

    Hepatic encephalopathy (HE) develops in about 50% of patients with cirrhosis and is one of the features of decompensated cirrhosis. The inpatient incidence of HE is approximately 23,000/year and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails two phases, induction and maintenance of remission. Most cases of significant hepatic encephalopathy are precipitated by infection, gastrointestinal bleeding, medications or other culprits. All patients should be evaluated for secondary triggers of HE and treatment should be initiated with a non-absorbable disaccharide (i.e. lactulose) in most cases. Rifaximin (off-label) can be added in patients not responding to lactulose. Neomycin is a less preferable alternative to rifaximin, due to its side effect profile. Other therapies including zinc, LOLA, and branch chain amino acids can be considered for patients not responding to a disaccharide and non-absorbable antibiotic. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe hepatic encephalopathy who do not respond to medical therapy. It is critically important that patients hospitalized with significant hepatic encephalopathy continue a maintenance medication(s) at the time of dismissal to prevent further episodes. Patients with a 1st time episode of HE can be placed on lactulose and careful instruction should be provided to patient and caregiver about titration of dose to achieve 3 bowel movements per day. Patients with recurrent HE episodes despite lactulose benefit from the addition of rifaximin which decreases the frequency of recurrent HE episodes and related hospitalizations. Lastly, patients and their families should be counselled about the risk of motor vehicle accidents which

  18. Minimal hepatic encephalopathy: A review.

    PubMed

    Nardone, Raffaele; Taylor, Alexandra C; Höller, Yvonne; Brigo, Francesco; Lochner, Piergiorgio; Trinka, Eugen

    2016-10-01

    Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of patients with liver cirrhosis. By definition, MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, but obvious clinical manifestation are lacking. MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis can be achieved through neuropsychological testing, recently developed computerized psychometric tests, such as the critical flicker frequency and the inhibitory control tests, as well as neurophysiological procedures. Event related potentials can reveal subtle changes in patients with normal neuropsychological performances. Spectral analysis of electroencephalography (EEG) and quantitative analysis of sleep EEG provide early markers of cerebral dysfunction in cirrhotic patients with MHE. Neuroimaging, in particular MRI, also increasingly reveals diffuse abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. Medical treatment for MHE to date has been focused on reducing serum ammonia levels and includes non-absorbable disaccharides, probiotics or rifaximin. Liver transplantation may not reverse the cognitive deficits associated with MHE. We performed here an updated review on epidemiology, burden and quality of life, neuropsychological testing, neuroimaging, neurophysiology and therapy in subjects with MHE. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  19. Refractory hepatic encephalopathy due to concomitant transjugular intrahepatic portosystemic shunt and spontaneous mesocaval shunt controlled by embolization of the competitive portosystemic shunt.

    PubMed

    Cura, Marco

    2009-01-01

    Spontaneous mesocaval shunt (SMCS) is an uncommon cause of refractory encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS) creation. We report a patient who presented with refractory hepatic encephalopathy (HE) post-TIPS creation for variceal bleeding in whom a SMCS was found. Percutaneous transhepatic occlusion of the SMCS reduced the portal vein flow diverted from the liver and provided sufficient liver perfusion to reverse the HE while maintaining satisfactory decompression of esophageal varices.

  20. Hepatic Encephalopathy in Liver Cirrhosis.

    PubMed

    Djiambou-Nganjeu, Herbert

    2017-03-01

    Liver cirrhosis is a worldwide gastroenterological condition, characterized by a slow, progressive and irreversible replacement of liver cells by fibrous tissue (scar) that prevents liver function. This condition often leads to the development of other syndromes. Cardiac complications can be indicated through abnormal QTc interval and arrhythmias, thereby their analysis aids in the prevention of cardiovascular events. Most cirrhotic cases have abnormal laboratory values (bilirubin, albumin, AST, ALT, AST/ALT, INR) indicating the presence of concomitant infection, inflammation and coagulopathy. In this case report, the usage Halstead-Reitan and Child-Pugh score helped in the assessment of the status of deterioration of brain. The knowledge of liver cirrhosis aetiologies help to determine the predisposition to development of hepatic encephalopathy and cardiomyopathy. The different values of liver enzymes and other blood laboratory analyses indicated the level of liver damage and poor prognosis.

  1. CLIF-SOFA score and SIRS are independent prognostic factors in patients with hepatic encephalopathy due to alcoholic liver cirrhosis.

    PubMed

    Jeong, Jin Hee; Park, In Sung; Kim, Dong Hoon; Kim, Seong Chun; Kang, Changwoo; Lee, Soo Hoon; Kim, Tae Yun; Lee, Sang Bong

    2016-06-01

    Hepatic encephalopathy (HE) is a complication associated with worst prognosis in decompensated liver cirrhosis (LC) patients. Previous studies have identified prognostic factors for HE, and recent studies reported an association between systemic inflammatory response syndrome (SIRS) and liver disease. This study aimed to identify prognostic factors for 30-day mortality in alcoholic LC patients with HE who visited the emergency department (ED).This was a retrospective study of alcoholic LC patients with HE from January 1, 2010, to April 30, 2015. The baseline characteristics, complications of portal hypertension, laboratory values, Child-Pugh class, Model for End-stage Liver Disease (MELD) score, chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score, and SIRS criteria were assessed. The presence of 2 or more SIRS criteria was considered SIRS. The primary outcomes were 30-day mortality and prognostic factors for patients with HE visiting the ED.In total, 105 patients who met the inclusion criteria were analyzed. Overall, the 30-day mortality rate was 6.7% (7 patients).Significant variables were hepatorenal syndrome, international normalized ratio, white blood cell count, total bilirubin level, MELD score CLIF-SOFA score, and SIRS in univariate analysis. CLIF-SOFA score and SIRS were the significant factors in the multivariate analysis (hazard ratio 5.56, 15.98; 95% confidence interval 1.18-26.18, 1.58-161.37; P = 0.03, P = 0.02). The mortality rates differed according to the CLIF-SOFA score (P < 0.01).The CLIF-SOFA score and SIRS in alcoholic LC patients with HE visiting the ED are independent predictors of 30-day mortality.

  2. Probiotics for people with hepatic encephalopathy.

    PubMed

    Dalal, Rohan; McGee, Richard G; Riordan, Stephen M; Webster, Angela C

    2017-02-23

    Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts, may confer a health benefit on the host. To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-effects model meta-analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration

  3. [Clinical importance and diagnostic methods of minimal hepatic encephalopathy].

    PubMed

    Stawicka, Agnieszka; Zbrzeźniak, Justyna; Świderska, Aleksandra; Kilisińska, Natalia; Świderska, Magdalena; Jaroszewicz, Jerzy; Flisiak, Robert

    2016-02-01

    Minimal hepatic encephalopathy (MHE) encompasses a number of neuropsychological and neurophysiological disorders in patients suffering from liver cirrhosis, who do not display abnormalities during a medical interview or physical examination. A negative influence of MHE on the quality of life of patients suffering from liver cirrhosis was confirmed, which include retardation of ability of operating motor vehicles and disruption of multiple health-related areas, as well as functioning in the society. The data on frequency of traffic offences and accidents amongst patients diagnosed with MHE in comparison to patients diagnosed with liver cirrhosis without MHE, as well as healthy persons is alarming. Those patients are unaware of their disorder and retardation of their ability to operate vehicles, therefore it is of utmost importance to define this group. The term minimal hepatic encephalopathy (formerly "subclinical" encephalopathy) erroneously suggested the unnecessity of diagnostic and therapeutic procedures in patients with liver cirrhosis. Diagnosing MHE is an important predictive factor for occurrence of overt encephalopathy - more than 50% of patients with this diagnosis develop overt encephalopathy during a period of 30 months after. Early diagnosing MHE gives a chance to implement proper treatment which can be a prevention of overt encephalopathy. Due to continuing lack of clinical research there exist no commonly agreed-upon standards for definition, diagnostics, classification and treatment of hepatic encephalopathy. This article introduces the newest findings regarding the importance of MHE, scientific recommendations and provides detailed descriptions of the most valuable diagnostic methods.

  4. Hepatic encephalopathy therapy: An overview.

    PubMed

    Riggio, Oliviero; Ridola, Lorenzo; Pasquale, Chiara

    2010-04-06

    Type-C hepatic encephalopathy (HE) is a severe complication of cirrhosis, which seriously affects quality of life and is strongly related to patient survival. Treatment based on a classical pharmacological approach that is aimed at reducing the production of gut-derived toxins, such as ammonia, is still under debate. Currently, results obtained from clinical trials do not support any specific treatment for HE and our competence in testing old and new treatment modalities by randomized controlled trials with appropriate clinically relevant end-points urgently needs to be improved. On the other hand, patients who are at risk for HE are now identifiable, based on studies on the natural history of the disease. Today, very few studies that are specifically aimed at establishing whether HE may be prevented are available or in progress. Recent studies have looked at non absorbable disaccharides or antibiotics and other treatment modalities, such as the modulation of intestinal flora. In the treatment of severe stage HE, artificial liver supports have been tested with initial positive results but more studies are needed.

  5. Minimal Hepatic Encephalopathy Impairs Quality of Life

    PubMed Central

    Agrawal, Swastik; Umapathy, Sridharan; Dhiman, Radha K.

    2015-01-01

    Minimal hepatic encephalopathy (MHE) is the mildest form of the spectrum of neurocognitive impairment in cirrhosis. It is a frequent occurrence in patients of cirrhosis and is detectable only by specialized neurocognitive testing. MHE is a clinically significant disorder which impairs daily functioning, driving performance, work capability and learning ability. It also predisposes to the development of overt hepatic encephalopathy, increased falls and increased mortality. This results in impaired quality of life for the patient as well as significant social and economic burden for health providers and care givers. Early detection and treatment of MHE with ammonia lowering therapy can reverse MHE and improve quality of life. PMID:26041957

  6. Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama).

    PubMed

    Pillitteri, C A; Craig, L E

    2013-01-01

    Hepatic encephalopathy has been listed as a differential for llamas displaying neurologic signs, but it has not been histopathologically described. This report details the neurologic histopathologic findings associated with 3 cases of hepatic lipidosis with concurrent neurologic signs and compares them to 3 cases of hepatic lipidosis in the absence of neurologic signs and 3 cases without hepatic lipidosis. Brain from all 3 llamas displaying neurologic signs contained Alzheimer type II cells, which were not detected in either subset of llamas without neurologic signs. Astrocytic immunohistochemical staining intensity for glial fibrillary acid protein was decreased in llamas with neurologic signs as compared to 2 of 3 llamas with hepatic lipidosis and without neurologic signs and to 2 of 3 llamas without hepatic lipidosis. Immunohistochemical staining for S100 did not vary between groups. These findings suggest that hepatic encephalopathy may be associated with hepatic lipidosis in llamas.

  7. Hepatic encephalopathy and fitness to drive.

    PubMed

    Kircheis, Gerald; Knoche, Anja; Hilger, Norbert; Manhart, Frank; Schnitzler, Alfons; Schulze, Horst; Häussinger, Dieter

    2009-11-01

    Low-grade hepatic encephalopathy (HE) may impair fitness to drive. Driving deficits have not yet been characterized, and their relation to psychometric test results is unclear. Fifty-one cirrhotic patients and 48 age-matched controls underwent real driving in a multiple sensor and camera-equipped car, laboratory and "in-car" computer psychometry, and driving instructor's assessment. Ten cirrhotic patients had no hepatic encephalopathy (HE0); 27 and 14 patients suffered from minimal HE (mHE) and overt HE grade I (oHE), respectively. During real driving, mHE and oHE patients showed significantly more violations of in-lane keeping, reduced break use, prolonged reaction times, and diminished stress tolerance compared with control or cirrhotic HE0 patients. In a self-evaluation questionnaire, mHE and oHE, but not the HE0, patients strongly overestimated their driving abilities. According to the driving instructor's assessment, 75%, 48%, and 39% of the patients with HE0, mHE, and oHE, respectively, were fit to drive, compared with 87% in the control group. Driving deficits in oHE patients were largely due to cognitive defects and prolonged reaction times, whereas, in mHE patients, mistakes and attention deficits predominated. Computer psychometric test results worsened with HE severity and age, whereas real driving was age independent. In 25 out of 94 patients, discordant results for driving fitness were obtained (driving instructor's assessment vs computer psychometry); in mHE and oHE patients, the concordance rates were only 62% and 64%, respectively. Despite significant driving deficits, HE patients overestimate their driving abilities. The presence of mHE does not necessarily predict driving unfitness, and computer-based testings cannot reliably predict driving fitness.

  8. Value of plasmapheresis in hepatic encephalopathy.

    PubMed

    Riviello, J J; Halligan, G E; Dunn, S P; Widzer, S J; Foley, C M; Breningstall, G N; Grover, W D

    1990-01-01

    Plasmapheresis is used for treating the complications of liver failure. We performed plasmapheresis on 6 children with hepatic encephalopathy resulting from acute hepatic failure and prospectively assessed its effects on neurologic and electrophysiologic (electroencephalography and evoked potentials) function. Clinical improvement was observed in 3 of 6 patients; changes in the serum ammonia value or the results of initial electrophysiologic tests did not predict the patient response. Two patients underwent transplantation after neurologic improvement was produced by plasmapheresis; however, despite plasmapheresis, 4 patients progressed to brain death. Our data demonstrate that plasmapheresis may transiently improve the encephalopathy of acute hepatic failure but is not curative alone. Therefore, plasmapheresis may be a useful adjunct in the treatment of liver failure, potentially improving the pretransplantation status of the patient.

  9. Qualifying and quantifying minimal hepatic encephalopathy.

    PubMed

    Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A; Jackson, Clive D; Kircheis, Gerald; Lauridsen, Mette M; Montagnese, Sara; Schiff, Sami; Weissenborn, Karin

    2016-12-01

    Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables. There is no gold standard for the diagnosis of this syndrome. As these patients have, by definition, no recognizable clinical features of brain dysfunction, the primary prerequisite for the diagnosis is careful exclusion of clinical symptoms and signs. A large number of psychometric tests/test systems have been evaluated in this patient group. Of these the best known and validated is the Portal Systemic Hepatic Encephalopathy Score (PHES) derived from a test battery of five paper and pencil tests; normative reference data are available in several countries. The electroencephalogram (EEG) has been used to diagnose hepatic encephalopathy since the 1950s but, once popular, the technology is not as accessible now as it once was. The performance characteristics of the EEG are critically dependent on the type of analysis undertaken; spectral analysis has better performance characteristics than visual analysis; evolving analytical techniques may provide better diagnostic information while the advent of portable wireless headsets may facilitate more widespread use. A large number of other diagnostic tools have been validated for the diagnosis of minimal hepatic encephalopathy including Critical Flicker Frequency, the Inhibitory Control Test, the Stroop test, the Scan package and the Continuous Reaction Time; each has its pros and cons; strengths and weaknesses; protagonists and detractors. Recent AASLD/EASL Practice Guidelines suggest that the diagnosis of minimal hepatic encephalopathy should be based on the PHES test together with one of the validated alternative techniques or the EEG. Minimal hepatic encephalopathy has a detrimental effect on the well-being of patients and their care

  10. Hepatic Encephalopathy: From the Pathogenesis to the New Treatments

    PubMed Central

    Cordoba, Juan

    2014-01-01

    Hepatic encephalopathy is a frequent and serious complication of liver cirrhosis; the pathophysiology of this complication is not fully understood although great efforts have been made during the last years. There are few prospective studies on the epidemiology of this complication; however, it is known that it confers with high short-term mortality. Hepatic encephalopathy has been classified into different groups depending on the degree of hepatic dysfunction, the presence of portal-systemic shunts, and the number of episodes. Due to the large clinical spectra of overt EH and the complexity of cirrhotic patients, it is very difficult to perform quality clinical trials for assessing the efficacy of the treatments proposed. The physiopathology, clinical manifestation, and the treatment of HE is a challenge because of the multiple factors that converge and coexist in an episode of overt HE. PMID:27335836

  11. Acetyl-L-carnitine in hepatic encephalopathy.

    PubMed

    Malaguarnera, Michele

    2013-06-01

    Hepatic encephalopathy is a common complication of hepatic cirrhosis. The clinical diagnosis is based on two concurrent types of symptoms: impaired mental status and impaired neuromotor function. Impaired mental status is characterized by deterioration in mental status with psychomotor dysfunction, impaired memory, and increased reaction time, sensory abnormalities, poor concentration, disorientation and coma. Impaired neuromotor function include hyperreflexia, rigidity, myoclonus and asterixis. The pathogenesis of hepatic encephalopathy has not been clearly defined. The general consensus is that elevated levels of ammonia and an inflammatory response work in synergy to cause astrocyte to swell and fluid to accumulate in the brain which is thought to explain the symptoms of hepatic encephalopathy. Acetyl-L-carnitine, the short-chain ester of carnitine is endogenously produced within mitochondria and peroxisomes and is involved in the transport of acetyl-moieties across the membranes of these organelles. Acetyl-L-carnitine administration has shown the recovery of neuropsychological activities related to attention/concentration, visual scanning and tracking, psychomotor speed and mental flexibility, language short-term memory, attention, and computing ability. In fact, Acetyl-L-carnitine induces ureagenesis leading to decreased blood and brain ammonia levels. Acetyl-L-carnitine treatment decreases the severity of mental and physical fatigue, depression cognitive impairment and improves health-related quality of life. The aim of this review was to provide an explanation on the possible toxic effects of ammonia in HE and evaluate the potential clinical benefits of ALC.

  12. Medium chain triglycerides and hepatic encephalopathy

    PubMed Central

    Morgan, M. Hilary; Bolton, C. H.; Morris, J. S.; Read, A. E.

    1974-01-01

    The oral administration of short (C6) and medium (C8 and (C10) chain triglycerides produced no clinical or electroencephalographic changes in patients with cirrhosis of the liver. Arterial ammonia levels were also monitored in these patients and showed no significant change after medium chain triglycerides. It was concluded that medium chain triglycerides, known to be of potential value in the treatment of malabsorption in patients with cirrhosis, are not clinically contraindicated, even in patients with evidence of hepatic encephalopathy. PMID:4841275

  13. Prognostic Assessment in Patients with Hepatic Encephalopathy

    PubMed Central

    García-Martínez, Rita; Simón-Talero, Macarena; Córdoba, Juan

    2011-01-01

    Hepatic encephalopathy (HE) is a common complication of liver failure that is associated with poor prognosis. However, the prognosis is not uniform and depends on the underlying liver disease. Acute liver failure is an uncommon cause of HE that carries bad prognosis but is potentially reversible. There are several prognostic systems that have been specifically developed for selecting patients for liver transplantation. In patients with cirrhosis the prognosis of the episode of HE is usually dictated by the underlying precipitating factor. Acute-on-chronic liver failure is the most severe form of decompensation of cirrhosis, the prognosis depends on the number of associated organ failures. Patients with cirrhosis that have experienced an episode of HE should be considered candidates for liver transplant. The selection depends on the underlying liver function assessed by the Model for End-stage Liver Disease (MELD) index. There is a subgroup that exhibits low MELD and recurrent HE, usually due to the coexistence of large portosystemic shunts. The recurrence of HE is more common in patients that develop progressive deterioration of liver function and hyponatremia. The bouts of HE may cause sequels that have been shown to persist after liver transplant. PMID:22045403

  14. Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme

    PubMed Central

    John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

    2017-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome. PMID:28127211

  15. Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme.

    PubMed

    John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

    2017-01-14

    Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome.

  16. Resolution of Hepatic Encephalopathy Following Hepatic Artery Embolization in a Patient with Well-Differentiated Neuroendocrine Tumor Metastatic to the Liver

    SciTech Connect

    Erinjeri, Joseph P. Deodhar, Ajita; Thornton, Raymond H.; Allen, Peter J.; Getrajdman, George I.; Brown, Karen T.; Sofocleous, Constantinos T.; Reidy, Diane L.

    2010-06-15

    Hepatic encephalopathy is considered a contraindication to hepatic artery embolization. We describe a patient with a well-differentiated neuroendocrine tumor metastatic to the liver with refractory hepatic encephalopathy and normal liver function tests. The encephalopathy was refractory to standard medical therapy with lactulose. The patient's mental status returned to baseline after three hepatic artery embolization procedures. Arteriography and ultrasound imaging before and after embolization suggest that the encephalopathy was due to arterioportal shunting causing hepatofugal portal venous flow and portosystemic shunting. In patients with a primary or metastatic well-differentiated neuroendocrine tumor whose refractory hepatic encephalopathy is due to portosystemic shunting (rather than global hepatic dysfunction secondary to tumor burden), hepatic artery embolization can be performed safely and effectively.

  17. Hepatic Encephalopathy and Sleepiness: An Interesting Connection?

    PubMed Central

    Montagnese, Sara; Turco, Matteo; Amodio, Piero

    2015-01-01

    Sleep-wake abnormalities in patients with cirrhosis have been traditionally associated with hepatic encephalopathy (HE). In recent years, a certain amount of work has been devoted to the study of this relationship. This has lead to a modified picture, with weakening of the association between HE and poor night sleep, and the emergence of stronger links between HE and excessive daytime sleepiness. This brief review focuses on the evidence in favor of the interpretation of HE as a sleepiness syndrome, and on the diagnostic, therapeutic and social implications of such an interpretation. PMID:26041958

  18. MRI and CT appearances in metabolic encephalopathies due to systemic diseases in adults.

    PubMed

    Bathla, G; Hegde, A N

    2013-06-01

    The term encephalopathy refers to a clinical scenario of diffuse brain dysfunction, commonly due to a systemic, metabolic, or toxic derangement. Often the clinical evaluation is unsatisfactory in this scenario and imaging plays an important role in the diagnosis, assessment of treatment response, and prognostication of the disorder. Hence, it is important for radiologists to be familiar with the imaging features of some relatively frequently acquired metabolic encephalopathies encountered in the hospital setting. This study reviews the computed tomography (CT) and magnetic resonance imaging (MRI) features of a number of metabolic encephalopathies that occur as part of systemic diseases in adults. The following conditions are covered in this review: hypoglycaemic encephalopathy, hypoxic ischaemic encephalopathy, non-ketotic hyperglycaemia, hepatic encephalopathy, uraemic encephalopathy, hyperammonaemic encephalopathy, and posterior reversible encephalopathy syndrome. MRI is the imaging method of choice in evaluating these conditions. Due to their high metabolic activity, bilateral basal ganglia changes are evident in the majority of cases. Concurrent imaging abnormalities in other parts of the central nervous system often provide useful diagnostic information about the likely underlying cause of the encephalopathy. Besides this, abnormal signal intensity and diffusion restriction patterns on MRI and MR spectroscopy features may provide important clues as to the diagnosis and guide further management. Frequently, the diagnosis is not straightforward and typical imaging features require correlation with clinical and laboratory data for accurate assessment. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  19. Rifaximin, Microbiota Biology, and Hepatic Encephalopathy

    PubMed Central

    Peleman, Cedric; Camilleri, Michael

    2016-01-01

    Rifaximin is beneficial in the treatment of minimal hepatic encephalopathy (MHE). Kang et al. (Clin Transl Gastroenterol 7: e187; doi:10.1038/ctg.2016.44) investigated the effects of rifaximin in a mouse model of MHE-associated microbiota without concomitant liver disease. In addition to some impact on the composition of microbiota, rifaximin altered bacterial functions, ameliorated local and systemic inflammation, and reduced enterocyte glutaminase activity. We discuss these effects as well as the interpretation of the permeability studies, given the potential interaction of dysbiosis with dysfunctional intestinal barrier, leading to systemic inflammation and increased uptake of bacterial metabolites that contribute to MHE in the presence of hepatic dysfunction. PMID:27711069

  20. Diagnosis and Management of Hepatic Encephalopathy in Fulminant Hepatic Failure.

    PubMed

    Kodali, Sudha; McGuire, Brendan M

    2015-08-01

    Hepatic encephalopathy (HE) is associated with cerebral edema (CE), increased intracranial pressure (ICP), and subsequent neurologic complications; it is the most important cause of morbidity and mortality in fulminant hepatic failure. The goal of therapy should be early diagnosis and treatment of HE with measures to reduce CE. A combination of clinical examination and diagnostic modalities can aid in prompt diagnosis. ICP monitoring and transcranial Doppler help diagnose and monitor response to treatment. Transfer to a transplant center and intensive care unit admission with airway management and reduction of CE with hypertonic saline, mannitol, hypothermia, and sedation are recommended as a bridge to liver transplantation.

  1. Factors affecting compliance and persistence with treatment for hepatic encephalopathy.

    PubMed

    Neff, Guy

    2010-05-01

    Noncompliance with treatment protocols produces an increased burden on the health care system. Reports show that 23% of annual admissions to nursing homes in the United States (380,000 patients) are due to noncompliance, resulting in overall costs of over $31 billion. More than 10% of all patients (3.5 million) are hospitalized each year due to complications related to noncompliance, with over $15 billion spent. In addition, nearly half of the 2 billion prescriptions filled each year are not taken correctly. Patients with cirrhosis and hepatic encephalopathy who are prescribed lactulose experience a greater frequency of adverse effects, require more hospitalizations, and suffer more disease recurrence than those prescribed rifaximin.

  2. Legal Responsibilities of Physicians When They Diagnose Hepatic Encephalopathy.

    PubMed

    Vierling, John M

    2015-08-01

    Both covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE) impair the ability to operate machinery. The legal responsibilities of US physicians who diagnose and treat patients with hepatic encephalopathy vary among states. It is imperative that physicians know the laws regarding reporting in their state. OHE represents a neuropsychiatric impairment that meets general reporting criteria. The medical advisory boards of the states have not identified OHE as a reportable condition. In the absence of validated diagnostic guidelines, physicians are not obligated to perform tests for CHE. There is a need for explicit guidance from professional associations regarding this issue.

  3. Clinical and Neurologic Manifestation of Minimal Hepatic Encephalopathy and Overt Hepatic Encephalopathy.

    PubMed

    Basu, P Patrick; Shah, Niraj James

    2015-08-01

    Hepatic encephalopathy (HE) shows a wide spectrum of neuropsychiatric manifestations. A combined effort with neuropsychological and psychometric evaluation has to be performed to recognize the syndrome, whereas minimal HE (MHE) is largely under-recognized. Subtle symptoms of MHE can only be diagnosed through specialized neuropsychiatric testing. Early diagnosis and treatment may drastically improve the quality of life for many cirrhotic patients. Further research to gain better insight into the pathophysiology and diagnostic accuracy of HE will help determine future management strategies.

  4. The role of methanethiol in the pathogenesis of hepatic encephalopathy.

    PubMed

    Blom, H J; Ferenci, P; Grimm, G; Yap, S H; Tangerman, A

    1991-03-01

    Mixed disulfides of methanethiol represent a relative estimate for an exposure to methanethiol. The concentrations of methanethiol-mixed disulfides, methionine, 4-methylthio-2-oxobutyrate and ammonia were measured in patients with different stages of hepatic encephalopathy, in patients with chronic kidney failure and in healthy subjects. In patients with hepatic encephalopathy, the mean serum concentrations of all these compounds were elevated. However, the elevations of methanethiol-mixed disulfides were small and partly caused by decreased renal function. In addition, the levels of methanethiol-mixed disulfides did not differ significantly between the different grades of hepatic encephalopathy. The concentrations of methanethiol-mixed disulfides were substantially lower than those previously observed in healthy subjects after an oral methionine load or in a patient with a deficiency in methionine adenosyltransferase, the latter without causing encephalopathy. We concluded that the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor, if not insignificant. In the patients with hepatic encephalopathy, a significant correlation was found between the concentrations of methionine and 4-methylthio-2-oxobutyrate and between 4-methylthio-2-oxobutyrate and methanethiol-mixed disulfides, supporting the theory that methanethiol is formed by way of the methionine transamination pathway. Evidence is provided that, besides the methionine transsulfuration pathway, the transamination pathway is also impaired in patients with hepatic encephalopathy.

  5. Management of hepatic encephalopathy in the hospital.

    PubMed

    Leise, Michael D; Poterucha, John J; Kamath, Patrick S; Kim, W Ray

    2014-02-01

    Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, L-ornithine-L-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes

  6. Neuronal cell death in hepatic encephalopathy.

    PubMed

    Butterworth, Roger F

    2007-12-01

    It is generally assumed that neuronal cell death is minimal in liver failure and is insufficient to account for the neuropsychiatric symptoms characteristic of hepatic encephalopathy. However, contrary to this assumption, neuronal cell damage and death are well documented in liver failure patients, taking the form of several distinct clinical entities namely acquired (non-Wilsonian) hepatocerebral degeneration, cirrhosis-related Parkinsonism, post-shunt myelopathy and cerebellar degeneration. In addition, there is evidence to suggest that liver failure contributes to the severity of neuronal loss in Wernicke's encephalopathy. The long-standing nature of the thalamic and cerebellar lesions, over 80% of which are missed by routine clinical evaluation, together with the probability that they are nutritional in origin, underscores the need for careful nutritional management (adequate dietary protein, Vitamin B(1)) in liver failure patients. Mechanisms identified with the potential to cause neuronal cell death in liver failure include NMDA receptor-mediated excitotoxicity, lactic acidosis, oxidative/nitrosative stress and the presence of pro-inflammatory cytokines. The extent of neuronal damage in liver failure may be attenuated by compensatory mechanisms that include down-regulation of NMDA receptors, hypothermia and the presence of neuroprotective steroids such as allopregnanolone. These findings suggest that some of the purported "sequelae" of liver transplantation (gait ataxia, memory loss, confusion) could reflect preexisting neuropathology.

  7. Nonconvulsive status epilepticus disguising as hepatic encephalopathy.

    PubMed

    Jo, Yong Min; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Ahn, Ji Hye; Choi, Won Jong; Lee, Ji Young; Kim, Sang Ho; Yoon, Byeol A

    2015-04-28

    Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconvulsive status epilepticus remains unknown, this disorder is thought to lead to neuronal damage, so its identification and treatment are important. Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status. We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status. He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram.

  8. Leucine metabolism in patients with Hepatic Encephalopathy

    SciTech Connect

    McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.

    1986-03-01

    A primed continuous infusion of (/sup 15/N, 1-/sup 13/C)leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet (0.6 g protein per kg ideal body weight (IBW)). An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO/sub 2/ enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy.

  9. Pathophysiology, diagnosis, and management of hepatic encephalopathy.

    PubMed

    Sheasgreen, Christopher; Lu, Lucy; Patel, Ameen

    2014-12-01

    Hepatic encephalopathy (HE) is a common complication of cirrhosis of the liver. It is also extremely debilitating, with an untreated 3-year survival of only 23 %. While the exact pathophysiology of HE has yet to be elucidated, a number of contributing factors have been described. Abnormal levels and altered metabolism of ammonia play a central role. Recently, inflammation has also been identified as a contributor to HE. Improved understanding of the pathophysiology of HE is crucial, as current therapy centers on reduction of the body's ammonia load. Lactulose is the first-line therapy for HE, with some antibiotics recently showing promise for improved outcomes in patients with HE. The role of anti-inflammatory therapies has yet to be evaluated.

  10. Pathogenesis, Diagnosis, and Treatment of Hepatic Encephalopathy

    PubMed Central

    Atluri, Dileep K; Prakash, Ravi; Mullen, Kevin D

    2011-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with advanced liver disease or porto-systemic shunts. Based on etiology and severity of HE, the World Congress of Gastroenterology has divided HE into categories and sub-categories. Many user-friendly computer-based neuropsychiatric tests are being validated for diagnosing covert HE. Currently, emphasis is being given to view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is believed to play crucial role in pathogenesis of HE via astrocyte swelling and cerebral edema. However, evidence has been building up which supports the synergistic role of oxidative stress, inflammation and neurosteroids in pathogenesis of HE. At present, treatment of HE aims at decreasing the production and intestinal absorption of ammonia. But as the role of new pathogenetic mechanisms becomes clear, many potential new treatment strategies may become available for clinician. PMID:25755319

  11. The Treatment of Hepatic Encephalopathy by Colectomy

    PubMed Central

    Singer, H.; Harrison, A. W.; Aggett, P. W.

    1965-01-01

    A 64-year-old alcoholic patient with cirrhosis and bleeding esophageal varices developed hepatic encephalopathy following portacaval shunt. The etiology of this syndrome is believed to be related to the absorption of toxic nitrogenous substances derived from the activity of bacteria in the large bowel. Treatment consisted of a low protein diet, frequent purgation, and oral neomycin. Even on a 20-g. protein diet the patient deteriorated to a state approaching coma. Colectomy with ileorectal anastomosis was performed with good result. The patient remained alert and active with no recurrences of cerebral disturbance while enjoying a 60-g. protein diet. No additional treatment was necessary. The literature on colectomy in the treatment of this condition, while brief, reports similar good results. Further trial of colectomy is recommended for cases refractory to more conservative methods of management. PMID:5831216

  12. Hyponatremia in hepatic encephalopathy: an accomplice or innocent bystander?

    PubMed

    Yun, Byung Cheol; Kim, W Ray

    2009-06-01

    Hyponatremia, a common complication inpatients with advanced liver disease and impaired free water clearance, has been shown to be an important predictor of short-term mortality. Hepatic encephalopathy, also a late complication of end-stage liver disease, has been associated with low-grade cerebral edema as a result of swelling of astrocytes. Guevara et al. hypothesized that hyponatremia and the resultant depletion of organic osmolytes (e.g.,myo-inositol) from brain cells contribute to brain edema, playing an important role in the pathogenesis of hepatic encephalopathy. Using a multivariable analysis, they demonstrated that hyponatremia increased the risk of hepatic encephalopathy more than eightfold, after adjustment for serum bilirubin and creatinine concentrations and previous history of encephalopathy. Their magnetic resonance spectroscopy data correlated low brain concentrations of myoinositol with hepatic encephalopathy. As both hyponatremia and encephalopathy occur in patients with advanced liver disease, it has been difficult to implicate hyponatremia independently in the pathogenesis of hepatic encephalopathy. Guevara's data do suggest that hyponatremia is more likely an accomplice than an innocent bystander.

  13. Hepatic encephalopathy: Ever closer to its big bang.

    PubMed

    Souto, Pablo A; Marcotegui, Ariel R; Orbea, Lisandro; Skerl, Juan; Perazzo, Juan Carlos

    2016-11-14

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder that commonly complicates the course of patients with liver disease. Despite the fact that the syndrome was probably first recognized hundreds of years ago, the exact pathogenesis still remains unclear. Minimal hepatic encephalopathy (MHE) is the earliest form of HE and is estimated to affect more that 75% of patients with liver cirrhosis. It is characterized by cognitive impairment predominantly attention, reactiveness and integrative function with very subtle clinical manifestations. The development of MHE is associated with worsen in driving skills, daily activities and the increase of overall mortality. Skeletal muscle has the ability to shift from ammonia producer to ammonia detoxifying organ. Due to its large size, becomes the main ammonia detoxifying organ in case of chronic liver failure and muscular glutamine-synthase becomes important due to the failing liver and brain metabolic activity. Gut is the major glutamine consumer and ammonia producer organ in the body. Hepatocellular dysfunction due to liver disease, results in an impaired clearance of ammonium and in its inter-organ trafficking. Intestinal bacteria, can also represent an extra source of ammonia production and in cirrhosis, small intestinal bacterial overgrowth and symbiosis can be observed. In the study of HE, to get close to MHE is to get closer to its big bang; and from here, to travel less transited roads such as skeletal muscle and intestine, is to go even closer. The aim of this editorial is to expose this road for further and deeper work.

  14. Hepatic encephalopathy: Ever closer to its big bang

    PubMed Central

    Souto, Pablo A; Marcotegui, Ariel R; Orbea, Lisandro; Skerl, Juan; Perazzo, Juan Carlos

    2016-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder that commonly complicates the course of patients with liver disease. Despite the fact that the syndrome was probably first recognized hundreds of years ago, the exact pathogenesis still remains unclear. Minimal hepatic encephalopathy (MHE) is the earliest form of HE and is estimated to affect more that 75% of patients with liver cirrhosis. It is characterized by cognitive impairment predominantly attention, reactiveness and integrative function with very subtle clinical manifestations. The development of MHE is associated with worsen in driving skills, daily activities and the increase of overall mortality. Skeletal muscle has the ability to shift from ammonia producer to ammonia detoxifying organ. Due to its large size, becomes the main ammonia detoxifying organ in case of chronic liver failure and muscular glutamine-synthase becomes important due to the failing liver and brain metabolic activity. Gut is the major glutamine consumer and ammonia producer organ in the body. Hepatocellular dysfunction due to liver disease, results in an impaired clearance of ammonium and in its inter-organ trafficking. Intestinal bacteria, can also represent an extra source of ammonia production and in cirrhosis, small intestinal bacterial overgrowth and symbiosis can be observed. In the study of HE, to get close to MHE is to get closer to its big bang; and from here, to travel less transited roads such as skeletal muscle and intestine, is to go even closer. The aim of this editorial is to expose this road for further and deeper work. PMID:27895414

  15. Hepatic Encephalopathy: An Update on the Pathophysiology and Therapeutic Options

    PubMed Central

    Elwir, Saleh; Rahimi, Robert S.

    2017-01-01

    Abstract Hepatic encephalopathy is a spectrum of reversible neuropsychiatric abnormalities, seen in patients with liver dysfunction and/or portosystemic shunting. One of the most debilitating complications of cirrhosis, encephalopathy affects 30–45% of cirrhotics. In addition to significantly affecting the lives of patients and their caregivers, it is also associated with increased morbidity and mortality as well as significant utilization of health care resources. In this paper, we provide an overview on the pathophysiology, diagnosis, management and newer therapies of hepatic encephalopathy. PMID:28660152

  16. Assessment of low-grade hepatic encephalopathy: a critical analysis.

    PubMed

    Kircheis, Gerald; Fleig, Wolfgang E; Görtelmeyer, Roman; Grafe, Susanne; Häussinger, Dieter

    2007-11-01

    The value of paper-pencil tests and West-Haven-criteria for assessment of low-grade hepatic encephalopathy under conditions of a randomized, double-blind, placebo-controlled, clinical trial was evaluated in a cohort of 217 cirrhotics. Patients were graded at least twice clinically for severity of hepatic encephalopathy and tested concomitantly with a recommended psychometric test battery. Re-evaluation of the study documentation showed that at study entry 33% and during the study even 50% of the patients were wrongly allocated to minimal or overt hepatic encephalopathy. Despite the participating physicians' training, 31% of the number-connection-tests-A, 20% of the number-connection-tests-B and 28% of the line-tracing-test were in retrospect considered invalid by an independent psychologist. Neither the Portosystemic-Encephalopathy-Syndrome (PSE) test nor the Psychometric-Hepatic-Encephalopathy-Sum (PHES)-score reliably picked up clinical improvement in the individual patient. Although these test scores could statistically differentiate between patients with minimal and overt hepatic encephalopathy, the clinical classification of individual patients into one of the groups will have a high rate of error. The PHES-Score was less balanced than the score derived from the PSE-Syndrome-Test. Inaccuracies in conducting paper-pencil tests together with the subjectivity and incorrectness of clinical HE-grading question the usefulness of West-Haven-criteria and paper-pencil tests including related scores for quantification of low-grade HE at least in multicenter approaches.

  17. Hepatic encephalopathy: An approach to its multiple pathophysiological features

    PubMed Central

    Perazzo, Juan Carlos; Tallis, Silvina; Delfante, Amalia; Souto, Pablo Andrés; Lemberg, Abraham; Eizayaga, Francisco Xavier; Romay, Salvador

    2012-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two- to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in

  18. [Minimal hepatic encephalopathy: characteristics, diagnosis and clinical implications].

    PubMed

    Torre Delgadillo, Aldo; Guerrero-Hernández, Ignacio; Uribe, Misael

    2006-01-01

    The term minimal hepatic encephalopathy (MHE) refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy; the prevalence is as high as 84% in patients with hepatic cirrhosis. This cirrhosis complication is generally not perceived by physician, and diagnosis can only be made by neuropsychological tests and other especial measurements like evoked potentials and image studies like positron emission tomography. Diagnosis of minimal hepatic encephalopathy may have prognostic and therapeutic implications in cirrhotic patients. The present review pretends to explore the clinic, therapeutic, diagnosis and prognostic aspects of this complication.

  19. Paroxysmal Amnesia Attacks due to Hashimoto's Encephalopathy

    PubMed Central

    Nar Senol, Pelin; Bican Demir, Aylin; Bora, Ibrahim; Bakar, Mustafa

    2016-01-01

    Hashimoto's encephalopathy is a rare disease which is thought to be autoimmune and steroid responsive. The syndrome is characterized by cognitive impairment, encephalopathy, psychiatric symptoms, and seizures associated with increased level of anti-thyroid antibodies. The exact pathophysiology underlying cerebral involvement is still lesser known. Although symptoms suggest a nonlesional encephalopathy in most of the cases, sometimes the clinical appearance can be subtle and may not respond to immunosuppressants or immunomodulatory agents. Here we report a case who presented with drowsiness and amnestic complaints associated with paroxysmal electroencephalography (EEG) abnormalities which could be treated only with an antiepileptic drug. PMID:27034679

  20. Hepatic encephalopathy in dogs and cats.

    PubMed

    Lidbury, Jonathan A; Cook, Audrey K; Steiner, Jörg M

    2016-07-01

    To comparatively review the pathogenesis, clinical presentation, diagnosis, and management of hepatic encephalopathy (HE) in dogs and cats. The Medline database was searched for articles related to HE in people, dogs, and cats. Articles published within the last 5 years were given special importance. The pathogenesis of HE is complex and incompletely understood, but ammonia appears to play a central role. Hyperammonemia leads to accumulation of glutamine in astrocytes, with subsequent astrocyte swelling and neurological dysfunction. The development of HE in patients with hepatic cirrhosis is a poor prognostic indicator. The fermentable disaccharide lactulose and the antimicrobial rifaximin are US Food and Drug Administration approved treatments for human HE. Severe protein restriction is no longer recommended for patients with this condition. HE is often associated with portosystemic shunting in dogs and cats. Ammonia plays a central role in the pathogenesis of HE in dogs and cats, but other factors such as manganese and endogenous benzodiazepines may also contribute. Recently, a soy protein-based diet was found to be beneficial in treating canine HE. Severe dietary protein restriction is likely to be detrimental in affected animals. There have been no clinical trials of drugs routinely used in the management HE in veterinary medicine, but lactulose and antimicrobials such as metronidazole are well-established treatments. HE is a potentially life-threatening condition that is probably underdiagnosed in companion animals. Although various treatment recommendations have been proposed, there is a lack of evidence in the veterinary literature regarding optimal strategies for the management of this condition. As our understanding of the pathogenesis of HE in dogs and cats evolves, novel diagnostic tests and therapeutic agents may become available. © Veterinary Emergency and Critical Care Society 2016.

  1. Antibiotics for the treatment of hepatic encephalopathy.

    PubMed

    Patidar, Kavish R; Bajaj, Jasmohan S

    2013-06-01

    The treatment of hepatic encephalopathy (HE) is complex and therapeutic regimens vary according to the acuity of presentation and the goals of therapy. Most treatments for HE rely on manipulating the intestinal milieu and therefore antibiotics that act on the gut form a key treatment strategy. Prominent antibiotics studied in HE are neomycin, metronidazole, vancomycin and rifaximin. For the management of the acute episode, all antibiotics have been tested. However the limited numbers studied, adverse effects (neomycin oto- and nephrotoxicity, metronidazole neurotoxicity) and potential for resistance emergence (vancomycin-resistant enterococcus) has limited the use of most antibiotics, apart from rifaximin which has the greatest evidence base. Rifaximin has also demonstrated, in conjunction with lactulose, to prevent overt HE recurrence in a multi-center, randomized trial. Despite its cost in the US, rifaximin may prove cost-saving by preventing hospitalizations for overt HE. In minimal/covert HE, rifaximin is the only systematically studied antibiotic. Rifaximin showed improvement in cognition, inflammation, quality-of-life and driving simulator performance but cost-analysis does not favor its use at the current time. Antibiotics, especially rifaximin, have a definite role in the management across the spectrum of HE.

  2. Hepatic encephalopathy: a critical current review.

    PubMed

    Hadjihambi, Anna; Arias, Natalia; Sheikh, Mohammed; Jalan, Rajiv

    2017-08-02

    Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of cirrhosis and/or porto-systemic shunting. The clinical symptoms are widely variable, extending from subtle impairment in mental state to coma. The utility of categorizing the severity of HE accurately and efficiently serves not only to provide practical functional information about the current clinical status of the patient but also gives valuable prognostic information. In the past 20-30 years, there has been rapid progress in understanding the pathophysiological basis of HE; however, the lack of direct correlation between pathogenic factors and the severity of HE make it difficult to select appropriate therapy for HE patients. In this review, we will discuss the classification system and its limitations, the neuropsychometric assessments and their challenges, as well as the present knowledge on the pathophysiological mechanisms. Despite the many prevalent hypotheses around the pathogenesis of the disease, most treatments focus on targeting and lowering the accumulation of ammonia as well as inflammation. However, treatment of minimal HE remains a huge unmet need and a big concerted effort is needed to better define this condition to allow the development of new therapies. We review the currently available therapies and future approaches to treat HE as well as the scientific and clinical data that support their effectiveness.

  3. The why and wherefore of hepatic encephalopathy

    PubMed Central

    Grover, Vijay PB; Tognarelli, Joshua M; Massie, Nicolas; Crossey, Mary ME; Cook, Nicola A; Taylor-Robinson, Simon D

    2015-01-01

    Hepatic encephalopathy is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease. It was probably first described by Hippocrates over 2000 years ago, who said that “those whose madness arises from phlegm are quiet and neither shout nor make a disturbance, while those whose madness arises from bile shout, play tricks and will not keep still, but are always up to some mischief ”. He was presumably describing the differences between patients with pneumonia and acute liver failure. Despite the fact that the syndrome was probably first recognized thousands of years ago, the exact pathogenesis still remains unclear. Furthermore, a precise definition of the syndrome is lacking, as are definitive methods of diagnosing this condition. It is important as both patients with cirrhosis and the general population with whom they interact may be affected as a consequence. At a minimum, the individual may be affected by impaired quality of life, impaired ability to work, and slowed reaction times, which are relevant to the population at large if affected individuals operate heavy machinery or drive a car. Pathogenic mechanisms, diagnostic tools, and treatment options are discussed. PMID:26719720

  4. Hepatic encephalopathy in acute-on-chronic liver failure.

    PubMed

    Lee, Guan-Huei

    2015-10-01

    The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

  5. Concise review of current concepts on nomenclature and pathophysiology of hepatic encephalopathy.

    PubMed

    Savlan, Ilona; Liakina, Valentina; Valantinas, Jonas

    2014-01-01

    Hepatic encephalopathy is a neuropsychiatric complication of liver cirrhosis the symptoms of which may vary from imperceptible to severe, invaliding, and even lethal. Minimal hepatic encephalopathy is also important because of its tendency to impair patients' cognitive functions and quality of life. The polyetiological pathogenesis of hepatic encephalopathy is intensively studied. A general consensus exists that not only excess of ammonia but also inflammatory, oxidative, and other processes are significant in the development of hepatic encephalopathy.

  6. Acetylcholinesterase activity in an experimental rat model of Type C hepatic encephalopathy.

    PubMed

    Méndez, Marta; Méndez-López, Magdalena; López, Laudino; Aller, María A; Arias, Jaime; Arias, Jorge L

    2011-05-01

    Patients with liver malfunction often suffer from hepatic encephalopathy, a neurological complication which can affect attention and cognition. Diverse experimental models have been used to study brain alterations that may be responsible for hepatic encephalopathy symptoms. The aim of the study was to determine whether cognitive impairment found in cirrhosis could be due to disturbance of acetylcholinesterase activity. Acetylcholinesterase activity was assessed in the brains of Wistar rats with thioacetamide-induced cirrhosis. The cirrhotic group displayed up-regulation of acetylcholinesterase levels in the entorrhinal cortex, anterodorsal and anteroventral thalamus and accumbens, whereas down-regulation was found in the CA1, CA3 and dentate gyrus of the hippocampus. Our results indicate that the experimental model of hepatic encephalopathy by chronic administration of thioacetamide presents alterations of acetylcholinesterase activity in brain limbic system regions, which play a role in attention and memory.

  7. Putative precipitating factors for hepatic encephalopathy in dogs: 118 cases (1991-2014).

    PubMed

    Lidbury, Jonathan A; Ivanek, Renata; Suchodolski, Jan S; Steiner, Jörg M

    2015-07-15

    To elucidate the relationship between plasma ammonia concentration and severity of hepatic encephalopathy and determine whether factors that precipitate hepatic encephalopathy in humans are associated with the presence of clinical signs of hepatic encephalopathy in dogs previously treated for the disease. Retrospective case series. 118 dogs with hepatic encephalopathy. The medical records database of a veterinary teaching hospital was searched for records of dogs in which hepatic encephalopathy was diagnosed between October 1, 1991, and September 1, 2014. Hepatic encephalopathy severity was graded on a 5-point scale, and the correlation between disease severity and plasma ammonia concentration was determined. Respective associations between hepatic encephalopathy and systemic inflammatory response syndrome, gastrointestinal hemorrhage, dietary indiscretion, constipation, furosemide treatment, azotemia, hypokalemia, hyponatremia, alkalosis, and hyperammonemia were assessed by Fisher exact tests followed by multivariable logistic regression. Severity of hepatic encephalopathy at hospital admission was not significantly correlated with plasma ammonia concentration. Dogs treated for hepatic encephalopathy prior to hospital admission were significantly less likely to have clinical signs of the disease at hospital admission, compared with dogs that were not treated for the disease (OR, 0.36; 95% confidence interval, 0.17 to 0.78). None of the putative precipitating factors for hepatic encephalopathy were significantly associated with the presence of clinical signs of the disease at hospital admission. Results indicated that hepatic encephalopathy treatment alleviated clinical signs of the disease. Further investigation is necessary to identify precipitating factors for hepatic encephalopathy in dogs.

  8. Covert and Overt Hepatic Encephalopathy: Diagnosis and Management.

    PubMed

    Patidar, Kavish R; Bajaj, Jasmohan S

    2015-11-01

    Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into 2 broad categories based on severity: covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE). CHE has a significant impact on a patient's quality of life, driving performance, and recently has been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, early diagnosis and management are imperative. In addition, focus also should be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of nonabsorbable disaccharides, antibiotics (ie, rifaximin), and, potentially, probiotics. Other therapies currently under further investigation include L-ornithine-L-aspartate, ornithine phenylacetate, glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion.

  9. Gut Microbiota: Its Role in Hepatic Encephalopathy

    PubMed Central

    Rai, Rahul; Saraswat, Vivek A.; Dhiman, Radha K.

    2015-01-01

    Ammonia, a key factor in the pathogenesis of hepatic encephalopathy (HE), is predominantly derived from urea breakdown by urease producing large intestinal bacteria and from small intestine and kidneys, where the enzyme glutaminases releases ammonia from circulating glutamine. Non-culture techniques like pyrosequencing of bacterial 16S ribosomal ribonucleic acid are used to characterize fecal microbiota. Fecal microbiota in patients with cirrhosis have been shown to alter with increasing Child-Turcotte-Pugh (CTP) and Model for End stage Liver Disease (MELD) scores, and with development of covert or overt HE. Cirrhosis dysbiosis ratio (CDR), the ratio of autochthonous/good bacteria (e.g. Lachnospiraceae, Ruminococcaceae and Clostridiales) to non-autochthonous/pathogenic bacteria (e.g. Enterobacteriaceae and Streptococcaceae), is significantly higher in controls and patients with compensated cirrhosis than patients with decompensated cirrhosis. Although their stool microbiota do not differ, sigmoid colonic mucosal microbiota in liver cirrhosis patients with and without HE, are different. Linkage of pathogenic colonic mucosal bacteria with poor cognition and inflammation suggests that important processes at the mucosal interface, such as bacterial translocation and immune dysfunction, are involved in the pathogenesis of HE. Fecal microbiome composition does not change significantly when HE is treated with lactulose or when HE recurs after lactulose withdrawal. Despite improving cognition and endotoxemia as well as shifting positive correlation of pathogenic bacteria with metabolites, linked to ammonia, aromatic amino acids and oxidative stress, to a negative correlation, rifaximin changes gut microbiome composition only modestly. These observations suggest that the beneficial effects of lactulose and rifaximin could be associated with a change in microbial metabolic function as well as an improvement in dysbiosis. PMID:26041954

  10. Higher Grades and Repeated Recurrence of Hepatic Encephalopathy May Be Related to High Serum Manganese Levels.

    PubMed

    Kobtan, Abdelrahman A; El-Kalla, Ferial S; Soliman, Hanan H; Zakaria, Soha S; Goda, Mohamed A

    2016-02-01

    Hepatic encephalopathy is a serious complication of liver failure. Until now, the precise pathophysiologic mechanisms are not fully determined. It has been demonstrated that manganese plays an important role in the pathogenesis of hepatic encephalopathy. Therefore, we studied manganese levels in serum of cirrhotic patients with hepatic encephalopathy in relation to grading and recurrence of hepatic encephalopathy. One hundred persons were enrolled in the study, 80 cirrhotic patients with or without encephalopathy and 20 healthy controls. Hepatic encephalopathy was diagnosed clinically and by laboratory findings. Serum manganese levels were measured in all participants. The grading of hepatic encephalopathy was significantly correlated to the severity of liver dysfunction. The mean serum manganese level was significantly higher in cirrhotic patients than in controls and in cirrhotic patients with encephalopathy than in those without encephalopathy. It was also significantly higher in patients with advanced grading of hepatic encephalopathy. Serum manganese level was positively correlated to number of recurrences of encephalopathy during a 6-month follow-up period. Serum manganese levels were able to predict recurrence of hepatic encephalopathy within 6 months following the episode. Serum manganese levels are positively correlated to the modified Child-Pugh score of cirrhosis as well as grading and number of recurrences of hepatic encephalopathy. Higher manganese levels seem to be related to worsening of the condition, and its measurement may be used as a predictor of repeated recurrences.

  11. Nutritional assessment in cirrhotic patients with hepatic encephalopathy

    PubMed Central

    Romeiro, Fernando Gomes; Augusti, Laís

    2015-01-01

    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. PMID:26730273

  12. Should We Treat Minimal/Covert Hepatic Encephalopathy, and with What?

    PubMed

    Henderson, Phillip K; Herrera, Jorge L

    2015-08-01

    Hepatic encephalopathy exists along a continuum from abnormal neuropsychiatric testing in the absence of clinical findings to varying degrees of detectable clinical findings. The International Society for Hepatic Encephalopathy and Nitrogen Metabolism has endorsed the term "covert" to encompass minimal hepatic encephalopathy and grade I overt hepatic encephalopathy. Covert hepatic encephalopathy has been associated with poor quality of life, decreased employment, increased falls, and increased traffic accidents that significantly impact quality of life and health care expenditures. Probiotics, nonabsorbable dissacharides, rifaximin, and l-ornithine-l-aspartate have been evaluated with varying levels of success. Because of the lack of universally accepted diagnostic tools, optimal timing of testing and treatment remains controversial.

  13. Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions.

    PubMed

    Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

    2016-07-15

    Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy.

  14. Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

    PubMed Central

    Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

    2016-01-01

    Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID:27377741

  15. Quantitative analysis of brain magnetic resonance imaging for hepatic encephalopathy

    NASA Astrophysics Data System (ADS)

    Syh, Hon-Wei; Chu, Wei-Kom; Ong, Chin-Sing

    1992-06-01

    High intensity lesions around ventricles have recently been observed in T1-weighted brain magnetic resonance images for patients suffering hepatic encephalopathy. The exact etiology that causes magnetic resonance imaging (MRI) gray scale changes has not been totally understood. The objective of our study was to investigate, through quantitative means, (1) the amount of changes to brain white matter due to the disease process, and (2) the extent and distribution of these high intensity lesions, since it is believed that the abnormality may not be entirely limited to the white matter only. Eleven patients with proven haptic encephalopathy and three normal persons without any evidence of liver abnormality constituted our current data base. Trans-axial, sagittal, and coronal brain MRI were obtained on a 1.5 Tesla scanner. All processing was carried out on a microcomputer-based image analysis system in an off-line manner. Histograms were decomposed into regular brain tissues and lesions. Gray scale ranges coded as lesion were then brought back to original images to identify distribution of abnormality. Our results indicated the disease process involved pallidus, mesencephalon, and subthalamic regions.

  16. The role of astrocytes in the development of hepatic encephalopathy.

    PubMed

    Matsushita, M; Yamamoto, T; Gemba, H

    1999-09-01

    Thioacetamide (TAA), a hepatotoxin used to ascertain the role of astrocytes in hepatic encephalopathy, was administered to prepare four experimental groups of rats. (The TAA1D, TAA1.5D, TAA2D, and TAA2.5D group rats were perfusion fixated with formalin at 1, 1.5, 2, and 2.5 days, respectively, after initial administration of TAA. In addition, TAA was readministered to the TAA2D and TAA2.5D rats 24 h after the first dose.) Abnormalities of higher brain function and equilibrium that progressed with time were apparent in the rats receiving TAA. On the other hand, innate reflexes (e.g. pupillary reflex) were similar to those in the normal control group. Astrocyte cell areas in the hippocampus, neocortex, hypothalamus, cerebellum, and basal ganglia (striatum) from the TAA rats were significantly larger than in corresponding sites from the normal rats (maximum in TAA1D and TAA1.5D groups). However, there were no differences with respect to the midbrain. Any morphological difference was not observed in neurons between the hepatic encephalopathy and normal rats. Administration of TAA caused hepatic tissue injury that progressed over time. Surprisingly, encephalopathy was apparent even when hepatic injury was mild. These findings suggest that abnormalities in astrocytes, which precede any abnormal change in neurons, play a role in the development of hepatic encephalopathy.

  17. Protein restriction in hepatic encephalopathy is appropriate for selected patients: a point of view.

    PubMed

    Nguyen, Douglas L; Morgan, Timothy

    2014-09-01

    Since the late nineteenth century, protein restriction has been shown to improve hepatic encephalopathy. However, malnutrition has been described in up to 60 % of cirrhotic patients and is associated with increased mortality. Furthermore, emerging clinical evidence has revealed that a large proportion of cirrhotic patients may tolerate normal protein intake. However, approximately one third of cirrhotic patients with hepatic encephalopathy may need a short course of protein restriction, in addition to maximum medical therapy, to ameliorate the clinical course of their hepatic encephalopathy. For patients with chronic hepatic encephalopathy who are protein-sensitive, modifying their sources of nitrogen by using more vegetable protein, less animal protein, and branched-chain amino acids may improve their encephalopathy without further loss of lean body mass. In conclusion, among cirrhotics with hepatic encephalopathy, modulation of normal protein intake must take into account the patient's hepatic reserve, severity of hepatic encephalopathy, and current nutritional status.

  18. Post-TIPS Hepatic Encephalopathy Treated by Occlusion Balloon-Assisted Retrograde Embolization of a Coexisting Spontaneous Splenorenal Shunt

    SciTech Connect

    Shioyama, Yasukazu; Matsueda, Kiyoshi; Horihata, Koushi; Kimura, Masashi; Nishida, Norifumi; Kishi, Kazushi; Terada, Masaki; Sato, Morio; Yamada, Ryusaku

    1996-11-15

    A 51-year-old man with posthepatitis cirrhosis underwent a transjugular intrahepatic portosystemic shunt (TIPS) for bleeding of recurrent esophageal varices. The patient had a coexisting, spontaneous, splenorenal shunt. He subsequently developed hepatic encephalopathy, presumably due to excessive portosystemic shunting. Since medical management resulted in no significant improvement, the splenorenal shunt was embolized from the jugular vein approach via renal vein access during temporary balloon occlusion. Within a few days, the patient's hepatic encephalopathy resolved. Twelve months later the patient showed no recurrence of encephalopathy and had maintained a patent TIPS.

  19. Blood manganese levels in patients with hepatic encephalopathy.

    PubMed

    Zerón, Hugo Mendieta; Rodríguez, Mónica Rodríguez; Montes, Sergio; Castañeda, Camilo Ríos

    2011-12-01

    Hepatic encephalopathy is an increasingly common disease. Identification of prognosis risk factors in patients with liver damage may lead to preventive actions, towards decreasing its mortality. Manganese (Mn) levels are increased in basal ganglia of patients with hepatic encephalopathy as well as in cases of cirrhotic and liver failure patients. The present is a clinical, prospective, prolective and observational study developed at the Internal Medicine Service from "Dr. Darío Fernández Fierro" General Hospital, ISSSTE, Mexico City. The objective of this work was to report whole blood Mn levels and mortality in encephalopathic patients. Consecutive patients over 18 years of age, diagnosed with hepatic encephalopathy were recruited at the emergency room service. An informed consent, signed by their families was collected. Patients' clinical characteristics, biochemical tests of renal function, hemoglobin, glucose, bilirubins and albumin levels were obtained along with a blood sample to analyze Mn. Patients evolution was followed up for 6 months. Blood Mn in patients [median, (range)] [20.5, (10.5-39.5) μg/L] were higher than blood levels from a group of healthy volunteers [7.5, (6.1-12.8) μg/L] (P<0.001). Among 9 patients studied four died, 2 women and 2 men, those patients showed higher (P=0.032) Mn levels [28, (17-39.5) μg/L] than those alive [13.5, (10.5-32) μg/L] after the follow up period. In this pilot study, Mn blood levels were higher in hepatic encephalopathy that died as consequence of the disease that those that survived in a 6 month follow up period. Blood Mn could be a potential prognosis factor for death in patients with hepatic encephalopathy. Copyright © 2011 Elsevier GmbH. All rights reserved.

  20. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

    SciTech Connect

    Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A. )

    1990-03-01

    Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. (3H) gamma-aminobutyric acid, (14C) butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of (3H) gamma-aminobutyric acid and (113mIn) transferrin were calculated using (14C) butanol as the highly extracted reference compound. The (113mIn) transferrin data were also used to correct the brain uptake index of (3H) gamma-aminobutyric acid for intravascular retention of (3H) gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid (3H) gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy.

  1. Hepatic Encephalopathy: Early Diagnosis in Pediatric Patients With Cirrhosis

    PubMed Central

    DARA, Naghi; SAYYARI, Ali-Akbar; IMANZADEH, Farid

    2014-01-01

    Objective As acute liver failure (ALF) and chronic liver disease (cirrhosis) continue to increase in prevalence, we will see more cases of hepatic encephalopathy. Primary care physician are often the first to suspect it, since they are familiar with the patient’s usual physical and mental status. This serious complication typically occurs in patients with severe comorbidities and needs multidisciplinary evaluation and care. Hepatic encephalopathy should be considered in any patient with acute liver failure and cirrhosis who presents with neuropsychiatric manifestations, decrease level of consciousness (coma), change of personality, intellectual and behavioral deterioration, speech and motor dysfunction. Every cirrhotic patient may be at risk; potential precipitating factors should be addressed in regular clinic visits. The encephalopathy of liver disease may be prominent, or can be present in subtle forms, such as decline of school performance, emotional outbursts, or depression. “Subtle form” of hepatic encephalopathy may not be obvious on clinical examination, but can be detected by neurophysiologic and neuropsychiatric testing. PMID:24665321

  2. Fatal rhinocerebral mucormycosis under the shade of hepatic encephalopathy.

    PubMed

    Ataseven, Hilmi; Yüksel, Ilhami; Gültuna, Selcan; Köklü, Seyfettin; Uysal, Serkan; Basar, Omer; Sasmaz, Nurgül

    2010-01-01

    Mucormycosis is an acutely fatal infection that occurs in immuncompromised patients. Cirrhosis is an acquired immune deficiency state and those patients are more prone to develop opportunistic infections. A 42-years-old cirrhotic man was admitted to our gastroenterology clinic with hepatic encephalopathy. Although he recovered from encephalopathy with supportive measurements, he developed paresthesia on the face. He was diagnosed with rhinocerebral mucormycosis and antifungal therapy was administered. Surgical treatment couldn.t be performed because of his bleeding diathesis and poor general condition. He succumbed on the 12th day of his admission.

  3. The Role of Sarcopenia and Frailty in Hepatic Encephalopathy Management.

    PubMed

    Lucero, Catherine; Verna, Elizabeth C

    2015-08-01

    Normal regulation of total body and circulating ammonia requires a delicate interplay in ammonia formation and breakdown between several organ systems. In the setting of cirrhosis and portal hypertension, the decreased hepatic clearance of ammonia leads to significant dependence on skeletal muscle for ammonia detoxification; however, cirrhosis is also associated with muscle depletion and decreased functional muscle mass. Thus, patients with diminished muscle mass and sarcopenia may have a decreased ability to compensate for hepatic insufficiency and a higher likelihood of developing physiologically significant hyperammonemia and hepatic encephalopathy.

  4. The burden of hepatic encephalopathy in Latin America.

    PubMed

    Dávalos Moscol, Milagros; Bustios Sanchez, Carla

    2011-06-01

    Hepatic encephalopathy (HE) is a neuropsychiatric syndrome characterized by changes in cognitive function, behavior, and personality, as well as by transient neurological symptoms and electroencephalographic changes, which occur in the context of acute or chronic liver failure. Cirrhosis is the main disease associated to HE, and it is known that its incidence is increasing worldwide. As a cause of mortality, cirrhosis is ranked 14 worldwide, but 10 in developed countries. It has been demonstrated that the incidence of liver disease is increasing, in part because of the ascending prevalence of NAFLD, HCV, HCC, as well of alcohol consumption. The real incidence of cirrhosis in Latin America is unknown, although in some Latin American countries that provided national data, cirrhosis death rates were between 5 and 17/100,000 for men and 3 and 5/100,000 for women. Disability, quality of life, and social aspects should be considered when assessing the impact of a disease. In this context, preliminary estimates of the global burden of disease attributable to chronic liver disease seem to be substantial. Hepatic encephalopathy, a main complication of liver failure, occurs in 30-45% of patients as overt encephalopathy, but when subclinical or minimal hepatic encephalopathy (MHE) is considered, estimates of the incidence of encephalopathy vary from 20 to 60%. In USA, the 2009 NIH Report on the Costs of Digestive Diseases stated that liver disease was the second most costly disease in direct and indirect costs (13.1 billion dollars). Although the economic cost of HE has not been assessed, it is obvious that the economic impact of HE on daily activities of living is extremely high, as the costs of diminished work performance and lost wages are substantial.

  5. Contributions of microdialysis to new alternative therapeutics for hepatic encephalopathy.

    PubMed

    Rivera-Espinosa, Liliana; Floriano-Sánchez, Esaú; Pedraza-Chaverrí, José; Coballase-Urrutia, Elvia; Sampieri, Aristides Iii; Ortega-Cuellar, Daniel; Cárdenas-Rodríguez, Noemí; Carmona-Aparicio, Liliana

    2013-08-05

    Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease.

  6. Contributions of Microdialysis to New Alternative Therapeutics for Hepatic Encephalopathy

    PubMed Central

    Rivera-Espinosa, Liliana; Floriano-Sánchez, Esaú; Pedraza-Chaverrí, José; Coballase-Urrutia, Elvia; Sampieri, Aristides; Ortega-Cuellar, Daniel; Cárdenas-Rodríguez, Noemí; Carmona-Aparicio, Liliana

    2013-01-01

    Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease. PMID:23921686

  7. Extracorporeal blood detoxification by sorbents in treatment of hepatic encephalopathy.

    PubMed

    Ash, Stephen R

    2002-01-01

    Extracorporeal blood detoxification by sorbent therapy long has been applied in treatment of hepatic failure and encephalopathy, starting with hemoperfusion columns and more recently with the currently marketed Liver Dialysis Unit. Liver Dialysis employs hemodiabsorption (dialysis of blood against powdered sorbents including charcoal and cation exchanger) to remove selectively numerous small-molecular-weight toxins of hepatic failure. Liver Dialysis is used in treatment of acute hepatic encephalopathy (AHE) because of decompensation of chronic liver disease (A-on-C) or fulminant hepatic failure (FHF). Controlled, prospective and randomized studies of daily 6-hour Liver Dialysis have shown physiologic and neurologic improvement of patients with AHE, regardless of etiology. Liver dialysis significantly improved the incidence of positive outcomes (recovery of hepatic function or improvement for transplant) of A-on-C patients versus controls (71.5% treated, and 35.7% control, P =.036), but had an insignificant improvement in outcome of patients with FHF as compared with the control group. Other extracorporeal sorbent devices are now in clinical testing phase. The molecular adsorbent regenerating system (MARS) device employs a polysulfone high-permeability dialyzer with albumin on the dialysate side to aid transfer of protein-bound toxins such as bilirubin and bile acids across the membranes. Sorbent columns of charcoal and an anion exchanger remove hepatic toxins from the albumin dialysate, and a second dialyzer removes water-soluble toxins, such as ammonium. Clinical results of daily MARS treatments of patients with hepatic failure are similar to that of Liver Dialysis, with neurologic and physical improvement occurs in most patients with AHE, and improved outcome for patients with A-on-C. The system extends the life of patients with hepatorenal syndrome. PF-Liver Dialysis is an experimental device combining hemodiabsorption with push-pull sorbent-based pheresis with

  8. Covert Hepatic Encephalopathy: Who Should Be Tested and Treated?

    PubMed

    Flamm, Steven L

    2015-08-01

    Covert hepatic encephalopathy is a common problem in cirrhosis, affecting up to 80% of patients. It is defined as test-dependent brain dysfunction with clinical consequences in the setting of cirrhosis in patients who are not disoriented. Because it is not apparent clinically, and diagnostic testing has not been standardized, the issue has often been ignored in clinical practice. Yet, the clinical consequences are notable, including impaired quality of life, diminished work productivity, and poor driving skills.

  9. Percutaneous transhepatic obliteration and percutaneous transhepatic sclerotherapy for intractable hepatic encephalopathy and gastric varices improves the hepatic function reserve.

    PubMed

    Ishikawa, Toru; Imai, Michitaka; Ko, Masayoshi; Sato, Hiroki; Nozawa, Yujiro; Sano, Tomoe; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

    2017-01-01

    Percutaneous transhepatic obliteration (PTO) and percutaneous transhepatic sclerotherapy (PTS) are widely performed as an emergency measure in cases of variceal hemorrhage and intractable hepatic encephalopathy. The PTO/PTS technique is capable of directly blocking the blood supply in cases in which balloon-occluded retrograde transvenous obliteration (B-RTO) is not effective, or in cases with complicated collateral flow. Although PTO/PTS is not currently the first choice due to the invasiveness of transhepatic puncture, this procedure can modify the blood flow in an antegrade manner. The present study examined the changes in hepatic function reserve following PTO/PTS for intractable hepatic encephalopathy and/or gastric varices. In total, the study included 37 patients (mean age, 61.75±12.77 years; age range, 32-88 years; male to female ratio, 23:14) with a variety of gastrorenal shunts, or B-RTO-intractable hepatic encephalopathy and gastric varices without gastrorenal shunts. The patients underwent PTO/PTS by embolizing a microcoil or injection of a sclerosing agent (5% ethanolamine oleate iopamidol). Alterations in hepatic function reserve prior to and following the procedure were compared. The patients were treated for hepatic encephalopathy in 11 patients, gastric varices in 19 patients, and both conditions in 7 patients. The results indicated that the blood ammonia level improved from 135.76±75.23 mg/dl to 88.00±42.16 and 61.81±33.75 mg/dl at 3 and 6 months after therapy, respectively. In addition, the Child-Pugh score improved from 8.48±2.01 prior to therapy to 7.70±1.84 and 7.22±2.01 at 3 and 6 months after the procedure, respectively. Although there was a concern that PTO/PTS may cause complications due to an increase in portal venous pressure (PVP) arising from shunt occlusion, no severe complications were observed. In conclusion, for patients with various gastrorenal shunts or those with B-RTO-intractable hepatic encephalopathy and gastric

  10. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline

    PubMed Central

    2014-01-01

    and that CCL2 is involved in both the microglia activation and neurological decline associated with hepatic encephalopathy. Methods used to modulate CCL2 levels and/or reduce CCR2/CCR4 activity may be potential therapeutic targets for the management of hepatic encephalopathy due to acute liver injury. PMID:25012628

  11. Surgical attenuation of spontaneous congenital portosystemic shunts in dogs resolves hepatic encephalopathy but not hypermanganesemia.

    PubMed

    Gow, Adam G; Frowde, Polly E; Elwood, Clive M; Burton, Carolyn A; Powell, Roger M; Tappin, Simon W; Foale, Rob D; Duncan, Andrew; Mellanby, Richard J

    2015-10-01

    Hypermanganesemia is commonly recognized in human patients with hepatic insufficiency and portosystemic shunting. Since manganese is neurotoxic, increases in brain manganese concentrations have been implicated in the development of hepatic encephalopathy although a direct causative role has yet to be demonstrated. Evaluate manganese concentrations in dogs with a naturally occurring congenital shunt before and after attenuation as well as longitudinally following the changes in hepatic encephalopathy grade. Our study demonstrated that attenuation of the shunt resolved encephalopathy, significantly reduced postprandial bile acids, yet a hypermanganasemic state persisted. This study demonstrates that resolution of hepatic encephalopathy can occur without the correction of hypermanganesemia, indicating that increased manganese concentrations alone do not play a causative role in encephalopathy. Our study further demonstrates the value of the canine congenital portosystemic shunt as a naturally occurring spontaneous model of human hepatic encephalopathy.

  12. Hepatic Encephalopathy Secondary to Intrahepatic Portosystemic Venous Shunt: Balloon-Occluded Retrograde Transvenous Embolization with n-Butyl Cyanoacrylate and Microcoils

    SciTech Connect

    Yamagami, Takuji; Nakamura, Toshiyuki; Iida, Shigeharu; Kato, Takeharu; Tanaka, Osamu; Matsushima, Shigenori; Ito, Hirotoshi; Okuyama, Chio; Ushijima, Yo; Shiga, Kensuke; Nishimura, Tsunehiko

    2002-06-15

    We report a 70-year-old woman with hepatic encephalopathy due to an intrahepatic portosystemic venous shunt that was successfully occluded by percutaneous transcatheter embolization with n-butyl cyanoacrylate and microcoils.

  13. Hepatic encephalopathy: what the multidisciplinary team can do

    PubMed Central

    Liu, Andy; Yoo, Eric R; Siddique, Osama; Perumpail, Ryan B; Cholankeril, George; Ahmed, Aijaz

    2017-01-01

    Hepatic encephalopathy (HE) is a complex disease requiring a multidisciplinary approach among specialists, primary care team, family, and caregivers. HE is currently a diagnosis of exclusion, requiring an extensive workup to exclude other possible etiologies, including mental status changes, metabolic, infectious, traumatic, and iatrogenic causes. The categorization of HE encompasses a continuum, varying from the clinically silent minimal HE (MHE), which is only detectable using psychometric tests, to overt HE, which is further divided into four grades of severity. While there has been an increased effort to create fast and reliable methods for the detection of MHE, screening is still underperformed due to the lack of standardization and efficient methods of diagnosis. The management of HE requires consultation from various disciplines, including hepatology, primary care physicians, neurology, psychiatry, dietician/nutritionist, social workers, and other medical and surgical subspecialties based on clinical presentation and clear communication among these disciplines to best manage patients with HE throughout their course. The first-line therapy for HE is lactulose with or without rifaximin. Following the initial episode of overt HE, secondary prophylaxis with lactulose and/or rifaximin is indicated with the goal to prevent recurrent episodes and improve quality of life. Recent studies have demonstrated the negative impact of MHE on quality of life and clinical outcomes. In light of all this, we emphasize the importance of screening and treating MHE in patients with liver cirrhosis, particularly through a multidisciplinary team approach. PMID:28392702

  14. Advances in cirrhosis: Optimizing the management of hepatic encephalopathy

    PubMed Central

    Liu, Andy; Perumpail, Ryan B; Kumari, Radhika; Younossi, Zobair M; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Hepatic encephalopathy (HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE (CHE) and overt HE (OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis. PMID:26692331

  15. Hyperammonemic encephalopathy due to suture line breakdown after bladder operation.

    PubMed

    Boogerd, W; Zoetmulder, F A; Moffie, D

    1990-01-01

    A patient is described with a severe encephalopathy and hyperammonemia in absence of liver dysfunction, attributed to urine absorption into the systemic circulation due to suture line breakdown after bladder dome resection. At autopsy characteristic Alzheimer type II astrocytes were found in the basal ganglia.

  16. Diagnosis and Treatment of Low-Grade Hepatic Encephalopathy.

    PubMed

    Direkze, Shamindra; Jalan, Rajiv

    2015-01-01

    Minimal hepatic encephalopathy (mHE) is common among patients with cirrhotic liver disease and causes significant morbidity and mortality. It may present as cognitive impairment, behavioural changes and, less frequently, with neurological symptoms which make diagnosis of the disease challenging. A history of falls and accidents may also be suggestive of mHE. Diagnosis primarily relies on at least two positive psychometric tests of which the psychometric hepatic encephalopathy score (PHES) is essential. Alternatively, PHES and an electroencephalogram may be used to establish a diagnosis. Biochemical markers of encephalopathy currently have no role in the diagnosis of mHE. Treatment is not always advocated for a diagnosis of mHE but is dependent on the degree of impairment caused by the symptoms. After treatment of other metabolic abnormalities and co-morbidities associated with cirrhosis, more specific treatment for mHE largely relies on therapies used to lower ammonia levels. Laxatives and rifaximin are commonly used in treatment and work through decreasing ammonia absorption from the gut. Other therapies, such as BCAA, LOLA, L-carnitine and phenylbutyrate, modify responses to ammonia as well as enhancing metabolism and excretion. mHE resulting from spontaneous portosystemic shunts or transhepatic intraportal systemic shunts may require ablation or reduction of the shunt. Early detection and appropriate treatment of mHE is important to prevent significant cognitive impairments and progression to overt HE.

  17. Evaluation of two experimental models of hepatic encephalopathy in rats.

    PubMed

    García-Moreno, L M; Conejo, N M; González-Pardo, H; Aller, M A; Nava, M P; Arias, J; Arias, J L

    2005-01-01

    The serious neuropsychological repercussions of hepatic encephalopathy have led to the creation of several experimental models in order to better understand the pathogenesis of the disease. In the present investigation, two possible causes of hepatic encephalopathy, cholestasis and portal hypertension, were chosen to study the behavioral impairments caused by the disease using an object recognition task. This working memory test is based on a paradigm of spontaneous delayed non-matching to sample and was performed 60 days after surgery. Male Wistar rats (225-250 g) were divided into three groups: two experimental groups, microsurgical cholestasis (N = 20) and extrahepatic portal hypertension (N = 20), and a control group (N = 20). A mild alteration of the recognition memory occurred in rats with cholestasis compared to control rats and portal hypertensive rats. The latter group showed the poorest performance on the basis of the behavioral indexes tested. In particular, only the control group spent significantly more time exploring novel objects compared to familiar ones (P < 0.001). In addition, the portal hypertension group spent the shortest time exploring both the novel and familiar objects (P < 0.001). These results suggest that the existence of portosystemic collateral circulation per se may be responsible for subclinical encephalopathy.

  18. [Role of rifaximin in the treatment of hepatic encephalopathy].

    PubMed

    Sanchez-Delgado, Jordi; Miquel, Mireia

    2016-04-01

    Hepatic encephalopathy (HE) is a frequent and serious complication of liver cirrhosis. In addition to correction of the precipitating factors, the most commonly used treatments are non-absorbable disaccharides and rifaximin. Many of the recommendations are based on current clinical practice and there are few randomized controlled trials. Currently, rifaximin should be initiated during an episode of EH if, after 24-48 hours of non-absorbable disaccharide therapy, there is no clinical improvement. In recurrent EH, it is advisable to add rifaximin in patients under non-absorbable disaccharide therapy who develop a new episode. Currently, standard treatment with rifaximin for minimal EH is not recommended. Rifaximin is effective in the acute treatment of overt encephalopathy and in preventing recurrence.

  19. Hyperekplexia and trismus due to brainstem encephalopathy

    PubMed Central

    Kellett, M.; Humphrey, P.; Tedman, B.; Steiger, M.

    1998-01-01

    The brainstem is said to be the generator of pathological startle responses due to reticular reflex myoclonus or hyperekplexia. A patient with facial weakness, nystagmus, and pyramidal tract signs had generalised reflex spasms in response to auditory, visual and tactile stimuli which clinically and neurophysiologically resembled hyperekplexia. The case is unusual because as well as hyperekplexia, the patient's initial presentation was with an equally rare manifestation of brainstem pathology—brainstem mediated trismus. The causes of brainstem trismus and exaggerated startle responses are discussed with respect to their underlying mechanisms. 

 PMID:9667574

  20. Hepatic encephalopathy: cause and possible management with botanicals.

    PubMed

    Tripathi, Suyash; Tripathi, Yamini B

    2014-01-01

    Hepatic encephalopathy is a brain functional disorder, characterized by neuropsychiatric abnormalities with liver failure. High blood ammonia, causing glutamate neurotoxicity is the basic cause, finally leading to low-grade cerebral edema. Its manifestation is more likely in patients of sepsis, oxidative stress, generalized inflammation, gut mal-functioning, amoebiaesis, viral hepatitis, nervous imbalance, etc. Thus, the therapeutic goals primarily include the maintenance of proper blood supply and prevention of hypoxic condition in liver, along with management of factors responsible for high blood ammonia, oxidative stress, inflammation, and high GI- serotonin. The drugs in clinical practice include lactulose, sodium benzoate, flumazenil and rifaximin, supplementation of zinc, branched chain amino acids (BCAA), l-ornithine-l aspartate, antioxidants and iNOS inhibitors. However, herbal formulations would be of great importance as it shows multi-targeted action because it possesses a natural cocktail of secondary metabolites. It can collectively act as an antioxidant, anti-inflammatory, prebiotic, hepatoprotective and neuron-protective agents. We have briefly outlined some of these plants and also recent patents useful in the management of hepatic encephalopathy.

  1. Ammonia and Its Role in the Pathogenesis of Hepatic Encephalopathy.

    PubMed

    Parekh, Parth J; Balart, Luis A

    2015-08-01

    Hepatic encephalopathy (HE) is a commonly encountered sequela of chronic liver disease and cirrhosis with significant associated morbidity and mortality. Although ammonia is implicated in the pathogenesis of HE, the exact underlying mechanisms still remain poorly understood. Its role in the urea cycle, astrocyte swelling, and glutamine and gamma-amino-n-butyric acid systems suggests that the pathogenesis is multifaceted. Greater understanding in its underlying mechanism may offer more targeted therapeutic options in the future, and thus further research is necessary to fully understand the pathogenesis of HE.

  2. Elevated cerebral lactate: Implications in the pathogenesis of hepatic encephalopathy.

    PubMed

    Bosoi, Cristina R; Rose, Christopher F

    2014-12-01

    Hepatic encephalopathy (HE), a complex neuropsychiatric syndrome, is a frequent complication of liver failure/disease. Increased concentrations of lactate are commonly observed in HE patients, in the systemic circulation, but also in the brain. Traditionally, increased cerebral lactate is considered a marker of energy failure/impairment however alterations in lactate homeostasis may also lead to a rise in brain lactate and result in neuronal dysfunction. The latter may involve the development of brain edema. This review will target the significance of increased cerebral lactate in the pathogenesis of HE.

  3. Current Concepts in the Pathophysiology and Management of Hepatic Encephalopathy

    PubMed Central

    2011-01-01

    Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or portosystemic shunting of blood flow. The pathophysiology of this disease is quite complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Recent hypotheses implicate low-grade cerebral edema as a final common pathway for the pathophysiology of HE. Management of this condition is multifaceted and requires several steps: elimination of precipitating factors; removal of toxins, both by reducing them at their source and by augmenting scavenging pathways; modulation of resident fecal flora; proper nutritional support; and downregulation of systemic and gut-derived inflammation. PMID:21857820

  4. Comparative Neuroprotective Effects of Dexamethasone and Minocycline during Hepatic Encephalopathy.

    PubMed

    Gamal, Maha; Abdel Wahab, Zainab; Eshra, Mohamed; Rashed, Laila; Sharawy, Nivin

    2014-01-01

    Objective. Encephalopathy and brain edema are serious complications of acute liver injury and may lead to rapid death of patients. The present study was designed to investigate the role of the inflammatory mediators and oxidative stress in the cytotoxic brain oedema and the neuroprotective effects of both minocycline and dexamethasone. Methods. 48 male albino rats were divided into 4 groups: control group, acute liver injury (ALI) group, minocycline pretreated ALI group, and dexamethasone pretreated ALI group. 24 hours after acute liver injury serum ammonia, liver enzymes, brain levels of heme oxygenase-1 gene, iNOS gene expression, nitrite/nitrate, and cytokines were measured. In addition, the grades of encephalopathy and brain water content were assessed. Results. ALI was associated with significant increases in all measured inflammatory mediators, oxidative stress, iNOS gene expression, and nitrite/nitrate. Both minocycline and dexamethasone significantly modulated the inflammatory changes and the oxidative/nitrosative stress associated with ALI. However, only minocycline but not dexamethasone significantly reduced the cytotoxic brain oedema. Conclusion. Both minocycline and dexamethasone could modulate inflammatory and oxidative changes observed in brain after ALI and could be novel preventative therapy for hepatic encephalopathy episodes.

  5. Abnormal cortical synaptic plasticity in minimal hepatic encephalopathy.

    PubMed

    Golaszewski, Stefan; Langthaler, Patrick B; Schwenker, Kerstin; Florea, Cristina; Christova, Monica; Brigo, Francesco; Trinka, Eugen; Nardone, Raffaele

    2016-07-01

    Minimal hepatic encephalopathy (MHE) represents the earliest stage of hepatic encephalopathy (HE). MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, while obvious clinical manifestations are lacking. In the present study, we aimed at assessing whether subjects with MHE showed alterations in synaptic plasticity within the motor cortex. Previous findings suggest that learning in human motor cortex occurs through long-term potentiation (LTP)-like mechanisms. We employed therefore the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in the motor cortex of normal subjects. Fifteen patients with MHE and 15 age- and sex-matched cirrhotic patients without MHE were recruited. PAS consisted of 180 electrical stimuli of the right median nerve paired with a single TMS over the hotspot of right abductor pollicis brevis (APB) at an ISI of 25ms (PAS25). We measured motor evoked potentials (MEPs) before and after each intervention for up to 30min. In healthy subjects the PAS25 protocol was followed by a significant increase of the MEP amplitude. On the contrary, in patients with MHE the MEP amplitude was slightly reduced after PAS. These findings demonstrated that associative sensorimotor plasticity, an indirect probe for motor learning, is impaired in MHE patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Focal neurological signs in hepatic encephalopathy in cirrhotic patients: an underestimated entity?

    PubMed

    Cadranel, J F; Lebiez, E; Di Martino, V; Bernard, B; El Koury, S; Tourbah, A; Pidoux, B; Valla, D; Opolon, P

    2001-02-01

    Focal neurological signs have been poorly documented in the course of hepatic encephalopathy in cirrhotic patients because they are not mentioned in any textbooks of liver diseases. Having the opportunity to observe such cases, we underwent a prospective study to determine incidence, characteristics, associated factors, prognostic significance, and outcome of this rare form of hepatic encephalopathy. Over a 12-month period, all cirrhotic patients hospitalized in the intensive care unit of our department for hepatic encephalopathy were prospectively studied. Patients with clinical and electroencephalogram evidences of hepatic encephalopathy were examined by a senior physician and, in cases of focal neurological signs, underwent examination by a neurologist, CT scan, lumbar punction, and cerebral magnetic resonance imaging and echo Doppler examination of neck and head vessels. Clinical and biological parameters were compared in patients during episodes with and without focal neurological signs, and outcome was noted. Thirty-four cirrhotic patients were hospitalized for 48 episodes of hepatic encephalopathy; two of these patients with cerebral hematoma were excluded. Twenty-four patients exhibited 38 hepatic encephalopathy episodes without focal neurological signs (82.6%), and eight patients exhibited eight hepatic encephalopathy episodes with focal neurological signs (17.4%) that were hemiplegia and hemiparesia in six patients (75%). In all patients, cerebral CT scan and cerebrospinal fluid examination disclosed no abnormalities, as neither did cerebral magnetic resonance imaging (n = 5) and echo Doppler examination of neck and head vessels (n = 5). Except for female sex, which was more often encountered in patients with focal neurological signs (p < 0.05), there were no differences between episodes with and without focal neurological signs for any of the parameters studied. In surviving patients who recovered from hepatic encephalopathy (7/8), focal neurological

  7. [A case of hepatic encephalopathy induced by adverse effect of morphine sulfate].

    PubMed

    Shinagawa, Jotaro; Hashimoto, Yoshihiro; Ohmae, Yoshio

    2008-06-01

    A 63-year-old man with liver cirrhosis and hepatocellular carcinoma presented with abrupt encephalopathy with markedly elevated blood ammonia levels. He was found lying down in front of the hospital 2 days after treatment of right hypochondrial pain with sustained-release oral morphine sulfate. He tended to be constipated before receiving morphine sulfate. The excess production of ammonia due to his constitutional constipation exacerbated by the use of oral morphine was thought to be the causal association with transient hepatic encephalopathy. He regained consciousness by receiving aminoleban intravenously and anticonstipating suppository. We realized that much care should be taken to avoid such opioid-related constipation at the time of pain management for quality of life improvement in patients with cancer pain.

  8. Associative learning deficit in two experimental models of hepatic encephalopathy.

    PubMed

    Méndez, Marta; Méndez-López, Magdalena; López, Laudino; Aller, María Angeles; Arias, Jaime; Arias, Jorge L

    2009-03-17

    People with hepatic insufficiency can develop hepatic encephalopathy (HE), a complex neuropsychological syndrome covering a wide range of neurological and cognitive and motor alterations. The cognitive deficits include disturbances in intellectual functions such as memory and learning. In spite of its high prevalence in western societies, the causes of HE have not yet been clearly established. For this reason, experimental models of HE are used to study this condition. In this work, two experimental models were used, one Type B HE (portacaval shunt) and the other Type C HE (cirrhosis by intoxication with thioacetamide), to evaluate its effect on two tasks of associative learning: two-way active avoidance and step-through passive avoidance. The results show an impediment both in acquisition and retention of active avoidance in both models of HE. However, in passive avoidance, only the rats with portacaval shunt presented a memory deficit for the aversive event. In our opinion, these results can be explained by alterations in the neurotransmission system presented by animals with hepatic insufficiency, which are mainly caused by a rise in cerebral histamine and a dysfunction of the glutamatergic system.

  9. Contemporary Understanding and Management of Overt and Covert Hepatic Encephalopathy

    PubMed Central

    NeSmith, Meghan; Ahn, Joseph

    2016-01-01

    Hepatic encephalopathy (HE) is a major complication of liver disease that leads to significant morbidity and mortality. Caring for hospitalized patients with HE is becoming more complex, and the economic burden of HE continues to rise. Defining and diagnosing HE, particularly covert HE (CHE), remain challenging. In this article, we review new tools and those currently under development for the diagnosis of CHE and the latest advances in the acute and long-term management of overt HE (OHE) and CHE. In particular, we review the latest data on the use of lactulose and rifaximin for treatment of OHE and summarize the data on adjunctive agents such as sodium benzoate and probiotics. PMID:27182210

  10. Covert and Overt Hepatic Encephalopathy: Diagnosis and Management

    PubMed Central

    Patidar, Kavish R.; Bajaj, Jasmohan S.

    2015-01-01

    Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into two broad categories based on severity, covert (CHE) and overt (CHE). CHE has a significant impact on a patient’s quality of life, driving performances, and has recently been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, it’s imperative for early diagnosis and management. In addition, a focus should also be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of non-absorbable disaccharides, antibiotics (i.e. rifaximin), and potentially probiotics. Other therapies currently under further investigation include: L-ornithine-L-aspartate, ornithine phenylacetate, glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion. PMID:26164219

  11. Mapping Metabolic Brain Activity in Three Models of Hepatic Encephalopathy

    PubMed Central

    Méndez, Marta; Fidalgo, Camino; Aller, María Ángeles; Arias, Jaime; Arias, Jorge L.

    2013-01-01

    Cirrhosis is a common disease in Western countries. Liver failure, hyperammonemia, and portal hypertension are the main factors that contribute to human cirrhosis that frequently leads to a neuropsychiatric disorder known as hepatic encephalopathy (HE). In this study, we examined the differential contribution of these leading factors to the oxidative metabolism of diverse brain limbic system regions frequently involved in memory process by histochemical labelling of cytochrome oxidase (COx). We have analyzed cortical structures such as the infralimbic and prelimbic cotices, subcortical structures such as hippocampus and ventral striatum, at thalamic level like the anterodorsal, anteroventral, and mediodorsal thalamus, and, finally, the hypothalamus, where the mammillary nuclei (medial and lateral) were measured. The severest alteration is found in the model that mimics intoxication by ammonia, followed by the thioacetamide-treated group and the portal hypertension group. No changes were found at the mammillary bodies for any of the experimental groups. PMID:23573412

  12. Improving the inhibitory control task to detect minimal hepatic encephalopathy.

    PubMed

    Amodio, Piero; Ridola, Lorenzo; Schiff, Sami; Montagnese, Sara; Pasquale, Chiara; Nardelli, Silvia; Pentassuglio, Ilaria; Trezza, Maria; Marzano, Chiara; Flaiban, Cristiana; Angeli, Paolo; Cona, Giorgia; Bisiacchi, Patrizia; Gatta, Angelo; Riggio, Oliviero

    2010-08-01

    Quantification of the number of noninhibited responses (lures) in the inhibitory control task (ICT) has been proposed for the diagnosis of minimal hepatic encephalopathy (MHE). We assessed the efficacy of ICT compared with recommended diagnostic standards. We studied patients with cirrhosis and healthy individuals (controls) who underwent the ICT at 2 centers (center A: n=51 patients and 41 controls, center B: n=24 patients and 14 controls). Subjects were evaluated for MHE by psychometric hepatic encephalopathy score (PHES). Patients from center B also were assessed for MHE by critical flicker frequency and spectral electroencephalogram analyses. Patients with cirrhosis had higher ICT lures (23.2+/-12.8 vs 12.9+/-5.8, respectively, P<.01) and lower ICT target accuracy (0.88+/-0.17 vs 0.96+/-0.03, respectively, P<.01) compared with controls. However, lures were comparable (25.2+/-12.5 vs 21.4+/-13.9, respectively, P=.32) among patients with/without altered PHES (center A). There was a reverse, U-shaped relationship between ICT lure and target accuracy; a variable adjusting lures was devised based on target accuracy (weighted lures at center B). This variable differed between patients with and without MHE. The variable weighted lures was then validated from data collected at center A by receiver operator characteristic curve analysis; it discriminated between patients with and without PHES alterations (area under the curve=0.71+/-0.07). However, target accuracy alone was as effective as a stand-alone variable (area under the curve=0.81+/-0.06). The ICT is not useful for the diagnosis of MHE, unless adjusted by target accuracy. Testing inhibition (lures) does not seem to be superior to testing attention (target accuracy) for the detection of MHE. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. [Research advances in diagnosis and treatment of post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy].

    PubMed

    Yang, J F; Zhang, B Q

    2016-07-20

    Transjugular intrahepatic portosystemic shunt (TIPS) has become an important minimally invasive interventional technique for the treatment of complications of cirrhotic portal hypertension, and currently, it is often used in cirrhotic patients with esophagogastric variceal bleeding (EVB), intractable ascites, hepatic hydrothorax, and Budd-Chiari syndrome. On one hand, TIPS can effectively reduce portal vein pressure and the risk of EVB and intractable ascites; on the other hand, it may reduce the blood flow in liver perfusion, aggravate liver impairment, and cause porto-systemic encephalopathy. Related influencing factors should be evaluated comprehensively in order to prevent the development of post-TIPS hepatic encephalopathy. The diagnosis and treatment of post-TIPS hepatic encephalopathy is still a great challenge in current clinical practice. This article reviews the diagnosis and treatment of post-TIPS hepatic encephalopathy to enhance people's knowledge of this disease.

  14. Brain concentrations of benzodiazepines are elevated in an animal model of hepatic encephalopathy

    SciTech Connect

    Basile, A.S.; Pannell, L.; Jaouni, T.; Gammal, S.H.; Fales, H.M.; Jones, E.A.; Skolnick, P. )

    1990-07-01

    Brain extracts from rats with hepatic encephalopathy due to thioacetamide-induced fulminant hepatic failure contained 4- to 6-fold higher concentrations of substances that inhibit radioligand binding to benzodiazepine receptors than corresponding control rat extracts. Both isocratic and gradient-elution HPLC indicated that this inhibitory activity was localized in 3-8 peaks with retention times corresponding to deschlorodiazepam, deschlorolorazepam, lorazepam, oxazepam, diazepam, and N-desmethyldiazepam. The presence of diazepam and N-desmethyldiazepam was confirmed by mass spectroscopy. Both mass spectroscopic and radiometric techniques indicated that the concentrations of N-desmethyldiazepam and diazepam in brain extracts from encephalopathic rats were 2-9 and 5-7 times higher, respectively, than in control brain extracts. While benzodiazepines have been identified previously in mammalian and plant tissues, this report demonstrates that concentrations of these substances are increased in a pathophysiological condition. These findings provide a rational basis for the use of benzodiazepine receptor antagonists in the management of hepatic encephalopathy in humans.

  15. Performance of the hepatic encephalopathy scoring algorithm in a clinical trial of patients with cirrhosis and severe hepatic encephalopathy.

    PubMed

    Hassanein, Tarek; Blei, Andres T; Perry, William; Hilsabeck, Robin; Stange, Jan; Larsen, Fin S; Brown, Robert S; Caldwell, Stephen; McGuire, Brendan; Nevens, Frederik; Fontana, Robert

    2009-06-01

    The grading of hepatic encephalopathy (HE) is based on a combination of indicators that reflect the state of consciousness, intellectual function, changes in behavior, and neuromuscular alterations seen in patients with liver failure. We modified the traditional West Haven criteria (WHC) to provide an objective assessment of the cognitive parameters to complement the subjective clinical ratings for the performance of extracorporeal albumin dialysis (ECAD) using a molecular adsorption recirculating system in patients with cirrhosis and severe (grade III / IV) encephalopathy. The HE Scoring Algorithm (HESA) combined clinical indicators with those derived from simple neuropsychological tests,the latter more often used in milder grades of HE (I / II). The performance of each indicator was compared across grades and sites. Results of HESA were also compared with the Glasgow Coma Scale. A total of 597 evaluations were performed in patients randomized to ECAD plus standard medical therapy or the latter only. Most parameters exhibited significant separation between grades; the most effective indicators were lack of verbal, eye, and motor response (grade IV), somnolence and disorientation to place (grade III), and lethargy and disorientation to time (grade II). Two clinical and four neuropsychological indicators were useful to classify patients as grade I. The Glasgow Coma Scale differed among the four stages of the WHC, but the differences between grades I and II were small and not clinically useful. HESA extends the traditional WHC for grading HE. In the absence of a "gold" standard, the most useful indicators noted in this trial should be further validated.

  16. Value of critical flicker frequency and psychometric hepatic encephalopathy score in diagnosis of low-grade hepatic encephalopathy.

    PubMed

    Kircheis, Gerald; Hilger, Norbert; Häussinger, Dieter

    2014-04-01

    Critical flicker frequency (CFF) and psychometric hepatic encephalopathy score (PHES) analyses are widely used to diagnose hepatic encephalopathy (HE), but little is known about their value in the diagnosis of low-grade HE. The diagnostic values of CFF and PHES were compared using a computerized test battery and West Haven criteria as reference. We performed CFF analysis on 559 patients with cirrhosis and 261 without (controls). Of these 820 patients, 448 were evaluated using a modified PHES system and 148 were also evaluated using the conventional PHES system. CFF distinguished between patients with overt HE and without minimal or overt HE in the entire study population with 98% sensitivity and 94% specificity and in the subgroup of patients who were evaluated by conventional PHES with 97% sensitivity and 100% specificity. Conventional PHES identified patients with overt HE with 73% sensitivity and 89% specificity. CFF distinguished between patients with and without minimal HE with only 37% sensitivity but 94% specificity (entire study population). In the subgroup of patients evaluated by conventional PHES, CFF distinguished between patients with and without minimal HE with 22% sensitivity and 100% specificity; these values were similar to those for conventional PHES (30% sensitivity and 89% specificity). The modified PHES distinguished between patients with and without minimal HE with 49% sensitivity and 74% specificity. The diagnostic agreement values between CFF and conventional or modified PHES in patients with minimal HE were only 54% or 47%, respectively. In an analysis of patients with cirrhosis and controls, CFF distinguished between patients with overt HE and without minimal or overt HE. PHES testing produced a statistically significant difference among groups, but there was considerable overlap between controls and patients with overt HE. PHES, CFF, and a combination of PHES and CFF could not reliably distinguish patients with minimal HE from controls or

  17. Persistent repeated measurements by magnetic resonance spectroscopy demonstrate minimal hepatic encephalopathy: a case report.

    PubMed

    Scheau, C; Popa, G A; Ghergus, A E; Preda, E M; Capsa, R A; Lupescu, I G

    2013-09-15

    Minimal Hepatic Encephalopathy (MHE), previously referred to as infraclinical or subclinical is a precursor in the development of clinical hepatic encephalopathy (HE). The demonstration of MHE is done through neuropsychological testing in the absence of clinical evidence of HE, patients showing only a mild cognitive impairment. Neuropsychological tests employed consist of Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and portosystemic encephalopathy (PSE) test score. Unfortunately, there are numerous occasions when the tests prove irrelevant: in the situation of inexperienced investigators, the patient's poor education, vision problems or concurring central nervous system disease, all of which may delay or deviate from the correct diagnosis.

  18. Ammonia and amino acid profiles in liver cirrhosis: effects of variables leading to hepatic encephalopathy.

    PubMed

    Holecek, Milan

    2015-01-01

    Hyperammonemia and severe amino acid imbalances play central role in hepatic encephalopathy (HE). In the article is demonstrated that the main source of ammonia in cirrhotic subjects is activated breakdown of glutamine (GLN) in enterocytes and the kidneys and the main source of GLN is ammonia detoxification to GLN in the brain and skeletal muscle. Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) decrease due to activated GLN synthesis in muscle. Aromatic amino acids (AAA; phenylalanine, tyrosine, and tryptophan) and methionine increase due to portosystemic shunts and reduced ability of diseased liver. The effects on aminoacidemia of the following variables that may affect the course of liver disease are discussed: nutritional status, starvation, protein intake, inflammation, acute hepatocellular damage, bleeding from varices, portosystemic shunts, hepatic cancer, and renal failure. It is concluded that (1) neither ammonia nor amino acid concentrations correlate closely with the severity of liver disease; (2) BCAA/AAA ratio could be used as a good index of liver impairment and for early detection of derangements in amino acid metabolism; (3) variables potentially leading to overt encephalopathy exert substantial but uneven effects; and (4) careful monitoring of ammonia and aminoacidemia may discover important break points in the course of liver disease and indicate appropriate therapeutic approach. Of special importance might be isoleucine deficiency in bleeding from varices, arginine deficiency in sepsis, and a marked rise of GLN and ammonia levels that may appear in all events leading to HE.

  19. Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

    PubMed Central

    Aldridge, Dominic R.; Tranah, Edward J.; Shawcross, Debbie L.

    2015-01-01

    The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. PMID:26041962

  20. How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist.

    PubMed

    Shawcross, Debbie L; Dunk, Arthur A; Jalan, Rajiv; Kircheis, Gerald; de Knegt, Robert J; Laleman, Wim; Ramage, John K; Wedemeyer, Heiner; Morgan, Ian E J

    2016-02-01

    Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common complication of cirrhosis that is associated with a poor prognosis. Patients with hepatic encephalopathy may present to healthcare providers who do not have primary responsibility for management of patients with cirrhosis. Therefore, we developed a series of 'consensus points' to provide some guidance on management. Using a modified 'Delphi' process, consensus statements were developed that summarize our recommendations for the diagnosis and management of patients with hepatic encephalopathy. Points on which full consensus could not be reached are also discussed. Our recommendations emphasize the role of all healthcare providers in the identification of cognitive impairment in patients with cirrhosis and provide guidance on steps that might be considered to make a diagnosis of overt hepatic encephalopathy. In addition, treatment recommendations are summarized. Minimal hepatic encephalopathy can have a significant impact on patients; however, in most circumstances identification and management of minimal hepatic encephalopathy remains the responsibility of specialists in liver diseases. Our opinion statements aim to define the roles and responsibilities of all healthcare providers who at times care for patients with cirrhosis and hepatic encephalopathy. We suggest that these recommendations be considered further by colleagues in other disciplines and hope that future guidelines consider the management of patients with cirrhosis and with a 'suspicion' of cognitive impairment through to a formal diagnosis of hepatic encephalopathy.

  1. Severe hypoglycemic encephalopathy due to hypoallergenic formula in an infant.

    PubMed

    Ogawa, Erika; Ishige, Mika; Takahashi, Yuno; Kodama, Hiroko; Fuchigami, Tatsuo; Takahashi, Shori

    2016-08-01

    A 7-month-old girl was brought to hospital due to vomiting. Upon admission, she was in a convulsive state and stupor with extremely low blood glucose. Head computed tomography showed brain edema, and comprehensive treatment for acute encephalopathy was initiated immediately. Severe hypoglycemia, metabolic acidosis, elevation of ammonia and serum transaminases and creatine kinase suggested metabolic decompensation. Infusion of a high-glucose solution containing vitamins, biotin, and l-carnitine resolved the metabolic crisis quickly, but brain damage was irreversible. She was found to have been fed exclusively on a hypoallergenic formula (HF) for 7 months, although she was found later to be non-allergic. Evidence of inborn metabolic diseases was absent, therefore biotin deficiency and carnitine deficiency were concluded to be a consequence of reliance on a HF for a prolonged period. Health-care professionals should warn parents of the consequences of using HF. © 2016 Japan Pediatric Society.

  2. Low phase angle is associated with the development of hepatic encephalopathy in patients with cirrhosis

    PubMed Central

    Ruiz-Margáin, Astrid; Macías-Rodríguez, Ricardo Ulises; Ampuero, Javier; Cubero, Francisco Javier; Chi-Cervera, Luis; Ríos-Torres, Silvia L; Duarte-Rojo, Andrés; Espinosa-Cuevas, Ángeles; Romero-Gómez, Manuel; Torre, Aldo

    2016-01-01

    AIM Evaluate the association between phase angle and the development of hepatic encephalopathy in the long-term follow-up of cirrhotic patients. METHODS This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. Mann-Whitney’s U and χ2 tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic encephalopathy. RESULTS Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy (18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. Kaplan-Meier curves showed a higher proportion of HE in the group with low phase angle (39%) compared to the normal phase angle group (13%) (P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80 (1.07-3.03)]. CONCLUSION In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis. PMID:28018114

  3. Hepatic encephalopathy: An updated approach from pathogenesis to treatment

    PubMed Central

    Toris, Giannakis T.; Bikis, Christos N.; Tsourouflis, Gerasimos S.; Theocharis, Stamatios E.

    2011-01-01

    Summary One of the most serious complications of chronic or fulminant liver failure is hepatic encephalopathy (HE), associated most commonly with cirrhosis. In the presence of chronic liver disease, HE is a sign of decompensation, while in fulminant liver failure its development represents a worrying sign and usually indicates that transplantation will be required. Despite the significance of HE in the course of liver disease, the progress in development of new therapeutic options has been unremarkable over the last 20 years. An up-to-date review regarding HE, including both research and review articles. HE is a serious and progressive, but potentially reversible, disorder with a wide spectrum of neuropsychiatric abnormalities and motor disturbances that ranges from mild alteration of cognitive and motor function to coma and death. Although a clear pathogenesis is yet to be determined, elevated ammonia in serum and the central nervous system is the mainstay for pathogenesis and treatment of HE. Management includes early diagnosis and prompt treatment of precipitating factors. Clinical trials and extensive clinical experience have established the efficacy of diverse substances in HE treatment. Novel therapies with clinical promise include: L-ornithine L-aspartate, sodium benzoate, phenylacetate, AST-120, and the molecular adsorbent recirculating system. Eventually, liver transplantation is often the most successful long-term therapy for HE. PMID:21278704

  4. What is new about diet in hepatic encephalopathy.

    PubMed

    Merli, Manuela; Iebba, Valerio; Giusto, Michela

    2016-12-01

    There is a relationship between hepatic encephalopathy (HE) protein malnutrition and muscle wasting. Muscle may play an alternative role in ammonia detoxification. Molecular mechanisms responsible for muscle depletion are under investigation. Specific nutrients may interact to reverse the molecular pathways involved in muscle wasting at an early stage. Training exercises have also been proposed to improve skeletal muscle mass. However, these data refer to small groups of patients. The amelioration of muscle mass may potentially help to prevent HE. The pathogenesis of HE is associated with modifications of the gut microbiota and diet is emerging to play a relevant role in the modulation of the gut milieu. Vegetarian and fibre-rich diets have been shown to induce beneficial changes on gut microbiota in healthy people, with reduction of Bacteroides spp., Enterobacteriaceae, and Clostridium cluster XIVa bacteria. By way of contrast, it has been suggested that a high-fat or protein diet may increase Firmicutes and reduce Bacteroidetes phylum. Milk-lysozyme and milk-oligosaccharides have also been proposed to induce a "healthy" microbiota. At present, no studies have been published describing the modification of the gut microbiota in cirrhotic patients with HE as a response to specific diets. New research is needed to evaluate the potentiality of foods in the modulation of gut microbiota in liver disease and HE.

  5. Comparison of Rifaximin Plus Lactulose with the Lactulose Alone for the Treatment of Hepatic Encephalopathy.

    PubMed

    Ahire, Kiran; Sonawale, Archana

    2017-08-01

    Hepatic encephalopathy is challenging complication of liver dysfunction. Therapeutic treatment options for hepatic encephalopathy are currently limited and have appreciable risks and benefits associated with their use. Rifaximin is a novel anti microbiological agent with wide spectrum of activity that has shown promise as an alternative option for hepatic encephalopathy. The present study was undertaken to compare the effectiveness of Rifaximin and Lactulose as a combination vs Lactulose alone, to compare the adverse effects and to study the rapidity of therapeutic effects of Rifaximin and Lactulose. It was a prospective observational study. 60 patients suffering from hepatic encephalopathy (HE) were studied. Patients were investigated and treated as per treating physician's decision. At the time of analysis, patients were divided into 2 groups, Rifaximin group who received Rifaximin+Lactulose (R+L) and Lactulose group(L), who received Lactulose only. Parameters such as mental status grade, Asterixis grade, Serum Ammonia grade, Number Connection Test grade (NCT grade), Hepatic Encephalopathy Index (HE index) were evaluated and compared in both groups. Clinical efficacy was determined using HE index improvement. Primary end points were decrease in HE index and reversal of HE grades. Secondary end points were mortality from HE or any other cause, decrease in mental status grade, asterixis grade, serum Ammonia grade, NCT grade. Out of 60 patients, 32 received Rifaximin+Lactulose combination and 28 patients received Lactulose alone. Mean Child-Turcotte-Pugh score (CTP score) was 10.6 in R+L group and 10.32 in L group. There was statistically significant improvement in mental status grade, Asterixis grade, Serum Ammonia grade, NCT grade, Hepatic encephalopathy index in both groups, p value <0.05 but no statistically significant difference between improvement in mental status grade, Asterixis grade, Serum Ammonia grade, NCT grade, HE index between the two groups

  6. The cost-effectiveness and budget impact of competing therapies in hepatic encephalopathy - a decision analysis.

    PubMed

    Huang, E; Esrailian, E; Spiegel, B M R

    2007-10-15

    Treatment options for hepatic encephalopathy have disparate risks and benefits. Non-absorbable disaccharides and neomycin are limited by uncertain efficacy and common dose-limiting side effects. In contrast, rifaximin is safe and effective in hepatic encephalopathy, but is more expensive. We conducted a decision analysis to calculate the cost-effectiveness of six strategies in hepatic encephalopathy: (i) no hepatic encephalopathy treatment, (ii) lactulose monotherapy, (iii) lactitol monotherapy, (iv) neomycin monotherapy, (v) rifaximin monotherapy and (vi) up-front lactulose with crossover to rifaximin if poor response or intolerance of lactulose ('rifaximin salvage'). The primary outcome was cost per quality-adjusted life-year gained. Under base-case conditions, 'do nothing' was least effective and rifaximin salvage was most effective. Lactulose monotherapy was least expensive, and rifaximin monotherapy was most expensive. When balancing cost and effectiveness, lactulose monotherapy and rifaximin salvage dominated alternative strategies. Compared to lactulose monotherapy, rifaximin salvage cost an incremental US$2315 per quality-adjusted life-year-gained. The cost of rifaximin had to fall below US$1.03/tab in order for rifaximin monotherapy to dominate lactulose monotherapy. Rifaximin monotherapy is not cost-effective in the treatment of chronic hepatic encephalopathy at current average wholesale prices. However, a hybrid salvage strategy, reserving rifaximin for lactulose-refractory patients, may be highly cost-effective.

  7. Intermittent hyperammonemic encephalopathy after ureterosigmoidostomy: spontaneous onset in the absence of hepatic failure

    PubMed Central

    Viertmann, Anne-Odette; Janßen, Claudia; Birklein, Frank; Thüroff, Joachim W.; Stein, Raimund

    2015-01-01

    Intermittent hyperammonemic encephalopathy after ureterosigmoidostomy is a rare, but if unrecognized, potentially lethal condition. Ureterosigmoidostomy was performed in a male patient with bladder extrophy. After 35 years, he developed hyperammonemic encephalopathy. Diagnostic procedures did not reveal hepatic nor metabolic disorders. Despite administration of preventive medical treatment, several episodes recurred. A durable prevention was finally achieved by conversion into an ileal conduit. Intermittent hyperammonemic encephalopathy can occur decades after ureterosigmoidostomy. In the case of absence of metabolic disorders and resistance to medical treatment, conversion into a urinary diversion using an ileal segment constitutes an effective ultima ratio. PMID:25914851

  8. Visual evoked potential: a diagnostic tool for the assessment of hepatic encephalopathy.

    PubMed Central

    Zeneroli, M L; Pinelli, G; Gollini, G; Penne, A; Messori, E; Zani, G; Ventura, E

    1984-01-01

    Visual evoked potential recordings were examined in 45 liver cirrhosis patients with (n = 29) and without (n = 16) encephalopathy, in 15 normal volunteers, and in one patient with an opioid induced stupor state. Visual evoked potential parameters were classified on the basis of EEG recordings. Plasma concentrations of amino acids, octopamine, and ammonia were assayed in order to document the metabolic change of hepatic encephalopathy. Latencies and wave patterns recorded after flash stimulation differentiated the four degrees of the coma one from another according to EEG classification in the 29 patients with encephalopathy. In the group of 16 patients without clinical and EEG evidence of encephalopathy the visual potential recordings discriminated a group of patients (n = 10) in a preclinical stage of encephalopathy. Biochemical parameters and subsequent clinical observation of patients confirmed our judgement of a preclinical stage of encephalopathy. These results suggest that visual evoked potentials are a simple, suitable and objective method for differentiating the degrees of encephalopathy and for identifying the preclinical stage of encephalopathy. PMID:6421664

  9. Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

    PubMed

    Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

    2015-07-01

    Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties.

  10. The slowed brain: cortical oscillatory activity in hepatic encephalopathy.

    PubMed

    Butz, Markus; May, Elisabeth S; Häussinger, Dieter; Schnitzler, Alfons

    2013-08-15

    Oscillatory activity of the human brain has received growing interest as a key mechanism of large-scale integration across different brain regions. Besides a crucial role of oscillatory activity in the emergence of other neurological and psychiatric diseases, recent evidence indicates a key role in the pathophysiology of hepatic encephalopathy (HE). This review summarizes the current knowledge on pathological alterations of oscillatory brain activity in association with liver dysfunction and HE in the context of spontaneous brain activity, motor symptoms, sensory processing, and attention. The existing literature demonstrates a prominent slowing of the frequency of oscillatory activity as shown for spontaneous brain activity at rest, with respect to deficits of motor behavior and motor symptoms, and in the context of visual attention processes. The observed slowing extends across different subsystems of the brain and has been confirmed across different frequency bands, providing evidence for ubiquitous changes of oscillatory activity in HE. For example, the frequency of cortico-muscular coherence in HE patients appears at the frequency of the mini-asterixis (⩽12Hz), while cirrhotics without overt signs of HE show coherence similar to healthy subjects, i.e. at 13-30Hz. Interestingly, the so-called critical flicker frequency (CFF) as a measure of the processing of an oscillating visual stimulus has emerged as a useful tool to quantify HE disease severity, correlating with behavioral and neurophysiological alterations. Moreover, the CFF reliably distinguishes patients with manifest HE from cirrhotics without any signs of HE and healthy controls using a cut-off frequency of 39Hz. In conclusion, oscillatory activity is globally slowed in HE in close association with HE symptoms and disease severity. Although the underlying causal mechanisms are not yet understood, these results indicate that pathological changes of oscillatory activity play an important role in the

  11. Limonene in exhaled breath is elevated in hepatic encephalopathy

    PubMed Central

    O’Hara, M E; Fernández del Río, R; Holt, A; Pemberton, P; Shah, T; Whitehouse, T; Mayhew, C A

    2016-01-01

    Abstract Breath samples were taken from 31 patients with liver disease and 30 controls in a clinical setting and proton transfer reaction quadrupole mass spectrometry (PTR-Quad-MS) used to measure the concentration of volatile organic compounds (VOCs). All patients had cirrhosis of various etiologies, with some also suffering from hepatocellular cancer (HCC) and/or hepatic encephalopathy (HE). Breath limonene was higher in patients with No-HCC than with HCC, median (lower/upper quartile) 14.2 (7.2/60.1) versus 3.6 (2.0/13.7) and 1.5 (1.1/2.3) nmol mol−1 in controls. This may reflect disease severity, as those with No-HCC had significantly higher UKELD (United Kingdom model for End stage Liver Disease) scores. Patients with HE were categorized as having HE symptoms presently, having a history but no current symptoms and having neither history nor current symptoms. Breath limonene in these groups was median (lower/upper quartile) 46.0 (14.0/103), 4.2 (2.6/6.4) and 7.2 (2.0/19.1) nmol mol−1, respectively. The higher concentration of limonene in those with current symptoms of HE than with a history but no current symptoms cannot be explained by disease severity as their UKELD scores were not significantly different. Longitudinal data from two patients admitted to hospital with HE show a large intra-subject variation in breath limonene, median (range) 18 (10–44) and 42 (32–58) nmol mol−1. PMID:27869108

  12. Rifaximin therapy and hepatic encephalopathy: Pros and cons.

    PubMed

    Zullo, Angelo; Hassan, Cesare; Ridola, Lorenzo; Lorenzetti, Roberto; Campo, Salvatore Ma; Riggio, Oliviero

    2012-08-06

    Hepatic encephalopathy (HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life. Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy. Non-absorbable antibiotics, such as neomycin and paramomycin, are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects. To overcome these limitations, rifaximin use has been proposed. Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention, with a similar incidence of side-effects. Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern. Following long-term rifaximin therapy, Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients. In addition, selection of resistant mutants of both Gram-negative and -positive bacteria in the gastrointestinal tract cannot be definitely ruled out. Electrolyte alterations (sodium and potassium) have been reported during rifaximin therapy, a warning for its long-term use in cirrhotics. Moreover, a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients. The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides. While waiting for further safety data, caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to non-absorbable disaccharides.

  13. Rifaximin therapy and hepatic encephalopathy: Pros and cons

    PubMed Central

    Zullo, Angelo; Hassan, Cesare; Ridola, Lorenzo; Lorenzetti, Roberto; Campo, Salvatore MA; Riggio, Oliviero

    2012-01-01

    Hepatic encephalopathy (HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life. Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy. Non-absorbable antibiotics, such as neomycin and paramomycin, are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects. To overcome these limitations, rifaximin use has been proposed. Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention, with a similar incidence of side-effects. Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern. Following long-term rifaximin therapy, Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients. In addition, selection of resistant mutants of both Gram-negative and -positive bacteria in the gastrointestinal tract cannot be definitely ruled out. Electrolyte alterations (sodium and potassium) have been reported during rifaximin therapy, a warning for its long-term use in cirrhotics. Moreover, a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients. The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides. While waiting for further safety data, caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to non-absorbable disaccharides. PMID:22966484

  14. Brain Training with Video Games in Covert Hepatic Encephalopathy.

    PubMed

    Bajaj, Jasmohan S; Ahluwalia, Vishwadeep; Thacker, Leroy R; Fagan, Andrew; Gavis, Edith A; Lennon, Michael; Heuman, Douglas M; Fuchs, Michael; Wade, James B

    2017-02-01

    Despite the associated adverse outcomes, pharmacologic intervention for covert hepatic encephalopathy (CHE) is not the standard of care. We hypothesized that a video game-based rehabilitation program would improve white matter integrity and brain connectivity in the visuospatial network on brain magnetic resonance imaging (MRI), resulting in improved cognitive function in CHE subjects on measures consistent with the cognitive skill set emphasized by the two video games (e.g., IQ Boost-visual working memory, and Aim and Fire Challenge-psychomotor speed), but also generalize to thinking skills beyond the focus of the cognitive training (Hopkins verbal learning test (HVLT)-verbal learning/memory) and improve their health-related quality of life (HRQOL). The trial included three phases over 8 weeks; during the learning phase (cognitive tests administered twice over 2 weeks without intervening intervention), training phase (daily video game training for 4 weeks), and post-training phase (testing 2 weeks after the video game training ended). Thirty CHE patients completed all visits with significant daily achievement on the video games. In a subset of 13 subjects that underwent brain MRI, there was a significant decrease in fractional anisotropy, and increased radial diffusivity (suggesting axonal sprouting or increased cross-fiber formation) involving similar brain regions (i.e., corpus callosum, internal capsule, and sections of the corticospinal tract) and improvement in the visuospatial resting-state connectivity corresponding to the video game training domains. No significant corresponding improvement in HRQOL or HVLT performance was noted, but cognitive performance did transiently improve on cognitive tests similar to the video games during training. Although multimodal brain imaging changes suggest reductions in tract edema and improved neural network connectivity, this trial of video game brain training did not improve the HRQOL or produce lasting improvement in

  15. Frontal assessment battery: A tool for screening minimal hepatic encephalopathy?

    PubMed Central

    de Souza, Karina Zamprogno; Zago-Gomes, Maria Penha

    2016-01-01

    AIM To apply the Frontal Assessment Battery to cirrhotic patients with or without overt hepatic encephalopathy (OHE) and controls. METHODS The frontal assessment battery (FAB) was applied to 87 patients with liver cirrhosis (16 with and 71 without OHE) and 40 control subjects without cirrhosis treated at the alcohol and liver outpatient clinics and the gastroenterology ward of the Cassiano Antônio de Moraes University Hospital (Hospital Universitário Cassiano Antônio de Moraes - HUCAM), Espírito Santo, Brazil. RESULTS The average FAB score was lower for the cirrhotic than for the non-cirrhotic patients (10.6 ± 3.67 vs 12.25 ± 2.72, P = 0.015). The FAB score was lower for the cirrhotic patients with OHE than for the patients without OHE (8.25 ± 4.55 vs 11.14 ± 3.25, P = 0.027). The total FAB score was lower for the cirrhotic patients without OHE than for the non-cirrhotic patients, although this difference was not significant (11.14 ± 3.25 vs 12.25 ± 2.72, P = 0.067). Nevertheless, the difference in the scores on the subtest that assessed the ability to inhibit a response previously conditioned to a stimulus was significant (1.72 ± 0.93 vs 2.2 ± 0.85, P = 0.011). CONCLUSION The present study indicates that the FAB is a promising tool for outpatient minimal HE screening and the assessment of HE severity. PMID:27843536

  16. Diagnosis of covert hepatic encephalopathy without specialized tests.

    PubMed

    Nabi, Eiman; Thacker, Leroy R; Wade, James B; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Heuman, Douglas M; Bouneva, Iliana; Sanyal, Arun J; Siddiqui, Mohammad S; Luketic, Velimir; White, Melanie B; Monteith, Pamela; Noble, Nicole A; Unser, Ariel; Bajaj, Jasmohan S

    2014-08-01

    Covert hepatic encephalopathy (CHE) impairs quality of life (QOL) and can be difficult to diagnose. Patient-administered methods that do not require specialized tests or equipment might increase rates of detection. We performed a longitudinal study to determine whether demographic data and responses to a validated QOL questionnaire, the Sickness Impact Profile (SIP), can identify patients with CHE. Patients with cirrhosis without prior overt HE were recruited from outpatient liver clinics at the Virginia Commonwealth University Medical Center, from August 2008 through February 2012. We performed cognitive tests on 170 patients (mean age, 55 y; mean model for end-stage liver disease score, 9; 50% with hepatitis C-associated and 11% with alcohol-associated cirrhosis). Patients also were given the SIP questionnaire (136 questions on 12 QOL topics, requiring a yes or no answer) at enrollment, at 6 months, and at 12 months. The proportion of patients that responded "yes" to each question was compared between those with and without CHE. Patient variables (noncognitive), demographics (age, education, sex, alcoholic etiology), and SIP questions that produced different responses between groups were analyzed by logistic regression and receiver operating characteristic analyses. Based on cognitive test results, 93 patients (55%) had CHE when the study began. They had a higher proportion of "yes" responses to 54 questions on the SIP questionnaire, across all categories. We developed a formula to identify patients with CHE based on age, sex, and responses to 4 SIP questions (a SIP CHE score). Baseline SIP CHE scores greater than 0 identified patients with CHE with 80% sensitivity and 79% specificity. Of the 98 patients who returned for the 6-month evaluation, 50% had CHE (the SIP CHE identified these patients with 88% sensitivity). Of the 50 patients who returned for the 12-month evaluation, 32% had CHE (the SIP CHE score identified these patients with 81% sensitivity). We

  17. Current diagnosis and management of post-transjugular intrahepatic portosystemic shunt refractory hepatic encephalopathy.

    PubMed

    Pereira, Keith; Carrion, Andres F; Martin, Paul; Vaheesan, Kirubahara; Salsamendi, Jason; Doshi, Mehul; Yrizarry, Jose M

    2015-12-01

    Transjugular intrahepatic portosystemic shunt has evolved into an important option for management of complications of portal hypertension. The use of polytetrafluoroethylene covered stents enhances shunt patency. Hepatic encephalopathy (HE) remains a significant problem after TIPS placement. The approach to management of patients with refractory hepatic encephalopathy typically requires collaboration between different specialties. Patient selection for TIPS requires careful evaluation of risk factors for HE. TIPS procedure-related technical factors like stent size, attention to portosystemic pressure gradient reduction and use of adjunctive variceal embolization maybe important. Conservative medical therapy in combination with endovascular therapies often results in resolution or substantial reduction of symptoms. Liver transplantation is, however, the ultimate treatment.

  18. Brain metabolism in patients with hepatic encephalopathy studied by PET and MR.

    PubMed

    Keiding, Susanne; Pavese, Nicola

    2013-08-15

    We review PET- and MR studies on hepatic encephalopathy (HE) metabolism in human subjects from the point of views of methods, methodological assumptions and use in studies of cirrhotic patients with clinically overt HE, cirrhotic patients with minimal HE, cirrhotic patients with no history of HE and healthy subjects. Key results are: (1) Cerebral oxygen uptake and blood flow are reduced to 2/3 in cirrhotic patients with clinically overt HE but not in cirrhotic patients with minimal HE or no HE compared to healthy subjects. (2) Cerebral ammonia metabolism is enhanced due to increased blood ammonia in cirrhotic patients but the kinetics of cerebral ammonia uptake and metabolism is not affected by hyperammonemia. (3) Recent advantages in MR demonstrate low-grade cerebral oedema not only in astrocytes but also in the white matter in cirrhotic patients with HE.

  19. Brain proton magnetic resonance spectroscopy for hepatic encephalopathy

    NASA Astrophysics Data System (ADS)

    Ong, Chin-Sing; McConnell, James R.; Chu, Wei-Kom

    1993-08-01

    Liver failure can induce gradations of encephalopathy from mild to stupor to deep coma. The objective of this study is to investigate and quantify the variation of biochemical compounds in the brain in patients with liver failure and encephalopathy, through the use of water- suppressed, localized in-vivo Proton Magnetic Resonance Spectroscopy (HMRS). The spectral parameters of the compounds quantitated are: N-Acetyl Aspartate (NAA) to Creatine (Cr) ratio, Choline (Cho) to Creatine ratio, Inositol (Ins) to Creatine ratio and Glutamine-Glutamate Amino Acid (AA) to Creatine ratio. The study group consisted of twelve patients with proven advanced chronic liver failure and symptoms of encephalopathy. Comparison has been done with results obtained from five normal subjects without any evidence of encephalopathy or liver diseases.

  20. Effects of raloxifene on portal hypertension and hepatic encephalopathy in cirrhotic rats.

    PubMed

    Chang, Ching-Chih; Lee, Wen-Shin; Chuang, Chiao-Lin; Hsin, I-Fang; Hsu, Shao-Jung; Chang, Ting; Huang, Hui-Chun; Lee, Fa-Yauh; Lee, Shou-Dong

    2017-05-05

    Raloxifene, a selective estrogen receptor modulator, has been used extensively for osteoporosis. In addition to the effect of osteoporosis treatment, emerging evidences show that raloxifene affects the vascular function in different tissues. Cirrhosis is characterized with portal hypertension and complicated with hepatic encephalopathy. Portal hypertension affects portal-systemic shunt which leads to hepatic encephalopathy that the vascular modulation might influence severity of hepatic encephalopathy. Herein, we evaluated the impact of raloxifene on bile duct ligation (BDL)-induced cirrhotic rats. The female Sprague-Dawley rats received BDL plus ovariectomy or sham-operation. Four weeks later, rats were divided into 2 subgroups respectively to receive of raloxifene (10mg/kg/day) or saline (vehicle) for 14 days. On the 43th day, motor activities and hemodynamic parameters were measured. Hepatic and vascular mRNA and protein expressions were determined. The histopathological change of liver was examined. We found that the liver biochemistry, ammonia level and motor activity were similar between cirrhotic rats with or without raloxifene administration. The hemodynamic parameters were not significantly different except that raloxifene reduced portal venous inflow. Raloxifene exacerbated hepatic fibrosis and up-regulated hepatic endothelin-1 and cyclooxygenase 2 protein expressions. In addition, raloxifene modulated the mRNA expressions of endothelial nitric oxide synthase, cyclooxygenase and endothelin-1 in the superior mesenteric artery and collateral vessel. In conclusion, raloxifene aggravates hepatic fibrosis and decreases portal venous inflow in cirrhotic rats without adversely affecting portal hypertension and hepatic encephalopathy. The modulation of hepatic and vascular endothelin-1, endothelial nitric oxide synthase and cyclooxygenase expressions may play a role in the mechanism.

  1. Hyperammonemia Is Associated with Increasing Severity of Both Liver Cirrhosis and Hepatic Encephalopathy

    PubMed Central

    Ayub, Maimoona; Khan, Wazir Mohammad

    2016-01-01

    Background. Hyperammonemia resulting from chronic liver disease (CLD) can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was 42.33 ± 7.60. The mean duration (years) of CLD was 10.15 ± 3.53 while the mean Child-Pugh (CP) score was 8.84 ± 3.30. Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE). The frequency of hyperammonemia was 67.3%, more frequent in males (N = 81, z-score = 2.4, and P < 0.05) than in females (N = 34, z-score = 2.4, and P < 0.05), and had a statistically significant relationship with increasing CP grade of cirrhosis (χ2(2) = 27.46, P < 0.001, Phi = 0.40, and P < 0.001). Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; P < 0.001. Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy. PMID:27847646

  2. Altered metal metabolism in patients with HCV-related cirrhosis and hepatic encephalopathy.

    PubMed

    Marano, Massimo; Vespasiani Gentilucci, Umberto; Altamura, Claudia; Siotto, Mariacristina; Squitti, Rosanna; Bucossi, Serena; Quintiliani, Livia; Migliore, Simone; Greco, Federico; Scarciolla, Laura; Quattrocchi, Carlo Cosimo; Picardi, Antonio; Vernieri, Fabrizio

    2015-12-01

    Dysfunctional metal homeostasis contributes to oxidative stress and neuronal damage. These have been implicated in hepatic encephalopathy pathogenesis. To investigate whether altered metal metabolism is associated with hepatic encephalopathy. Twenty-one controls and 34 HCV-cirrhotic patients (ENC/NEC patients according to presence/absence of previous overt episodes of hepatic encephalopathy) and a control group were studied. Serum iron, copper, ceruloplasmin, ceruloplasmin activity, transferrin, and ceruloplasmin/transferrin ratio were determined. Neuropsychological tests were performed by the repeatable battery of neuropsychological status. Magnetic resonance assessed basal ganglia volumes and metal deposition (pallidal index and T2*). Cirrhotic patients performed worse than controls at cognitive tests, especially ENC patients,. At biochemical analysis copper concentrations, ceruloplasmin activity and transferrin levels were lower in ENC than in NEC patients and controls (p < 0.05 and p < 0.01, respectively). Ceruloplasmin/transferrin ratio was higher in ENC compared to NEC patients (p < 0.05), and controls (p < 0.01). By brain magnetic resonance, ENC patients showed reduced caudate and globus pallidus volumes compared to controls (p < 0.05), and ENC and NEC patients an increased pallidal index compared to controls (p < 0.01). In ENC patients, ceruloplasmin activity correlated with caudate volume and pallidal index (ρ = 0.773 and ρ = -0.683, p < 0.05). Altered metal metabolism likely contributes to cirrhotic hepatic encephalopathy.

  3. Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy

    PubMed Central

    Das, Bidyut Kumar

    2011-01-01

    Azithromycin is a widely used macrolide derivative and has generally been considered to be a very safe medication. Though gastrointestinal symptoms and reversible hearing loss are common, potentially serious side effects including angioedema and cholestatic jaundice occurred in less than one percent of patients. We report a case of asymptomatic dilated cardiomyopathy with Azithromycin induced severe hepatocellular toxicity and hepatic encephalopathy. PMID:22144789

  4. Synbiotic formulation of probiotic and lactulose combination for hepatic encephalopathy treatment: a realistic hope?

    PubMed

    Sekhar, M Sonal; Unnikrishnan, M K; Rodrigues, Gabriel Sunil; Mukhopadhyay, Chiranjay

    2013-08-01

    Gut-produced ammonia plays a vital role in the pathogenesis of hepatic encephalopathy because cirrhotic liver fails to clear toxic metabolites. Small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhosis add to the pathogenesis. Lactulose is a mainstay in the treatment of hepatic encephalopathy. Another benefit of lactulose is its prebiotic effect on probiotics that reduce the activity of bacterial urease, resulting in decreased hyperammoneamia and increased elimination of ammonia and other nitrogenous waste through enteric toxin reduction technology. Synbiotic formulation of probiotic and lactulose can synergistically/additively reduce ammonia production, increase utilization and excretion of ammonia and other nitrogenous wastes, thereby improving the well-being of patients with hepatic encephalopathy. We hypothesize that oral administration of a synbiotic formulation prepared from a combination of selected microbial strains of probiotics and lactulose will offer additional protection against hepatic encephalopathy via intra-intestinal extraction of toxic solutes in patients with cirrhosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist

    PubMed Central

    Dunk, Arthur A.; Jalan, Rajiv; Kircheis, Gerald; de Knegt, Robert J.; Laleman, Wim; Ramage, John K.; Wedemeyer, Heiner; Morgan, Ian E.J.

    2016-01-01

    Introduction Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common complication of cirrhosis that is associated with a poor prognosis. Patients with hepatic encephalopathy may present to healthcare providers who do not have primary responsibility for management of patients with cirrhosis. Therefore, we developed a series of ‘consensus points’ to provide some guidance on management. Methods Using a modified ‘Delphi’ process, consensus statements were developed that summarize our recommendations for the diagnosis and management of patients with hepatic encephalopathy. Points on which full consensus could not be reached are also discussed. Results Our recommendations emphasize the role of all healthcare providers in the identification of cognitive impairment in patients with cirrhosis and provide guidance on steps that might be considered to make a diagnosis of overt hepatic encephalopathy. In addition, treatment recommendations are summarized. Minimal hepatic encephalopathy can have a significant impact on patients; however, in most circumstances identification and management of minimal hepatic encephalopathy remains the responsibility of specialists in liver diseases. Conclusion Our opinion statements aim to define the roles and responsibilities of all healthcare providers who at times care for patients with cirrhosis and hepatic encephalopathy. We suggest that these recommendations be considered further by colleagues in other disciplines and hope that future guidelines consider the management of patients with cirrhosis and with a ‘suspicion’ of cognitive impairment through to a formal diagnosis of hepatic encephalopathy. PMID:26600154

  6. Zonisamide eradicated paroxysmal headache with EEG abnormalities triggered by hypertensive encephalopathy due to purpura nephritic syndrome.

    PubMed

    Anzai, Yuki; Hayashi, Masaharu; Ohya, Tatsuo

    2006-10-01

    Generally, prognosis of hypertensive encephalopathy in childhood is favorable. We reported a 5-year-old girl who presented with a headache attack and EEG abnormalities after hypertensive encephalopathy due to purpura nephritis. The patient had suffered from hypertensive encephalopathy due to purpura nephritis, which soon ameliorated. Five months later, she developed attacks of headache, vomiting and disturbed consciousness with left side-predominant EEG abnormalities. Although carbamazepine and sodium valproate failed to improve her condition, zonisamide eradicated both the symptoms and EEG abnormalities, and an attack has not reoccurred for 5 years since completion of her treatment. It is noteworthy that delayed-onset complications can occur in child hypertensive encephalopathy, cases of which should be followed up prudently. Zonisamide should be considered for treatment of attacks of headaches with an epileptic character.

  7. Reversible weakness and encephalopathy while on long-term valproate treatment due to carnitine deficiency.

    PubMed

    Al-sharefi, Ahmed; Bilous, Rudy

    2015-09-02

    We describe a case of a 35-year-old woman who presented with bilateral leg weakness and encephalopathy while on long-term valproate therapy. She was diagnosed with valproate-induced encephalopathy due to carnitine deficiency. Clinical improvement occurred with oral carnitine supplementation. Our case report highlights the importance of considering carnitine deficiency in patients presenting with unexplained neurological signs while on long-term valproate treatment.

  8. Reversible weakness and encephalopathy while on long-term valproate treatment due to carnitine deficiency

    PubMed Central

    Al-sharefi, Ahmed; Bilous, Rudy

    2015-01-01

    We describe a case of a 35-year-old woman who presented with bilateral leg weakness and encephalopathy while on long-term valproate therapy. She was diagnosed with valproate-induced encephalopathy due to carnitine deficiency. Clinical improvement occurred with oral carnitine supplementation. Our case report highlights the importance of considering carnitine deficiency in patients presenting with unexplained neurological signs while on long-term valproate treatment. PMID:26336183

  9. Role of Nutrition in the Management of Hepatic Encephalopathy in End-Stage Liver Failure

    PubMed Central

    Bémeur, Chantal; Desjardins, Paul; Butterworth, Roger F.

    2010-01-01

    Malnutrition is common in patients with end-stage liver failure and hepatic encephalopathy, and is considered a significant prognostic factor affecting quality of life, outcome, and survival. The liver plays a crucial role in the regulation of nutrition by trafficking the metabolism of nutrients, their distribution and appropriate use by the body. Nutritional consequences with the potential to cause nervous system dysfunction occur in liver failure, and many factors contribute to malnutrition in hepatic failure. Among them are inadequate dietary intake, malabsorption, increased protein losses, hypermetabolism, insulin resistance, gastrointestinal bleeding, ascites, inflammation/infection, and hyponatremia. Patients at risk of malnutrition are relatively difficult to identify since liver disease may interfere with biomarkers of malnutrition. The supplementation of the diet with amino acids, antioxidants, vitamins as well as probiotics in addition to meeting energy and protein requirements may improve nutritional status, liver function, and hepatic encephalopathy in patients with end-stage liver failure. PMID:21234351

  10. Correlation of hyponatremia with hepatic encephalopathy and severity of liver disease.

    PubMed

    Qureshi, Muhammad Omar; Khokhar, Nasir; Saleem, Atif; Niazi, Tariq Khan

    2014-02-01

    To assess the frequency of low serum sodium levels and to correlate it with the severity of liver disease and hepatic encephalopathy (HE) in patients coming to the tertiary care hospital. Observational study. Shifa International Hospital, Islamabad, from January 2011 to January 2012. A total of 202 patients with hepatic encephalopathy and chronic liver disease had serum sodium measured. The HE was graded according to the West Haven classification (4 grades). Relationship of hyponatremia was correlated with severity grade of encephalopathy using Spearman rank correlation test. Out of 202 patients, 62 (30.7%) patients had serum sodium less than 130 meq/l. Out of 202, HE was present in 69 (34.15%) patients and out of these, 38 had grade III-IV HE and 31 had grade I - II HE. Out of 69 patients with HE 57 had sodium less than 135 (p < 0.001). Hyponatremia was a common feature in patients with cirrhosis and its severity increased with the severity of liver disease. The existence of serum sodium concentration < 135 mmol/L was associated with greater frequency of hepatic encephalopathy compared with patients with serum sodium concentration > 135 mmol/L.

  11. Klüver-Bucy syndrome following status epilepticus associated with hepatic encephalopathy.

    PubMed

    Naito, Kosuke; Hashimoto, Takao; Ikeda, Shu-ichi

    2008-02-01

    Described here is the case of a patient with liver cirrhosis who developed bilateral temporo-occipital lobe lesions on MRI and Klüver-Bucy syndrome following status epilepticus. Herpes encephalitis, paraneoplastic syndrome, Hashimoto's encephalopathy, reversible posterior leukoencephalopathy syndrome, mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode syndrome were judged not to be involved on the basis of laboratory results. The possible cause of the temporo-occipital lesions on MRI in this patient was cortical damage related mainly to status epilepticus and partially to coexisting hepatic encephalopathy.

  12. Capsaicin affects brain function in a model of hepatic encephalopathy associated with fulminant hepatic failure in mice

    PubMed Central

    Avraham, Y; Grigoriadis, NC; Magen, I; Poutahidis, T; Vorobiav, L; Zolotarev, O; Ilan, Y; Mechoulam, R; Berry, EM

    2009-01-01

    Background and purpose: Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver failure. In view of the effects of cannabinoids in a thioacetamide-induced model of hepatic encephalopathy and liver disease and the beneficial effect of capsaicin (a TRPV1 agonist) in liver disease, we assumed that capsaicin may also affect hepatic encephalopathy. Experimental approach: Fulminant hepatic failure was induced in mice by thioacetamide and 24 h later, the animals were injected with one of the following compound(s): 2-arachidonoylglycerol (CB1, CB2 and TRPV1 receptor agonist); HU308 (CB2 receptor agonist), SR141716A (CB1 receptor antagonist); SR141716A+2-arachidonoylglycerol; SR144528 (CB2 receptor antagonist); capsaicin; and capsazepine (TRPV1 receptor agonist and antagonist respectively). Their neurological effects were evaluated on the basis of activity in the open field, cognitive function in an eight-arm maze and a neurological severity score. The mice were killed 3 or 14 days after thioacetamide administration. 2-arachidonoylglycerol and 5-hydroxytryptamine (5-HT) levels were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography with electrochemical detection, respectively. Results: Capsaicin had a neuroprotective effect in this animal model as shown by the neurological score, activity and cognitive function. The effect of capsaicin was blocked by capsazepine. Thioacetamide induced astrogliosis in the hippocampus and the cerebellum and raised brain 5-hydroxytryptamine levels, which were decreased by capsaicin, SR141716A and HU-308. Thioacetamide lowered brain 2-arachidonoylglycerol levels, an effect reversed by capsaicin. Conclusions: Capsaicin improved both liver and brain dysfunction caused by thioacetamide, suggesting that both the endocannabinoid and the vanilloid systems play important roles in hepatic encephalopathy. Modulation of these systems may have therapeutic value. PMID:19764982

  13. Reversal of Transjugular Intrahepatic Portosystemic Shunt (TIPS)-Induced Hepatic Encephalopathy Using a Strictured Self-Expanding Covered Stent

    SciTech Connect

    Cox, Mitchell W.; Soltes, George D.; Lin, Peter H. Bush, Ruth L.; Lumsden, Alan B.

    2003-11-15

    Hepatic encephalopathy is a known complication following percutaneous transjugular intrahepatic portosystemic shunt (TIPS) placement. We describe herein a simple and effective strategy of TIPS revision by creating an intraluminal stricture within a self-expanding covered stent, which is deployed in the portosystemic shunt to reduce the TIPS blood flow. This technique was successful in reversing a TIPS-induced hepatic encephalopathy in our patient.

  14. Creutzfeldt-Jakob-Like Syndrome due to Hypercalcemic Encephalopathy.

    PubMed

    Rösche, Johannes; Sieveking, Catharina; Kampf, Christina; Benecke, Reiner

    2015-10-01

    Hypercalcemia can cause a subacute syndrome of progressive dementia and marked changes in the electroencephalogram (EEG). We report a case of iatrogenic hypercalcemia with a close correlation between the clinical course and the EEG changes. A 73-year-old woman presented with a subacute syndrome of progressive dementia and bursts of 1.5 to 2 Hz intermittent rhythmic delta activity superimposed on a low-voltage background activity in the EEG. Clinical and EEG abnormalities rapidly resolved after normalization of serum calcium levels. As part of the diagnostic workup of a subacute progressive dementia, a serum calcium level and an EEG should be obtained to detect a Creutzfeldt-Jakob like syndrome in hypercalcemia. Unlike in Creutzfeldt-Jakob disease, and Creutzfeldt-Jakob-like syndrome induced by lithium intoxication, there are rarely myoclonic jerks and periodic discharges in hypercalcemic encephalopathy.

  15. The abnormality of thyroid hormones in patients with type A hepatic encephalopathy.

    PubMed

    Wang, Lin; Yu, Wanyou; Cao, Wukui; Lu, Wei

    2017-09-15

    Abnormality of thyroid hormones in liver diseases is common, but data is lacking in patients with type A hepatic encephalopathy (HE). The present study was aimed to determine whether there was an abnormality in thyroid hormones among patients with type A HE. We measured the levels of thyroid hormones in 36 acute liver failure (ALF) patients with type A HE and in 29 acute liver injury patients (international normalized ratio, INR ≥ 1.5) without encephalopathy as control. The clinical parameters associated with abnormality of thyroid hormones were evaluated. ALF patients with type A HE exhibited decreased TSH levels compared to patients without encephalopathy (0.17 vs 1.08 μIU/mL, P < 0.001). There was no difference in T3 and T4 levels (both total and free) between the two groups. The logistic regression analysis identified type A HE as an independent related factor for the occurrence of low TSH (Odds Ratio = 12.32) in patients with ALF. Correlation analysis showed that there was an inverse correlation between TSH level and the grade of encephalopathy (r = -0.795). Furthermore, patients with low TSH depicted poor survival rate than those with normal TSH level (29.3% vs 44.1%, P = 0.003). Patients with type A HE exhibited subclinical central hypothyroidism, and had significant decreased TSH level, which had inverse correlation with the grade of encephalopathy. The reduced TSH was associated with poor survival rate.

  16. Phospholipid and cholesterol alterations accompany structural disarray in myelin membrane of rats with hepatic encephalopathy induced by thioacetamide.

    PubMed

    Swapna, I; Kumar, K V Sathya Sai; Reddy, P Vijaya Bhaskar; Murthy, Ch R K; Reddanna, P; Senthilkumaran, B

    2006-08-01

    Fulminant hepatic failure is often associated with a wide range of neurological symptoms which are collectively referred to as hepatic encephalopathy. Fulminant hepatic failure with associated hepatic encephalopathy has a poor prognosis with the currently available sure treatment being only liver transplantation. This is largely owing to the lack of understanding of critical factors involved in the etiology of the condition. Lipid changes have been implicated in cerebral derangements characteristic of hepatic encephalopathy. About 79% of the brain lipid is concentrated in the myelin fraction where they play an important role in ion balance and conduction of nerve impulses. Hence, in the present study we aimed to investigate changes in myelin lipid composition and structure. Myelin was isolated by sucrose density gradient centrifugation from cerebral cortex of male Wistar rats (250-300 g body weight) treated with 300 mg/kg body weight thioacetamide administered twice at 24h interval to induce hepatic encephalopathy. Significant decrease was observed in the cholesterol and phospholipids content of myelin from treated rats. Sphingomyelin, phosphatidylserine and phosphatidylethanolamine content also decreased significantly following 18 h of thioacetamide administration. However, phosphatidylcholine levels remained unaltered. Transmission electron microscopic observation of myelin membrane from cerebral cortex sections showed considerable disorganization in myelin structure. Increase in malondialdehyde levels precede lipid changes leading to the speculation that oxidative damage may be the critical factor leading to decrease in the anionic phospholipids. Changes in myelin were evident only in later stages of hepatic encephalopathy indicating that myelin alteration may not play a role in early stages of hepatic encephalopathy. Nevertheless, myelin alteration may have a crucial role to play in various psycho-motor alterations during later stages of hepatic encephalopathy.

  17. Recent developments in the diagnosis and treatment of covert/minimal hepatic encephalopathy.

    PubMed

    De Rui, M; Montagnese, S; Amodio, P

    2016-01-01

    The terms minimal hepatic encephalopathy and covert hepatic encephalopathy are defined. Clinical assessment is unreliable and both require the use of diagnostic tools. Of these, psychometric tests are the most widely used. They require proper standardization and may be biased by patient cooperation or lack thereof. The measure of the critical flicker frequency and of the electroencephalogram, possibly quantified, are also useful. The alteration of any of them is not strictly parallel in size and may vary from patient to patient. When possible, the use of multiple measures might increase diagnostic reliability. These functional measures should be interpreted within the clinical/biochemical profile of the patient to exclude other disorders. A flow chart for treatment is proposed on the basis of current knowledge.

  18. To pee or not to pee: ammonia hypothesis of hepatic encephalopathy revisited.

    PubMed

    Mpabanzi, Liliane; Olde Damink, Steven W M; van de Poll, Marcel C G; Soeters, Peter B; Jalan, Rajiv; Dejong, Cees H C

    2011-06-01

    Hepatic encephalopathy is a neuropsychiatric syndrome associated with liver failure. Its aetiology has been debated for the past 100 years. Nevertheless, elevated ammonia levels are still believed to play a central role in its pathogenesis. After intestinal production, ammonia is detoxified by the liver. In liver failure, skeletal muscle and brain have been proposed to be alternative, although temporary, ammonia detoxifying organs. However, there is an increasing body of evidence that the kidney, in addition to the gut, is a pivotal organ determining systemic ammonia levels. In the last 20 years, it has been shown that the kidney can switch from an organ of systemic net ammonia production to a net ammonia excretion organ. The kidney plays a central role in the determination of ammonia levels. It is at least as important as the gut and could therefore serve as a target for new treatments for hepatic encephalopathy.

  19. Efficacy of lactulose in the prophylaxis of hepatic encephalopathy in cirrhotic patients presenting gastrointestinal bleeding.

    PubMed

    Aires, Felipe Toyama; Ramos, Paola Teruya; Bernardo, Wanderley Marques

    2016-01-01

    Hepatic encephalopathy (HE) is a bad prognostic factor in patients with liver cirrhosis and its incidence is associated with several triggering factors being the most prevalent gastrointestinal bleeding. Lactulose, despite its questionable efficacy in the literature, is considered a first line treatment in patients with HE. To evaluate the effectiveness of lactulose in preventing HE in cirrhotic patients with gastrointestinal bleeding. A systematic review of the literature using the Medline scientific database. Only randomized controlled clinical trials evaluating the efficacy of lactulose for HE prophylaxis in cirrhotic patients with gastrointestinal bleeding were included. The incidence of HE in the intervention group was 7%, while the control group was 26% (p=0.01). There was no significant difference in the incidence of mortality in the group treated with lactulose compared to the group that was not treated (p=0.48). Administering lactulose to cirrhotic patients with upper gastrointestinal bleeding reduces the incidence of hepatic encephalopathy.

  20. Hepatic encephalopathy with reversible focal neurologic signs resembling acute stroke: case report.

    PubMed

    Yamamoto, Yoshiya; Nishiyama, Yasuhiro; Katsura, Ken-Ichiro; Yamazaki, Mineo; Katayama, Yasuo

    2011-01-01

    A 64-year-old female with a history of primary biliary cirrhosis and esophageal varices starting at age 39 was brought to our Stroke Care Unit by ambulance with right-side weakness and speech difficulty. Physical examination revealed right hemiparesis (including the face), sensory disturbances, pathological reflexes, and slightly decreased consciousness, with a Glasgow Coma Scale rating of E3V4M6. Flapping tremors and speech disturbance, as well as anarithmia, construction apraxia, and ideomotor apraxia, were noted, and her National Institutes of Health Stroke Scale score was 13. Initially, the patient was diagnosed with acute stroke and treated accordingly; however, subsequent findings from clinical images and electroencephalography led to a diagnosis of focal neurologic signs due to hepatic encephalopathy (HE). The patient had significantly reduced cerebral blood flow in the left side of the brain, probably due to microsurgical repair of an aneurysm done 2 years earlier. HE with exaggerated chronic liver damage might have made the previously silent ischemia clinically apparent. This interpretation is supported by the fact that the patient's neurologic deficits resolved once HE was adequately controlled. This case illustrates the need for careful assessment of background pathophysiology when diagnosing patients with stroke-like symptoms.

  1. Clinical scenarios for the use of S100β as a marker of hepatic encephalopathy

    PubMed Central

    Duarte-Rojo, Andrés; Ruiz-Margáin, Astrid; Macias-Rodriguez, Ricardo U; Cubero, Francisco Javier; Estradas-Trujillo, José; Muñoz-Fuentes, Rosa Ma; Torre, Aldo

    2016-01-01

    AIM: To evaluate the association between serum concentrations of S100β in patients with cirrhosis and the presence of low grade hepatic encephalopathy (HE). METHODS: This was a cross-sectional study. The population was categorized into four groups healthy subjects, cirrhosis without HE, cirrhosis with covert hepatic encephalopathy (CHE) and cirrhosis with overt HE. Kruskal-Wallis, Mann Whitney’s U with Bonferroni adjustment Spearman correlations and area under the ROC were used as appropriate. RESULTS: A total of 61 subjects were included, 46 cirrhotic patients and 15 healthy volunteers. S100β values were different among all groups, and differences remained significant between groups 1 and 2 (P < 0.001), and also between groups 2 and 3 (P = 0.016), but not between groups 3 and 4. In cirrhotic patients with HE S100β was higher than in patients without HE [0.18 (0.14-0.28) ng/mL vs 0.11 (0.06-0.14) ng/mL, P < 0.001]. There was a close correlation between serum concentrations of S100β and psychometric hepatic encephalopathy score in patients with cirrhosis without HE compared to the patients with cirrhosis with CHE (r = -0.413, P = 0.019). ROC curve analysis yielded > 0.13 ng/mL as the best cutoff value of S100β for the diagnosis of HE (sensitivity 83.3%, specificity 63.6%). CONCLUSION: Serum concentrations of S100β are higher in patients with cirrhosis than in healthy volunteers, and are further increased in the presence of hepatic encephalopathy. The results suggest that serum biomarkers such as S100β could help in the correct characterization of incipient stages of HE. PMID:27158209

  2. Methanethiol metabolism and its role in the pathogenesis of hepatic encephalopathy in rats and dogs.

    PubMed

    Blom, H J; Chamuleau, R A; Rothuizen, J; Deutz, N E; Tangerman, A

    1990-04-01

    The metabolism of methanethiol was studied in rats. Administration of a noncomatogenic dose of methanethiol through inspired air or injection into the upper colon resulted in an elevation of the concentrations of methanethiol mixed disulfides in serum (protein--S--S--CH3 and X--S--S--CH3, X yet unknown) and in urine (X--S--S--CH3). The concentrations of methanethiol mixed disulfides proved to be a relative measure of exposure to methanethiol. The levels of volatile sulfur compounds methanethiol, dimethylsulfide and dimethyldisulfide in the air expired by rats exposed to a noncomatogenic dose of methanethiol through the colon were also elevated. Rats with acute hepatic encephalopathy caused by liver ischemia also showed elevation of methanethiol mixed disulfide levels on challenge of methanethiol through the colon or inspired air, but to a significantly smaller extent than did the corresponding sham-operated rats. This suggests that the liver is at least partly responsible for formation of methanethiol mixed disulfides. No additional toxic effects were observed in the rats with ischemic livers on methanethiol exposition when compared with normal rats, suggesting that the liver does not play an essential role in methanethiol detoxification. Metabolism of methanethiol by blood to sulfate, for example, might be more important. In rats with acute hepatic encephalopathy caused by liver ischemia and in dogs suffering from hepatic encephalopathy resulting from chronic liver disease, large and significant increases in ammonia levels were measured. However, the mean levels of methanethiol mixed disulfides in rats and dogs with hepatic encephalopathy were not different from the mean normal levels in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Reversible brainstem edema due to hypertensive encephalopathy in an 8-year-old girl.

    PubMed

    Moosa, Ahsan N V; Eagam, Mamata; Moodley, Manikum

    2011-08-01

    The authors report an 8-year-old girl with refractory status epilepticus due to hypertensive encephalopathy, secondary to end-stage renal disease. Brain magnetic resonance imaging (MRI) in the acute phase showed striking hyperintensities in the brain stem and medial thalamus along with subtle cortical lesions. After successful control of hypertensive crisis and status epilepticus, the patient recovered to her baseline. Near total resolution of the lesions was noted on follow-up imaging performed 9 days later. Predominant brainstem involvement as a feature of posterior reversible encephalopathy syndrome due to hypertensive crisis is extremely rare in children and has not been well documented.

  4. Interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in minimal hepatic encephalopathy.

    PubMed

    Llansola, Marta; Montoliu, Carmina; Agusti, Ana; Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Gomez-Gimenez, Belen; Malaguarnera, Michele; Dadsetan, Sherry; Belghiti, Majedeline; Garcia-Garcia, Raquel; Balzano, Tiziano; Taoro, Lucas; Felipo, Vicente

    2015-09-01

    The cognitive and motor alterations in hepatic encephalopathy (HE) are the final result of altered neurotransmission and communication between neurons in neuronal networks and circuits. Different neurotransmitter systems cooperate to modulate cognitive and motor function, with a main role for glutamatergic and GABAergic neurotransmission in different brain areas and neuronal circuits. There is an interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in HE. This interplay may occur: (a) in different brain areas involved in specific neuronal circuits; (b) in the same brain area through cross-modulation of glutamatergic and GABAergic neurotransmission. We will summarize some examples of the (1) interplay between glutamatergic and GABAergic neurotransmission alterations in different areas in the basal ganglia-thalamus-cortex circuit in the motor alterations in minimal hepatic encephalopathy (MHE); (2) interplay between glutamatergic and GABAergic neurotransmission alterations in cerebellum in the impairment of cognitive function in MHE through altered function of the glutamate-nitric oxide-cGMP pathway. We will also comment the therapeutic implications of the above studies and the utility of modulators of glutamate and GABA receptors to restore cognitive and motor function in rats with hyperammonemia and hepatic encephalopathy.

  5. [Association of plasma ammonia and GABA levels and the degree of hepatic encephalopathy].

    PubMed

    Campollo, O; MacGillivray, B B; McIntyre, N

    1992-01-01

    Several toxic factors have been implicated in the pathogenesis of hepatic encephalopathy (PSE) among which ammonia plays a dominant role. More recently, the gamma-aminobutyric acid (GABA) hypothesis in which an increase in the GABA-ergic tone and the presence of one or more GABA/benzodiazepine receptor ligands which interact with that receptor, has been proposed. We investigated the levels of GABA and ammonia in plasma of patients with acute PSE to test the hypothesis that elevated plasma GABA levels would be found in acute encephalopathy and that GABA levels would correlate with the degree of hepatic encephalopathy. We measured plasma levels of GABA and ammonia during an acute episode of PSE, spontaneous or precipitated by gastrointestinal bleeding or sepsis, and performed assessments of PSE by the PSE index. Patients were evaluated before and two days after standard treatment with lactulose. We also measured plasma GABA levels in the hepatic vein of a selected group of patients undergoing hemodynamic studies. Plasma GABA levels were significantly higher in patients with acute PSE (458 +/- 108 pmol/mL) when compared with normal subjects (110 +/- 23 pmol/mL) (p < 0.01) although no correlation was found between plasma GABA concentration and the degree of PSE. Changes in plasma ammonia, however, correlated with improvements in the PSE index (r = 0.56; p < 0.02) and with abnormalities in the EEG (r = 0.65; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. [Clinical research on microecologic treatment combined enteral nutrition for hepatic encephalopathy].

    PubMed

    Dai, Gaiguo; Wu, Denghai; Lian, Jianan; Ma, Hongmei; Jiang, Binhua

    2014-12-01

    To evaluate the effect of microecologic treatment combined enteral nutrition on serum endotoxin, tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), blood ammonia levels and nutritional status in patients with hepatic encephalopathy. 60 patients with hepatic encephalopathy were allocted randomly into 3 groups, on the basis of conventional liver protective therapy and uragogue with one group given probiotics plus enteral nutrition, one given probiotics only, and the 3rd group given intravenous nutrition. The whole course of treatment was four weeks. Serum levels of endotoxin, TNF-α, IL-18, ammonia and albumin were determined before and on the 7th and 14th day after treatment. The levels of serum endotoxin, TNF-α, IL-18 and blood ammonia in the combined treatment group decreased remarkably after treatment, while the level of serum albumin elevated markedly. The difference was significant at statistics as compared with the only probiotics group and intravenous nutrition group (P < 0.05). Microecologic treatment combined enteral nutrition could effectively reduce blood ammonia and serum endotoxin levels, protect intestinal mucosal barrier, as well as improve nutritional status of patients with hepatic encephalopathy, which was considered as a safe and efficient therapy.

  7. Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study

    PubMed Central

    Paik, Yong-Han; Han, Kwang-Hyub; Song, Kun Hoon; Kim, Myoung Hwan; Moon, Byung Soo; Ahn, Sang Hoon; Lee, Se Joon; Park, Hyo Jin; Lee, Dong Ki; Chon, Chae Yoon; Lee, Sang In; Moon, Young Myoung

    2005-01-01

    Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p=0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the posttreatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0→4.2, p=0.000); lactulose group (11.3→5.0, p=0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy. PMID:15988813

  8. Functional brain network changes associated with clinical and biochemical measures of the severity of hepatic encephalopathy.

    PubMed

    Jao, Tun; Schröter, Manuel; Chen, Chao-Long; Cheng, Yu-Fan; Lo, Chun-Yi Zac; Chou, Kun-Hsien; Patel, Ameera X; Lin, Wei-Che; Lin, Ching-Po; Bullmore, Edward T

    2015-11-15

    Functional properties of the brain may be associated with changes in complex brain networks. However, little is known about how properties of large-scale functional brain networks may be altered stepwise in patients with disturbance of consciousness, e.g., an encephalopathy. We used resting-state fMRI data on patients suffering from various degrees of hepatic encephalopathy (HE) to explore how topological and spatial network properties of functional brain networks changed at different cognitive and consciousness states. Severity of HE was measured clinically and by neuropsychological tests. Fifty-eight non-alcoholic liver cirrhosis patients and 62 normal controls were studied. Patients were subdivided into liver cirrhosis with no outstanding HE (NoHE, n=23), minimal HE with cognitive impairment only detectable by neuropsychological tests (MHE, n=28), and clinically overt HE (OHE, n=7). From the earliest stage, the NoHE, functional brain networks were progressively more random, less clustered, and less modular. Since the intermediate stage (MHE), increased ammonia level was accompanied by concomitant exponential decay of mean connectivity strength, especially in the primary cortical areas and midline brain structures. Finally, at the OHE stage, there were radical reorganization of the topological centrality-i.e., the relative importance-of the hubs and reorientation of functional connections between nodes. In summary, this study illustrated progressively greater abnormalities in functional brain network organization in patients with clinical and biochemical evidence of more severe hepatic encephalopathy. The early-than-expected brain network dysfunction in cirrhotic patients suggests that brain functional connectivity and network analysis may provide useful and complementary biomarkers for more aggressive and earlier intervention of hepatic encephalopathy. Moreover, the stepwise deterioration of functional brain networks in HE patients may suggest that hierarchical

  9. Magnetic Resonance Spectroscopy for Evaluating Portal-Systemic Encephalopathy in Patients with Chronic Hepatic Schistosomiasis Japonicum.

    PubMed

    Li, Ying; Mei, Lihong; Qiang, Jinwei; Ju, Shuai; Zhao, Shuhui

    2016-12-01

    Portal-systemic encephalopathy (PSE) is classified as type B hepatic encephalopathy. Portal-systemic shunting rather than liver dysfunction is the main cause of PSE in chronic hepatic schistosomiasis japonicum (HSJ) patients. Owing to lack of detectable evidence of intrinsic liver disease, chronic HSJ patients with PSE are frequently clinically undetected or misdiagnosed, especially chronic HSJ patients with covert PSE (subclinical encephalopathy). In this study, we investigated whether magnetic resonance spectroscopy (MRS) could be a useful tool for diagnosing PSE in chronic HSJ patients. Magnetic resonance (MR) T1-weighted imaging, diffusion-weighted imaging, and MRS were performed in 41 chronic HSJ patients with suspected PSE and in 21 age-matched controls. The T1 signal intensity index (T1SI) and apparent diffusion coefficient (ADC) value were obtained in the Globus pallidus. Liver function was also investigated via serum ammonia and liver function tests. Higher T1SI and ADC values, increased lactate and glutamine levels, and decreased myo-inositol were found in the bilateral Globus pallidus in chronic HSJ patients with PSE. No significantly abnormal serum ammonia or liver function tests were observed in chronic HSJ patients with PSE. On the basis of these findings, we propose a diagnostic procedure for PSE in chronic HSJ patients. This study reveals that MRS can be useful for diagnosing PSE in chronic HSJ patients.

  10. Magnetic Resonance Spectroscopy for Evaluating Portal-Systemic Encephalopathy in Patients with Chronic Hepatic Schistosomiasis Japonicum

    PubMed Central

    Li, Ying; Mei, Lihong; Qiang, Jinwei; Ju, Shuai; Zhao, Shuhui

    2016-01-01

    Portal-systemic encephalopathy (PSE) is classified as type B hepatic encephalopathy. Portal-systemic shunting rather than liver dysfunction is the main cause of PSE in chronic hepatic schistosomiasis japonicum (HSJ) patients. Owing to lack of detectable evidence of intrinsic liver disease, chronic HSJ patients with PSE are frequently clinically undetected or misdiagnosed, especially chronic HSJ patients with covert PSE (subclinical encephalopathy). In this study, we investigated whether magnetic resonance spectroscopy (MRS) could be a useful tool for diagnosing PSE in chronic HSJ patients. Magnetic resonance (MR) T1-weighted imaging, diffusion-weighted imaging, and MRS were performed in 41 chronic HSJ patients with suspected PSE and in 21 age-matched controls. The T1 signal intensity index (T1SI) and apparent diffusion coefficient (ADC) value were obtained in the Globus pallidus. Liver function was also investigated via serum ammonia and liver function tests. Higher T1SI and ADC values, increased lactate and glutamine levels, and decreased myo-inositol were found in the bilateral Globus pallidus in chronic HSJ patients with PSE. No significantly abnormal serum ammonia or liver function tests were observed in chronic HSJ patients with PSE. On the basis of these findings, we propose a diagnostic procedure for PSE in chronic HSJ patients. This study reveals that MRS can be useful for diagnosing PSE in chronic HSJ patients. PMID:27977668

  11. Comparison of the most favoured methods for the diagnosis of hepatic encephalopathy in liver transplantation candidates.

    PubMed

    Goldbecker, Annemarie; Weissenborn, Karin; Hamidi Shahrezaei, Golschan; Afshar, Kambiz; Rümke, Stefan; Barg-Hock, Hannelore; Strassburg, Christian P; Hecker, Hartmut; Tryc, Anita Blanka

    2013-10-01

    Hepatic encephalopathy (HE) is a common complication of liver insufficiency. While there is widespread acceptance of its importance, there is no consensus on how best to diagnose and monitor HE. To compare the four most favoured methods for the diagnosis of HE. 170 patients who were on the waiting list for liver transplantation as well as 86 healthy controls were included in the study. All patients and controls underwent the portosystemic encephalopathy syndrome test yielding the psychometric hepatic encephalopathy score (PHES), the repeatable battery for the assessment of neuropsychological status (RBANS), the inhibitory control test (ICT) and critical flicker frequency (CFF) measurement. PHES and ICT targets had the best sensitivity (85.7% vs 85.7%) and specificity (96.5% vs 97.6%) for the diagnosis of overt HE. CFF showed inferior sensitivity (40.9%) for the diagnosis of HE and dependency from previous alcohol abuse (p=0.015). Multiple regression analysis showed that all test results apart from PHES were influenced by secondary diagnoses such as diabetes mellitus and renal insufficiency. In the German population of patients awaiting liver transplantation, PHES is the most robust method for the diagnosis and follow-up of HE.

  12. Correlations between magnetic resonance spectroscopy alterations and cerebral ammonia and glucose metabolism in cirrhotic patients with and without hepatic encephalopathy

    PubMed Central

    Weissenborn, Karin; Ahl, Björn; Fischer‐Wasels, Daniela; van den Hoff, Joerg; Hecker, Hartmut; Burchert, Wolfgang; Köstler, Herbert

    2007-01-01

    Background Hepatic encephalopathy is considered to be mainly caused by increased ammonia metabolism of the brain. If this hypothesis is true, cerebral glucose utilisation, which is considered to represent brain function, should be closely related to cerebral ammonia metabolism. The aim of the present study was to analyse whether cerebral ammonia and glucose metabolism in cirrhotic patients with early grades of hepatic encephalopathy are as closely related as could be expected from current hypotheses on hepatic encephalopathy. Methods 13N‐ammonia and 18F‐fluorodesoxyglucose positron emission tomography, magnetic resonance imaging and magnetic resonance spectroscopy (MRS) were performed in 21 cirrhotic patients with grade 0–1 hepatic encephalopathy. Quantitative values of cerebral ammonia uptake and retention rate and glucose utilisation were derived for several regions of interest and were correlated with the MRS data of the basal ganglia, white matter and frontal cortex. Results A significant correlation between plasma ammonia levels and cerebral ammonia metabolism, respectively, and MRS alterations could be shown only for white matter. In contrast, MRS alterations in all three regions studied were significantly correlated with the glucose utilisation of several brain regions. Cerebral ammonia and glucose metabolism were not correlated. Conclusion Increase of cerebral ammonia metabolism is an important but not exclusive causal factor for the development of hepatic encephalopathy. PMID:17660226

  13. [A case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis caused by chronic hepatitis C].

    PubMed

    Choi, Hye Mi; Jung, Gum Mo; Lee, Woong Ki; Lee, Hyeuk Soo; Kim, Byung Sun; Seong, Choong Sil; Yoon, So Hee; Cho, Yong Keun

    2014-11-01

    Cryptococcus neoformans, an encapsulated fungus, is an important opportunistic pathogen that can cause meningitis in im-munocompromised patients. Since patients with cryptococcemia have high mortality, it is essential to make an early diagnosis and promptly initiate antifungal therapy. However, it is often very difficult to differentiate between cryptococcal meningitis and hepatic encephalopathy in patients with liver cirrhosis, and there is delay in making the diagnosis. Therefore, these patients have a particularly grave prognosis and consequently many patients die before culture results become available. In one study, starting antifungal therapy within 48 hours of the blood culture was associated with improved survival, but patients with liver cirrhosis were significantly less likely to receive antifungal therapy within 48 hours compared to those without liver cirrhosis. Recently, the authors experience a case of a 68-year-old woman with liver cirrhosis who presented with fever and a drowsy mental status. She had a previous history of having been admitted for infection-associated hepatic encephlopathy. Cryptococcal meningitis and cryptococcemia were diagnosed by spinal puncture and culture of cerebrospinal fluid. In spite of adequate treatment, the patient developed multi-system organ failure and eventually expired. Herein, we report a case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis.

  14. Hepatic encephalopathy in a pregnant mare: identification of histopathological changes in the brain of a mare and fetus.

    PubMed

    Johns, I C; Del Piero, F; Wilkins, P A

    2007-08-01

    An 11-year-old Thoroughbred broodmare was evaluated for suspected hepatic dysfunction. Clinical signs of hepatic encephalopathy were evident at admission. Hepatic ultrasonographic evaluation revealed an increase in hepatic size, rounded borders and normal echogenicity. There was no evidence of cholelithiasis or bile duct distention. Increased activity of hepatic enzymes, increased bile acid and bilirubin concentration and an increased ammonia concentration were supportive of a diagnosis of hepatic disease and hepatic encephalopathy. Histopathological evaluation of a liver biopsy specimen was consistent with chronic active hepatitis. The mare was treated with intravenous fluids and antimicrobials, pentoxyfilline, branched-chain amino acids and dietary manipulation. Clinical improvement was observed initially; however, 3 weeks later, deterioration in the mare's condition necessitated euthanasia. Pathological lesions at necropsy were restricted to the liver and brain. The liver was diffusely firm with a prominent reticular pattern on the cut surface. A large choledocholith was present in the main bile duct of the left liver lobe. Histopathological examination of the liver revealed severe fibrosis, with hyperplastic bile ducts and mononuclear and neutrophilic inflammation. Pathological changes consistent with hepatic encephalopathy, (Alzheimer type II cells), were evident in the cerebrum of both the mare and the fetus.

  15. Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

    PubMed Central

    Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

    2011-01-01

    BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

  16. The role of antioxidants and zinc in minimal hepatic encephalopathy: a randomized trial

    PubMed Central

    Mousa, Nasser; Abdel-Razik, Ahmed; Zaher, Ashraf; Hamed, Magdy; Shiha, Gamal; Effat, Narmin; Elbaz, Sherif; Elhelaly, Rania; Hafez, Mohamed; El-Wakeel, Niveen; Eldars, Waleed

    2016-01-01

    Background: Minimal hepatic encephalopathy (MHE) has a far-reaching impact on quality and function ability in daily life and may progress to overt hepatic encephalopathy. There is a synergistic effect between systemic oxidative stress and ammonia that is implicated in the pathogenesis of hepatic encephalopathy. The aim of this study is to investigate the effectiveness of oral supplementation of antioxidants and zinc gluconate on MHE versus lactulose. Methods: Our study included 58 patients with cirrhosis diagnosed as having MHE by neuropsychometric tests, including number connection test part A (NCT-A), digit symbol test (DST) and block design tests (BDTs). Patients were randomized to receive 175 mg zinc gluconate, 50,000 IU vitamin A, 500 mg vitamin C and 100 mg vitamin E once daily plus lactulose, dose 30–60 ml/day for 3 months [group A (n = 31)] or initiated and maintained on lactulose dose 30–60 ml/day for 3 months [group B (n = 27)]. Neuropsychometric tests and laboratory investigations were repeated after 3 months of therapy. Results: Compared with the baseline neuropsychometric tests, a significant improvement was reported in patients with MHE after 3 months of antioxidant and zinc therapy (group A) versus patients with lactulose therapy (group B) (NCT-A, p <0.001; DST, p = 0.006; BDT, p < 0.001). Antioxidant and zinc supplementation significantly decreased arterial ammonia level, alanine aminotransferase (ALT), aspartate aminotransferase (AST) (p < 0.001) and improved Child–Pugh score in MHE after 3 months of therapy (p= 0.024). Conclusion: Antioxidant and zinc supplementation can improve MHE in patients with liver cirrhosis. PMID:27582881

  17. Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy.

    PubMed

    Tapper, Elliot B; Jiang, Z Gordon; Patwardhan, Vilas R

    2015-05-01

    Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the

  18. Improvement in survival associated with embolisation of spontaneous portosystemic shunt in patients with recurrent hepatic encephalopathy.

    PubMed

    An, J; Kim, K W; Han, S; Lee, J; Lim, Y-S

    2014-06-01

    Spontaneous portosystemic shunt (SPSS) is a frequent cause of recurrent hepatic encephalopathy (HE) in patients with cirrhosis. To assess the effectiveness and optimal candidate selection for embolisation of SPSS, for the treatment of recurrent HE in patients with cirrhosis. This retrospective cohort study compared 17 patients with recurrent HE who achieved complete occlusion of SPSS by angiographic embolisation and 17 control patients. Most baseline characteristics were similar in the two groups. The 2-year HE recurrence rate was significantly lower in the embolisation than in the control group (39.9% vs. 79.9%, P = 0.02), whereas their 2-year overall survival rates were similar (64.7% vs. 53.4%, P = 0.98). Model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) score were significant predictors of 2-year patient mortality in the embolisation group. Analysis of patients with MELD <15 in the absence of hepatocellular carcinoma (HCC) showed that 2-year overall survival rate was significantly higher in the embolisation group than in the control group (100% vs. 60%, P = 0.03). The median changes in MELD (-1.6 vs. 2.5, P < 0.01), CTP score (-3 vs. 0, P < 0.01), and liver volume (61 mL vs. -117 mL; P = 0.046) at 1 year significantly favoured the embolisation group. Serious clinical complications after embolisation occurred only in patients who had MELD ≥15 and/or HCC at baseline, with all six dying within 1 year. Embolisation of a large spontaneous portosystemic shunt may be associated with improved survival and liver function, as well as prevention of hepatic encephalopathy in cirrhotic patients with recurrent hepatic encephalopathy and modestly preserved liver function. © 2014 John Wiley & Sons Ltd.

  19. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy.

    PubMed

    Kimer, N; Krag, A; Møller, S; Bendtsen, F; Gluud, L L

    2014-07-01

    Rifaximin is recommended for prevention of hepatic encephalopathy (HE). The effects of rifaximin on overt and minimal HE are debated. To perform a systematic review and meta-analysis of randomised controlled trials (RCTs) on rifaximin for HE. We performed electronic and manual searches, gathered information from the U.S. Food and Drug Administration Home Page, and obtained unpublished information on trial design and outcome measures from authors and pharmaceutical companies. Meta-analyses were performed and results presented as risk ratios (RR) with 95% confidence intervals (CI) and the number needed to treat. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate the risk of bias and sources of heterogeneity. We included 19 RCTs with 1370 patients. Outcomes were recalculated based on unpublished information of 11 trials. Overall, rifaximin had a beneficial effect on secondary prevention of HE (RR: 1.32; 95% CI 1.06-1.65), but not in a sensitivity analysis on rifaximin after TIPSS (RR: 1.27; 95% CI 1.00-1.53). Rifaximin increased the proportion of patients who recovered from HE (RR: 0.59; 95% CI: 0.46-0.76) and reduced mortality (RR: 0.68, 95% CI 0.48-0.97). The results were robust to adjustments for bias control. No small study effects were identified. The sequential analyses only confirmed the results of the analysis on HE recovery. Rifaximin has a beneficial effect on hepatic encephalopathy and may reduce mortality. The combined evidence suggests that rifaximin may be considered in the evidence-based management of hepatic encephalopathy. © 2014 John Wiley & Sons Ltd.

  20. [Efficiency of includes of bioactive substances in diet of patient with hepatic encephalopathy].

    PubMed

    Kaziulin, A N; Petukhov, A B; Kucheriavyĭ, Iu A

    2006-01-01

    We includes 66 patients with liver cirrhosis of Child-Pugh B class with hepatic encephalopathy of 0 to 2nd stages in randomized interventional study. 36 patients received standard treatment and 30 patients received standard treatment + bioactive substances in formula CognoBlend in capsules (2 capsules twice a day) in course of 5 weeks. Formula includes extracts of plants: Bacopa monneria, Gingko biloba, Cat's Claw, Gotu Kola, Rosemary. In group combined treatment was significant improvement of clinical signs, psychometric tests, electroencephalography and serum biochemistry than in group with standard therapy, on term of 2 to 5 weeks.

  1. Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials.

    PubMed

    Saab, Sammy; Suraweera, Duminda; Au, Jennifer; Saab, Elena G; Alper, Tori S; Tong, Myron J

    2016-07-01

    Hepatic encephalopathy (HE) is a major complication of cirrhosis and is associated with decreased survival and increased health care utilization. The aim of this study was to evaluate the efficacy of probiotics in the management minimal hepatic encephalopathy HE (MHE) and overt HE (OHE) in comparison to no treatment/placebo and lactulose. The main outcomes measured were mortality, improvement in MHE, progression to OHE in patients with MHE and hospitalization. We calculated odds ratios (OR) with 95% confidence intervals (CI). Study heterogeneity was assessed using the I(2) statistic. Fourteen studies totalling 1152 patients were included in the analysis. The use of probiotics had no impact on the overall mortality when compared to either lactulose (OR: 1.07, 95% CI: 0.47-2.44, P = 0.88) or no treatment/placebo (OR: 0.69, 95% CI: 0.42-1.14, P = 0.15). When probiotics was compared to no treatment/placebo, it was associated with a significant improvement in MHE (OR: 3.91, 95% CI: 2.25-6.80, P < 0.00001), decreased hospitalization rates (OR: 0.53, 95% CI: 0.33-0.86, P = 0.01) and decreased progression to overt hepatic encephalopathy (OR: 0.40, 95% CI: 0.26-0.60, P < 0.0001). However when compared to lactulose, probiotics did not show a significant difference in improvement of MHE (OR: 0.81, 95% CI: 0.52-1.27, P = 0.35), hospitalization rates (OR: 1.02, 95% CI: 0.52-1.99, P = 0.96) or progression to overt hepatic encephalopathy (OR: 1.24, 95% CI 0.73-2.10, P = 0.42). Overall the use of probiotics was more effective in decreasing hospitalization rates, improving MHE and preventing progression to OHE in patients with underlying MHE than placebo, but similar to that seen with lactulose. The use of probiotics did not affect mortality rates. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Pathological Role for Exocytotic Glutamate Release from Astrocytes in Hepatic Encephalopathy

    PubMed Central

    Montana, Vedrana; Verkhratsky, Alexei; Parpura, Vladimir

    2014-01-01

    Liver failure can lead to generalized hyperammonemia, which is thought to be the underlying cause of hepatic encephalopathy. This neuropsychiatric syndrome is accompanied by functional changes of astrocytes. These glial cells enter ammonia-induced self-amplifying cycle characterized by brain oedema, oxidative and osmotic stress that causes modification of proteins and RNA. Consequently, protein expression and function are affected, including that of glutamine synthetase and plasmalemmal glutamate transporters, leading to glutamate excitotoxicity; Ca2+-dependent exocytotic glutamate release from astrocytes contributes to this extracellular glutamate overload. PMID:25342940

  3. Cholestatic hepatitis due to Ecballium elaterium ingestion.

    PubMed

    Bizid, Sondès; Sabbah, Mériam; Msakni, Issam; Ben Slimene, Baha; Mohamed, Ghanem; Bouali, Riadh; Ben Abdallah, Hatem; Abdelli, Nabil

    2015-10-01

    Ecballium elaterium is an herbaceous plant belonging to the Cucurbitaceae family. This plant is fairly common in the Mediterranean regions. It is frequently consumed in infusion, mixture of fruit or even in aerosol in cases of fever or flu. This plant is known for its respiratory and ocular toxicity. Hepatotoxicity has never been described in the literature. We report a case of acute cholestatic hepatitis due to Ecballium elaterium in a 39 years old patient, with no past medical history.

  4. Albumin dialysis has a favorable effect on amino acid profile in hepatic encephalopathy.

    PubMed

    Koivusalo, Anna-Maria; Teikari, Taru; Höckerstedt, Krister; Isoniemi, Helena

    2008-12-01

    According to one popular theory, hepatic encephalopathy (HE) is partly caused by an imbalance in plasma amino acid levels. The Fischer's ratio between branched chain amino acids (BCAAs) and aromatic amino acids (AAAs) correlates with the degree of HE; the lower Fischer's ratio, the higher the grade of HE. Extra-corporeal liver support systems, like MARS(R)-albumin dialysis (Molecular Adsorbents Recirculating System), can improve HE. The MARS(R) system uses a hyperosmolar albumin circuit to remove both water-soluble and albumin-bound substances. Plasma levels of neuroactive amino acids were analyzed in 82 consecutive patients with life-threatening liver failure admitted to our ICU. All patients fulfilled our indications for MARS treatment and most also fulfilled the criteria for liver transplantation (LTx). In patients with acute liver failure (ALF), as compared to those with acute decompensation of chronic liver failure (AcOChr), levels of leucine and isoleucine were significantly higher before MARS(R) treatment. In all patients, before MARS(R) treatment the higher the grade of HE grade the lower was the Fischer's ratio and higher were the levels of inhibitory neuroactive amino acids. During MARS(R) treatments the Fischer's ratio increased, and the grade of HE decreased. The increase in Fischer's ratio was mainly due to the decrease in AAAs. The plasma levels of neuroactive amino acids, methionine, glutamine, glutamate, histidine and taurine decreased during MARS(R)-treatment. In this study MARS(R)-albumin dialysis had a favorable effect on the plasma amino acid profile of patients with HE.

  5. Pannexin1 as a novel cerebral target in pathogenesis of hepatic encephalopathy.

    PubMed

    Mondal, Papia; Trigun, Surendra Kumar

    2014-12-01

    Hepatic encephalopathy (HE) represents a nervous system disorder caused due to liver dysfunction. HE is broadly classified as acute/overt and moderate-minimal HE. Since HE syndrome severely affects quality of life of the patients and it may be life threatening, it is important to develop effective therapeutic strategy against HE. Mainly ammonia neurotoxicity is considered accountable for HE. Increased level of ammonia in the brain activates glutamate-NMDA (N-methyl-D-aspartate) receptor (NMDAR) pathway leading to Ca(2+) influx, energy deficit and oxidative stress in the post synaptic neurons. Moreover, NMDAR blockage has been found to be a poor therapeutic option, as this neurotransmitter receptor plays important role in maintaining normal neurophysiology of the brain. Thus, searching new molecular players in HE pathogenesis is of current concern. There is an evolving concept about roles of the trans-membrane channels in the pathogenesis of a number of neurological complications. Pannexin1 (Panx1) is one of them and has been described to be implicated in stroke, epilepsy and ischemia. Importantly, the pathogenesis of these complications relates to some extent with NMDAR over activation. Thus, it is speculated that HE pathogenesis might also involve Panx1. Indeed, some recent observations in the animal models of HE provide support to this argument. Since opening of Panx1 channel is mostly associated with the neuronal dysfunctions, down regulation of this channel could serve as a relevant therapeutic strategy without producing any serious side effects. In the review article an attempt has been made to summarize the current information on implication of Panx1 in the brain disorders and its prospects for being examined as pharmacological target in HE pathogenesis.

  6. p38 MAP kinase is a therapeutic target for hepatic encephalopathy in rats with portacaval shunts.

    PubMed

    Agusti, Ana; Cauli, Omar; Rodrigo, Regina; Llansola, Marta; Hernández-Rabaza, Vicente; Felipo, Vicente

    2011-11-01

    Inflammation plays a role in neurological alterations in patients with hepatic encephalopathy (HE). Animal models of HE show neuroinflammation. Treatment with ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), reduces neuroinflammation and restores cognitive and motor function in rats with HE due to portacaval shunts (PCS). This suggests that reducing neuroinflammation would improve neurological status in patients with minimal or clinical HE. NSAID induce kidney damage in patients with cirrhosis and PCS rats and are not suitable for clinical use. It is therefore necessary to look for procedures to eliminate neuroinflammation without inducing secondary effects in the kidney. Inhibition of p38 MAPK is being tested as a therapeutic target in inflammatory diseases and reduces microglial activation. This study aimed to assess whether inhibiting p38 with SB239063 reduces neuroinflammation and improves cognitive and motor function in PCS rats without affecting the kidney. p38 activity is increased in the brains of PCS rats and treatment with SB239063 reduces microglial activation, as well as inflammatory markers in brain (prostaglandin E2, cyclooxygenase activity, iNOS, IL-1β, TNFα) and blood (prostaglandin E2 and TNFα). PCS rats showed increased ammonia and glutamine in the brain, which was not affected by SB239063. PCS rats showed reduced ability to learn a Y-maze conditional discrimination task, reduced motor activity and impaired motor coordination, as assessed in the rotarod. Treatment with SB239063 completely restored learning ability, motor activity and coordination in PCS rats. SB239063 did not affect creatinine or sodium levels in serum, indicating that it does not induce kidney damage. These findings suggest that reducing neuroinflammation by using inhibitors of p38 would improve the neurological status in HE without inducing secondary effects in the kidney.

  7. Sildenafil reduces neuroinflammation and restores spatial learning in rats with hepatic encephalopathy: underlying mechanisms.

    PubMed

    Hernandez-Rabaza, Vicente; Agusti, Ana; Cabrera-Pastor, Andrea; Fustero, Santos; Delgado, Oscar; Taoro-Gonzalez, Lucas; Montoliu, Carmina; Llansola, Marta; Felipo, Vicente

    2015-10-29

    There are no specific treatments for the neurological alterations of cirrhotic patients with minimal hepatic encephalopathy (MHE). Rats with MHE due to portacaval shunt (PCS) show impaired spatial learning. The underlying mechanisms remain unknown. The aims of this work were to assess: (a) whether PCS rats show neuroinflammation in hippocampus, (b) whether treatment with sildenafil reduces neuroinflammation and restores spatial learning in PCS rats, and (c) analyze the underlying mechanisms. Neuroinflammation was assessed by determining inflammatory markers by Western blot. Phosphorylation of MAP-kinase p38 was assessed by immunohistochemistry. Membrane expression of GABA and glutamate receptors was analyzed using BS3 cross-linker. Spatial learning was analyzed using the radial and Morris water mazes. To assess if sildenafil reverses the alterations, rats were treated with sildenafil in the drinking water. PCS rats show increased IL-1β and TNF-α levels and phosphorylation (activity) of p38 in hippocampus. Membrane expression of subunits α1 of GABAA receptor and GluR2 of AMPA receptor are increased in PCS rats, while subunits GluR1 of AMPA receptors and NR1 and NR2a of NMDA receptors are reduced. PCS rats show reduced spatial learning in the radial and Morris water mazes. Sildenafil treatment normalizes IL-1β and TNF-α levels, p38 phosphorylation, and membrane expression of GABAA, AMPA, and NMDA receptors and restores spatial learning. Increased IL-1β alters GABAergic and glutamatergic neurotransmission in hippocampus and impairs spatial learning in rats with MHE. Sildenafil reduces neuroinflammation and restores learning. Phosphodiesterase-5 inhibitors may be useful to improve cognitive function in patients with MHE.

  8. Central-Variant Posterior Reversible Encephalopathy due to Sulfasalazine: A Case Report.

    PubMed

    Ocek, Levent; Sener, Ufuk; Demirtas, Burcu S; Ozcelik, Metin M; Oztekin, Ozgur; Zorlu, Yasar

    2015-01-01

    To report a rare case with central-variant posterior reversible encephalopathy syndrome due to sulfasalazine. A 55-year-old female patient presented with seizure and acute-onset hemiparesia. Thirty days earlier, treatment with sulfasalazine was commenced in response to a diagnosis of psoriatic arthritis. Laboratory examinations were normal. Brain magnetic resonance imaging showed symmetric edema within basal ganglia and thalami with sparing of the cerebral cortices. After stopping the treatment of sulfasalazine, clinical and radiological findings regressed dramatically. This was a case of central-variant posterior reversible encephalopathy syndrome due to sulfasalazine, and atypical imaging findings should be kept in mind for early diagnosis. © 2015 S. Karger AG, Basel.

  9. Plasma concentrations of endogenous benzodiazepine-receptor ligands in patients with hepatic encephalopathy: a comparative study.

    PubMed Central

    Hernández-Avila, C A; Shoemaker, W J; Ortega-Soto, H A

    1998-01-01

    OBJECTIVE: Hepatic encephalopathy (HE) is a complex neuropsychiatric disorder secondary to acute or chronic liver failure. Although the exact causes of HE have not been clarified, enhanced central nervous system inhibition at the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex, mediated by increased levels of endogenous benzodiazepine-receptor ligands (BZRL), has been proposed. Research exploring this hypothesis has yielded contradictory findings. This study evaluated the presence and levels of BZRL in plasma from patients with HE and 3 comparison groups. DESIGN: Cross-sectional study. PATIENTS: Twenty-four patients with HE, 10 patients with liver cirrhosis without encephalopathy (LC), 4 patients with uremic encephalopathy (UE), and 9 healthy subjects. INTERVENTIONS: Radio-receptor assay of plasma samples from patients and controls. MAIN OUTCOME MEASURES: Plasma levels of BZRL. RESULTS: The patients in the HE group had significantly higher plasma BZRL levels than the patients with UE and the healthy subjects, but not than those with LC, in whom these compounds were also detected in significant concentrations. When patients were classified according to the severity of HE, plasma of BZRL showed a modest correlation with stage of severity (r = 0.37). Interestingly, approximately one-third of the patients with HE did not have detectable levels of BZRL. CONCLUSION: Endogenous BZRL may play a role in the pathogenesis of HE, although neuropsychiatric symptoms in HE are difficult to explain in terms of these compounds alone. Images Fig. 1 PMID:9785700

  10. Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia.

    PubMed

    Muniraman, Hemananda; Gardner, Danielle; Skinner, Jane; Paweletz, Anna; Vayalakkad, Anitha; Chee, Ying Hui; Clifford, Clare; Sanka, Sunil; Venkatesh, Vidheya; Curley, Anna; Victor, Suresh; Turner, Mark A; Clarke, Paul

    2017-07-24

    Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001). We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: • Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). • The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: • Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. • An elevated CRP concentration during the first postnatal week may be regarded as

  11. Is it time to target gut dysbiosis and immune dysfunction in the therapy of hepatic encephalopathy?

    PubMed

    Shawcross, Debbie L

    2015-05-01

    The development of overt hepatic encephalopathy (HE) in a patient with cirrhosis confers a damning prognosis with a 1-year mortality approaching 64%. This complex neuropsychiatric syndrome arises as a consequence of a dysfunctional gut-liver-brain axis. HE has been largely neglected over the past 30 years, with the reliance on therapies aimed at lowering ammonia production or increasing metabolism following the seminal observation that the hepatic urea cycle is the major mammalian ammonia detoxification pathway and is key in the pathogenesis of HE. The relationship with ammonia is more clear-cut in acute liver failure; but in cirrhosis, it has become apparent that inflammation is a key driver and that a disrupted microbiome resulting in gut dysbiosis, bacterial overgrowth and translocation, systemic endotoxemia and immune dysfunction may be more important drivers. Therefore, it is important to re-focus our efforts into developing therapies that modulate the disrupted microbiome or alleviating its downstream consequences.

  12. Posterior reversible encephalopathy syndrome in a patient with hepatitis B induced type 1 membranoproliferative glomerulonephritis.

    PubMed

    Sathyanarayanan, Vishwanath; Razak, Abdul; Narayan, Girish; Prabhu, Mukhyaprana; Ramachandran, Balasubramanian; Ranjini, Kudva; Vidya, Monappa; Joshi, Kusum

    2010-12-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare complication of nephrotic syndrome and corticosteroid therapy. Here, we discuss an 18 year old man with type 1 membranoproliferative glomerulonephritis (MPGN) secondary to hepatitis B infection who developed posterior leukoencephalopathy while on therapy with lamivudine and prednisone. He developed seizures and vision loss. He also had hypertension, but no sudden elevation was recorded at any time. Magnetic resonance imaging revealed patchy areas of altered signal intensity involving cortical gray and subcortical white matter in the bilateral frontoparietal regions, occipital cortices, temporal cortices and cerebellar hemispheres, and hyperintensity on T2W and FLAIR sequences. Tapering of prednisone and controlling hypertension resulted in clinical improvement within a few days, and in a month MRI was normal. Diagnosing PRES requires a high index of suspicion when treating similarly susceptible patients. PRES as a complication during the treatment of MPGN secondary to hepatitis B has, to our knowledge, never been reported previously in the literature.

  13. Intracortical inhibitory and excitatory circuits in subjects with minimal hepatic encephalopathy: a TMS study.

    PubMed

    Nardone, Raffaele; De Blasi, Pierpaolo; Höller, Yvonne; Brigo, Francesco; Golaszewski, Stefan; Frey, Vanessa N; Orioli, Andrea; Trinka, Eugen

    2016-10-01

    Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy (HE) and affects up to 80 % of patients with liver cirrhosis. By definition, MHE is characterized by psychomotor slowing and subtle cognitive deficits,  but obvious clinical manifestations are lacking. Given its covert nature, MHE is often underdiagnosed. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the HE. We investigated motor cortex excitability in 15 patients with MHE and in 15 age-matched age-matched cirrhotic patients without MHE; the resting motor threshold, the short-interval intracortical inhibition (SICI) and the intracortical facilitation (ICF) were examined. Paired-pulse TMS revealed significant increased SICI and reduced ICF in the patients with MHE. These findings may reflect abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. In particular, the results suggest a shift in the balance between intracortical inhibitory and excitatory mechanisms towards a net increase of inhibitory neurotransmission. Together with other neurophysiological (in particular EEG) and neuroimaging techniques, TMS may thus provide early markers of cerebral dysfunction in cirrhotic patients with MHE.

  14. Embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy

    SciTech Connect

    Sakurabayashi, Shin; Sezai, Shuichi; Yamamoto, Yoshihiro; Hirano, Masanori; Oka, Hiroshi

    1997-03-15

    Purpose. To evaluate the efficacy of embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy (CRHE). Methods. Seven cirrhotic patients with CRHE refractory to medical treatment (3 men and 4 women, mean age 66 years) were studied. Five patients had splenorenal shunts, 1 had a gastrorenal shunt, and 1 had an intrahepatic portal vein-hepatic vein shunt. Shunt embolization was performed using stainless steel coils, with a percutaneous transhepatic portal vein approach in 4 patients and a transrenal vein approach in 3 patients. Results. After embolization, the shunt disappeared in 4 patients on either ultrasound pulsed Doppler monitoring or portography. Complications observed in the 7 patients were fever, transient pleural effusion, ascites, and mild esophageal varices. For 3-6 months after embolization, the 4 patients whose shunts disappeared showed minimal or no reappearance of a shunt, and had no recurrence of encephalopathy. The serum ammonia levels decreased and electroencephalograms also improved. One of the 4 patients, who developed mild esophageal varices, required no treatment. Treatment was effective in 3 of the 4 patients (75%) who underwent embolization via a transhepatic portal vein. Conclusion. Transvascular embolization of shunts improved the outcome in 4 of 7 patients. The most effective embolization was achieved via the percutaneous transhepatic portal vein approach.

  15. Low-protein diets for hepatic encephalopathy debunked: let them eat steak.

    PubMed

    Cabral, Chad Michael; Burns, David L

    2011-04-01

    Hepatic encephalopathy (HE) is an incompletely understood phenomenon and serves as a poor prognosis in patients with cirrhosis. Confusion from HE can affect the ability to eat adequately. Despite the prevalence of malnutrition in cirrhotic patients in the 1950s, it was reported that bouts of overt HE were controlled with low protein intake. This largely uncontrolled observation led to restriction of protein intake in cirrhotic patients with or without HE and was an accepted standard of care for many decades to follow. Published in 2004, the pivotal article "Normal Protein Diet for Episodic Hepatic Encephalopathy: Results of a Randomized Study" by Cordoba and colleagues was the first controlled study randomizing cirrhotic patients with HE to receive different amounts of dietary protein. At the completion of the study, the authors concluded that a normal-protein diet was safe and did not exacerbate HE. The Cordoba study suggests that low-protein diets should be abandoned. In light of this evidence, nutrition guidelines have proposed that protein restriction should be avoided in patients with HE as protein requirements are increased in cirrhosis. Despite the advice of experts in the field, it has been shown in recent years that some physicians still believe that protein restriction is needed in patients with HE. This belief has not been substantiated in controlled studies, and societal recommendations have changed. There is no real evidence documenting the advantages of protein restriction in HE. On the contrary, Cordoba and colleagues' article has shown that there are disadvantages to restricting protein in HE.

  16. Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats.

    PubMed

    Ilic, Spomenko; Drmic, Domagoj; Zarkovic, Kamelija; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Djuzel, Viktor; Blagaic, Alenka Boban; Romic, Zeljko; Dzidic, Senka; Kalogjera, Livije; Seiwerth, Sven; Sikiric, Predrag

    2011-09-30

    Chronic ibuprofen (0.4 g/kg intraperitoneally, once daily for 4 weeks) evidenced a series of pathologies, not previously reported in ibuprofen-dosed rats, namely hepatic encephalopathy, gastric lesions, hepatomegaly, increased AST and ALT serum values with prolonged sedation/unconsciousness, and weight loss. In particular, ibuprofen toxicity was brain edema, particularly in the cerebellum, with the white matter being more affected than in gray matter. In addition, damaged and red neurons, in the absence of anti-inflammatory reaction was observed, particularly in the cerebral cortex and cerebellar nuclei, but was also present although to a lesser extent in the hippocampus, dentate nucleus and Purkinje cells. An anti-ulcer peptide shown to have no toxicity, the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, 10 μg, 10 ng/kg) inhibited the pathology seen with ibuprofen (i) when given intraperitoneally, immediately after ibuprofen daily or (ii) when given in drinking water (0.16 μg, 0.16 ng/ml). Counteracted were all adverse effects, such as hepatic encephalopathy, the gastric lesions, hepatomegaly, increased liver serum values. In addition, BPC 157 treated rats showed no behavioral disturbances and maintained normal weight gain. Thus, apart from efficacy in inflammatory bowel disease and various wound treatments, BPC 157 was also effective when given after ibuprofen.

  17. Disrupted topological organization of brain structural network associated with prior overt hepatic encephalopathy in cirrhotic patients.

    PubMed

    Chen, Hua-Jun; Shi, Hai-Bin; Jiang, Long-Feng; Li, Lan; Chen, Rong

    2017-06-30

    To investigate structural brain connectome alterations in cirrhotic patients with prior overt hepatic encephalopathy (OHE). Seventeen cirrhotic patients with prior OHE (prior-OHE), 18 cirrhotic patients without prior OHE (non-prior-OHE) and 18 healthy controls (HC) underwent diffusion tensor imaging. Neurocognitive functioning was assessed with Psychometric Hepatic Encephalopathy Score (PHES). Using a probabilistic fibre tracking approach, we depicted the whole-brain structural network as a connectivity matrix of 90 regions (derived from the Automated Anatomic Labeling atlas). Graph theory-based analyses were performed to analyse topological properties of the brain network. The analysis of variance showed significant group effects on several topological properties, including network strength, global efficiency and local efficiency. A progressive decrease trend for these metrics was found from non-prior-OHE to prior-OHE, compared with HC. Among the three groups, the regions with altered nodal efficiency were mainly distributed in the frontal and occipital cortices, paralimbic system and subcortical regions. The topological metrics, such as network strength and global efficiency, were correlated with PHES among cirrhotic patients. The cirrhotic patients developed structural brain connectome alterations; this is aggravated by prior OHE episode. Disrupted topological organization of the brain structural network may account for cognitive impairments related to prior OHE. • Altered structural brain connectome is found in cirrhotic patients. • Structural brain connectome alterations could be aggravated by prior-OHE episode. • Altered structural brain connectome may account for cognitive impairments associated with prior OHE.

  18. The impact on hospital resource utilisation of treatment of hepatic encephalopathy with rifaximin-α.

    PubMed

    Orr, James G; Currie, Craig J; Berni, Ellen; Goel, Anurag; Moriarty, Kieran J; Sinha, Ashish; Gordon, Fiona; Dethier, Anne; Dillon, John F; Clark, Katie; Richardson, Paul; Middleton, Paul; Patel, Vishal; Shawcross, Debbie; Preedy, Helen; Aspinall, Richard J; Hudson, Mark

    2016-09-01

    Rifaximin-α reduces the risk of recurrence of overt hepatic encephalopathy. However, there remain concerns regarding the financial cost of the drug. We aimed to study the impact of treatment with rifaximin-α on healthcare resource utilisation using data from seven UK liver treatment centres. All seven centres agreed a standardised data set and data characterising clinical, demographic and emergency hospital admissions were collected retrospectively for the time periods 3, 6 and 12 months before and following initiation of rifaximin-α. Admission rates and hospital length of stay before and during therapy were compared. Costs of admissions and drug acquisition were estimated using published sources. Multivariate analyses were carried out to assess the relative impact of various factors on hospital length of stay. Data were available from 326 patients. Following the commencement of rifaximin, the total hospital length of stay reduced by an estimated 31-53%, equating to a reduction in inpatient costs of between £4858 and £6607 per year. Taking into account drug costs of £3379 for 1-year treatment with rifaximin-α, there was an estimated annual mean saving of £1480-£3228 per patient. Initiation of treatment with rifaximin-α was associated with a marked reduction in the number of hospital admissions and hospital length of stay. These data suggest that treatment of patients with rifaximin-α for hepatic encephalopathy was generally cost saving. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Lactitol in the treatment of chronic hepatic encephalopathy: an open comparison with lactulose.

    PubMed Central

    Lanthier, P L; Morgan, M Y

    1985-01-01

    Lactulose is currently the drug of choice for the treatment of hepatic encephalopathy. It is, however, only available as a syrup which is contaminated with other sugars. Consequently patients may express aversion to its excessively sweet taste and many experience nausea because of its hyperosmolarity. Lactitol is a disaccharide analogue of lactulose which can be produced as a pure crystalline powder with a low relative sweetness. Theoretically it should have the same therapeutic effects as lactulose but fewer side effects. Five patients with chronic hepatic encephalopathy on maintenance lactulose were monitored clinically, psychometrically, and by measurement of venous blood ammonia, electroencephalogram mean cycle frequency, and cerebral blood flow during three months treatment with lactulose and a similar period on lactitol. Lactitol was at least as efficacious as lactulose but was more acceptable because its cathartic effect was more predictable, its formulation was more convenient and its less sweet taste preferred. Lactitol is the ideal successor to lactulose for treatment of this condition. PMID:3979914

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

    PubMed

    McClain, C J; Zieve, L; Doizaki, W M; Gilberstadt, S; Onstad, G R

    1980-04-01

    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.

  1. Conventional diet therapy for hyperammonemia is risky in the treatment of hepatic encephalopathy associated with citrin deficiency.

    PubMed

    Fukushima, Kazuhiro; Yazaki, Masahide; Nakamura, Mio; Tanaka, Naoki; Kobayashi, Keiko; Saheki, Takeyori; Takei, Hideki; Ikeda, Shu-ichi

    2010-01-01

    Citrin deficiency caused by SLC25A13 gene mutations develops into adult-onset type II citrullinemia (CTLN2) presenting with hepatic encephalopathy. Recent studies have suggested that excessive loading of carbohydrates is harmful in citrin-deficient individuals. Here we report a CTLN2 patient who showed further deterioration of encephalopathy after the employment of conventional low-protein diet therapy for chronic liver failure. Owing to the high carbohydrate content, the conventional low-protein diet therapy should be avoided in patients with hepatic encephalopathy associated with citrin deficiency. In addition, our observation may suggest that carbohydrate-restricted diet in which the content of carbohydrate is below 50% of daily energy intake can have therapeutic efficacy in CTLN2 patients.

  2. Congenital portosystemic shunts and hepatic encephalopathy in goat kids in California: 11 cases (1999-2012).

    PubMed

    Kinde, Hailu; Pesavento, Patricia A; Loretti, Alexandre P; Adaska, John M; Barr, Bradd C; Moore, Janet D; Anderson, Mark L; Rimoldi, Guillermo; Hill, Ashley E; Jones, Megan E B

    2014-01-01

    Between 1999 and 2012, 11 cases of congenital portosystemic shunts (cPSS) resulting in hepatic encephalopathy were diagnosed in goat kids necropsied at the California Animal Health and Food Safety Laboratory System and at the Department of Pathology, Immunology & Microbiology, School of Veterinary Medicine, University of California-Davis. Affected animals included 6 females and 5 males of various breeds including Boer (5/11), Nigerian Dwarf (1/11), Saanen (1/11), Toggenburg (1/11), and mixed-breed (3/11) aged between 1.5 months and 11 months, submitted live (2/11) or dead (9/11) for necropsy. The most frequent clinical signs in these goats were ataxia, blindness, tremors, head bobbing, head pressing, seizures, circling, weakness, and ill thrift. Bile acids were measured in 2 animals, and were elevated in both cases (134 and 209 µmol/l, reference interval = 0-50 µmol/l). Necropsy findings were poor to fair body condition. Grossly, the livers of 4 animals were subjectively small. Microscopic lesions included portal spaces with increased numbers of arteriolar profiles and hypoplastic or absent portal veins, diffuse atrophy of the hepatic parenchyma with the presence of small hepatocytes and, in some cases, multifocal hepatocellular macrovesicular vacuolation. In the brain and spinal cord of all animals, there was bilateral and symmetric spongy degeneration affecting the cerebrum, mesencephalon, cerebellum, brainstem, and cervical spinal cord. In all cases, the brain lesions were consistent with hepatic encephalopathy. Congenital portosystemic shunts should be considered in the differential diagnosis of young goats with a history of ill thrift, and nonspecific neurological signs.

  3. Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution for Treatment of Overt Hepatic Encephalopathy

    PubMed Central

    Rahimi, Robert S.; Singal, Amit G.; Cuthbert, Jennifer A.; Rockey, Don C.

    2017-01-01

    IMPORTANCE Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades. OBJECTIVE To compare polyethylene glycol 3350–electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose. DESIGN, SETTING, AND PARTICIPANTS The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE. INTERVENTIONS Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization. MAIN OUTCOMES AND MEASURES The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay. RESULTS A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely

  4. [Analysis of L-asparaginase induced elevation of blood ammonia and hepatic encephalopathy].

    PubMed

    Li, Yuan; Ren, Han-yun; Cen, Xi-nan; Yin, Yue; Liang, Ze-yin

    2013-07-01

    To summarize the incidence of various adverse reactions in the clinical application of L-asparaginase (L-Asp), and to analyze the cause of hepatic encephalopathy in three cases. The complete data of 23 patients in our department from December 2009 to December 2010 were collected. Their blood ammonia levels, transaminase, serum albumin and blood coagulation function before, during and after the L-Asp application were assayed. (1) All patients had elevated blood ammonia level after the L- Asp application. This occurred 2 days after the beginning of treatment and the median time to reach peak level (ranged from 194 to 446 μmol/L, with a median value of 300 μmol/L) was 4 days. It returned to normal level after a median time of 5 days (ranged 3-7 days) with drug withdrawal. Of the 23 patients studied, 3 developed hepatic encephalopathy. (2) All patients appeared lower blood fibrinogen, 10 cases (43.5%) with lower fibrinogen only, while 13 cases (56.5%) with both prolonged APTT and lower fibrinogen. The lowest level of fibrinogen was detected at 1 week after drug application. Of the 23 patients, 14 (60.9%) had mild lower blood fibrinogen (1-2 g/L), and 9 (39.1%) had significantly lower fibrinogen (0-1 g/L). (3) Six cases (26.1%) had slightly elevated level of transaminase (<2 times the upper limits of normal), 8 (34.8%) appeared hypoalbuminemia. As the incidence of elevated blood ammonia levels was high in the application of L-Asp, the level of blood ammonia should be closely monitored to avoid the occurrence of hepatic encephalopathy, especially in elderly patients and patients with previous liver disease or long-term heavy drinking. L-Asp can also lead to low fibrinogen level, hypoalbuminemia and abnormal transaminase. Monitoring the blood coagulation function and liver function is required and, if necessary, plasma infusion and liver protection therapy are required.

  5. Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests

    PubMed Central

    Felipo, Vicente; Urios, Amparo; Giménez-Garzó, Carla; Cauli, Omar; Andrés-Costa, Maria-Jesús; González, Olga; Serra, Miguel A; Sánchez-González, Javier; Aliaga, Roberto; Giner-Durán, Remedios; Belloch, Vicente; Montoliu, Carmina

    2014-01-01

    AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins (IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated. RESULTS: In patients with MHE, BF was increased in cerebellar hemisphere (P = 0.03) and vermis (P = 0.012) and reduced in occipital lobe (P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE (P = 0.02). Bimanual coordination was impaired in patients without MHE (P = 0.05) and much more in patients with MHE (P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE (P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE (P < 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A (NCT-A), B (NCT-B)and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with

  6. Spectral electroencephalogram in liver cirrhosis with minimal hepatic encephalopathy before and after lactulose therapy.

    PubMed

    Singh, Jatinderpal; Sharma, Barjesh Chander; Maharshi, Sudhir; Puri, Vinod; Srivastava, Siddharth

    2016-06-01

    Minimal hepatic encephalopathy (MHE) represents the mildest form of hepatic encephalopathy. Spectral electroencephalogram (sEEG) analysis improves the recognition of MHE by decreasing inter-operator variability and providing quantitative parameters of brain dysfunction. We compared sEEG in patients with cirrhosis with and without MHE and the effects of lactulose on sEEG in patients with MHE. One hundred patients with cirrhosis (50 with and 50 without MHE) were enrolled. Diagnosis of MHE was based on psychometric hepatic encephalopathy score (PHES) of ≤ -5. Critical flicker frequency, model of end-stage liver disease score, and sEEG were performed at baseline in all patients. The spectral variables considered were the mean dominant frequency (MDF) and relative power in beta, alpha, theta, and delta bands. Patients with MHE were given 3 months of lactulose, and all parameters were repeated. Spectral electroencephalogram analysis showed lower MDF (7.8 ± 1.7 vs 8.7 ± 1.3 Hz, P < 0.05) and higher theta relative power (34.29 ± 4.8 vs 24 ± 6.7%, P = 001) while lower alpha relative power (28.6 ± 4.0 vs 33.5 ± 5.3%, P = .001) in patients with MHE than in patients without MHE. With theta relative power, sensitivity 96%, specificity 84%, and accuracy of 90% were obtained for diagnosis of MHE. After lactulose treatment, MHE improved in 21 patients, and significant changes were seen in MDF (7.8 ± 0.5 vs 8.5 ± 0.6), theta (34.2 ± 4.8 vs 23.3 ± 4.1%), alpha (28.6 ± 4.0 vs 35.5 ± 4.5%), and delta relative power (13.7 ± 3.5 vs 17.0 ± 3.3%) after treatment (P ≤ 0.05). Spectral EEG is a useful objective and quantitative tool for diagnosis and to assess the response to treatment in patients with cirrhosis with MHE. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  7. Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm.

    PubMed

    Pereira, Keith; Carrion, Andres F; Salsamendi, Jason; Doshi, Mehul; Baker, Reginald; Kably, Issam

    2016-02-01

    Transjugular intrahepatic portosystemic shunt (TIPS) has evolved as an effective intervention for treatment of complications of portal hypertension. The use of polytetrafluoroethylene-covered stents have improved the patency of the shunts and diminished the incidence of TIPS dysfunction. However, TIPS-related refractory hepatic encephalopathy (rHE) poses a significant challenge. Approximately 3-7 % of patients with TIPS develop rHE. Refractory hepatic encephalopathy is defined as a recurrent or persistent encephalopathy despite appropriate medical treatment. Hepatic encephalopathy can be an extremely debilitating complication that profoundly affects quality of life. The approach to management of patients with rHE is complex and typically requires collaboration between different specialties. Liver transplantation is the ultimate treatment for rHE; however, the ongoing shortage of organ donation markedly limits this treatment option. Alternative therapies such as shunt occlusion or reduction can control symptoms and serve as a 'bridge' therapy to liver transplantation. Therefore, interventional radiologists play a key role in the management of these patients by offering a variety of endovascular techniques. The purpose of this review is to highlight some of these endovascular techniques and to develop a therapeutic algorithm that can be applied in clinical practice for the management of rHE.

  8. Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm

    SciTech Connect

    Pereira, Keith

    2016-02-15

    Transjugular intrahepatic portosystemic shunt (TIPS) has evolved as an effective intervention for treatment of complications of portal hypertension. The use of polytetrafluoroethylene-covered stents have improved the patency of the shunts and diminished the incidence of TIPS dysfunction. However, TIPS-related refractory hepatic encephalopathy (rHE) poses a significant challenge. Approximately 3–7 % of patients with TIPS develop rHE. Refractory hepatic encephalopathy is defined as a recurrent or persistent encephalopathy despite appropriate medical treatment. Hepatic encephalopathy can be an extremely debilitating complication that profoundly affects quality of life. The approach to management of patients with rHE is complex and typically requires collaboration between different specialties. Liver transplantation is the ultimate treatment for rHE; however, the ongoing shortage of organ donation markedly limits this treatment option. Alternative therapies such as shunt occlusion or reduction can control symptoms and serve as a ‘bridge’ therapy to liver transplantation. Therefore, interventional radiologists play a key role in the management of these patients by offering a variety of endovascular techniques. The purpose of this review is to highlight some of these endovascular techniques and to develop a therapeutic algorithm that can be applied in clinical practice for the management of rHE.

  9. Resting-state functional magnetic resonance imaging in hepatic encephalopathy: current status and perspectives.

    PubMed

    Zhang, Long Jiang; Wu, Shengyong; Ren, Jiaqian; Lu, Guang Ming

    2014-09-01

    Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which develops in patients with severe liver diseases and/or portal-systemic shunting. Minimal HE, the earliest manifestation of HE, has drawn increasing attention in the last decade. Minimal HE is associated with a series of brain functional changes, such as attention, working memory, and so on. Blood oxygen level dependent (BOLD) functional MRI (fMRI), especially resting-state fMRI has been used to explore the brain functional changes of HE, yielding important insights for understanding pathophysiological mechanisms and functional reorganization of HE. This paper briefly reviews the principles of BOLD fMRI, potential applications of resting-state fMRI with advanced post-processing algorithms such as regional homogeneity, amplitude of low frequency fluctuation, functional connectivity and future research perspective in this field.

  10. Microcirculation Approach in HELLP Syndrome Complicated by Posterior Reversible Encephalopathy Syndrome and Massive Hepatic Infarction

    PubMed Central

    Sarmento, Stephanno Gomes Pereira; Santana, Eduardo Feliz Martins; Campanharo, Felipe Favorette; Machado, Flavia Ribeiro; Moron, Antonio Fernandes

    2014-01-01

    HELLP syndrome is a complication of severe forms of preeclampsia and occurs mainly in the third trimester of pregnancy. In extreme cases, it may evolve unfavorably and substantially increase maternal mortality. We present the case of an 18-year-old pregnant woman who was admitted to our emergency service in her 31st week, presenting with headache, visual disturbances, and epigastralgia, with progression to a severe condition of HELLP syndrome followed by posterior reversible encephalopathy syndrome (PRES) and hepatic infarction. We highlight the approach taken towards this patient and the case management, in which, in addition to the imaging examinations routinely available, we also used the sidestream dark field (SDF) technique to evaluate the systemic microcirculation. PMID:25485160

  11. Plasmapheresis as adjuvant therapy in Stevens-Johnson syndrome and hepatic encephalopathy.

    PubMed

    Hung, Po-Cheng; Wang, Huei-Shyong; Hsia, Shao-Hsuan; Wong, Alex M-C

    2014-04-01

    Stevens-Johnson syndrome (SJS) is a severe idiosyncratic reaction, most commonly triggered by medications, which is characterized by fever and mucocutaneous lesions, leading to necrosis and sloughing of the epidermis. Aside from skin and mucosal manifestations, SJS may also compromise heart, liver, kidney, lung, and gastrointestinal tract. Although cholestatic liver disease has been reported to occur in SJS, hepatic encephalopathy (HE) as a delayed complication has never been reported. We report a 4-year-old female child with anticonvulsant-induced SJS complicated by HE who was completely cured with a combination of systemic corticosteroid, intravenous immunoglobulin (IVIG), and plasmapheresis therapy. We suggested that plasmapheresis may be used as an adjuvant therapy for SJS with HE.

  12. Piscine Insights into Comparisons of Anoxia Tolerance, Ammonia Toxicity, Stroke and Hepatic Encephalopathy*

    PubMed Central

    Walsh, Patrick J.; Veauvy, Clemence M.; McDonald, M. Danielle; Pamenter, Matthew E.; Buck, Leslie T.; Wilkie, Michael P.

    2007-01-01

    Although the number of fish species that have been studied for both hypoxia/anoxia tolerance and ammonia tolerance are few, there appears to be a correlation between the ability to survive these two insults. After establishing this correlation with examples from the literature, and after examining the role Peter Lutz played in catalyzing this convergent interest in two variables, this article explores potential mechanisms underpinning this correlation. We draw especially on the larger body of information for two human diseases with the same effected organ (brain), namely stroke and hepatic encephalopathy. While several dissimilarities exist between the responses of vertebrates to anoxia and hyperammonemia, one consistent observation in both conditions is an overactivation of NMDA receptors or glutamate neurotoxicity. We propose a glutamate excitotoxicity hypothesis to explain the correlation between ammonia and hypoxia resistance in fish. Furthermore, we suggest several experimental paths to test this hypothesis. PMID:17046301

  13. Lack of Clostridium difficile infection in patients treated with rifaximin for hepatic encephalopathy: a retrospective analysis.

    PubMed

    Neff, Guy W; Jones, Michael; Jonas, Mark; Ravinuthala, Ravi; Novick, David; Kaiser, Tiffany E; Kemmer, Nyingi

    2013-02-01

    The purpose of this study was to assess the incidence of Clostridium difficile infection in patients who received rifaximin for the treatment of hepatic encephalopathy (HE). Medical charts of patients who received rifaximin for the treatment of HE were reviewed. The number of patients who developed diarrhea during treatment with rifaximin and results of latex agglutination assays to detect C. difficile in stool samples were analyzed. A total of 211 patients received rifaximin for HE. Of these, 152 were treated in a university practice and 59 were treated in community practices. The mean dose of rifaximin was 1055 mg/d (range, 600 to 1600 mg/d) for a mean duration of 250 days (range, 180 to 385 d). Eighteen patients developed diarrhea during rifaximin treatment. None of these patients tested positive for C. difficile. This study demonstrates that treatment of HE with the safe, nonsystemic, gut-selective antibiotic rifaximin was not associated with the development of C. difficile infection.

  14. Reversibility of minimal hepatic encephalopathy following liver transplantation in Egyptian cirrhotic patients

    PubMed Central

    Osman, Mahmoud A; Sayed, Moataz M; Mansour, Khaled A; Saleh, Shereen A; Ibrahim, Wesam A; Abdelhakam, Sara M; Bahaa, Mohamed; Yousry, Wael A; Elbaz, Hosam S; Mikhail, Reginia N; Hassan, Azza M; Elsayed, Ehab H; Mahmoud, Dalia A

    2016-01-01

    AIM To evaluate the reversibility of minimal hepatic encephalopathy (MHE) following liver transplantation (LT) in Egyptian cirrhotic patients. METHODS This prospective study included twenty patients with biopsy-proven liver cirrhosis listed for LT and twenty age- and sex-matched healthy control subjects. All underwent neuro-psychiatric examination, laboratory investigations, radiological studies and psychometric tests including trail making test A (TMT A), TMT B, digit symbol test and serial dotting test. The psychometric hepatic encephalopathy score (PHES) was calculated for patients to diagnose MHE. Psychometric tests were repeated six months following LT in the cirrhotic patient group. RESULTS Before LT, psychometric tests showed highly significant deficits in cirrhotic patients in comparison to controls (P < 0.001). There was a statistically significant improvement in test values in the patient group after LT; however, their values were still significantly worse than those of the controls (P < 0.001). The PHES detected MHE in 16 patients (80%) before LT with a median value of -7 ± 3.5. The median PHES value was significantly improved following LT, reaching -4.5 ± 5 (P < 0.001), and the number of patients with MHE decreased to 11 (55%). The pre-transplant model for end-stage liver disease (MELD) score ≥ 15 was significantly related to the presence of post-transplant MHE (P = 0.005). More patients in whom reversal of MHE was observed had a pre-transplant MELD score < 15. CONCLUSION Reversal of MHE in cirrhotic patients could be achieved by LT, especially in those with a MELD score < 15. PMID:27843538

  15. Low-light-level therapy as a treatment for minimal hepatic encephalopathy: behavioural and brain assessment.

    PubMed

    Arias, Natalia; Méndez, Marta; Arias, Jorge L

    2016-11-01

    Minimal hepatic encephalopathy (MHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments involved in MHE. We studied one of its precipitating factors, portal hypertension. The purpose was to evaluate an enhancement in neuronal metabolism through low-light-level therapy (LLLT) and whether this therapy has effects on behavioural task acquisition. Rats were trained to perform a stimulus-response task using the Morris water maze. Three groups of animals were used: a SHAM (sham-operated) group (n = 7), a portal hypertension (PH) group (n = 7) and a PH + LLLT group (n = 7). The triple portal vein ligation method was used to create an animal model of the early developmental phase of HE, and then the animals were exposed to 670 + 10 nm LED light at a dose of 9 J/cm(2) once a day for 7 days. The metabolic activity of the brains was studied with cytochrome c oxidase histochemistry. There were differences in behavioural performance, with an improvement in the PH + LLLT group. Energetic brain metabolism revealed significant differences between the groups in all the brain structures analysed, except the anterodorsal thalamus. At the same time, in different brain networks, the PH group showed a more complicated relationship among the structures, while the SHAM and PH + LLLT groups had similar patterns. In this study, we provide the first preliminary insights into the validity of LLLT as a possible intervention to improve memory under minimal hepatic encephalopathy conditions.

  16. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity.

    PubMed

    Chen, Hua-Jun; Zhang, Ling; Jiang, Long-Feng; Chen, Qiu-Feng; Li, Jun; Shi, Hai-Bin

    2016-08-01

    It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients.

  17. Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis.

    PubMed

    Bajaj, J S; Barrett, A C; Bortey, E; Paterson, C; Forbes, W P

    2015-01-01

    Rifaximin therapy reduced risk of hepatic encephalopathy (HE) recurrence and HE-related hospitalisations during a 6-month, randomised, placebo-controlled trial (RCT) and a 24-month open-label maintenance (OLM) study. However, the impact of crossover from placebo to rifaximin therapy is unclear. To study the impact of crossing over from placebo to rifaximin treatment on breakthrough HE and hospitalisation rates using a within-subjects design. Adults with cirrhosis and history of overt HE episodes, currently in HE remission, received placebo during the RCT and crossed over to rifaximin 550 mg twice daily during the OLM study. Rate of breakthrough overt HE episodes, hospitalisations and incidence and rate of adverse events (AEs) were analysed during RCT and first 6 months of OLM. Of 82 patients randomised to placebo in the RCT who crossed over to the OLM study, 39 experienced an HE episode during the RCT compared with 14 during the OLM study (P < 0.0001). Significantly lower rates of HE events were observed with rifaximin treatment compared with placebo treatment (P < 0.0001). Rates of HE-related hospitalisation were numerically lower during rifaximin treatment compared with placebo treatment, although not significant. Rates of most common AEs, serious AEs and infection-related AEs were similar between the two treatments. This analysis confirms the repeatability of results from the RCT on safety and efficacy of rifaximin 550 mg twice daily in reducing the risk of hepatic encephalopathy recurrence, and suggests these findings are translatable outside of a rigorous, controlled trial setting. © 2014 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

  18. Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis

    PubMed Central

    Bajaj, J S; Barrett, A C; Bortey, E; Paterson, C; Forbes, W P

    2015-01-01

    Background Rifaximin therapy reduced risk of hepatic encephalopathy (HE) recurrence and HE-related hospitalisations during a 6-month, randomised, placebo-controlled trial (RCT) and a 24-month open-label maintenance (OLM) study. However, the impact of crossover from placebo to rifaximin therapy is unclear. Aim To study the impact of crossing over from placebo to rifaximin treatment on breakthrough HE and hospitalisation rates using a within-subjects design. Methods Adults with cirrhosis and history of overt HE episodes, currently in HE remission, received placebo during the RCT and crossed over to rifaximin 550 mg twice daily during the OLM study. Rate of breakthrough overt HE episodes, hospitalisations and incidence and rate of adverse events (AEs) were analysed during RCT and first 6 months of OLM. Results Of 82 patients randomised to placebo in the RCT who crossed over to the OLM study, 39 experienced an HE episode during the RCT compared with 14 during the OLM study (P < 0.0001). Significantly lower rates of HE events were observed with rifaximin treatment compared with placebo treatment (P < 0.0001). Rates of HE-related hospitalisation were numerically lower during rifaximin treatment compared with placebo treatment, although not significant. Rates of most common AEs, serious AEs and infection-related AEs were similar between the two treatments. Conclusions This analysis confirms the repeatability of results from the RCT on safety and efficacy of rifaximin 550 mg twice daily in reducing the risk of hepatic encephalopathy recurrence, and suggests these findings are translatable outside of a rigorous, controlled trial setting. PMID:25339518

  19. Profile of Hepatic Encephalopathy in Children with Cirrhosis and Response to Lactulose

    PubMed Central

    Sharma, Praveen; Sharma, Barjesh C.

    2011-01-01

    Background/Aim: Hepatic encephalopathy (HE) is associated with a poor prognosis. There is paucity of data on the treatment of HE with lactulose in children with cirrhosis. Patients and Methods: Retrospective analysis of consecutive cirrhotic patients (<18 years) with HE was done. HE was defined according to West-Haven criteria. Response was defined as complete if patients recovered completely from HE, partial response was defined as improvement of encephalopathy by one or more grades from admission but not complete recovery, and defined as non response if patient did not show any improvement or deteriorated further even after 10 days of lactulose therapy. Results: A total of 300 patients were admitted with cirrhosis and HE (278 adults and 22 children). Of 22 patients, 16 (73%) patients had complete response to lactulose and six (27%) patients did not [three (13.5%) patients worsened (non response) and three (13.5%) did not recover fully even after 10 days of treatment (partial response)]. Comparing baseline characteristics of patients who had complete response (n=16) versus partial (n=3) and non response (n=3), there was significant difference in mean arterial pressure (78.1±10.7 vs 62.6±5.0 mmHg, P=0.003), serum sodium (131.3±3.2 vs 126.5±5.2, P=0.01) and serum creatinine (0.78±0.3 vs 1.1±0.3 mg/dl, P=0.02). We did not find any difference in baseline characteristics of these patients regarding CTP score (9.6±1.2 vs 10.6±1.2), MELD score (17.6±2.9 vs 17.1±3.4), severity of HE (2.5±0.6 vs 2.6±0.5) and etiology of precipitating factors (P=0.78). Conclusions: Lactulose therapy causes complete recovery from hepatic encephalopathy in 73% of pediatrics patients with cirrhosis. PMID:21372353

  20. [Acute encephalopathy due to late-onset maple syrup urine disease in a school boy].

    PubMed

    Qu, Su-Qing; Yang, Li-Cai; Luan, Zuo; Du, Kan; Yang, Hui

    2012-03-01

    Maple syrup urine disease is a common amino acids metabolic disease. In most patients, onset occurs in the neonatal period and infancy. In this study, the case of a school boy with acute encephalopathy due to late-onset maple syrup urine disease is summarized. The boy (8.5 years) was admitted because of acute encephalopathy after suffering from infection for two days at the age of eight and a half years. Metabolic acidosis, hyperuricemia and decreased protein level in cerebrospinal fluid were found by general laboratory tests. Magnetic resonance imaging of the brain revealed signal intensity abnormalities in the bilateral cerebellum dentate nucleus, brainstem, thalamus, putamen, caudate nucleus and cortex of the cerebral hemispheres. On T1WI and T2WI scanning, hyperintensive signal was found. Blood leucine and valine were significantly elevated. Urinary 2-hydroxy isovaleric acid, 3-hydroxybutyric acid, 2-keto isovaleric acid, and 2-keto acid also increased. Both the blood amino acid and urine organic acid profiles led to the diagnosis of maple syrup urine disease. In the acute period, the patient was treated with a large dose of vitamin B1, glucose, L-carnitine and a protein-restrict diet. The patient's condition improved significantly after five days of treatment, and he recovered completely two days later. Afterwards, treatment with vitamin B1, L-carnitine and a protein-restrict diet (1 g/kg/day) was continued. One and a half months later, blood amino acids and urine organic acids returned to normal. Magnetic resonance imaging of the brain also indicated a great improvement. It was concluded that inborn metabolic disease should be considered in the patients with an onset similar to acute encephalopathy. Early diagnosis and proper treatment can prevent brain damage and improve prognosis.

  1. Sildenafil reduces neuroinflammation in cerebellum, restores GABAergic tone, and improves motor in-coordination in rats with hepatic encephalopathy.

    PubMed

    Agusti, Ana; Hernández-Rabaza, Vicente; Balzano, Tiziano; Taoro-Gonzalez, Lucas; Ibañez-Grau, Andrea; Cabrera-Pastor, Andrea; Fustero, Santos; Llansola, Marta; Montoliu, Carmina; Felipo, Vicente

    2017-05-01

    Patients with liver disease may develop hepatic encephalopathy (HE), with cognitive impairment and motor in-coordination. Rats with HE due to portacaval shunts (PCS) show motor in-coordination. We hypothesized that in PCS rats: (i) Motor in-coordination would be due to enhanced GABAergic tone in cerebellum; (ii) increased GABAergic tone would be due to neuroinflammation; (iii) increasing cGMP would reduce neuroinflammation and GABAergic tone and restore motor coordination. To assess these hypotheses, we assessed if (i) treatment with sildenafil reduces neuroinflammation; (ii) reduced neuroinflammation is associated with reduced GABAergic tone and restored motor coordination. Rats were treated with sildenafil to increase cGMP. Microglia and astrocytes activation were analyzed by immunohistochemistry, extracellular GABA by microdialysis, and motor coordination in the beam walking. PCS rats show neuroinflammation in cerebellum, with microglia and astrocytes activation, increased IL-1b and TNF-a and reduced YM-1 and IL-4. Membrane expression of the GABA transporter GAT1 is reduced, while GAT3 is increased. Extracellular GABA and motor in-coordination are increased. Sildenafil treatment eliminates neuroinflammation, microglia and astrocytes activation; changes in membrane expression of GABA transporters; and restores motor coordination. This study supports an interplay between cGMP-neuroinflammation and GABAergic neurotransmission in impairing motor coordination in PCS rats. © 2017 John Wiley & Sons Ltd.

  2. Ketogenic diet in early myoclonic encephalopathy due to non ketotic hyperglycinemia.

    PubMed

    Cusmai, Raffaella; Martinelli, Diego; Moavero, Romina; Dionisi Vici, Carlo; Vigevano, Federico; Castana, Cinzia; Elia, Mirella; Bernabei, Silvia; Bevivino, Elsa

    2012-09-01

    Non ketotic hyperglycinemia is a rare inborn error of glycine metabolism due to deficient activity of glycine cleavage system, a multienzymatic complex consisting of four protein subunits: the P-protein, the H-protein, the T-protein and the L-protein. The neonatal form of non ketotic hyperglycinemia presents in the first days of life with encephalopathy, seizures, multifocal myoclonus and characteristic "hiccups". Rapid progression may lead to intractable seizures, coma and respiratory failure requiring mechanical ventilation. Clinical trial with scavenges drugs decreasing glycine levels such as sodium benzoate, and with drugs reducing NMDA receptors excitatory properties, such as ketamine and dextromethorphan, have been tried but the outcome is usually poor; antiepileptic therapy, moreover, is unable to control epileptic seizures. Ketogenic diet has been successfully tried for refractory epilepsy in pediatric patients. We report three cases affected by neonatal non ketotic hyperglycinemia and early myoclonic encephalopathy treated with ketogenic diet. In our patients ketogenic diet, in association with standard pharmacological therapy, determined dramatic reduction of seizures and improved quality of life.

  3. Pathological Predictors of Shunt Stenosis and Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt.

    PubMed

    He, Fuliang; Dai, Shan; Xiao, Zhibo; Wang, Lei; Yue, Zhendong; Zhao, Hongwei; Zhao, Mengfei; Lin, Qiushi; Dong, Xiaoqun; Liu, Fuquan

    2016-01-01

    Background. Transjugular intrahepatic portosystemic shunt (TIPS) is an artificial channel from the portal vein to the hepatic vein or vena cava for controlling portal vein hypertension. The major drawbacks of TIPS are shunt stenosis and hepatic encephalopathy (HE); previous studies showed that post-TIPS shunt stenosis and HE might be correlated with the pathological features of the liver tissues. Therefore, we analyzed the pathological predictors for clinical outcome, to determine the risk factors for shunt stenosis and HE after TIPS. Methods. We recruited 361 patients who suffered from portal hypertension symptoms and were treated with TIPS from January 2009 to December 2012. Results. Multivariate logistic regression analysis showed that the risk of shunt stenosis was increased with more severe inflammation in the liver tissue (OR, 2.864; 95% CI: 1.466-5.592; P = 0.002), HE comorbidity (OR, 6.266; 95% CI, 3.141-12.501; P < 0.001), or higher MELD score (95% CI, 1.298-1.731; P < 0.001). Higher risk of HE was associated with shunt stenosis comorbidity (OR, 6.266; 95% CI, 3.141-12.501; P < 0.001), higher stage of the liver fibrosis (OR, 2.431; 95% CI, 1.355-4.359; P = 0.003), and higher MELD score (95% CI, 1.711-2.406; P < 0.001). Conclusion. The pathological features can predict individual susceptibility to shunt stenosis and HE.

  4. The contribution of endogenous benzodiazepine receptor ligands to the pathogenesis of hepatic encephalopathy

    SciTech Connect

    Basile, A.S. )

    1991-02-01

    The involvement of the gamma-aminobutyric acid A(GABAA) receptor complex in the pathogenesis of hepatic encephalopathy (HE) was examined in galactosamine-treated rabbits with HE caused by fulminant hepatic failure. Radioligand binding to the constituent components of the GABAA receptor complex was unchanged in rabbits with HE. However, partially purified extracts from encephalopathic rabbit brain were approximately three times more potent in inhibiting ({sup 3}H)Ro 15-1788 binding to benzodiazepine (BZ) receptors than extracts from control rabbits. The inhibition of radioligand binding to the BZ receptor produced by these extracts was competitive and reversible and was significantly enhanced by GABA. Further purification of these extracts by high-performance liquid chromatography (HPLC) indicated that the inhibitory activity was localized in several peaks, some of which had retention times corresponding to 1,4-benzodiazepine standards. The presence of diazepam in these extracts was confirmed using mass spectroscopy. Both mass spectroscopic and radiometric techniques demonstrated that the concentration of diazepam in brain extracts from encephalopathic rabbits was approximately 4 times greater than control extracts. These findings link the presence of BZ receptor agonists to the development of a neuropathological condition, thereby providing a rational basis for the use of BZ receptor antagonists in the management of HE in man.

  5. Reduced brain levels of DHEAS in hepatic coma patients: significance for increased GABAergic tone in hepatic encephalopathy.

    PubMed

    Ahboucha, Samir; Talani, Giuseppe; Fanutza, Tomas; Sanna, Enrico; Biggio, Giovanni; Gamrani, Halima; Butterworth, Roger F

    2012-07-01

    Increased neurosteroids with allosteric modulatory activity on GABA(A) receptors such as 3α-5α tertrahydroprogesterone; allopregnanolone (ALLO), are candidates to explain the phenomenon of "increased GABAergic tone" in hepatic encephalopathy (HE). However, it is not known how changes of other GABA(A) receptor modulators such as dehydroepiandrosterone sulfate (DHEAS) contribute to altered GABAergic tone in HE. Concentrations of DHEAS were measured by radioimmunoassay in frontal cortex samples obtained at autopsy from 11 cirrhotic patients who died in hepatic coma and from an equal number of controls matched for age, gender, and autopsy delay intervals free from hepatic or neurological diseases. To assess whether reduced brain DHEAS contributes to increased GABAergic tone, in vitro patch clamp recordings in rat prefrontal cortex neurons were performed. A significant reduction of DHEAS (5.81±0.88 ng/g tissue) compared to control values (9.70±0.79 ng/g, p<0.01) was found. Brain levels of DHEAS in patients with liver disease who died without HE (11.43±1.74 ng/g tissue), and in a patient who died in uremic coma (12.56 ng/g tissue) were within the control range. Increasing ALLO enhances GABAergic tonic currents concentration-dependently, but increasing DHEAS reduces these currents. High concentrations of DHEAS (50 μM) reduce GABAergic tonic currents in the presence of ALLO, whereas reduced concentrations of DHEAS (1 μM) further stimulate these currents. These findings demonstrate that decreased concentrations of DHEAS together with increased brain concentrations of ALLO increase GABAergic tonic currents synergistically; suggesting that reduced brain DHEAS could further increase GABAergic tone in human HE.

  6. Reduction of cerebral blood flow in subclinical hepatic encephalopathy and its correlation with plasma-free tryptophan

    SciTech Connect

    Rodriguez, G.; Testa, R.; Celle, G.; Gris, A.; Marenco, S.; Nobili, F.; Novellone, G.; Rosadini, G.

    1987-12-01

    Cerebral blood flow (CBF), measured by the noninvasive xenon-133 inhalation method, EEG, and plasma levels of ammonia (NH/sub 3/) and free tryptophan were determined in 18 hospitalized cirrhotic patients affected with subclinical hepatic encephalopathy, as diagnosed by the Kurtz test. CBF results were significantly lower (p less than 0.001) in the patients' group as compared with a sex- and age-matched normal control population, although seven patients had values in the normal range. NH/sub 3/ was increased only in six, while free tryptophan was increased in all but two patients. A significant negative correlation (p = 0.02) between CBF and free tryptophan was found, even though it appears to be difficult to interpret. We suggest that CBF impairment in some cirrhotic patients with subclinical hepatic encephalopathy may be related to the systemic metabolic derangement caused by the liver disease; free tryptophan could have some implication in producing CBF reduction.

  7. Rifaximin vs conventional oral therapy for hepatic encephalopathy: A meta-analysis

    PubMed Central

    Eltawil, Karim M; Laryea, Marie; Peltekian, Kevork; Molinari, Michele

    2012-01-01

    AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identified through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics [odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profile (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical significance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any significant difference in the above findings. CONCLUSION: Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profile. PMID:22371636

  8. Effect of antibiotics, prebiotics and probiotics in treatment for hepatic encephalopathy.

    PubMed

    Bongaerts, Ger; Severijnen, René; Timmerman, Harro

    2005-01-01

    In order to reduce ammonia production by urease-positive bacteria Solga recently hypothesised (S.F. Solga, Probiotics can treat hepatic encephalopathy, Medical Hypotheses 2003; 61: 307-13), that probiotics are new therapeutics for hepatic encephalopathy (HE), and that they may replace antibiotics and lactulose. This influenced our view of the effect of antibiotics, prebiotics, e.g., lactulose, and probiotics on intestinal bacteria in the treatment of HE. Intestinal ammonia arises from aminoacids after bacterial de-amination and not from urea making urease-positive bacteria irrelevant. Antibiotics are not preferred in the treatment of HE, since ammonia-producing antibiotic-resistant bacteria may survive and replace ammonia-producing antibiotic-susceptible bacteria. Intestinal prebiotics are carbohydrate-like compounds, such as lactulose and resistant starch, that beneficially affects host's health in a different manner than normal food. In the small bowel prebiotics are not absorbed and digested, but are fermented in the colon by colonic bacteria. Fermentation of prebiotics yields lactic, acetic and butyric acids, as well as gas especially hydrogen (H2). The massive H2 volumes cause rapid intestinal hurry and thus massive amounts of colonic bacteria, not only urease-positive bacteria, but also deaminating bacteria, are removed and intestinal uptake of toxic bacterial metabolites, e.g., ammonia, reduced. As living non-pathogenic micro-organisms, probiotics beneficially affect the host's health by fermenting non-absorbed sugars, especially in the small bowel. Thus, they reduce the substrate of the other bacteria, and simultaneously they create a surplus of fermentation products which may affect the non-probiotic flora. Regarding the fermentation products (lactic acid, ethanol, acetic acid and CO2) five groups of probiotic micro-organisms are known. It is argued that probiotic, CO2-producing (facultatively) heterolactic lactobacilli, i.e., lactobacilli, that produce

  9. Lactulose reduces bacterial DNA translocation, which worsens neurocognitive shape in cirrhotic patients with minimal hepatic encephalopathy.

    PubMed

    Moratalla, Alba; Ampuero, Javier; Bellot, Pablo; Gallego-Durán, Rocío; Zapater, Pedro; Roger, Manuela; Figueruela, Blanca; Martínez-Moreno, Belén; González-Navajas, José M; Such, José; Romero-Gómez, Manuel; Francés, Rubén

    2017-02-01

    Minimal hepatic encephalopathy is associated with poor prognosis and mortality in patients with cirrhosis. We aimed at investigating whether bacterial-DNA translocation affects hyperammonaemia and neurocognitive scores in patients with mHE according to the use of lactulose. Observational study including 72 mHE cirrhotic patients, as defined by a psychometric hepatic encephalopathy score (PHES)<-4 and/or a critical flicker frequency (CFF)<39 Hz. Bacterial-DNA, serum ammonia, pro-inflammatory cytokines and nitric oxide levels were evaluated. A second cohort of 40 lactulose-untreated patients were evaluated before and 6-month after lactulose administration (30-60 mL/d). In the first cohort, bacterial-DNA rate was significantly higher in patients without lactulose (39% vs 23%, P=.03). Serum ammonia and inflammatory markers were significantly increased in patients with bacterial-DNA, regardless the use of lactulose, and correlated with the amount of amplified bacterial-DNA. Neurocognitive scores were significantly worse in bacterial-DNA positive vs negative patients (PHES -7.6±1.1 vs -5.5±1.0; CFF 32.5±2.6 vs 36.2±2.8, P=.01). Lactulose was associated with improved neurocognitive scores in patients without bacterial-DNA. Serum ammonia levels inversely correlated with neurocognitive scores in patients with bacterial-DNA (PHES r=-.84; CFF r=-.72, P=.001). In the second cohort, lactulose reduced bacterial-DNA translocation (36%-16%, P=.02). Neurocognitive scores were significantly improved in bacterial-DNA positive patients who cleared bacterial-DNA during the period on lactulose. Serum ammonia levels correlated with both neurocognitive scores in patients with bacterial-DNA, either before or after lactulose. Bacterial-DNA translocation worsens neurocognitive scores in mHE patients and it is reduced by lactulose, enhancing the relevance of controlling bacterial antigen translocation in these patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Clinical efficacy and safety of lactulose for minimal hepatic encephalopathy: a meta-analysis.

    PubMed

    Luo, Ming; Li, Lei; Lu, Chen-Zheng; Cao, Wu-Kui

    2011-11-01

    To evaluate the clinical efficacy of lactulose in patients with minimal hepatic encephalopathy (MHE). Randomized controlled trials (RCTs) comparing lactulose with placebo or with no intervention in the management of MHE that were conducted from January 1990 to July 2011 were searched from MEDLINE, EMBASE, SCI, Cochrane Controlled Trials Register, and China Biological Medicine Database. Studies with a Jadad score higher than 3 were included in the meta-analysis and evaluated using RevMan5.0 software for relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (95% CI). Sensitivity analysis was performed on the ethnical differences and quality of the trials. Publication bias was observed using an inverted funnel plot. Nine studies with 434 patients were included in the meta-analysis. Compared with placebo or no intervention, lactulose significantly reduced the risk of no improvement in neuropsychological tests (RR: 0.52, 95% CI: 0.44-0.62, P<0.00001), the time required for the completion of the number connection test-A (WMD: -26.95, 95% CI: -37.81 to -16.10, P<0.00001), and the mean number of abnormal neuropsychological tests (WMD: -1.76, 95% CI: -1.96 to -1.56, P<0.00001). Furthermore, the meta-analysis also showed that lactulose prevented the progression to overt hepatic encephalopathy (RR: 0.17, 95% CI: 0.06-0.52, P=0.002), reduced blood ammonia levels (WMD: -9.89 µmol/l, 95% CI: -11.01 to -8.77 µmol/l, P<0.00001), and improve health-related quality of life (WMD: -6.05, 95% CI: -6.30 to -5.20, P<0.00001). However, no significant difference was observed in the mortality of patients with MHE (RR: 0.75, 95% CI: 0.21-2.72, P=0.66), and lactulose significantly increased the incidence of diarrhea (RR: 4.38, 95% CI: 1.35-14.25, P=0.01). Lactulose has significant beneficial effects for patients with MHE compared with placebo or no intervention.

  11. Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: a PET study with [11C]acetate in humans

    PubMed Central

    Iversen, Peter; Mouridsen, Kim; Hansen, Mikkel B.; Jensen, Svend B.; Sørensen, Michael; Bak, Lasse K.; Waagepetersen, Helle S.; Schousboe, Arne; Ott, Peter; Vilstrup, Hendrik; Keiding, Susanne; Gjedde, Albert

    2014-01-01

    In patients with impaired liver function and hepatic encephalopathy (HE), consistent elevations of blood ammonia concentration suggest a crucial role in the pathogenesis of HE. Ammonia and acetate are metabolized in brain both primarily in astrocytes. Here, we used dynamic [11C]acetate PET of the brain to measure the contribution of astrocytes to the previously observed reduction of brain oxidative metabolism in patients with liver cirrhosis and HE, compared to patients with cirrhosis without HE, and to healthy subjects. We used a new kinetic model to estimate uptake from blood to astrocytes and astrocyte metabolism of [11C]acetate. No significant differences of the rate constant of oxidation of [11C]acetate (k3) were found among the three groups of subjects. The net metabolic clearance of [11C]acetate from blood was lower in the group of patients with cirrhosis and HE than in the group of healthy subjects (P < 0.05), which we interpret to be an effect of reduced cerebral blood flow rather than a reflection of low [11C]acetate metabolism. We conclude that the characteristic decline of whole-brain oxidative metabolism in patients with cirrhosis with HE is not due to malfunction of oxidative metabolism in astrocytes. Thus, the observed decline of brain oxidative metabolism implicates changes of neurons and their energy turnover in patients with HE. PMID:25404890

  12. Pharmacological manipulation of cyclic GMP levels in brain restores learning ability in animal models of hepatic encephalopathy: therapeutic implications

    PubMed Central

    Rodrigo, Regina; Monfort, Pilar; Cauli, Omar; Erceg, Slaven; Felipo, Vicente

    2006-01-01

    Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome present in patients with liver disease that includes impaired intellectual function. To develop therapeutic treatments to restore cognitive function, it is important to understand the molecular mechanisms that impair cognitive function in HE. This review summarizes data showing that: (a) cognitive function and learning are impaired in patients with liver disease and in animal models of chronic liver failure or hyperammonemia; (b) the glutamate–NO–cGMP pathway modulates some forms of learning; and (c) the function of this pathway is impaired in brain in vivo in rats with chronic hyperammonemia or liver failure and from patients who died from HE. Learning ability of hyperammonemic rats was restored by increasing cGMP by: (1) continuous intracerebral administration of zaprinast, an inhibitor of the cGMP-degrading phosphodiesterase; (2) chronic oral administration of sildenafil, an inhibitor of the phosphodiesterase that crosses the blood–brain barrier; and (3) continuous intracerebral administration of cGMP. The data summarized indicate that impairment of learning ability in rats with chronic liver failure or hyperammonemia is due to impairment of the glutamate–NO–cGMP pathway. Moreover, increasing extracellular cGMP by pharmacological means may be a new therapeutic approach to improve cognitive function in patients with HE. PMID:19412446

  13. Genistein Alleviates Neuroinflammation and Restores Cognitive Function in Rat Model of Hepatic Encephalopathy: Underlying Mechanisms.

    PubMed

    Ganai, Ajaz Ahmad; Husain, Mohammad

    2017-02-21

    Hepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from acute liver failure. Previously, we demonstrated hepatoprotective effects of genistein in D-galactosamine (D-GalN)-induced fulminant hepatic failure (FHF). In this study, we evaluated behavioural and neuroprotective effects of genistein in rat model of HE. HE was induced by intraperitonial administration of D-GalN (250 mg/kg BW) twice a week for 30 days Genistein was given as co-treatment through oral gavage daily at dose of 5 mg/kg BW. D-GalN administration significantly resulted in acute liver failure which was further associated with hyperammonemia, neurological dysfunction, as evident from behavioural and functional impairment and reduced learning ability in Morris water maze. Genistein significantly alleviated behavioural and functional impairment and restored learning ability in Morris water maze. Considerable histopathological changes, including portal inflammation, sinusoidal dilation, necrotic lesions and swelled astrocytes with pale nuclei, were seen in the liver and brain sections of D-GalN-challenged rats while genistein co-treated rats revealed normal cellular and morphological architecture as no pathological features were seen. Furthermore, pro-inflammatory markers (interleukin (IL)-10, IL-4, IL-1β and TNF-α) and membrane expression of subunits α1 of GABAA receptor and GluR2 of AMPA marked significant increase, while subunits GluR1 of AMPA receptors showed reduced expression in D-GalN-challenged rats leading to neuroinflammation and dysregulated neurotransmission. Genistein significantly normalized altered expression of pro-inflammatory cytokines and membrane receptor of GABA and GluR. Our study suggests strong therapeutic potential of genistein in animal model of HE. Genistein can be used a strong anti-oxidant to attenuate neurotoxic effects of xenobiotics.

  14. Finasteride improves motor, EEG, and cellular changes in rat brain in thioacetamide-induced hepatic encephalopathy.

    PubMed

    Mladenović, Dušan; Hrnčić, Dragan; Petronijević, Nataša; Jevtić, Gordana; Radosavljević, Tatjana; Rašić-Marković, Aleksandra; Puškaš, Nela; Maksić, Nebojša; Stanojlović, Olivera

    2014-11-01

    Neurosteroids are involved in the pathogenesis of hepatic encephalopathy (HE). This study evaluated the effects of finasteride, inhibitor of neurosteroid synthesis, on motor, EEG, and cellular changes in rat brain in thioacetamide-induced HE. Male Wistar rats were divided into the following groups: 1) control; 2) thioacetamide-treated group, TAA (300 mg·kg(-1)·day(-1)); 3) finasteride-treated group, FIN (50 mg·kg(-1)·day(-1)); and 4) group treated with FIN and TAA (FIN + TAA). Daily doses of TAA and FIN were administered in three subsequent days intraperitoneally, and in the FIN + TAA group FIN was administered 2 h before every dose of TAA. Motor and reflex activity was determined at 0, 2, 4, 6, and 24 h, whereas EEG activity was registered about 24 h after treatment. The expressions of neuronal (NeuN), astrocytic [glial fibrilary acidic protein (GFAP)], microglial (Iba1), and oligodendrocyte (myelin oligodendrocyte glycoprotein) marker were determined 24 h after treatment. While TAA decreased all tests, FIN pretreatment (FIN + TAA) significantly improved equilibrium, placement test, auditory startle, head shake reflex, motor activity, and exploratory behavior vs. the TAA group. Vital reflexes (withdrawal, grasping, righting and corneal reflex) together with mean EEG voltage were significantly higher (P < 0.01) in the FIN + TAA vs. the TAA group. Hippocampal NeuN expression was significantly lower in TAA vs. control (P < 0.05). Cortical Iba1 expression was significantly higher in experimental groups vs. control (P < 0.05), whereas hippocampal GFAP expression was increased in TAA and decreased in the FIN + TAA group vs. control (P < 0.05). Finasteride improves motor and EEG changes in TAA-induced HE and completely prevents the development of hepatic coma.

  15. Pathological Predictors of Shunt Stenosis and Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt

    PubMed Central

    He, Fuliang; Dai, Shan; Xiao, Zhibo; Wang, Lei; Yue, Zhendong; Zhao, Hongwei; Zhao, Mengfei; Lin, Qiushi; Dong, Xiaoqun

    2016-01-01

    Background. Transjugular intrahepatic portosystemic shunt (TIPS) is an artificial channel from the portal vein to the hepatic vein or vena cava for controlling portal vein hypertension. The major drawbacks of TIPS are shunt stenosis and hepatic encephalopathy (HE); previous studies showed that post-TIPS shunt stenosis and HE might be correlated with the pathological features of the liver tissues. Therefore, we analyzed the pathological predictors for clinical outcome, to determine the risk factors for shunt stenosis and HE after TIPS. Methods. We recruited 361 patients who suffered from portal hypertension symptoms and were treated with TIPS from January 2009 to December 2012. Results. Multivariate logistic regression analysis showed that the risk of shunt stenosis was increased with more severe inflammation in the liver tissue (OR, 2.864; 95% CI: 1.466–5.592; P = 0.002), HE comorbidity (OR, 6.266; 95% CI, 3.141–12.501; P < 0.001), or higher MELD score (95% CI, 1.298–1.731; P < 0.001). Higher risk of HE was associated with shunt stenosis comorbidity (OR, 6.266; 95% CI, 3.141–12.501; P < 0.001), higher stage of the liver fibrosis (OR, 2.431; 95% CI, 1.355–4.359; P = 0.003), and higher MELD score (95% CI, 1.711–2.406; P < 0.001). Conclusion. The pathological features can predict individual susceptibility to shunt stenosis and HE. PMID:27975051

  16. Co-administration of C-Phycocyanin ameliorates thioacetamide-induced hepatic encephalopathy in Wistar rats.

    PubMed

    Sathyasaikumar, K V; Swapna, I; Reddy, P V B; Murthy, Ch R K; Roy, K R; Dutta Gupta, A; Senthilkumaran, B; Reddanna, P

    2007-01-15

    Fulminant hepatic failure (FHF) is a condition with a sudden onset of necrosis followed by degeneration of hepatocytes, without any previously established liver disease, generally occurring within hours or days. FHF is associated with a wide spectrum of neuropsychiatric alterations ranging from stupor to coma, culminating in death. In the present study FHF was induced in rats by the administration of thioacetamide (TAA). Oxidative stress is thought to play a prominent role in the pathophysiology of cerebral changes during FHF leading to the assumption that antioxidants might offer protection. Hence, in the present study the protective effect of C-Phycocyanin (C-PC), a natural antioxidant, was evaluated on TAA-induced tissue damage. C-Phycocyanin was administered intraperitoneally twice at 24 h interval (50 mg/kg body weight) along with the hepatotoxin TAA (300 mg/kg body weight). The animals were sacrificed 18 h after the second injection of TAA treatment and various biochemical parameters were analysed in liver, serum and brain tissues. These studies revealed significant prevention of TAA-induced liver damage by C-PC, as evidenced by a) increase in survival rate; b) the prevention of leakage of liver enzymes (AAT and AST) and ammonia into serum; c) increase in prothrombin time and d) liver histopathology. Ultrastructural studies of astrocytes of different regions of brain clearly showed a decrease in edema after C-PC treatment. TAA-induced histopathological lesions in different regions of the brain namely cerebral cortex, cerebellum and pons medulla were significantly reduced by the co-administration of C-PC with TAA. Further C-PC treatment resulted in a) decrease in the levels of tryptophan and markers of lipid peroxidation and b) elevation in the activity levels of catalase, glutathione peroxidase in different regions of brain. These studies reveal the potential of C-PC in ameliorating TAA-induced hepatic encephalopathy by improving antioxidant defenses.

  17. The role of magnetic resonance imaging and spectroscopy in hepatic encephalopathy.

    PubMed

    McPhail, Mark J W; Taylor-Robinson, Simon D

    2010-03-01

    Hepatic encephalopathy (HE) is a diverse manifestation of acute and chronic liver failure, ranging from cognitive impairment, only detectable on psychometric evaluation through to confusion, coma and death from cerebral oedema. While there is widespread acceptance of its importance, there is little consensus on how best to diagnose and monitor HE. Clinical descriptions, psychometric testing, electroencephalography and magnetic resonance (MR) imaging (and lately, MR spectroscopy) have all been proposed. MR techniques, in contrast to other modalities, have the benefit of objectivity and of being able to interrogate the brain directly with respect to changes in brain size, function and the metabolic disturbances thought to underlie HE, particularly in the context of astrocyte swelling. Modern clinical MRI scanners with multinuclear MR spectroscopy capabilities and brain mapping software can demonstrate structural and functional cellular changes using volumetric MRI, magnetization transfer MRI, diffusion-weighting MRI, functional MRI with oxygenation measurements and in vivo and in vitro (1)H and (31)P MR spectroscopy. This review describes the relative merits of these techniques and provides guidance on the directions for future research and translation into clinical practice.

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

    PubMed

    Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

    2015-11-07

    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.

  19. Changes in the regional homogeneity of resting-state brain activity in minimal hepatic encephalopathy.

    PubMed

    Chen, Hua-Jun; Zhu, Xi-Qi; Yang, Ming; Liu, Bin; Zhang, Yi; Wang, Yu; Teng, Gao-Jun

    2012-01-17

    Resting-state functional magnetic resonance imaging (fMRI) has facilitated the study of spontaneous brain activity by measuring low-frequency oscillations in blood-oxygen-level-dependent signals. Analyses of regional homogeneity (ReHo), which reflects the local synchrony of neural activity, have been used to reveal the mechanisms underlying the brain dysfunction in various neuropsychiatric diseases. However, it is not known whether the ReHo is altered in cirrhotic patients with minimal hepatic encephalopathy (MHE). We recruited 18 healthy controls and 18 patients with MHE. The ReHo was calculated to assess the strength of the local signal synchrony. Compared with the healthy controls, the patients with MHE had significantly decreased ReHo in the cuneus and adjacent precuneus, and left inferior parietal lobe, whereas the regions showing increased ReHo in patients with MHE included the left parahippocampal gyrus, right cerebellar vermis, and bilateral anterior cerebellar lobes. We found a positive correlation between the mean ReHo in the cuneus and adjacent precuneus and the score on the digit-symbol test in the patient group. In conclusion, the analysis of the regional homogeneity of resting-state brain activity may provide additional information with respect to a clinical definition of MHE.

  20. THDP17 Decreases Ammonia Production through Glutaminase Inhibition. A New Drug for Hepatic Encephalopathy Therapy

    PubMed Central

    Carbonero-Aguilar, Pilar; Vega-Pérez, José M.; Iglesias-Guerra, Fernando; Periñán, Ignacio; Miñano, Francisco J.; Bautista, Juan; Romero-Gómez, Manuel

    2014-01-01

    Ammonia production is implicated in the pathogenesis of hepatic encephalopathy (HE), being intestinal glutaminase activity the main source for ammonia. Management of ammonia formation can be effective in HE treatment by lowering intestinal ammonia production. The use of glutaminase inhibitors represents one way to achieve this goal. In this work, we have performed a search for specific inhibitors that could decrease glutaminase activity by screening two different groups of compounds: i) a group integrated by a diverse, highly pure small molecule compounds derived from thiourea ranging from 200 to 800 Daltons; and ii) a group integrated by commonly use compounds in the treatment of HE. Results shown that THDP-17 (10 µM), a thiourea derivate product, could inhibit the intestinal glutaminase activity (57.4±6.7%). Inhibitory effect was tissue dependent, ranging from 40±5.5% to 80±7.8% in an uncompetitive manner, showing Vmax and Km values of 384.62 µmol min−1, 13.62 mM with THDP-17 10 µM, respectively. This compound also decreased the glutaminase activity in Caco-2 cell cultures, showing a reduction of ammonia and glutamate production, compared to control cultures. Therefore, the THDP-17 compound could be a good candidate for HE management, by lowering ammonia production. PMID:25329718

  1. Evaluation of the impact of rehospitalization in the management of hepatic encephalopathy

    PubMed Central

    Saab, Sammy

    2015-01-01

    Background Overt hepatic encephalopathy (HE), which is associated with neuropsychiatric symptoms and neuromuscular dysfunction in patients with liver cirrhosis, is often managed in the hospital setting. Approximately 60% of eligible patients do not receive prophylactic therapy after an overt HE episode. Objective The aim of this review is to evaluate the impact of rehospitalization on costs and clinical outcomes in HE. Methods A PubMed search of English-language articles through July 9, 2014 was conducted, and bibliographies of identified publications were reviewed. Abstracts from relevant professional society meetings from 2010 to 2014 were searched. The selected references and abstracts reported on the prevalence, costs, or clinical consequences of rehospitalization in adults with HE. Data synthesis HE is a key reason for readmission among patients hospitalized for complications of cirrhosis. Almost 40% of patients previously hospitalized for HE may be readmitted within 1 year for HE-related reasons. Furthermore, in-hospital US mortality for patients admitted for HE is about 7% to 15%. Recurrent HE and hospitalization for cirrhosis complications are associated with impaired quality of life. In addition, recurrences (especially those requiring hospitalization) may contribute to persistent cognitive deficits (eg, impairments in reaction time, attention, and working memory) after resolution of an acute episode of overt HE. Conclusion The economic and clinical consequences of rehospitalization for patients with overt HE underscore the importance of secondary prevention and highlight the need to identify reasons for the undertreatment of patients after hospitalization for overt HE. PMID:25999756

  2. Evaluation of the impact of rehospitalization in the management of hepatic encephalopathy.

    PubMed

    Saab, Sammy

    2015-01-01

    Overt hepatic encephalopathy (HE), which is associated with neuropsychiatric symptoms and neuromuscular dysfunction in patients with liver cirrhosis, is often managed in the hospital setting. Approximately 60% of eligible patients do not receive prophylactic therapy after an overt HE episode. The aim of this review is to evaluate the impact of rehospitalization on costs and clinical outcomes in HE. A PubMed search of English-language articles through July 9, 2014 was conducted, and bibliographies of identified publications were reviewed. Abstracts from relevant professional society meetings from 2010 to 2014 were searched. The selected references and abstracts reported on the prevalence, costs, or clinical consequences of rehospitalization in adults with HE. HE is a key reason for readmission among patients hospitalized for complications of cirrhosis. Almost 40% of patients previously hospitalized for HE may be readmitted within 1 year for HE-related reasons. Furthermore, in-hospital US mortality for patients admitted for HE is about 7% to 15%. Recurrent HE and hospitalization for cirrhosis complications are associated with impaired quality of life. In addition, recurrences (especially those requiring hospitalization) may contribute to persistent cognitive deficits (eg, impairments in reaction time, attention, and working memory) after resolution of an acute episode of overt HE. The economic and clinical consequences of rehospitalization for patients with overt HE underscore the importance of secondary prevention and highlight the need to identify reasons for the undertreatment of patients after hospitalization for overt HE.

  3. Ayurveda in critical care: Illustrating Ayurvedic intervention in a case of hepatic encephalopathy

    PubMed Central

    Rastogi, Sanjeev; Srivastav, P. S.

    2011-01-01

    Ayurvedic interventions have largely been considered helpful in chronic debilitating conditions where active management of a clinical condition is not required. It is for this notion; Ayurvedic therapies have never been approached in any critical care condition requiring an active management. A perception that herbo-metallic components of various Ayurvedic drugs may actually harm the patients who are in compromised vital status has further added to this apprehension against use of such medicines in critical care. Contrary to the conventional belief, we observed a case of grade three hepatic encephalopathy with severely compromised liver function that was successfully treated with Ayurvedic therapy containing many heavy metal containing compounds. The liver function got improved in this case following the Ayurvedic intervention. The symptomatic improvements in this case were also identifiable through biochemical tests showing the functional status of liver. This case therefore is worthy of taking a note for possible inclusion of Ayurvedic interventions in critical care where Ayurvedic therapies are discarded without being given a chance of getting evaluated. PMID:22529648

  4. Ayurveda in critical care: Illustrating Ayurvedic intervention in a case of hepatic encephalopathy.

    PubMed

    Rastogi, Sanjeev; Srivastav, P S

    2011-07-01

    Ayurvedic interventions have largely been considered helpful in chronic debilitating conditions where active management of a clinical condition is not required. It is for this notion; Ayurvedic therapies have never been approached in any critical care condition requiring an active management. A perception that herbo-metallic components of various Ayurvedic drugs may actually harm the patients who are in compromised vital status has further added to this apprehension against use of such medicines in critical care. Contrary to the conventional belief, we observed a case of grade three hepatic encephalopathy with severely compromised liver function that was successfully treated with Ayurvedic therapy containing many heavy metal containing compounds. The liver function got improved in this case following the Ayurvedic intervention. The symptomatic improvements in this case were also identifiable through biochemical tests showing the functional status of liver. This case therefore is worthy of taking a note for possible inclusion of Ayurvedic interventions in critical care where Ayurvedic therapies are discarded without being given a chance of getting evaluated.

  5. Abnormal spontaneous brain activity in minimal hepatic encephalopathy: resting-state fMRI study.

    PubMed

    Zhong, Wei-Jia; Zhou, Zhi-Ming; Zhao, Jian-Nong; Wu, Wei; Guo, Da-Jing

    2016-01-01

    We aimed to assess the abnormality of baseline spontaneous brain activity in minimal hepatic encephalopathy (MHE) by amplitude of low frequency fluctuation (ALFF) and fraction ALFF (fALFF). A total of 14 MHE patients and 14 healthy controls were included in our study. Both ALFF and fALFF of functional magnetic resonance imaging were calculated for statistical analysis. Compared with healthy controls, patients with MHE had significantly decreased ALFF in the bilateral medial prefrontal cortex (MPFC), left superior frontal gyrus, right precentral gyrus, left opercular part of inferior frontal gyrus, left gyrus rectus, bilateral precuneus, and the posterior lobe of right cerebellum; and they had significantly decreased fALFF in the bilateral MPFC, right middle frontal gyrus, right superior temporal gyrus, and the posterior lobe of left cerebellum. ALFF and fALFF changes in many brain regions demonstrate abnormality of the spontaneous neuronal activity in MHE. Especially the impairment of right precuneus and left MPFC may play a critical role in manifestation of MHE. Changes of ALFF and fALFF in the precuneus and the MPFC can be used as a potential marker for MHE.

  6. Rifaximin: a review of its use in reducing recurrence of overt hepatic encephalopathy episodes.

    PubMed

    Scott, Lesley J

    2014-12-01

    Oral rifaximin 550 mg (Refero(®); Targaxan(®); Tixteller(®); Xifaxan(®)) twice daily, either alone or more commonly with medicines containing lactulose, is approved in several countries, including the UK, EU and USA, for use in adults with liver disease to reduce the recurrence of episodes of overt hepatic encephalopathy (HE). Rifaximin is a broad-spectrum antibacterial that acts locally in the gut to reduce intestinal flora, including ammonia-producing species, with hyperammonaemia considered to play a central role in the pathogenesis of HE. In a 6-month, multinational trial in patients with liver disease, rifaximin 550 mg twice daily (± lactulose) was an effective and well tolerated treatment for reducing the recurrence of HE episodes. At study end, rifaximin therapy significantly prolonged the time to the first breakthrough HE episode compared with placebo (± lactulose), irrespective of geographical region or baseline patient and disease characteristics. Rifaximin treatment also significantly reduced HE-related hospitalizations and improved health-related quality of life compared with placebo. Furthermore, the efficacy of rifaximin with or without lactulose in reducing the recurrence of overt HE episodes was maintained after up to 2.5 years of treatment, with no new safety signals arising during this period. This article reviews the pharmacology and therapeutic efficacy of rifaximin 550 mg twice daily in reducing the recurrence of overt HE episodes in adults with liver disease.

  7. Voxel-based analyses of magnetization transfer imaging of the brain in hepatic encephalopathy

    PubMed Central

    Miese, Falk R; Wittsack, Hans-Jörg; Kircheis, Gerald; Holstein, Arne; Mathys, Christian; Mödder, Ulrich; Cohnen, Mathias

    2009-01-01

    AIM: To evaluate the spatial distribution of cerebral abnormalities in cirrhotic subjects with and without hepatic encephalopathy (HE) found with magnetization transfer imaging (MTI). METHODS: Nineteen cirrhotic patients graded from neurologically normal to HE grade 2 and 18 healthy control subjects underwent magnetic resonance imaging. They gave institutional-review-board-approved written consent. Magnetization transfer ratio (MTR) maps were generated from MTI. We tested for significant differences compared to the control group using statistical non-parametric mapping (SnPM) for a voxel-based evaluation. RESULTS: The MTR of grey and white matter was lower in subjects with more severe HE. Changes were found in patients with cirrhosis without neurological deficits in the basal ganglia and bilateral white matter. The loss in magnetization transfer increased in severity and spatial extent in patients with overt HE. Patients with HE grade 2 showed an MTR decrease in white and grey matter: the maximum loss of magnetization transfer effect was located in the basal ganglia [SnPM (pseudo-)t = 17.98, P = 0.0001]. CONCLUSION: The distribution of MTR changes in HE points to an early involvement of basal ganglia and white matter in HE. PMID:19891014

  8. Observational cohort study of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS).

    PubMed

    Routhu, Michaela; Safka, Vaclav; Routhu, Sunil Kumar; Fejfar, Tomas; Jirkovsky, Vaclav; Krajina, Antonin; Cermakova, Eva; Hosak, Ladislav; Hulek, Petr

    2017-01-01

    Introduction and Aim: Hepatic encephalopathy (HE) is a common complication of transjugular intrahepatic portosystemic shunting (TIPS). It is associated with a reduced quality of life and poor prognosis. The aim of this study was to compare two groups of patients who did and did not develop overt HE after TIPS. We looked for differences between these groups before TIPS. A study of 895 patients was conducted based on a retrospective analysis of clinical data. Data was analyzed using Fisher's exact test, Chi-square, Mann Whitney test, unpaired t-test and logistic regression. After the initial analyses, we have looked at a regression models for the factors associated with development of HE after TIPS. 257 (37.9%) patients developed HE after TIPS. Patients' age, pre-TIPS portal venous pressure, serum creatinine, aspartate transaminase, albumin, presence of diabetes mellitus and etiology of portal hypertension were statistically significantly associated with the occurrence of HE after TIPS (p < 0.01). However, only the age, pre-TIPS portal venous pressure, serum creatinine, presence of diabetes mellitus and etiology of portal hypertension contributed to the regression model. Patients age, serum creatinine, presence of diabetes mellitus and portal vein pressure formed the model describing development of HE after TIPS for a subgroup of patients with refractory ascites. we have identified, using a substantial sample, several factors associated with the development of HE after TIPS. This could be helpful in further research.

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

    PubMed Central

    Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

    2015-01-01

    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. PMID:26557005

  10. Treatment of Acute Hepatic Encephalopathy: Comparing the Effects of Adding Rifaximin to Lactulose on Patient Outcomes.

    PubMed

    Courson, Alesa; Jones, G Morgan; Twilla, Jennifer D

    2016-06-01

    Rifaximin is approved for the reduction of hepatic encephalopathy (HE) recurrence in patients with chronic liver disease (CLD); however, few studies have evaluated the benefit of adding rifaximin to lactulose for treatment of acute HE. The aim of this study was to determine the impact of combination therapy with lactulose and rifaximin on hospital length of stay (LOS) and readmission rates. A retrospective study of patients admitted to an adult hospital within the Methodist LeBonheur Healthcare (MLH) System in Memphis, Tennessee, between 2007 and 2012 was conducted. Patients were identified via International Classification of Diseases, Ninth Revision (ICD-9) coding for liver cirrhosis. Of the 173 patients included, 87 (50%) received lactulose monotherapy and 62 (36%) combination therapy, while 24 (14%) underwent therapy escalation. Median LOS was 6 days in monotherapy group and 8 days in combination group (P = .9). At 180 days, patients receiving combination therapy had fewer readmissions for HE than those receiving monotherapy (2.4% vs 16.2%, P = .02). Addition of rifaximin to lactulose for treatment of acute HE did not reduce hospital LOS; however, it did result in lower readmission rates for HE at 180 days. © The Author(s) 2015.

  11. Development of a three-factor neuropsychological approach for detecting minimal hepatic encephalopathy.

    PubMed

    Stewart, Charmaine A; Enders, Felicity T B; Schneider, Niccole; Felmlee-Devine, Donna; Kamath, Patrick S; Smith, Glenn E

    2010-07-01

    Minimal hepatic encephalopathy (HE) has profoundly negative effects on daily functioning ad quality of life. However, standard psychometric procedures have not been widely incorporated into efforts to develop a neuropsychological battery for this condition. To establish the construct and diagnostic validity of a neuropsychological approach for the recognition of minimal HE in patients with cirrhosis. A comprehensive battery of neuropsychological tests was administered to cirrhotic patients with at most grade 1 HE, recruited from the liver transplant and advanced liver disease clinics. An inflammatory bowel disease comparison group was similarly evaluated, thus controlling for the secondary effects of chronic illness on cognition. Testing results for the cirrhosis group were subjected to principal component analysis to establish the relevant cognitive constructs and associated measures. Factor analysis was applied to the neuropsychological battery of 20 tests to determine the cognitive factors to be used. Age-adjusted standardized neuropsychological factor scores were then compared for the two groups. Factor analysis revealed that our battery of 20 tests was measuring three cognitive factors. Based on the pattern of factor loadings, we labeled these important cognitive factors: global cognitive function; psychomotor speed; and learning and memory. Logistic regression revealed that only impaired psychomotor speed distinguished cirrhotics with no more than grade 1 HE from medically ill controls. The cirrhosis group was characterized by a pattern of preserved global cognitive functioning, mild memory impairment, and moderate psychomotor speed impairment. This distinctive pattern of focal psychomotor speed deficits is suggestive of subcortical pathway involvement in minimal HE.

  12. Hypercalcemia due to Primary Hepatic Lymphoma

    PubMed Central

    Gagnier, Michael; Ryer, Elizabeth; Salhab, Mohammed; Rosmarin, Alan G.

    2016-01-01

    A 65-year-old female with a history of mixed connective tissue disease and pulmonary fibrosis on azathioprine, hydroxychloroquine, and prednisone (osteoporosis on teriparatide) presented with a 1-month history of hypercalcemia. After discontinuation of teriparatide, the patient's hypercalcemia persisted. Further evaluation revealed primary hepatic lymphoma as the source of her hypercalcemia. PMID:28116183

  13. Reversible Encephalopathy due to Valproic Acid Induced Hyperammonemia in a Patient with Bipolar I Disorder: A Cautionary Report

    PubMed Central

    Patel, Neel; Landry, Katherine B.; Fargason, Rachel E.; Birur, Badari

    2017-01-01

    Valproic acid (VPA) is an FDA-approved medication widely prescribed for seizures, migraines, and mixed or manic episodes in bipolar disorder. Hyperammonemia is a rare complication of VPA use, which can result in high morbidity and occasionally fatal encephalopathy. The scant literature on Valproate Induced Hyperammonemic Encephalopathy (VIHE) is characterized by acute onset of decreasing level of consciousness, drowsiness, lethargy which in rare instances can lead to seizures, stupor, coma, and persistent morbidity and cortical damage. Below we describe a case report of a patient with Bipolar I Disorder with no primary evidence of hepatic dysfunction that was initiated on VPA and olanzapine to address manic and psychotic symptoms. This patient subsequently developed elevated ammonia (NH4) levels that led to a reversible encephalopathy. This cautionary case report highlights the potential for a rare but serious complication from VPA, a medication increasingly used in both neurologic and neuropsychiatric settings. It is imperative that clinicians perform a thorough physical, neurological and diagnostic evaluation, routinely check NH4 and VPA levels when prescribing these agents and exercise caution when VPA is concomitantly prescribed with antipsychotics and cytochrome P450 inducing antiepileptic medications. PMID:28138203

  14. Treatment of encephalopathy during fulminant hepatic failure by haemodialysis with high permeability membrane.

    PubMed Central

    Denis, J; Opolon, P; Nusinovici, V; Granger, A; Darnis, F

    1978-01-01

    Forty-one patients with fulminant hepatic failure and coma underwent 180 periods of haemodialysis with polyacrylonitrile membrane (AN 69 HD). Hepatic failure was due to viral hepatitis in 40 and drugs in one. Total recovery of consciousness occurred in 17 patients (43.6%), and partial in seven (17.9%)--that is, an overall figure of 61.5%. Regain of consciousness was not related to liver regeneration as assessed by levels of factor V and hepatocyte volume fraction. At the time of the first haemodialysis, neurological status was significantly impaired in the patients who could not be aroused. Mean duration of coma grade IV averaged 6.1 +/- 4.3 days and mean duration of illness until death or decerebration 8.6 +/- 8.3 days. Of the 17 patients who totally regained consciousness, nine recovered and eight died (three from intercurrent complications and five with no liver regeneration). PMID:710967

  15. Ketogenic diet - A novel treatment for early epileptic encephalopathy due to PIGA deficiency.

    PubMed

    Joshi, Charuta; Kolbe, Diana L; Mansilla, M Adela; Mason, Sara; Smith, Richard J H; Campbell, Colleen A

    2016-10-01

    We describe the presentation and workup of two brothers with early-onset epileptic encephalopathy who became seizure-free on a ketogenic diet. Extensive testing culminated in whole exome sequencing, which led to the diagnosis of phosphatidyl inositol glycan biosynthesis class A protein (PIGA) deficiency. This familial case highlights the importance of genetic testing for early-onset epileptic encephalopathies and underscores the potential value of a ketogenic diet in the treatment of this condition.

  16. Main target of minimal hepatic encephalopathy: Morphophysiological, inflammatory and metabolic view.

    PubMed

    Arias, Natalia; Méndez, Marta; Gómez-Lázaro, Eneritz; Azpiroz, Arantxa; Arias, Jorge L

    2015-10-01

    Although often not considered clinically relevant and, therefore, not diagnosed or treated, minimal hepatic encephalopathy (MHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. To discover early impairments involved in MHE, we studied one of its precipitating factors, portal hypertension. Rats were trained on a stimulus-response task using the Morris water maze. Two groups of animals were used: a SHAM (sham-operated) group (n= 13) and a portal hypertension (PH) group (n= 13). The triple portal vein ligation method was used to create an animal model of an early developmental phase of HE. Brain metabolic activity was studied with cytochrome c-oxidase histochemistry (C.O.). Neuronal nuclear volume was assessed by nucleator probe; the number of glial fibrillary acidic protein-immunoreactive astrocytes (GFAP-IR) and proinflammatory mediators was measured. The results revealed that the PH group was not able to reach the behavioural criterion, in contrast to the SHAM group. The metabolic brain consumption revealed decreased C.O. activity in the ventral striatum. The PH group showed lower density of GFAP-IR and an increase in the tumour necrotic factor-α (TNF-α). The PH group showed decreased neuronal nuclear volume in the dorsal striatum. On the contrary, increased neuronal nuclear volume was found in the ventral striatum. For the first time, a relationship has been established between inflammation, astrocytic and neural damage, and brain metabolic impairment in a model of MHE. Disruption of the striatum and related structures was highlighted as the main target in early stages of HE. Finally, a simple task was presented to assess the subtle impairments found in the clinic, which could provide fresh insights into the development of new tools for the assessment of MHE.

  17. Natural history of covert hepatic encephalopathy: An observational study of 366 cirrhotic patients.

    PubMed

    Wang, An-Jiang; Peng, A-Ping; Li, Bi-Min; Gan, Na; Pei, Li; Zheng, Xue-Lian; Hong, Jun-Bo; Xiao, Hai-Ying; Zhong, Jia-Wei; Zhu, Xuan

    2017-09-14

    To explore the natural history of covert hepatic encephalopathy (CHE) in absence of medication intervention. Consecutive outpatient cirrhotic patients in a Chinese tertiary care hospital were enrolled and evaluated for CHE diagnosis. They were followed up for a mean of 11.2 ± 1.3 mo. Time to the first cirrhosis-related complications requiring hospitalization, including overt HE (OHE), resolution of CHE and death/transplantation, were compared between CHE and no-CHE patients. Predictors for complication(s) and death/transplantation were also analyzed. A total of 366 patients (age: 47.2 ± 8.6 years, male: 73.0%) were enrolled. CHE was identified in 131 patients (35.8%). CHE patients had higher rates of death and incidence of complications requiring hospitalization, including OHE, compared to unimpaired patients. Moreover, 17.6% of CHE patients developed OHE, 42.0% suffered persistent CHE, and 19.8% of CHE spontaneously resolved. In CHE patients, serum albumin < 30 g/L (HR = 5.22, P = 0.03) was the sole predictor for developing OHE, and blood creatinine > 133 μmol/L (HR = 4.75, P = 0.036) predicted mortality. Child-Pugh B/C (HR = 0.084, P < 0.001) and OHE history (HR = 0.15, P = 0.014) were predictors of spontaneous resolution of CHE. CHE exacerbates, persists or resolves without medication intervention in clinically stable cirrhosis. Triage of patients based on these predictors will allow for more cost-effect management of CHE.

  18. Factors associated with consciousness recovery time after liver transplantation in recipients with hepatic encephalopathy.

    PubMed

    Kim, K M; Kim, G S; Ko, J S; Gwak, M S; Lee, S-K; Son, M G

    2014-04-01

    Hepatic encephalopathy (HE) occurs as a result of liver failure and is often considered to be a clinical indication for liver transplantation (LT). An assessment of post-transplantation consciousness level in recipients with HE is crucial, because recovery of consciousness implies reestablishment of transplant liver function and lack of perioperative brain damage. The purpose of this study is to evaluate factors associated with consciousness recovery time after LT in recipients with HE. Out of 633 adult recipients who underwent LT, recipients who exhibited HE at the time of LT were analyzed retrospectively. The time between graft reperfusion and postoperative consciousness recovery was determined, and recipients were divided into 2 groups: group E with recovery of consciousness early (≤48 hours), and group L with recovery of consciousness late (>48 hours). Analyzed variables included recipient sex, age, graft type, Model for End-Stage Liver Disease score, HE history/duration/type/grade, and preoperative laboratory values, including blood ammonia concentration. HE was present at the time of LT in 69 (10.9%) of 633 recipients. Among the 69 recipients, 11 recipients who died or underwent reoperation before consciousness recovery were excluded, and 58 recipients (group E: n = 32; group L: n = 26) were enrolled into analysis. Multivariate analysis showed that HE duration >5 days (odds ratio [OR], 15.58; 95% confidence interval [CI], 1.35-179.56; P = .028) and HE type C (OR, 30.90; 95% CI, 1.67-573.48; P = .021) were the independent factors associated with late recovery from HE after LT. We suggest that recipients with long-duration or type C HE should be carefully managed during the post-transplantation period to prevent deterioration of HE. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Osmotic and oxidative/nitrosative stress in ammonia toxicity and hepatic encephalopathy.

    PubMed

    Görg, Boris; Schliess, Freimut; Häussinger, Dieter

    2013-08-15

    Hepatic encephalopathy (HE) is a neuropsychiatric complication of acute or chronic liver failure. Currently, HE in cirrhotic patients is seen as a clinical manifestation of a low grade cerebral edema which exacerbates in response to a variety of precipitating factors after an ammonia-induced exhaustion of the volume-regulatory capacity of the astrocyte. Astrocyte swelling triggers a complex signaling cascade which relies on NMDA receptor activation, elevation of intracellular Ca(2+) concentration and prostanoid-driven glutamate exocytosis, which result in increased formation of reactive nitrogen and oxygen species (RNOS) through activation of NADPH oxidase and nitric oxide synthase. Since RNOS in turn promote astrocyte swelling, a self-amplifying signaling loop between osmotic- and oxidative stress ensues, which triggers a variety of downstream consequences. These include protein tyrosine nitration (PTN), oxidation of RNA, mobilization of zinc, alterations in intra- and intercellular signaling and multiple effects on gene transcription. Whereas PTN can affect the function of a variety of proteins, such as glutamine synthetase, oxidized RNA may affect local protein synthesis at synapses, thereby potentially interfering with protein synthesis-dependent memory formation. PTN and RNA oxidation are also found in post mortem human cerebral cortex of cirrhotic patients with HE but not in those without HE, thereby confirming a role for oxidative stress in the pathophysiology of HE. Evidence derived from animal experiments and human post mortem brain tissue also indicates an up-regulation of microglia activation markers in the absence of increased synthesis of pro-inflammatory cytokines. However, the role of activated microglia in the pathophysiology of HE needs to be worked out in more detail. Most recent observations made in whole genome micro-array analyses of post mortem human brain tissue point to a hitherto unrecognized activation of multiple anti

  20. Probiotics can improve the clinical outcomes of hepatic encephalopathy: An update meta-analysis.

    PubMed

    Zhao, Li-Na; Yu, Tao; Lan, Shao-Yang; Hou, Jiang-Tao; Zhang, Zheng-Zheng; Wang, Shuang-Shuang; Liu, Feng-Bin

    2015-12-01

    Although the efficacy of probiotics has been extensively studied in hepatic encephalopathy (HE), the results remain controversial. The objective of this study is to identify and update the association between probiotics and HE. Up to December 2014, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant articles about probiotics and HE. Jadad score was used to evaluate the quality of studies. Pooled relative risk (RR), publication bias and heterogeneity were assessed. Nine studies met the inclusion criteria. Probiotics was associated with improvement of minimal HE and prophylaxis of overt HE [RR 1.52; 95% confidence intervals (95% CI) 1.00-2.33]. Studies with probiotics showed reduction of ammonia concentration [standard mean difference (SMD) -0.32, 95% CI -0.54 to -0.11]. Probiotics could reduce physical and psychosocial sickness impact profile (SIP) score with weight mean difference (WMD) -3.13 (95% CI -4.10 to -2.17) and WMD -3.50 (95% CI -4.91 to -2.08), respectively. Similar result was obtained with total SIP score (WMD -4.83; 95% CI -6.24 to -3.43). Reduction of severe adverse events, defined as minimal HE developing into overt HE, hospitalizations, infections or unrelated emergency room (ER) visits, was observed in HE with probiotics (RR 0.59; 95% CI 0.39-0.90). Our pooled results indicated that probiotics was associated with improvement of minimal HE, prophylaxis of overt HE, and reduction of SIP score and severe adverse events. Large well-designed randomised controlled trials are needed to confirm these results. Copyright © 2015. Published by Elsevier Masson SAS.

  1. Salivary Microbiota Reflects Changes in Gut Microbiota in Cirrhosis with Hepatic Encephalopathy

    PubMed Central

    Bajaj, Jasmohan S; Betrapally, Naga S; Hylemon, Phillip B; Heuman, Douglas M; Daita, Kalyani; White, Melanie B; Unser, Ariel; Thacker, Leroy R; Sanyal, Arun J; Kang, Dae Joong; Sikaroodi, Masoumeh; Gillevet, Patrick M

    2015-01-01

    Background Altered gut microbiome is associated with systemic inflammation and cirrhosis decompensation. However, the correlation of the oral microbiome with inflammation in cirrhosis is unclear. Aim Evaluate the oral microbiome in cirrhosis and compare with stool microbiome. Methods Cirrhotic outpatients [with/without hepatic encephalopathy (HE)] and controls underwent stool/saliva microbiome analysis (for composition and function) and also systemic inflammatory evaluation. 90-day liver-related hospitalizations were recorded. Salivary inflammation was studied using Th1 cytokines/secretory IgA, histatins and lysozyme in a subsequent group. Results 102 cirrhotics (43 prior-HE) and 32 age-matched controls were included. On PCO, stool and saliva microbiome clustered far apart showing differences between sites as a whole. Salivary microbiome With prior-HE, relative abundance of autochthonous families decreased while potentially pathogenic ones (Enterobacteriaceae, Enterococcaceae) increased in saliva. Endotoxin-related predicted functions were significantly higher in cirrhotic saliva. Stool microbiome Relative autochthonous taxa abundance reduced in prior-HE, along with increased Enterobacteriaceae and Enterococcaceae. Cirrhotic stool microbiota demonstrated a significantly higher correlation with systemic inflammation compared to saliva microbiota on correlation networks. Outcomes 38 patients were hospitalized within 90 days. Their salivary dysbiosis was significantly worse and predicted this outcome independent of cirrhosis severity. Salivary inflammation was studied in an additional 86 age-matched subjects (43 controls/43 cirrhotics); significantly higher IL-6/IL-1β, secretory IgA and lower lysozyme, and histatins 1 and 5 were found in cirrhotics compared to controls. Conclusions Dysbiosis, represented by reduction in autochthonous bacteria, is present in both saliva and stool in cirrhosis patients compared to controls. Cirrhotic patients have impaired salivary

  2. MINIMAL HEPATIC ENCEPHALOPATHY IS ASSOCIATED WITH MOTOR VEHICLE CRASHES: THE REALITY BEYOND THE DRIVING TEST

    PubMed Central

    Bajaj, Jasmohan S; Saeian, Kia; Schubert, Christine M; Hafeezullah, Muhammad; Franco, Jose; Varma, Rajiv R; Gibson, Douglas P; Hoffmann, Raymond G; Stravitz, R Todd; Heuman, Douglas M; Sterling, Richard K; Shiffman, Mitchell; Topaz, Allyne; Boyett, Sherry; Bell, Debulon; Sanyal, Arun J

    2009-01-01

    Patients with minimal hepatic encephalopathy (MHE) have impaired driving skills, but association of MHE with motor vehicle crashes is unclear. Standard psychometric tests (SPT) or inhibitory control test (ICT) can be used to diagnose MHE. The aim was to determine the association of MHE with crashes and traffic violations over the preceding year and on 1-year follow-up. Cirrhotics were diagnosed with MHE by ICT (MHEICT) and SPT (MHESPT). Self and department-of-transportation (DOT)-reports were used to determine crashes and violations over the preceding year. Agreement between self and DOT-reports was analyzed. Patients then underwent 1 year follow-up for crash/violation occurrence. Crashes in those with/without MHEICT and MHESPT were compared. 167 cirrhotics had DOT-reports, of which 120 also had self-reports. A significantly higher proportion of MHEICT cirrhotics experienced crashes in the preceding year compared to those without MHE by self-report (17% vs. 0%, p=0.0004) and DOT-reports (17% vs. 3%, p=0.004, relative risk:5.77). SPT did not differentiate between those with/without crashes. A significantly higher proportion of patients with crashes had MHEICT compared to MHESPT, both self-reported (100% vs. 50%, p=0.03) and DOT-reported (89% vs. 44%, p=0.01). There was excellent agreement between self and DOT-reports for crashes and violations (Kappa 0.90 and 0.80). 109 patients were followed prospectively. MHEICT patients had a significantly higher future crashes/violations compared to those without (22% vs. 7%, p=0.03) but MHESPT did not. MHEICT (Odds ratio:4.51) and prior year crash/violation (Odds ratio:2.96) were significantly associated with future crash/violation occurrence. PMID:19670416

  3. Retrospective Cross-Sectional Pilot Study of Rifaximin Dosing for the Prevention of Recurrent Hepatic Encephalopathy.

    PubMed

    Lyon, Kelsey C; Likar, Eric; Martello, Jay L; Regier, Michael

    2017-02-08

    Standard treatment for hepatic encephalopathy (HE) includes medications that reduce ammonia and bacterial translocation in the gut. Rifaximin can be used off-label for the reduction of overt HE. The study purpose was to determine efficacy of traditional rifaximin dosing (400 mg three times daily) compared to newer dosing (550 mg twice daily) via readmission rates for the prevention of recurrent HE. This was a retrospective, observational, cross-sectional pilot study conducted in a tertiary medical center. A total of 226 patients 18-89 years of age with documentation of HE via ICD-9 code who started rifaximin therapy while inpatient between April 2009 and June 2014 were evaluated. Data collected included rifaximin dosing, other medications used to treat HE, duration of therapy, time to readmission, and various laboratory values. There were no differences in readmission rates at 30 days, 60 days, or 6 months between treatment groups. Additionally, there was no difference in the odds of readmission between the treatment groups (OR = 0.77, 95% CI: (0.201, 4.365), p = 0.718). Patients had a low overall probability of readmission over the observational period. Based on average wholesale price (AWP) data, the cost for a 9 day supply of rifaximin for the 400 mg dosing regimen is $952.56 versus $605.16 for the 550 mg dosing regimen. The rifaximin 550 mg dosing strategy should be utilized in hospitalized patients for the prevention of recurrent HE as there was no difference in readmission rate or time to readmission between dosing groups. The 550 mg regimen had a lower acquisition cost for a 9-day duration of treatment in the studied institution.

  4. Clues for minimal hepatic encephalopathy in children with noncirrhotic portal hypertension.

    PubMed

    D'Antiga, Lorenzo; Dacchille, Patrizia; Boniver, Clementina; Poledri, Sara; Schiff, Sami; Zancan, Lucia; Amodio, Piero

    2014-12-01

    In children with noncirrhotic extrahepatic portal vein obstruction (EHPVO), minimal hepatic encephalopathy (MHE) was reported in a few series, but neither is it routinely investigated nor does consensus about its diagnosis exist. In this prospective observational study we aimed at detecting the prevalence of MHE in children with EHPVO and providing a practical diagnostic protocol. A consecutive sample of 13 noncirrhotic children (age range 4-18 years) with EHPVO underwent a screening for MHE based on level of fasting ammonia, quantified electroencephalogram (EEG) evaluation, and a wide battery of 26 psychometric tests exploring learning ability, abstract reasoning, phonemic and semantic fluency, selective attention, executive functions, short-term verbal and visual memory, long-term verbal memory, and visuopractic ability. Five children had at least 2 altered psychometric tests. Selective attention, executive function, and short-term visual memory were the domains more frequently altered, and 4 tests were enough to detect 80% of these children. Fasting ammonia plasma level was increased in 6 children. EEG mean dominant frequency adjusted for age was associated with serum ammonia concentration (β = -0.44 ± 0.19, P < 0.05). As a whole, children with EHPVO showed trends for lower α (median 41% vs 49%) and higher θ power than controls (median 41% vs 49% and 29% vs 20%, respectively). MHE affects approximately 50% of children with EHPVO and, therefore, is worthwhile to be investigated. Three simple tools, serum ammonia, quantified EEG, and neuropsychological examination, focused on selective attention, executive function, and short-term visual memory can be used effectively in the evaluation of MHE in this setting.

  5. Clinical and Pathophysiological Characteristics of Cirrhotic Patients with Grade 1 and Minimal Hepatic Encephalopathy

    PubMed Central

    Thomsen, Karen Louise; Macnaughtan, Jane; Tritto, Giovanni; Mookerjee, Rajeshwar P.; Jalan, Rajiv

    2016-01-01

    Background and Aims EASL/AASLD hepatic encephalopathy (HE) guidelines proposed the alternative use of the term ‘Covert HE’ combining minimal HE (mHE) and Grade 1 HE into a single entity. However, longitudinal data to indicate that these are indeed a single entity are lacking. The aims of this study were to determine whether the occurrence of complications of cirrhosis requiring hospital admission and mortality were similar in these sub-groups of patients. Methods Clinically-stable cirrhotic patients (n = 106) with no previous history of ‘Overt HE’ were included over a 2-year period and classified as having no HE (n = 23), mHE (n = 39) or Grade 1 HE (n = 44). Standard biochemistry, venous ammonia, bacterial DNA and neutrophil function were measured at inclusion and the patients were followed for a mean of 230±95 days. Results Patients with Grade 1 HE had significantly more complications requiring hospitalisation (infection 9/18/34%; HE 4/8/18%; other 13/10/11%; P = 0.02) and significantly greater mortality (4/5/20%; P = 0.04) compared to patients with no HE or mHE respectively. Patients with mHE and grade 1 HE had similar ammonia levels, but higher than the no HE group (P<0.001). MELD score was similar between groups but Grade 1 HE patients had increased frequency of bacterial translocation (P = 0.06) and neutrophil spontaneous respiratory burst (P = 0.02) compared to patients with mHE. Conclusions The results of this study show for the first time that ‘Covert HE’ is a heterogeneous entity with significantly greater hospitalisations and mortality in the Grade 1 HE patients compared with mHE. Further prospective longer-term studies are required before EASL/AASLD guidance is fully implemented. PMID:26745876

  6. Clearing the Confusion over Hepatic Encephalopathy After TIPS Creation: Incidence, Prognostic Factors, and Clinical Outcomes.

    PubMed

    Casadaban, Leigh C; Parvinian, Ahmad; Minocha, Jeet; Lakhoo, Janesh; Grant, Christopher W; Ray, Charles E; Knuttinen, M Grace; Bui, James T; Gaba, Ron C

    2015-04-01

    To assess the incidence, prognostic factors, and clinical outcomes of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation. In this single-institution retrospective study, 191 patients (m:f = 114:77, median age 54 years, median Model for End-Stage Liver Disease or MELD score 14) who underwent TIPS creation between 1999 and 2013 were studied. Medical record review was used to identify demographic characteristics, liver disease, procedure, and outcome data. Post-TIPS HE within 30 days was defined by new mental status changes and was graded according to the West Haven classification system. The influence of data parameters on HE occurrence and 90-day mortality was assessed using binary logistic regression. TIPS was successfully created with hemodynamic success in 99 % of cases. Median final PSG was 7 mmHg. HE incidence within 30 days was 42 % (81/191; 22 % de novo, 12 % stable, and 8 % worsening). Degrees of HE included grade 1 (46 %), grade 2 (29 %), grade 3 (18 %), and grade 4 (7 %). Medical therapy typically addressed HE, and shunt reduction was necessary in only three cases. MELD score (P = 0.020) and age (P = 0.009) were significantly associated with HE development on multivariate analysis. Occurrence of de novo HE post-TIPS did not associate with 90-day mortality (P = 0.400), in contrast to worsening HE (P < 0.001). The incidence of post-TIPS HE is non-trivial, but symptoms are typically mild and medically managed. HE rates are higher in older patients and those with worse liver function and should be contemplated when counseling on expected TIPS outcomes and post-procedure course.

  7. Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy.

    PubMed

    Bajaj, Jasmohan S; Heuman, Douglas M; Sanyal, Arun J; Hylemon, Phillip B; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Ridlon, Jason M; Daita, Kalyani; Monteith, Pamela; Noble, Nicole A; White, Melanie B; Fisher, Andmorgan; Sikaroodi, Masoumeh; Rangwala, Huzefa; Gillevet, Patrick M

    2013-01-01

    Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE. Twenty cirrhotics with MHE underwent cognitive testing, endotoxin analysis, urine/serum metabolomics (GC and LC-MS) and fecal microbiome assessment (multi-tagged pyrosequencing) at baseline and 8 weeks post-rifaximin 550 mg BID. Changes in cognition, endotoxin, serum/urine metabolites (and microbiome were analyzed using recommended systems biology techniques. Specifically, correlation networks between microbiota and metabolome were analyzed before and after rifaximin. There was a significant improvement in cognition(six of seven tests improved, p<0.01) and endotoxemia (0.55 to 0.48 Eu/ml, p = 0.02) after rifaximin. There was a significant increase in serum saturated (myristic, caprylic, palmitic, palmitoleic, oleic and eicosanoic) and unsaturated (linoleic, linolenic, gamma-linolenic and arachnidonic) fatty acids post-rifaximin. No significant microbial change apart from a modest decrease in Veillonellaceae and increase in Eubacteriaceae was observed. Rifaximin resulted in a significant reduction in network connectivity and clustering on the correlation networks. The networks centered on Enterobacteriaceae, Porphyromonadaceae and Bacteroidaceae indicated a shift from pathogenic to beneficial metabolite linkages and better cognition while those centered on autochthonous taxa remained similar

  8. Rifaximin Improves Driving Simulator Performance in a Randomized Trial of Patients with Minimal Hepatic Encephalopathy

    PubMed Central

    Bajaj, Jasmohan S; Heuman, Douglas M; Wade, James B; Gibson, Douglas P; Saeian, Kia; Wegelin, Jacob A; Hafeezullah, Muhammad; Bell, Debulon E; Sterling, Richard K; Stravitz, R. Todd; Fuchs, Michael; Luketic, Velimir; Sanyal, Arun J

    2010-01-01

    Background & Aims Patients with cirrhosis and minimal hepatic encephalopathy (MHE) have driving difficulties but the effects of therapy on driving performance have not been assessed. We evaluated whether performance on a driving simulator improves in patients with MHE following treatment with rifaximin. Methods Patients with MHE who were current drivers were randomly assigned to placebo or rifaximin groups and followed for 8 weeks (n=42). Patients underwent driving simulation (driving and navigation tasks) at the start (baseline) and end of the study. We evaluated patients’ cognitive abilities, quality-of-life (using the Sickness Impact Profile [SIP]), serum levels of ammonia, levels of inflammatory cytokines, and MELD scores. The primary outcome was percent who improved in driving performance, calculated by: total driving errors=speeding + illegal turns + collisions. Results Over the 8-week study period, patients given rifaximin made significantly greater improvements than those given placebo in avoiding total driving errors (76% vs. 31%, P=0.013), speeding (81% vs. 33%, P=0.005), and illegal turns (62% vs. 19%, P=0.01). Of patients given rifaximin, 91% improved their cognitive performance, compared with 61% of patients given placebo (P=0.01); they also made improvements in the psycho-social dimension of the SIP, compared with the placebo group (P=0.04). Adherence to the assigned drug averaged 92%. Neither group had changes in ammonia levels or MELD scores, but patients in the rifaximin group had increased levels of the anti-inflammatory cytokine interleukin-10. Conclusions Patients with MHE significantly improve driving simulator performance following treatment with rifaximin, compared with placebo. PMID:20849805

  9. Precipitants of hepatic encephalopathy induce rapid astrocyte swelling in an oxidative stress dependent manner.

    PubMed

    Lachmann, Vera; Görg, Boris; Bidmon, Hans Jürgen; Keitel, Verena; Häussinger, Dieter

    2013-08-15

    Hepatic encephalopathy (HE) is seen as the clinical manifestation of a low grade cerebral edema with formation of reactive oxygen and nitrogen species (RNOS). Astrocyte swelling is a crucial event and in cultured astrocytes HE-relevant factors almost instantaneously induce the formation of RNOS. However, short term effects of ammonia, inflammatory cytokines and RNOS on the volume of astrocytes and other brain cells as well as the underlying mechanisms are largely unknown, although a pathogenic link between RNOS formation and swelling in HE has been proposed. This issue was addressed in the present study by means of live-cell volume microscopy of brain cells in vitro. Ammonia, diazepam and pro-inflammatory cytokines such as tumor-necrosis factor-α (TNF-α), interferon-γ, interleukin-1β induced within 20min astrocyte swelling by about 25% accompanied by nuclear swelling of similar magnitude. Astrocyte swelling in response to NH4Cl, TNF-α or diazepam was abolished by the antioxidant epigallocatechin-gallate pointing to an involvement of RNOS. NH4Cl-induced astrocyte swelling was sensitive to inhibition of glutamine synthetase, NADPH oxidase or nitric oxide synthases. In line with a NMDA receptor-, prostanoid- and Ca(2+)-dependence of NH4Cl-induced RNOS formation, Ca(2+) chelation and inhibition of NMDA receptors or cyclooxygenase suppressed NH4Cl-induced astrocyte swelling, whereas the Ca(2+)-ionophore ionomycin, NMDA, glutamate and prostanoids induced rapid astrocyte swelling. NH4Cl also induced swelling of cultured microglia in a glutamine-synthesis dependent way, but had no effect on cell volume of cultured neurons. It is concluded that the pathways which trigger RNOS formation in astrocytes also trigger astrocyte swelling, whereas conversely and as shown previously hypoosmotic astrocyte swelling can induce RNOS formation. This establishes a complex interplay with an auto-amplificatory loop between RNOS formation and astrocyte swelling as an important event in

  10. Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy

    PubMed Central

    Rockey, Don C; Vierling, John M; Mantry, Parvez; Ghabril, Marwan; Brown, Robert S; Alexeeva, Olga; Zupanets, Igor A; Grinevich, Vladimir; Baranovsky, Andrey; Dudar, Larysa; Fadieienko, Galyna; Kharchenko, Nataliya; Klaryts'ka, Iryna; Morozov, Vyacheslav; Grewal, Priya; McCashland, Timothy; Reddy, K Gautham; Reddy, K Rajender; Syplyviy, Vasyl; Bass, Nathan M; Dickinson, Klara; Norris, Catherine; Coakley, Dion; Mokhtarani, Masoud; Scharschmidt, Bruce F

    2014-01-01

    Glycerol phenylbutyrate (GPB) lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion in the form of phenylacetyl glutamine, which is excreted in urine. This randomized, double-blind, placebo-controlled phase II trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more hepatic encephalopathy (HE) events in the previous 6 months. The primary endpoint was the proportion of patients with HE events. Other endpoints included the time to first event, total number of events, HE hospitalizations, symptomatic days, and safety. GPB, at 6 mL orally twice-daily, significantly reduced the proportion of patients who experienced an HE event (21% versus 36%; P = 0.02), time to first event (hazard ratio [HR] = 0.56; P < 0.05), as well as total events (35 versus 57; P = 0.04), and was associated with fewer HE hospitalizations (13 versus 25; P = 0.06). Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% versus 32%; P < 0.01), time to first event (HR = 0.29; P < 0.01), and total events (7 versus 31; P < 0.01). Plasma ammonia was significantly lower in patients on GPB and correlated with HE events when measured either at baseline or during the study. A similar proportion of patients in the GPB (79%) and placebo groups (76%) experienced adverse events. Conclusion: GPB reduced HE events as well as ammonia in patients with cirrhosis and HE and its safety profile was similar to placebo. The findings implicate ammonia in the pathogenesis of HE and suggest that GPB has therapeutic potential in this population. (Clinicaltrials.gov, NCT00999167). (Hepatology 2014;59:1073-1083) PMID:23847109

  11. Mitochondrial dysfunction as a mediator of hippocampal apoptosis in a model of hepatic encephalopathy.

    PubMed

    Bustamante, J; Lores-Arnaiz, S; Tallis, S; Roselló, D M; Lago, N; Lemberg, A; Boveris, A; Perazzo, J C

    2011-08-01

    In this study, we describe the presence of apoptosis, associated with a mitochondrial dysfunction in the hippocampus of animals in an experimental model defined as minimal hepatic encephalopathy (MHE). This experimental model was studied after 10 days of induced portal vein calibrated stricture, leading to portal hypertension and to a moderate hyperammonemia, without the presence of other evident central nervous system changes. The molecular mechanisms here proposed indicate the presence of apoptotic intrinsic pathways that point to hippocampal mitochondria as an important mediator of apoptosis in this experimental model. In this model of MHE, the presence of DNA fragmentation is documented by 2.3-times increased number of TUNEL-positive cells. These findings together with a higher ratio of the Bcl-2 family members Bax/Bcl-xL in the outer mitochondrial membrane of the MHE animals together with 11% of cytochrome c release indicate the presence of apoptosis in this experimental model. A detailed analysis of the hippocampal mitochondrial physiology was performed after mitochondrial isolation. The determination of the respiratory rate in the presence of malate plus glutamate and ADP showed a 45% decrease in respiratory control in MHE animals as compared with the sham group. A marked decrease of cytochrome oxidase (complex IV of the electron transport chain) was also observed, showing 46% less activity in hippocampal mitochondria from MHE animals. In addition, mitochondria from these animals showed less ability to maintain membrane potential (ΔΨ (m)) which was 13% lower than the sham group. Light scattering experiments showed that mitochondria from MHE animals were more sensitive to swell in the presence of increased calcium concentrations as compared with the sham group. In addition, in vitro studies performed in mitochondria from sham animals showed that mitochondrial permeability transition (MPT) could be a mitochondrial mediator of the apoptotic signaling in the

  12. A longitudinal systems biology analysis of lactulose withdrawal in hepatic encephalopathy.

    PubMed

    Bajaj, Jasmohan S; Gillevet, Patrick M; Patel, Neeral R; Ahluwalia, Vishwadeep; Ridlon, Jason M; Kettenmann, Birgit; Schubert, Christine M; Sikaroodi, Masoumeh; Heuman, Douglas M; Crossey, Mary M E; Bell, Debulon E; Hylemon, Philip B; Fatouros, Panos P; Taylor-Robinson, Simon D

    2012-06-01

    The pathogenesis of hepatic encephalopathy(HE) is unclear. However gut flora changes, inflammation and neuro-glial injury have been implicated. The aim was to evaluate factors that were associated with HE recurrence after lactulose withdrawal by analyzing the clinical phenotype, stool microbiome and systemic metabolome longitudinally. HE patients on a standard diet who were adherent on lactulose underwent characterization of their phenotype [cognition, inflammatory cytokines, in-vivo brain MR spectroscopy(MRS)], gut microbiome (stool Multitag Pyrosequencing) and metabolome (urine/serum ex-vivo MRS) analysis while on lactulose and on days 2, 14 and 30 post-withdrawal. Patients whose HE recurred post-withdrawal were compared to those without recurrence. We included seven men (53 ± 8 years) who were adherent on lactulose after a precipitated HE episode were included. HE recurred in three men 32 ± 6 days post-withdrawal. In-vivo brain MRS showed increased glutamine+glutamate (Glx) and decreased myoinositol with a reduction in stool Faecalibacterium spp., post-withdrawal. HE recurrence was predicted by poor baseline inhibitory control and block design performance and was associated with a shift of choline metabolism from tri-methylamine oxide formation towards the development of di-methylglycine, glycine and creatinine. This was accompanied by a mixed effect on the immune response (suppressed IL-10 and Th1/Th2/Th17 response). The correlation network showed Prevotella to be linked to improved cognition and decreased inflammation in patients without HE recurrence. We conclude that lactulose withdrawal results in worsening cognition, mixed inflammatory response effect, lowered stool Faecalibacterium and increase in MR-measurable brain Glx. HE recurrence post-lactulose withdrawal can be predicted by baseline cognitive performance and is accompanied by disrupted choline metabolism.

  13. Lactulose for minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction.

    PubMed

    Sharma, Praveen; Sharma, Barjesh Chander

    2012-01-01

    Minimal hepatic encephalopathy (MHE) is common in patients with extrahepatic portal vein obstruction (EHPVO). There is no study on the treatment of MHE using lactulose in patients with EHPVO. Consecutive EHPVO patients were assessed by psychometric (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests, CFF, and were reassessed after 3 months. Of the 70 patients screened, the prevalence of abnormal psychometric test was as follows: NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%), and LTT (44%). Thirty patients (43%) had two or more than two abnormal (>2 SD) psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. Arterial ammonia decreased after lactulose treatment compared to baseline (83.7±19.1 vs. 65.1±19.3 μmol/l, P=0.001). A total of 9 (75%) of 12 patients with large spontaneous shunt and 7 (39%) of 18 patients without spontaneous shunt improved with lactulose (P=0.07). CFF in patients with MHE (n=30) was significantly lower than those without MHE (n=40) (38.1±2.4 vs. 41.5±3.1 Hz, P=0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose needed reduction, 3 (10%) did not like its taste but have continued, and 2 (6%) developed abdominal bloating sensation. Lactulose is effective in the treatment of MHE in patients with EHPVO.

  14. Lactulose for Minimal Hepatic Encephalopathy in Patients with Extrahepatic Portal Vein Obstruction

    PubMed Central

    Sharma, Praveen; Sharma, Barjesh Chander

    2012-01-01

    Background/Aims: Minimal hepatic encephalopathy (MHE) is common in patients with extrahepatic portal vein obstruction (EHPVO). There is no study on the treatment of MHE using lactulose in patients with EHPVO. Patients and Methods: Consecutive EHPVO patients were assessed by psychometric (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests, CFF, and were reassessed after 3 months. Results: Of the 70 patients screened, the prevalence of abnormal psychometric test was as follows: NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%), and LTT (44%). Thirty patients (43%) had two or more than two abnormal (>2 SD) psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. Arterial ammonia decreased after lactulose treatment compared to baseline (83.7±19.1 vs. 65.1±19.3 μmol/l, P=0.001). A total of 9 (75%) of 12 patients with large spontaneous shunt and 7 (39%) of 18 patients without spontaneous shunt improved with lactulose (P=0.07). CFF in patients with MHE (n=30) was significantly lower than those without MHE (n=40) (38.1±2.4 vs. 41.5±3.1 Hz, P=0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose needed reduction, 3 (10%) did not like its taste but have continued, and 2 (6%) developed abdominal bloating sensation. Conclusions: Lactulose is effective in the treatment of MHE in patients with EHPVO. PMID:22626795

  15. Reduction of manganese intake improves neuropsychological manifestations in rats with minimal hepatic encephalopathy.

    PubMed

    Li, Ying; Mei, Li Hong; Qiang, Jin Wei; Ji, Chang Xue; Ju, Shuai

    2017-04-07

    Brain manganese deposition is led by liver dysfunction and/or portal-systemic shunting in minimal hepatic encephalopathy (MHE). Manganese is toxic and can cause cognitive disorders and extrapyramidal symptoms. Thus, reduction of manganese intake might be considered as a potential treatment strategy for MHE. In this study we aimed to investigate whether low- or no-manganese feed can improve the neuropsychological manifestations in MHE rats. Rats with MHE were established by partially ligating the portal vein and fed a manganese diet (MHE-M, 10mg per kg feed; n=24), a no-manganese diet (MHE-N; n=24) and a half-manganese diet (MHE-H; n=24) for 2, 4, 6 and 8weeks, with six rats in each subgroup. Morris water maze (MWM), open-field test and narrow beam test (NBT) were used to evaluate the cognitive and locomotor situations. Fasted blood ammonia, manganese content and glutamine synthetase (GS) activity in basal ganglia and cortex were measured. A significantly longer MWM escape latency, less locomotor activity, longer NBT latency and total time, higher blood ammonia, higher brain manganese content and GS activity were found in MHE-M rats. However, a significantly shorter MWM escape latency, increased locomotor activity, shorter NBT latency and total time, lower blood ammonia, lower brain manganese content and lower GS activity were found in MHE-N rats after no-manganese feed treatment. Partial improvements were found in MHE rats with half-manganese feed treatment. Reduction of manganese intake can significantly improve the cognitive and locomotor situations in MHE rats by reducing brain manganese content and regulating GS activity.

  16. 23.4% saline decreases brain tissue volume in severe hepatic encephalopathy as assessed by a quantitative computed tomography marker

    PubMed Central

    Liotta, Eric M; Lizza, Bryan D; Romanova, Anna L; Guth, James C; Berman, Michael D; Carroll, Timothy J; Francis, Brandon; Ganger, Daniel; Ladner, Daniela P; Maas, Matthew B; Naidech, Andrew M

    2016-01-01

    Objective Cerebral edema is common in severe hepatic encephalopathy and may be life-threatening. Bolus 23.4% hypertonic saline (HTS) improves surveillance neuromonitoring scores, although its mechanism of action is not clearly established. We investigated the hypothesis that bolus HTS decreases cerebral edema in severe hepatic encephalopathy utilizing a quantitative technique to measure brain and CSF volume changes. Design Retrospective analysis of serial computed tomography (CT) scans and clinical data for a case-control series was performed. Setting Intensive care units of a tertiary care hospital. Patients Patients with severe hepatic encephalopathy treated with 23.4% HTS and control patients who did not receive 23.4% HTS. Methods We used clinically obtained CT scans to measure volumes of the ventricles, intracranial CSF, and brain using a previously validated semi-automated technique (Analyze Direct; Overland Park, KS). Volumes before and after 23.4% HTS were compared with Wilcoxon signed-rank test. Associations between total CSF volume, ventricular volume, serum sodium, and Glasgow Coma Scale Scores were assessed using Spearman correlation. Results Eleven patients with 18 administrations of 23.4% HTS met inclusion criteria. Total CSF (median 47.6 [35.1–69.4] to 61.9 [47.7–87.0] mL, p<0.001) and ventricular volumes (median 8.0 [6.9–9.5] to 9.2 [7.8–11.9] mL, p=0.002) increased and Glasgow Coma Scale Scores improved (median 4 [3–6] to 7 [6–9], p=0.008) after 23.4% HTS. In contrast, total CSF and ventricular volumes decreased in untreated control patients. Serum sodium increase was associated with increase in total CSF volume (r=0.83, p<0.001) and change in total CSF volume was associated with ventricular volume change (r=0.86, p<0.001). Conclusions Total CSF and ventricular volumes increased after 23.4% HTS, consistent with a reduction in brain tissue volume. Total CSF and ventricular volume change may be useful quantitative measures to assess

  17. Comparison of probiotics and lactulose in the treatment of minimal hepatic encephalopathy in rats

    PubMed Central

    Jia, Lin; Zhang, Mei-Hua

    2005-01-01

    AIM: To compare the efficacy of probiotic preparation Golden Bifid and lactulose on rat experimental model of minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA). METHODS: MHE was induced by intraperitoneal injection of TAA (200 mg/kg) every 24 h for two consecutive days. Thirty-six male MHE models were then randomly divided into 3 groups: TAA group (n = 12) received tap water ad libitum only; lactulose group (n = 12) and probiotics group (n = 12) were gavaged, respectively with 8 mL/kg of lactulose and 1.5 g/kg of probiotic preparation Golden Bifid (highly concentrated combination of probiotic) dissolved in 2 mL of normal saline, once a day for 8 d (from the 5th d before the experiment to the 3rd d of the experiment). The latency of brainstem auditory evoked potentials (BAEP) I was used as an objective index of MHE. The incidence of MHE, the level of serum endotoxin, ammonia, liver function and histological grade of hepatic injury of rats were examined individually. RESULTS: There were no overt HE and rat deaths in 3 groups. The incidence of MHE, the levels of blood ammonia and endotoxin in TAA group, which were 83.3% (10/12), 168.33±15.44 mg/dL and 0.36±0.04 EU/mL, respectively, were significantly higher than those in lactulose group, which were 33.3% (4/12), 110.25±7.39 mg/dL and 0.19±0.02 EU/mL, and probiotics group, which were 33.3% (4/12), 108.58±10.24 mg/dL and 0.13±0.03 EU/mL respectively (P <0.001). It showed that either probiotics or lactulose could significantly lower the level of hyperammonemia and hyper-endotoxemia, lighten centrolobular necrotic areas as well as inflammatory reaction in the liver of rats, normalize the latency of BAEP, and decrease the incidence of MHE. However, no significant differences were observed between these two groups (P >0.05). CONCLUSION: Probiotic compound Golden Bifid is at least as useful as lactulose for the prevention and treatment of MHE. Probiotic therapy may be a safe, natural, well

  18. Assessment of health-related quality of life in Chinese patients with minimal hepatic encephalopathy.

    PubMed

    Bao, Zhi-Jun; Qiu, De-Kai; Ma, Xiong; Fan, Zhu-Ping; Zhang, Gan-Sheng; Huang, Yi-Qin; Yu, Xiao-Feng; Zeng, Min-De

    2007-06-07

    To evaluate the health-related quality of life (HRQOL) based on the Chinese version of SF-36 and Chronic Liver Disease Questionnaire (CLDQ) in subjects with chronic hepatitis B, liver cirrhosis, including patients with minimal hepatic encephalopathy (MHE). The SF-36 and CLDQ were administered to 160 healthy volunteers, 20 subjects with chronic hepatitis B and 106 patients with cirrhosis (33 cases exhibited MHE). HRQOL scores were compared among the different study groups. The SF-36 includes eight health concepts: physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotion, and mental health. Six domains of CLDQ were assessed: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry. Compared with healthy controls (96.9 +/- 4.5, 86.6 +/- 18.4, 90.1 +/- 12.5, 89.0 +/- 5.7, 87.5 +/- 4.3, 95.8 +/- 7.1, 88.5 +/- 15.9, 88.7 +/- 5.2 in SF-36 and 6.7 +/- 0.5, 6.1 +/- 0.6, 6.3 +/- 0.6, 6.5 +/- 0.5, 6.3 +/- 0.5, 6.8 +/- 0.4 in CLDQ), patients with chronic hepatitis B (86.3 +/- 11.0, 68.8 +/- 21.3, 78.9 +/- 14.4, 60.8 +/- 10.5, 70.8 +/- 8.6, 76.1 +/- 12.6, 50.0 +/- 22.9, 72.2 +/- 10.6 and 5.5 +/- 1.0, 4.5 +/- 1.0, 5.2 +/- 1.1, 5.3 +/- 0.9, 4.8 +/- 0.9, 4.9 +/- 1.0) and cirrhosis (52.8 +/- 17.4, 32.8 +/- 27.9, 61.6 +/- 18.9, 30.2 +/- 18.3, 47.9 +/- 20.1, 54.0 +/- 19.2, 28.9 +/- 26.1, 51.1 +/- 17.8 and 4.7 +/- 1.2, 3.9 +/- 1.2, 4.7 +/- 1.2, 4.7 +/- 1.3, 4.7 +/- 1.0, 4.4 +/- 1.1) had lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increasing severity of liver cirrhosis (based on the Child-Pugh score/presence or absence of MHE) was associated with a decrease in most components of SF-36 and CLDQ, especially SF-36. The Chinese version of SF-36 along with CLDQ is a valid and reliable method for testing MHE in patients with liver cirrhosis. Cirrhosis and MHE are associated with decreased HRQOL.

  19. Evidence of a vicious cycle in glutamine synthesis and breakdown in pathogenesis of hepatic encephalopathy-therapeutic perspectives.

    PubMed

    Holecek, Milan

    2014-03-01

    There is substantial clinical and experimental evidence that ammonia is a major factor in the pathogenesis of hepatic encephalopathy. In the article is demonstrated that in hepatocellular dysfunction, ammonia detoxification to glutamine (GLN) in skeletal muscle, brain, and likely the lungs, is activated. In addition to ammonia detoxification, enhanced GLN production may exert beneficial effects on the immune system and gut barrier function. However, enhanced GLN synthesis may exert adverse effects in the brain (swelling of astrocytes or altered neurotransmission) and stimulate catabolism of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in skeletal muscle. Furthermore, the majority of GLN produced is released to the blood and catabolized in enterocytes and the kidneys to ammonia, which due to liver injury escapes detoxification to urea and appears in peripheral blood. As only one molecule of ammonia is detoxified in GLN synthesis whereas two molecules may appear in GLN breakdown, these events can be seen as a vicious cycle in which enhanced ammonia concentration activates synthesis of GLN leading to its subsequent catabolism and increase in ammonia levels in the blood. These alterations may explain why therapies targeted to intestinal bacteria have only a limited effect on ammonia levels in patients with liver failure and indicate the needs of new therapeutic strategies focused on GLN metabolism. It is demonstrated that each of the various treatment options targeting only one the of the ammonia-lowering mechanisms that affect GLN metabolism, such as enhancing GLN synthesis (BCAA), suppressing ammonia production from GLN breakdown (glutaminase inhibitors and alpha-ketoglutarate), and promoting GLN elimination (phenylbutyrate) exerts substantial adverse effects that can be avoided if their combination is tailored to the specific needs of each patient.

  20. Roles of changes in active glutamine transport in brain edema development during hepatic encephalopathy: an emerging concept.

    PubMed

    Zielińska, Magdalena; Popek, Mariusz; Albrecht, Jan

    2014-01-01

    Excessive glutamine (Gln) synthesis in ammonia-overloaded astrocytes contributes to astrocytic swelling and brain edema, the major complication of hepatic encephalopathy (HE). Much of the newly formed Gln is believed to enter mitochondria, where it is recycled to ammonia, which causes mitochondrial dysfunction (a "Trojan horse" mode of action). A portion of Gln may increase osmotic pressure in astrocytes and the interstitial space, directly and independently contributing to brain tissue swelling. Here we discuss the possibility that altered functioning of Gln transport proteins located in the cellular or mitochondrial membranes, modulates the effects of increased Gln synthesis. Accumulation of excess Gln in mitochondria involves a carrier-mediated transport which is activated by ammonia. Studies on the expression of the cell membrane N-system transporters SN1 (SNAT3) and SN2 (SNAT5), which mediate Gln efflux from astrocytes rendered HE model-dependent effects. HE lowered the expression of SN1 at the RNA and protein level in the cerebral cortex (cc) in the thioacetamide (TAA) model of HE and the effect paralleled induction of cerebral cortical edema. Neither SN1 nor SN2 expression was affected by simple hyperammonemia, which produces no cc edema. TAA-induced HE is also associated with decreased expression of mRNA coding for the system A carriers SAT1 and SAT2, which stimulate Gln influx to neurons. Taken together, changes in the expression of Gln transporters during HE appear to favor retention of Gln in astrocytes and/or the interstitial space of the brain. HE may also affect arginine (Arg)/Gln exchange across the astrocytic cell membrane due to changes in the expression of the hybrid Arg/Gln transporter y(+)LAT2. Gln export from brain across the blood-brain barrier may be stimulated by HE via its increased exchange with peripheral tryptophan.

  1. Successful Colectomy for Hemorrhagic Colitis with Hemolytic Uremic Syndrome and Acute Encephalopathy due to Escherichia coli O157 Infection.

    PubMed

    Tominaga, Tetsuro; Oikawa, Masahiro; Takeshita, Hiroaki; Kunizaki, Masaki; Tou, Kazuo; Abo, Takafumi; Hidaka, Shigekazu; Nanashima, Atsushi; Sawai, Terumitsu; Nagayasu, Takeshi

    2014-01-01

    An 81-year-old man was admitted to a primary care hospital due to bloody diarrhea. The findings of abdominal computed tomography indicated ischemic colitis, so conservative therapy was started. On the 4th hospital day, the patient was transferred to our hospital because of renal dysfunction. Physical examination showed clouding of consciousness and abdominal distention. Abdominal computed tomography revealed massive ascites and thickening of the whole colonic wall. With a diagnosis of acute abdomen, an emergent laparotomy was performed. Extended right hemicolectomy was performed because of severe ischemic change and necrosis of the right side of the colon. In the stool culture before the operation, Escherichia coli O157 and verotoxin were found, so this case was diagnosed as hemorrhagic colitis with hemolytic uremic syndrome and acute encephalopathy due to Escherichia coli O157 infection. Postoperatively, the hemolytic uremic syndrome and acute encephalopathy were prolonged. However, with intensive care, the patient recovered and was discharged on the 33rd postoperative day.

  2. Liver Failure due to Acute Viral Hepatitis (A-E).

    PubMed

    Manka, Paul; Verheyen, Jens; Gerken, Guido; Canbay, Ali

    2016-04-01

    Viral hepatitis is still one of the key causes of acute liver failure (ALF) in the world. A selective literature search of the PubMed database was conducted, including current studies, reviews, meta-analyses, and guidelines. We obtained an overview of ALF due to viral hepatitis in terms of epidemiology, course, and treatment options. Most fulminant viral courses are reported after infection with hepatitis A, B, and B/D, but not with hepatitis C. Hepatitis E is also known to cause ALF but has not gained much attention in recent years. However, more and more autochthonous hepatitis E virus infections have been recently observed in Europe. Reactivation of hepatitis B virus (HBV) under immunosuppressive conditions, such as after intensive chemotherapy, is also an increasing problem. For most viral-induced cases of ALF, liver transplantation represented the only therapeutic option in the past. Today, immediate treatment of HBV-induced ALF with nucleotide or nucleoside analogs is well tolerated and beneficially affects the course of the disease. Although numbers in Western European countries are decreasing rapidly, reliable diagnostic screening for hepatitis A-E is necessary to identify the etiology and to determine those most at risk of developing ALF.

  3. Liver Failure due to Acute Viral Hepatitis (A-E)

    PubMed Central

    Manka, Paul; Verheyen, Jens; Gerken, Guido; Canbay, Ali

    2016-01-01

    Background Viral hepatitis is still one of the key causes of acute liver failure (ALF) in the world. Methods A selective literature search of the PubMed database was conducted, including current studies, reviews, meta-analyses, and guidelines. We obtained an overview of ALF due to viral hepatitis in terms of epidemiology, course, and treatment options. Results Most fulminant viral courses are reported after infection with hepatitis A, B, and B/D, but not with hepatitis C. Hepatitis E is also known to cause ALF but has not gained much attention in recent years. However, more and more autochthonous hepatitis E virus infections have been recently observed in Europe. Reactivation of hepatitis B virus (HBV) under immunosuppressive conditions, such as after intensive chemotherapy, is also an increasing problem. For most viral-induced cases of ALF, liver transplantation represented the only therapeutic option in the past. Today, immediate treatment of HBV-induced ALF with nucleotide or nucleoside analogs is well tolerated and beneficially affects the course of the disease. Conclusion Although numbers in Western European countries are decreasing rapidly, reliable diagnostic screening for hepatitis A-E is necessary to identify the etiology and to determine those most at risk of developing ALF. PMID:27413724

  4. Renal injury due to hepatic hydatid disease.

    PubMed

    Altay, Mustafa; Unverdi, Selman; Altay, Fatma Aybala; Ceri, Mevlüt; Akay, Hatice; Ozer, Hüseyin; Kiraç, Halil; Denizli, Nazim; Yilmaz, Bilal; Güvence, Necmettin; Duranay, Murat

    2010-08-01

    Many studies on renal hydatid disease have been reported in the literature, and the disease process appears to be well defined. However, renal injury without direct renal invasion remains poorly understood. The present study aims to define the frequency and the property of the renal involvement in hydatid disease. Eighty patients older than 18 years and diagnosed with liver echinococcosis were included in the study. The echinococcosis was diagnosed by the haemagglutination test and abdominal ultrasonography. Twenty-four-hour protein excretion was measured for patients who had elevated serum creatinine levels or whose urinalyses were positive for haematuria or proteinuria. Subsequently, renal biopsy was performed, and the specimens were examined by light microscopy and immunofluorescence staining. Haematuria was detected in 11 patients (13.75%), and proteinuria was detected in nine patients (11.25%). Percutaneous renal biopsy was applied to nine patients who gave signed consents to undergo the test. We detected four immunoglobulin A nephritis (together with tubulointerstitial nephritis in one patient), one membranoproliferative glomerulonephritis, one immunoglobulin M nephritis together with mesangiocapillary glomerulonephritis, one membranous glomerulonephritis, one amyloidosis and one tubulointerstitial nephritis. Renal hydatid cyst was detected only in four patients (5%). Hydatid disease, which affects the kidney, is not rare, and we suggest that urinalysis and, if indicated, renal biopsy should be performed for hepatic hydatid disease diagnosis.

  5. Hyperammonemic encephalopathy in a child with ornithine transcarbamylase deficiency due to a novel combined heterozygous mutations.

    PubMed

    Gao, Jiandi; Gao, Feng; Hong, Fang; Yu, Huimin; Jiang, Peifang

    2015-03-01

    Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder of metabolism of the urea cycle. It usually causes hyperammonemic encephalopathy in males during the neonatal to-infantile period, whereas female carriers present with variable manifestations depending on their pattern of random chromosome X inactivation in the liver. Early clinical manifestations of hyperammonemiaare nonspecific often leading to a delay in the diagnosis of OTCD.Unfortunately, delays in initiating treatment often lead to poor neurologic outcomes and overall survival. Presentation of hyperammonemic encephalopathy in children with OTCD is rare, and the mortality and morbidity rates are high. The diagnosis of OTCD and aggressive management of hyperammonemia were of paramount importance for appropriate treatment and successful recovery. Here, we report theclinical, biochemical, and molecular findings in a child with OTCD who presented with acute hyperammonemic encephalopathy.

  6. Hyperammonemic coma after craniotomy: Hepatic encephalopathy from upper gastrointestinal hemorrhage or valproate side effect?: Case report and literature review.

    PubMed

    Guo, Xiaopeng; Wei, Junji; Gao, Lu; Xing, Bing; Xu, Zhiqin

    2017-04-01

    Postoperative coma is not uncommon in patients after craniotomy. It generally presents as mental state changes and is usually caused by intracranial hematoma, brain edema, or swelling. Hyperammonemia can also result in postoperative coma; however, it is rarely recognized as a potential cause in coma patients. Hyperammonemic coma is determined through a complicated differential diagnosis, and although it can also be induced as a side effect of valproate (VPA), this cause is frequently unrecognized or confused with upper gastrointestinal hemorrhage (UGH)-induced hepatic encephalopathy. We herein present a case of valproate-induced hyperammonemic encephalopathy (VHE) to illustrate the rarity of such cases and emphasize the importance of correct diagnosis and proper treatment. A 61-year-old woman with meningioma was admitted into our hospital. Radical resection of the tumor was performed, and the patient recovered well as expected. After administration of valproate for 7 days, the patient was suddenly found in a deep coma, and her mental state deteriorated rapidly. The diagnoses of hepatic encephalopathy was confirmed. However, whether it origins from upper gastrointestinal hemorrhage or valproate side effect is uncertain. The patient's condition fluctuated without improvement during the subsequent 3 days under the treatment of reducing ammonia. With the discontinuation of valproate treatment, the patient regained complete consciousness within 48 hours, and her blood ammonia decreased to the normal range within 4 days. VHE is a rare but serious complication in patients after craniotomy and is diagnosed by mental state changes and elevated blood ammonia. Thus, the regular perioperative administration of VPA, which is frequently neglected as a cause of VHE, should be emphasized. In addition, excluding UGH prior to providing a diagnosis and immediately discontinuing VPA administration are recommended.

  7. Reversal learning impairment and alterations in the prefrontal cortex and the hippocampus in a model of portosystemic hepatic encephalopathy.

    PubMed

    Méndez, Marta; Méndez-López, Magdalena; López, Laudino; Begega, Azucena; Aller, María Angeles; Arias, Jaime; Arias, Jorge L

    2010-09-01

    Patients with liver dysfunction often suffer from hepatic encephalopathy (HE), a neurological complication that affects attention and memory. Various experimental animal models have been used to study HE, the most frequently used being the portocaval shunt (PCS). In order to determine brain substrates of cognitive impairment in this model, we assessed reversal learning and c-Fos expression in a rat model of portosystemic derivation. PCS and sham-operated rats (SHAM) were tested for reversal learning. Brains were processed for c-Fos immunocytochemistry. The total number of c-Fos positive nuclei was quantified in the prefrontal cortex and hippocampus. The spatial reference memory task showed no differences between groups in escape latencies. The no-platform probe test showed that both the PCS and the SHAM learned the location of platform. However, the PCS group perseverated in the old target during reversal. The PCS group presented less c-Fos- positive cells in prelimbic cortex, CA1 and dentate gyrus of the dorsal hippocampus than SHAM. Overall, these results suggest that this specific model of portosystemic hepatic encephalopathy produces reversal learning impairment that could be linked to dysfunction in neuronal activity in the prefrontal cortex and hippocampus.

  8. Review article: potential mechanisms of action of rifaximin in the management of hepatic encephalopathy and other complications of cirrhosis.

    PubMed

    Bajaj, J S

    2016-01-01

    Progressive gut milieu (microbiota) changes occur in patients with cirrhosis and are associated with complications [e.g. hepatic encephalopathy (HE)]. To examine the role of rifaximin in the management of HE and other complications of cirrhosis, including potential mechanisms of action and the need for future studies. A literature search was conducted using the keywords 'rifaximin', 'hepatic encephalopathy', 'ascites', 'variceal bleeding', 'peritonitis', 'portal hypertension', 'portopulmonary hypertension' and 'hepatorenal syndrome'. The nonsystemic agent rifaximin reduces the risk of HE recurrence and HE-related hospitalisations in cirrhosis. In patients with cirrhosis, rifaximin modulates the bacterial composition of the gut microbiota without a consistent effect on overall faecal microbiota composition. However, rifaximin can impact the function or activities of the gut microbiota. For example, rifaximin significantly increased serum levels of long-chain fatty acids and carbohydrate metabolism intermediates in patients with minimal HE. Rifaximin also favourably affects serum proinflammatory cytokine and faecal secondary bile acid levels. The gut microenvironment and associated microbiota play an important role in the pathogenesis of HE and other cirrhosis-related complications. Rifaximin's clinical activity may be attributed to effects on metabolic function of the gut microbiota, rather than a change in the relative bacterial abundance. © 2015 John Wiley & Sons Ltd.

  9. In patients with liver cirrhosis, proinflammatory interleukins correlate with health-related quality of life irrespective of minimal hepatic encephalopathy.

    PubMed

    Wunsch, Ewa; Koziarska, Dorota; Milkiewicz, Małgorzata; Naprawa, Grzegorz; Nowacki, Przemysław; Hartleb, Marek; Milkiewicz, Piotr

    2013-12-01

    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.

  10. [Disorders of mental function in patients with circulatory encephalopathy due to hypertension and atherosclerosis].

    PubMed

    Voloshin, P V; Kryzhenko, T V; Mishchenko, T S; Shestopalova, L F

    1989-07-01

    The authors described the dynamics of disorders of memory, attention and thinking in the course of treatment of patients with circulatory encephalopathy. It was shown that treatment resulted a prevailing regression of neurodynamic disorders of the higher psychic functions that was more productive at early stages of cerebrovascular insufficiency.

  11. Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy.

    PubMed

    Bajaj, Jasmohan S; Betrapally, Naga S; Hylemon, Phillip B; Heuman, Douglas M; Daita, Kalyani; White, Melanie B; Unser, Ariel; Thacker, Leroy R; Sanyal, Arun J; Kang, Dae Joong; Sikaroodi, Masoumeh; Gillevet, Patrick M

    2015-10-01

    Altered gut microbiome is associated with systemic inflammation and cirrhosis decompensation. However, the correlation of the oral microbiome with inflammation in cirrhosis is unclear. Our aim was to evaluate the oral microbiome in cirrhosis and compare with stool microbiome. Outpatients with cirrhosis (with/without hepatic encephalopathy [HE]) and controls underwent stool/saliva microbiome analysis (for composition and function) and also systemic inflammatory evaluation. Ninety-day liver-related hospitalizations were recorded. Salivary inflammation was studied using T helper 1 cytokines/secretory immunoglobulin A (IgA), histatins and lysozyme in a subsequent group. A total of 102 patients with cirrhosis (43 previous HE) and 32 age-matched controls were included. On principal component analysis (PCA), stool and saliva microbiome clustered far apart, showing differences between sites as a whole. In salivary microbiome, with previous HE, relative abundance of autochthonous families decreased whereas potentially pathogenic ones (Enterobacteriaceae, Enterococcaceae) increased in saliva. Endotoxin-related predicted functions were significantly higher in cirrhotic saliva. In stool microbiome, relative autochthonous taxa abundance reduced in previous HE, along with increased Enterobacteriaceae and Enterococcaceae. Cirrhotic stool microbiota demonstrated a significantly higher correlation with systemic inflammation, compared to saliva microbiota, on correlation networks. Thirty-eight patients were hospitalized within 90 days. Their salivary dysbiosis was significantly worse and predicted this outcome independent of cirrhosis severity. Salivary inflammation was studied in an additional 86 age-matched subjects (43 controls/43 patients with cirrhosis); significantly higher interleukin (IL)-6/IL-1β, secretory IgA, and lower lysozyme, and histatins 1 and 5 were found in patients with cirrhosis, compared to controls. Dysbiosis, represented by reduction in autochthonous bacteria

  12. Covert Hepatic Encephalopathy: Does the Mini-Mental State Examination Help?

    PubMed Central

    Corrias, Michela; Turco, Matteo; Rui, Michele D.; Gatta, Angelo; Angeli, Paolo; Merkel, Carlo; Amodio, Piero; Schiff, Sami; Montagnese, Sara

    2014-01-01

    Background/objectives The Mini-Mental State Examination (MMSE) has been utilized for the diagnosis of hepatic encephalopathy (HE). However, its threshold of abnormality has not been formally tested in patients with cirrhosis and its diagnostic/prognostic validity remains unknown. The aim of this study was to assess it in a large group of well-characterized outpatients with cirrhosis and no overt HE. Methods One-hundred-and-ninety-one patients underwent clinical assessment, MMSE, electroencephalography (EEG) and paper-and-pencil psychometry (PHES); 117 were followed up for 8 ± 5 months in relation to the occurrence of HE-related hospitalizations. Results On the day of study, 81 patients (42%) had abnormal EEG and 67 (35%) abnormal PHES; 103 (60%) had a history of HE. Average MMSE was 26.6 ± 3.5; 22 (19%) patients had abnormal MMSE based on the standard threshold of 24. Patients with abnormal EEG/PHES/history of HE had worse MMSE performance than their counterparts with normal tests/negative history (25.7 ± 4.2 vs. 27.3 ± 2.7; P < 0.01; 25.5 ± 3.2 vs. 27.9 ± 1.8, P < 0.0001; 26.3 ± 3.7 vs. 27.4 ± 2.6, P < 0.05, respectively). Based on the above results, MMSE thresholds of 26 and 27 were tested against abnormalities in clinical/EEG/PHES indices and significant associations were observed. An MMSE threshold of 26 was also a predictor of HE-related hospitalization (Cox–Mantel: P = 0.001); patients with MMSE <26 were significantly older than those with MMSE ≥26 but comparable in terms of liver dysfunction and ammonia levels. When MMSE items were considered separately, those which correlated most significantly with standard HE indices where spatial orientation and writing. Conclusion In conclusion, an MMSE <26 identifies older patients with cirrhosis who are more prone to manifest HE signs. PMID:25755545

  13. Modulation of the Metabiome by Rifaximin in Patients with Cirrhosis and Minimal Hepatic Encephalopathy

    PubMed Central

    Bajaj, Jasmohan S.; Heuman, Douglas M.; Sanyal, Arun J.; Hylemon, Phillip B.; Sterling, Richard K.; Stravitz, R. Todd; Fuchs, Michael; Ridlon, Jason M.; Daita, Kalyani; Monteith, Pamela; Noble, Nicole A.; White, Melanie B.; Fisher, Andmorgan; Sikaroodi, Masoumeh; Rangwala, Huzefa; Gillevet, Patrick M.

    2013-01-01

    Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE. Methods Twenty cirrhotics with MHE underwent cognitive testing, endotoxin analysis, urine/serum metabolomics (GC and LC-MS) and fecal microbiome assessment (multi-tagged pyrosequencing) at baseline and 8 weeks post-rifaximin 550 mg BID. Changes in cognition, endotoxin, serum/urine metabolites (and microbiome were analyzed using recommended systems biology techniques. Specifically, correlation networks between microbiota and metabolome were analyzed before and after rifaximin. Results There was a significant improvement in cognition(six of seven tests improved,p<0.01) and endotoxemia (0.55 to 0.48 Eu/ml, p = 0.02) after rifaximin. There was a significant increase in serum saturated (myristic, caprylic, palmitic, palmitoleic, oleic and eicosanoic) and unsaturated (linoleic, linolenic, gamma-linolenic and arachnidonic) fatty acids post-rifaximin. No significant microbial change apart from a modest decrease in Veillonellaceae and increase in Eubacteriaceae was observed. Rifaximin resulted in a significant reduction in network connectivity and clustering on the correlation networks. The networks centered on Enterobacteriaceae, Porphyromonadaceae and Bacteroidaceae indicated a shift from pathogenic to beneficial metabolite linkages and better cognition while those centered on autochthonous taxa

  14. Reducing Peripheral Inflammation with Infliximab Reduces Neuroinflammation and Improves Cognition in Rats with Hepatic Encephalopathy

    PubMed Central

    Dadsetan, Sherry; Balzano, Tiziano; Forteza, Jerónimo; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Hernandez-Rabaza, Vicente; Gil-Perotín, Sara; Cubas-Núñez, Laura; García-Verdugo, José-Manuel; Agusti, Ana; Llansola, Marta; Felipo, Vicente

    2016-01-01

    Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these data, we hypothesized that in rats with HE: (1) peripheral inflammation is a main contributor to neuroinflammation; (2) neuroinflammation in hippocampus impairs spatial learning by altering AMPA and/or NMDA receptors membrane expression; (3) reducing peripheral inflammation with infliximab (anti-TNF-a) would improve spatial learning; (4) this would be associated with reduced neuroinflammation and normalization of the membrane expression of glutamate receptors. The aims of this work were to assess these hypotheses. We analyzed in rats with portacaval shunt (PCS) and control rats, treated or not with infliximab: (a) peripheral inflammation by measuring prostaglandin E2, IL10, IL-17, and IL-6; (b) neuroinflammation in hippocampus by analyzing microglial activation and the content of TNF-a and IL-1b; (c) AMPA and NMDA receptors membrane expression in hippocampus; and (d) spatial learning in the Radial and Morris water mazes. We assessed the effects of treatment with infliximab on peripheral inflammation, on neuroinflammation and AMPA and NMDA receptors membrane expression in hippocampus and on spatial learning and memory. PCS rats show increased serum prostaglandin E2, IL-17, and IL-6 and reduced IL-10 levels, indicating increased peripheral inflammation. PCS rats also show microglial activation and increased nuclear NF-kB and expression of TNF-a and IL-1b in hippocampus. This was associated with altered AMPA and NMDA receptors membrane expression in hippocampus and impaired spatial learning and memory in the radial and Morris water maze. Treatment with infliximab reduces peripheral inflammation in PCS rats, normalizing prostaglandin E2, IL-17, IL-6, and

  15. Eight millimetre covered TIPS does not compromise shunt function but reduces hepatic encephalopathy in preventing variceal rebleeding.

    PubMed

    Wang, Qiuhe; Lv, Yong; Bai, Ming; Wang, Zhengyu; Liu, Haibo; He, Chuangye; Niu, Jing; Guo, Wengang; Luo, Bohan; Yin, Zhanxin; Bai, Wei; Chen, Hui; Wang, Enxin; Xia, Dongdong; Li, Xiaomei; Yuan, Jie; Han, Na; Cai, Hongwei; Li, Tao; Xie, Huahong; Xia, Jielai; Wang, Jianhong; Zhang, Hongbo; Wu, Kaichun; Fan, Daiming; Han, Guohong

    2017-09-01

    Currently, there are no recommendations in guidelines concerning the preferred diameter of stents for transjugular intrahepatic portosystemic shunt (TIPS), owing to the lack of adequate evidence. We therefore compared 8mm stents with 10mm stents, to evaluate whether 8mm stents would achieve similar shunt function, with less hepatic encephalopathy (HE) and better liver function. Cirrhotic patients were randomly assigned to receive TIPS with an 8mm or 10mm covered stent to prevent variceal rebleeding. The primary endpoint was shunt dysfunction. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival, their composite endpoint, overt HE (overall and spontaneous) and liver function were designated as the secondary endpoints. From July 2012 to January 2014, 64 and 63 patients were allocated to the 8mm and 10mm groups, respectively. During a median follow-up of 27months in both arms, dysfunction rates (16% vs. 16% at two years, p=0.62), two-year rebleeding (16% vs. 17%, p=0.65), OLT-free survival (95% vs. 86%, p=0.37), and the composite endpoint (p=0.62) were not statistically different between the groups. Despite a marginal decrease in overall overt HE, there were significantly fewer spontaneous overt HE incidents in the 8mm group within two years (27% vs. 43%, p=0.03), with a risk reduction of 47%. Notably, patients receiving 8mm stents also developed less hepatic impairment. TIPS with 8mm covered stents showed similar shunt function to TIPS with 10mm stents, but halved the risk of spontaneous overt HE and reduced hepatic impairment. Therefore, 8mm TIPS stents should be preferred for the prevention of variceal rebleeding in cirrhotic patients. Lay summary: The optimal diameter for transjugular intrahepatic portosystemic shunt (TIPS) remained uncertain. This study showed that TIPS with 8mm covered stents did not compromise shunt patency, or influence the efficacy of variceal rebleeding prevention compared to TIPS with 10mm stents, but reduced the risk

  16. Polyethylene Glycol and Lactulose versus Lactulose Alone in the Treatment of Hepatic Encephalopathy in Patients with Cirrhosis: A Non-Inferiority Randomized Controlled Trial

    PubMed Central

    Naderian, Mohammadreza; Akbari, Heshmatollah; Saeedi, Morteza; Sohrabpour, Amir Ali

    2017-01-01

    BACKGROUND In this clinical trial, polyethylene glycol (PEG) solution was compared with lactulose in the treatment of hepatic encephalopathy in patients with cirrhosis. METHODS This randomized controlled trial was performed on 40 patients in two groups. The patients in the lactulose group received either 20-30 grams of lactulose orally or by a nasogastric tube, or 200 grams of lactulose enema by a rectal tube. The patients in the PEG–lactulose group received the same amount of oral or rectal lactulose, plus 280 grams of PEG in 4 liters of water orally as a single dose in 30-120 minutes. Serial physical examinations, hepatic encephalopathy scoring algorithm (HESA), blood level of ammonia, and serum biochemical studies were used to evaluate the severity of hepatic encephalopathy. RESULTS In comparison with lactulose alone, PEG-lactulose could improve HESA score in 24 hours more effectively (p =0.04). Overall, PEG-lactulose regimen was associated with a decrease in length of hospital stay compared with lactulose treatment (p =0.03) but in subgroup analysis we found that PEG-lactulose regimen could only decrease the length of hospital stay in women significantly (p =0.01). CONCLUSION The use of PEG along with lactulose in comparison with lactulose alone is more effective in the treatment of hepatic encephalopathy in patients with cirrhosis and results in more rapid discharge from hospital. PMID:28316761

  17. Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial.

    PubMed

    Rahimi, Robert S; Singal, Amit G; Cuthbert, Jennifer A; Rockey, Don C

    2014-11-01

    Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades. To compare polyethylene glycol 3350-electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose. The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE. Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization. The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay. A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related. PEG led to more rapid HE resolution than standard therapy, suggesting that

  18. Obstructive jaundice due to radiation-induced hepatic duct stricture

    SciTech Connect

    Chandrasekhara, K.L.; Iyer, S.K.

    1984-10-01

    A case of obstructive jaundice due to radiation-induced hepatic duct stricture is reported. The patient received postoperative radiation for left adrenal carcinoma, seven years prior to this admission. The sequelae of hepatobiliary radiation and their management are discussed briefly.

  19. Albumin dialysis with molecular adsorbent recirculating system (MARS) for the treatment of hepatic encephalopathy in liver failure.

    PubMed

    Kobashi-Margáin, Ramón A; Gavilanes-Espinar, Juan G; Gutiérrez-Grobe, Ylse; Gutiérrez-Jiménez, Angel A; Chávez-Tapia, Norberto; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez Sánchez, Nahum

    2011-06-01

    Acute, acute-on-chronic and chronic liver diseases are major health issues worldwide, and most cases end with the need for liver transplantation. Up to 90% of the patients die waiting for an organ to be transplanted. Hepatic encephalopathy is a common neuropsychiatric syndrome that usually accompanies liver failure and impacts greatly on the quality of life. The molecular adsorbent recirculating system (MARS) is a recently developed form of artificial liver support that functions on a base of albumin dialysis. It facilitates the dialysis of albumin-bound and water-soluble toxins, allowing the patient to survive and even improving some clinical features of liver failure. The following manuscript reviews the technical features of MARS operation and some of the clinical trials that analyze the efficacy of the system in the therapy of liver diseases.

  20. A survey of patterns of practice and perception of minimal hepatic encephalopathy: a nationwide survey in India.

    PubMed

    Sharma, Praveen; Sharma, Barjesh C

    2014-01-01

    Minimal hepatic encephalopathy (MHE) leads to overt hepatic encephalopathy (HE) and impairs quality of life in patients with cirrhosis. Awareness of MHE and its management among physicians is not known. We conducted a survey among 673 physicians in India from academic and nonacademic institutes to understand the clinical burden, perceived severity, management patterns, and the barriers to providing care for this condition. Overall awareness of MHE in this survey was 75% (n = 504). Awareness of MHE was significantly higher in physicians working in teaching hospitals compared with those in nonteaching hospitals (79% vs 71%, P = 0.02). Similarly, gastroenterologists were more aware of MHE compared with nongastroenterologists (91% vs 66%, P = 0.001). Only 6.3% physicians screened all of their patients for MHE, whereas frequency of testing for MHE, either being nil or less than 10% of their patients was 64.7%. The most common test was paper and pencil test (86%) and the reason for nonscreening was nonavailability of time to test and also equipment or method (81%). A majority of physicians (88%) think that MHE affects quality of life. Physicians (61%) had an opinion that there should be some registry of MHE regardless of the cost and effort involved. Lactulose was used in 93% of cases, followed by rifaximin (82%) in the management of MHE. The overall awareness of MHE was 75% and it was significantly more in physicians of academic institutes. Despite awareness of its effect on quality of life, a majority of physicians did not test for MHE in their day-to-day practice.

  1. Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.

    PubMed

    Kang, S H; Lee, Y B; Lee, J-H; Nam, J Y; Chang, Y; Cho, H; Yoo, J-J; Cho, Y Y; Cho, E J; Yu, S J; Kim, M Y; Kim, Y J; Baik, S K; Yoon, J-H

    2017-08-24

    Rifaximin might decrease the risk of portal hypertension-related complications by controlling small intestinal bacterial overgrowth. To evaluate whether rifaximin was associated with the risk of death and cirrhotic complications. We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non-HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding. In the non-HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio [aHR], 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile-associated diarrhoea was not different between the groups (aHR, 0.028; P = .338). In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy. © 2017 John Wiley & Sons Ltd.

  2. Comparison of the effects of Hepatic-Aid and a Casein modular diet on encephalopathy, plasma amino acids, and nitrogen balance in cirrhotic patients.

    PubMed Central

    McGhee, A; Henderson, J M; Millikan, W J; Bleier, J C; Vogel, R; Kassouny, M; Rudman, D

    1983-01-01

    Hepatic-Aid is purported to ameliorate encephalopathy and promote positive nitrogen balance in protein-intolerant, cirrhotic patients by correcting their imbalanced amino acid profile. This study evaluated Hepatic-Acid by comparing a 50-g Casein diet with an identical diet with 20-g Casein/30-g Hepatic-Aid per day in a cross-over study. Four patients with biopsy-proven stable cirrhosis, encephalopathy, and under-nutrition were studied. Each study period included three days of equilibration and eight days of metabolic balance, with the following measured at baseline and on balance days 5 and 8: routine biochemistry, fasting ammonia, psychometric tests, EEG, and plasma amino acid profiles. There was no significant change in clinical status, routine biochemistry, fasting ammonia, psychometrics or EEG between the two study periods. Mean (+/-SD) nitrogen balance on the Casein diet at 1.5 +/- 1.5 g/day was not significantly different from that on the Hepatic-Aid diet at 1.5 +/- 1.2 g/day. Plasma amino acid profiles showed a significant fall (p less than 0.05) in fasting and intraprandial tyrosine (tyr) and phenylalanine (phe) on Hepatic-Aid, but only intraprandial leucine (leu), isoleucine (ile), and valine (val) were significantly increased (p less than 0.05) on Hepatic-Aid. The ratio leu + ile + val to tyr + phe was significantly increased (p less than 0.05) on Hepatic-Aid. It is concluded that Hepatic-Aid, as given in this study, maintains N balance similar to Casein, alters the amino acid profile towards normal, but does not ameliorate encephalopathy. PMID:6830337

  3. Wernicke's encephalopathy due to hyperemesis gravidarum: Clinical and magnetic resonance imaging characteristics.

    PubMed

    Ashraf, V V; Prijesh, J; Praveenkumar, R; Saifudheen, K

    2016-01-01

    Hyperemesis gravidarum-induced Wernicke's encephalopathy (WE) is an underestimated condition. The purpose of this study is to improve its awareness and early diagnosis. We report five cases of WE secondary to hyperemesis gravidarum. Classic triad of encephalopathy, ataxia, and ocular signs was seen in four out of five patients. Two unusual features noted in this series were papilledema in one patient and severe sensory-motor peripheral neuropathy in one patient. Magnetic resonance imaging (MRI) was abnormal in all the five patients, and high signal in medial thalamus and surrounding the aqueduct was the most common abnormality (5/5). Involvement of caudate nucleus was seen in two patients with severe psychosis, and two patients had bilateral cerebellar peduncle involvement. Median time delay between onset of neurological symptoms and diagnosis was 7 days. All patients improved with thiamine, but minor sequelae were seen in four patients at 12 months follow-up. One patient had a fetal demise. Hyperemesis gravidarum-induced WE is a common cause of maternal morbidity. Typical MRI findings of symmetric medial thalamic and periaqueductal signal changes may permit a specific diagnosis. A delay in diagnosis, therefore treatment, leads to worse prognosis.

  4. Wernicke's encephalopathy due to hyperemesis gravidarum: Clinical and magnetic resonance imaging characteristics

    PubMed Central

    Ashraf, VV; Prijesh, J; Praveenkumar, R; Saifudheen, K

    2016-01-01

    Hyperemesis gravidarum-induced Wernicke's encephalopathy (WE) is an underestimated condition. The purpose of this study is to improve its awareness and early diagnosis. We report five cases of WE secondary to hyperemesis gravidarum. Classic triad of encephalopathy, ataxia, and ocular signs was seen in four out of five patients. Two unusual features noted in this series were papilledema in one patient and severe sensory-motor peripheral neuropathy in one patient. Magnetic resonance imaging (MRI) was abnormal in all the five patients, and high signal in medial thalamus and surrounding the aqueduct was the most common abnormality (5/5). Involvement of caudate nucleus was seen in two patients with severe psychosis, and two patients had bilateral cerebellar peduncle involvement. Median time delay between onset of neurological symptoms and diagnosis was 7 days. All patients improved with thiamine, but minor sequelae were seen in four patients at 12 months follow-up. One patient had a fetal demise. Hyperemesis gravidarum-induced WE is a common cause of maternal morbidity. Typical MRI findings of symmetric medial thalamic and periaqueductal signal changes may permit a specific diagnosis. A delay in diagnosis, therefore treatment, leads to worse prognosis. PMID:27763485

  5. The Effect of Hepatic Encephalopathy, Hepatic Failure, and Portosystemic Shunt on Brain Volume of Cirrhotic Patients: A Voxel-Based Morphometry Study

    PubMed Central

    Zhong, Jianhui; Xu, Qiang; Zheng, Gang; Lu, Guang Ming

    2012-01-01

    Purpose To evaluate the effect of hepatic encephalopathy (HE), hepatic failure, and portosystemic shunt (PS) on the brain volume alteration in cirrhotic patients with MRI voxel-based morphometry (VBM). Methods Sixty cirrhotic patients (overt HE [OHE], n = 11; minimal HE [MHE], n = 19; non HE [nHE], n = 30) including 12 with pre- and post-transjugular intrahepatic portosystemic shunt (TIPS) scanning and 40 healthy controls were recruited. Neuropsychological and laboratory tests were performed in all patients. VBM was analyzed with ANOVA test among 4 groups, and t-tests for patients with different hepatic function, PS scores, and TIPS. Multiple linear regression was performed to investigate the effect of venous blood ammonia levels, Child-Pugh scores, and PS on the brain volumes in all patients. Results Cirrhotic patients exhibited decreased volume in many areas of gray matter (GM), increased volume in thalamus, and increased whiter matter (WM) volume, with the extent of affected brain volume greater in HE patients than nHE patients. Hepatic failure also resulted in decreased GM volume. Patients with high PS scores and TIPS displayed decreased GM and increased WM volume in some regions. Post-TIPS patients displayed increased GM volume in the thalamus. Multiple covariate regression results suggested that Child-Pugh score was a major factor to affect GM volume, while PS mainly affected WM volume. Conclusion Brain structure abnormalities appeared bilaterally symmetrical in cirrhotic patients, and the impairment was more extensive in HE patients than those without HE. Increased thalamus volume was not associated with HE progression. Hepatic failure and PS altered cirrhotic patients’ brain structure. PMID:22912746

  6. Successful Colectomy for Hemorrhagic Colitis with Hemolytic Uremic Syndrome and Acute Encephalopathy due to Escherichia coli O157 Infection

    PubMed Central

    Tominaga, Tetsuro; Oikawa, Masahiro; Takeshita, Hiroaki; Kunizaki, Masaki; Tou, Kazuo; Abo, Takafumi; Hidaka, Shigekazu; Nanashima, Atsushi; Sawai, Terumitsu; Nagayasu, Takeshi

    2014-01-01

    An 81-year-old man was admitted to a primary care hospital due to bloody diarrhea. The findings of abdominal computed tomography indicated ischemic colitis, so conservative therapy was started. On the 4th hospital day, the patient was transferred to our hospital because of renal dysfunction. Physical examination showed clouding of consciousness and abdominal distention. Abdominal computed tomography revealed massive ascites and thickening of the whole colonic wall. With a diagnosis of acute abdomen, an emergent laparotomy was performed. Extended right hemicolectomy was performed because of severe ischemic change and necrosis of the right side of the colon. In the stool culture before the operation, Escherichia coli O157 and verotoxin were found, so this case was diagnosed as hemorrhagic colitis with hemolytic uremic syndrome and acute encephalopathy due to Escherichia coli O157 infection. Postoperatively, the hemolytic uremic syndrome and acute encephalopathy were prolonged. However, with intensive care, the patient recovered and was discharged on the 33rd postoperative day. PMID:24803891

  7. Acute Acalculous Cholecystitis due to Viral Hepatitis A

    PubMed Central

    Kaya, Safak; Ay, Nurettin; Baysal, Birol; Bahadir, Mehmet Veysi; Onur, Arzu; Duymus, Recai

    2013-01-01

    Inflammation of the gallbladder without evidence of calculi is known as acute acalculous cholecystitis (AAC). AAC is frequently associated with gangrene, perforation, and empyema. Due to these associated complications, AAC can be associated with high morbidity and mortality. Medical or surgical treatments can be chosen according to the general condition of the patient, underlying disease and agent. Particularly in acute acalculous cholecystitis cases, early diagnosis and early medical treatment have a positive effect on the patient and protect them from surgical trauma. ACC is a rare complication of acute viral hepatitis A. Herein, we present an adult patient of acalculous cholecystitis due to acute viral hepatitis A. She responded to the conservative management. PMID:24106622

  8. Nitric oxide mediates effects of acute, not chronic, naltrexone on LPS-induced hepatic encephalopathy in cirrhotic rats.

    PubMed

    Ghiassy, Bentolhoda; Rahimi, Nastaran; Javadi-Paydar, Mehrak; Gharedaghi, Mohammad Hadi; Norouzi-Javidan, Abbas; Dehpour, Ahmad R

    2017-01-01

    Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE scoring, hepatic histology, and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute and chronic treatment with naltrexone in cirrhotic rats. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma NOx concentrations elevated in BDL rats, which were decreased after acute and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.

  9. Vitamin B1 in the treatment of Wernicke's encephalopathy due to hyperemesis after gastroplasty.

    PubMed

    Kühn, A L; Hertel, F; Boulanger, T; Diederich, N J

    2012-09-01

    Wernicke's encephalopathy (WE) is a severe brain disorder, first described in 1881, and is caused by a nutritional deficiency of thiamine (vitamin B1) found mostly in patients suffering from chronic alcoholism. In addition, WE can also complicate bariatric surgery if adequate vitamin supplementation is not insured. Without immediate treatment, the prognosis is poor and the mortality rate is high. Most patients present with atypical neurological symptoms, which hampers rapid diagnosis. We present a 40-year-old woman who underwent gastroplasty combined with gastric banding for severe obesity. She experienced repetitive vomiting and her diet was without vitamin supplementation. After three months she developed convergent strabismus, apathy and urinary incontinence, which was diagnosed as WE and treated as such. Six months later her recovery was incomplete, still showing gait difficulties and nystagmus. We aim to show that adequate vitamin supplementation in patients undergoing gastroplasty is necessary, especially considering the risk of permanent neurological deficits.

  10. Pre-transjugular intrahepatic portosystemic shunts (TIPS) prediction of post-TIPS overt hepatic encephalopathy: the critical flicker frequency is more accurate than psychometric tests.

    PubMed

    Berlioux, Pierre; Robic, Marie Angèle; Poirson, Hélèe; Métivier, Sophie; Otal, Philippe; Barret, Carine; Lopez, Frédéric; Péron, Jean Marie; Vinel, Jean Pierre; Bureau, Christophe

    2014-02-01

    Transjugular intrahepatic portosystemic shunts (TIPS) is a second-line treatment because of an increased incidence of overt hepatic encephalopathy (OHE). A better selection of patients to decrease this risk is needed and one promising approach could be the detection of minimal hepatic encephalopathy (MHE). The aim of the present prospective study was to determine whether pre-TIPS minimal hepatic encephalopathy was predictive of post-TIPS OHE and to compare Psychometric Hepatic Encephalopathy Sum Score(PHES) and the Critical Flicker Frequency (CFF) in this setting. From May 2008 to January 2011, 54 consecutive patients treated with TIPS were included. PHES and CFF were performed 1 to 7 days before and after TIPS at months 1, 3, 6, 9, and 12 or until liver transplantation or death. Before TIPS, MHE was detected by PHES and CFF in 33% and 39% of patients, respectively. After the TIPS procedure, 19 patients (35%) experienced a total of 64 episodes of OHE. OHE developed significantly more often inpatients for whom an indication for TIPS had been refractory ascites, with a history of OHE or of renal failure, lower hemoglobin level, or MHE as diagnosed by CFF. Post-TIPS OHE was more accurately predicted by CFF than by PHES. Absence of MHE at CFF had a good negative predictive value (91%) for the risk of post-TIPS recurrent OHE, defined as the occurrence of three or more episodes of OHE or of one episode which lasted more than 15 days. The absence of pre-TIPS history of OHE and a CFF value equal to or greater than 39 Hz had a 100% negative predictive value for post-TIPS recurrent OHE. Aiming to decrease the rate of post-TIPS HE, the use of CFF could help selecting patients for TIPS.

  11. 1H nuclear magnetic resonance spectroscopy-based metabonomic study in patients with cirrhosis and hepatic encephalopathy

    PubMed Central

    Dabos, Konstantinos John; Parkinson, John Andrew; Sadler, Ian Howard; Plevris, John Nicholas; Hayes, Peter Clive

    2015-01-01

    AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and encephalopathics. METHODS: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using 1H - nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients (FID’s) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three groups. RESULTS: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate (0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate (0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine (0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine (0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine (0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate (1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate (1.53 ± 0

  12. Acetylcholinesterase inhibitor treatment alleviated cognitive impairment caused by delayed encephalopathy due to carbon monoxide poisoning: Two case reports and a review of the literature.

    PubMed

    Yanagiha, Kumi; Ishii, Kazuhiro; Tamaoka, Akira

    2017-02-01

    Delayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective. We report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission. Although hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score ffom 9 to 28 points in Case 1 and an improved Hasegawa's dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning. Physicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning.

  13. GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy

    PubMed Central

    Johansson, Maja; Agusti, Ana; Llansola, Marta; Montoliu, Carmina; Strömberg, Jessica; Malinina, Evgenya; Ragagnin, Gianna; Doverskog, Magnus; Bäckström, Torbjörn

    2015-01-01

    Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABAA receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABAA receptors by neurosteroids such as allopregnanolone and 3α,21-dihydroxy-5α-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE. PMID:26138462

  14. GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy.

    PubMed

    Johansson, Maja; Agusti, Ana; Llansola, Marta; Montoliu, Carmina; Strömberg, Jessica; Malinina, Evgenya; Ragagnin, Gianna; Doverskog, Magnus; Bäckström, Torbjörn; Felipo, Vicente

    2015-09-01

    Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABAA receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABAA receptors by neurosteroids such as allopregnanolone and 3α,21-dihydroxy-5α-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE.

  15. [Toxic hepatitis due to the use of Ruta herbal medicine].

    PubMed

    Rabaev, Elena; Zeller, Lior; Biton, Amnon; Barski, Leonid

    2011-03-01

    In recent years, the use of herbal medicine by the general population is increasing. There are many known side effects resulting from these treatments. Despite the known side effects, physicians tend to neglect the anamnesis details regarding this issue and research budgets of these drugs are relatively low compared with conventional medicine, thus causing a lack of updated information. In this case report, we present an example of toxic hepatitis due to use of Ruta herbal medicine, an unfamiliar side effect of the common herbal medicine Ruta.

  16. A homosexual Japanese man with acute hepatitis due to hepatitis B virus genotype ae, concurrent with amebic colitis.

    PubMed

    Miyake, Yasuhiro; Iwasaki, Yoshiaki; Ishikawa, Shin; Tatsukawa, Masashi; Nawa, Toru; Kato, Jun; Takaki, Akinobu; Kobashi, Haruhiko; Sakaguchi, Kohsaku; Shiratori, Yasushi

    2007-02-01

    We report herein a case with acute hepatitis due to hepatitis B virus genotype Ae, concurrent with amebic colitis. A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice. Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen. The hepatitis B virus genotype was determined to be Ae. Furthermore, a mud-like stool with blood and mucous had sometimes been noted during the past 3 years, and amebic colitis was shown by colonofiberscopy during hospitalization. The patient was diagnosed with acute hepatitis B, concurrent with amebic colitis, and was successfully treated with lamivudine and metronidazole. In Japanese patients with acute hepatitis B virus genotype A infection, homosexual activity tends to be high. Furthermore, in Japanese homosexual men, amebiasis has been increasing. Thus, in Japanese patients with acute hepatitis B, a determination of genotype should be performed in order to investigate the route of transmission of hepatitis B virus, and a search for amebiasis should be performed in patients with acute hepatitis due to hepatitis B virus genotype A. Furthermore, education of homosexual men regarding hepatitis B virus, hepatitis B virus vaccination, and amebiasis is urgently required.

  17. Differential Impact of Hyponatremia and Hepatic Encephalopathy on Health-Related Quality of Life and Brain Metabolite Abnormalities in Cirrhosis

    PubMed Central

    Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, HoChong; Heuman, Douglas M; Bajaj, Jasmohan S

    2013-01-01

    Background Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality-of-life (HRQOL) and cognition in cirrhosis. Aim To study effect of hyponatremia on cognition, HRQOL and brain MR spectroscopy (MRS) independent of HE. Methods Four cirrhotic groups(no HE/HN, HE alone, HN alone (sodium<130mEq/L),HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psycho-social and physical sub-scores) and brain MRS (myoinositol(mI) and glutamate+glutamine(Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. Results 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN and 10 HN, MELD 12, 63% Hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN:3, HN:3.5, HE:6.5,HE+HN:7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP(p<0.0001, all comparisons). Brain MRS showed lowest Glx in HN and highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE,HE+HN and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psycho-social SIP scores. Conclusions Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. PMID:23665182

  18. Dopamine Burden Triggers Neurodegeneration via Production and Release of TNF-α from Astrocytes in Minimal Hepatic Encephalopathy.

    PubMed

    Ding, Saidan; Wang, Weikan; Wang, Xuebao; Liang, Yong; Liu, Leping; Ye, Yiru; Yang, Jianjing; Gao, Hongchang; Zhuge, Qichuan

    2016-10-01

    Dopamine (DA)-induced learning and memory impairment is well documented in minimal hepatic encephalopathy (MHE), but the contribution of DA to neurodegeneration and the involved underlying mechanisms are not fully understood. In this study, the effect of DA on neuronal apoptosis was initially detected. The results showed that MHE/DA (10 μg)-treated rats displayed neuronal apoptosis. However, we found that DA (10 μM) treatment did not induce evident apoptosis in primary cultured neurons (PCNs) but did produce TNF-α in primary cultured astrocytes (PCAs). Furthermore, co-cultures between PCAs and PCNs exposed to DA exhibited increased astrocytic TNF-α levels and neuronal apoptosis compared with co-cultures exposed to the vehicle, indicating the attribution of the neuronal apoptosis to astrocytic TNF-α. We also demonstrated that DA enhanced TNF-α production from astrocytes by activation of the TLR4/MyD88/NF-κB pathway, and secreted astrocytic TNF-α-potentiated neuronal apoptosis through inactivation of the PI3K/Akt/mTOR pathway. Overall, the findings from this study suggest that DA stimulates substantial production and secretion of astrocytic TNF-α, consequently and indirectly triggering progressive neurodegeneration, resulting in cognitive decline and memory loss in MHE.

  19. Nitrosative Stress-Induced Disruption of Baroreflex Neural Circuits in a Rat Model of Hepatic Encephalopathy: A DTI Study

    PubMed Central

    Tsai, Ching-Yi; Su, Chia-Hao; Chan, Julie Y. H.; Chan, Samuel H. H.

    2017-01-01

    The onset of hepatic encephalopathy (HE) in liver failure is associated with high mortality; the underlying mechanism is undecided. Here we report that in an acute liver failure model employing intraperitoneal administration of thioacetamide in Sprague-Dawley rats, diffusion weighted imaging revealed a progressive reduction in apparent diffusion coefficient in the brain stem. Diffusion tensor imaging further showed that the connectivity between nucleus tractus solitarii (NTS), the terminal site of baroreceptor afferents in brain stem and rostral ventrolateral medulla (RVLM), the origin of sympathetic innervation of blood vessels, was progressively disrupted until its disappearance, coincidental with the irreversible cessation of baroreflex-mediated sympathetic vasomotor tone signifying clinically the occurrence of brain death. In addition, superoxide, nitric oxide, peroxynitrite and ammonia levels in the NTS or RVLM were elevated, alongside swelling of astroctytes. A scavenger of peroxynitrite, but not an antioxidant, delivered intracisternally reversed all these events. We conclude that nitrosative stress because of augmented peroxynitrite related to accumulation of ammonia and swelling of astrocytes in the NTS or RVLM, leading to cytotoxic edema in the brain stem and severance of the NTS-RVLM connectivity, underpins the defunct baroreflex-mediated sympathetic vasomotor tone that accounts for the high mortality associated with HE. PMID:28079146

  20. The Mind and Liver Test: A New Approach to the Diagnosis of Minimal Hepatic Encephalopathy in Resource-Poor Settings

    PubMed Central

    Ali, Sajjadh M. J.; Seward, James; Venkataraman, Jayanthi

    2014-01-01

    Background and Aims. Minimal hepatic encephalopathy (MHE) is diagnosed using neuropsychometric tests or neurophysiological tests that are either inapplicable to illiterate patient population in resource-poor settings or require sophisticated and expensive equipment. The available tests assess discrete domains of mental impairment. Our aim was (a) to design a neuropsychometric test that measures all domains of mental impairment in MHE using one metric; (b) to evaluate its sensitivity, specificity, and reproducibility. Methods. The mind and liver test (MALT), a psychometric test assessing cognition, memory, and psychometric impairment, each on a scale of 20, was designed keeping in mind the requirements of a universal test. 40 cirrhotics and 36 controls were subjected to critical flicker frequency (CFF) and MALT in same sitting. ROC curve was plotted for MALT using CFF as gold standard. Bland-Altman plot was used to find test-retest agreement. Results. CFF values and MALT scores varied significantly between the cases and the controls (P < 0.05). MALT was 94% sensitive and 83% specific. Using ROC with CFF as gold standard, the AUC for diagnosis of MHE using MALT score was 0.89. Test-retest agreement was high (ICC = 0.89). Conclusion. In this pilot study, MALT proved to be highly sensitive, specific, inexpensive, and reproducible. PMID:25548682

  1. Hashimoto's encephalopathy.

    PubMed

    Chen, H C; Marsharani, U

    2000-05-01

    Hashimoto's encephalopathy is a subacute condition associated with autoimmune thyroiditis. Its presentation varies from focal neurologic deficits to global confusion. Unlike encephalopathy associated with hypothyroidism, Hashimoto's encephalopathy responds to steroid therapy and not thyroxine replacement.

  2. α-Ketoglutaramate: An overlooked metabolite of glutamine and a biomarker for hepatic encephalopathy and inborn errors of the urea cycle

    PubMed Central

    Cooper, Arthur J. L.; Kuhara, Tomiko

    2013-01-01

    Glutamine metabolism is generally regarded as proceeding via glutaminase-catalyzed hydrolysis to glutamate and ammonia, followed by conversion of glutamate to α-ketoglutarate catalyzed by glutamate dehydrogenase or by a glutamate-linked aminotransferase (transaminase). However, another pathway exists for the conversion of glutamine to α-ketoglutarate that is often overlooked, but is widely distributed in nature. This pathway, referred to as the glutaminase II pathway, consists of a glutamine transaminase coupled to ω-amidase. Transamination of glutamine results in formation of the corresponding α-keto acid, namely, α-ketoglutaramate (KGM). KGM is hydrolyzed by ω-amidase to α-ketoglutarate and ammonia. The net glutaminase II reaction is: L-Glutamine + α-keto acid + H2O → α-ketoglutarate + L-amino acid + ammonia. In this mini-review the biochemical importance of the glutaminase II pathway is summarized, with emphasis on the key component KGM. Forty years ago it was noted that the concentration of KGM is increased in the cerebrospinal fluid (CSF) of patients with hepatic encephalopathy (HE) and that the level of KGM in the CSF correlates well with the degree of encephalopathy. In more recent work, we have shown that KGM is markedly elevated in the urine of patients with inborn errors of the urea cycle. It is suggested that KGM may be a useful biomarker for many hyperammonemic diseases including hepatic encephalopathy, inborn errors of the urea cycle, citrin deficiency and lysinuric protein intolerance. PMID:24234505

  3. Intensive enteral feeding in advanced cirrhosis: reversal of malnutrition without precipitation of hepatic encephalopathy.

    PubMed

    Charlton, C P; Buchanan, E; Holden, C E; Preece, M A; Green, A; Booth, I W; Tarlow, M J

    1992-05-01

    Ten children with advanced cirrhosis and malnutrition (less than 90% weight for height) were fed for eight weeks with a nasogastric feed comprising whey protein (enriched with branched chain amino acids), fat as 34% medium chain and 66% long chain triglycerides, and glucose polymer. Six of the children were studied for an eight week control period before feeding. Weight, triceps skinfold thickness, mid-arm circumference, mid-arm muscle area, and fasting plasma ammonia and amino acid concentrations were measured before and after the control period and after the consequent feed period. Results showed that despite high energy and protein intakes the children remained malnourished over the control period. All anthropometric indices improved significantly during the feed period, and no child developed clinical encephalopathy. The feed period was associated with a small, and not clinically significant, increase in the plasma ammonia concentration, but no consistent trend in the plasma amino acid concentrations. Thus, in children with advanced hepatobiliary disease awaiting liver transplantation, enteral feeding improved nutritional status without adverse clinical or biochemical effects.

  4. Sterile hepatic abscess due to umbilical venous catheterization.

    PubMed

    Bayhan, Cihangül; Takcı, Şahin; Ciftçi, Türkmen Turan; Yurdakök, Murat

    2012-01-01

    A preterm infant with isolated fetal ascites was admitted to the neonatal intensive care unit due to the appearance of respiratory distress at birth. An umbilical venous catheter (UVC) was inserted. Abdominal ultrasonography (US) showed localization of the catheter tip in the portal vein. It was removed and replaced with a newer one. UVC tip location was confirmed with X-ray. His condition had been improving until he worsened suddenly on the sixth day of life. US showed hepatic abscess and intraabdominal hemorrhage derived from the malpositioned UVC. A drainage catheter was inserted to the abscess and paracentesis was applied. Practitioners should be cautious about any signs of UVC complications, even if true localization of the catheter tip is proven at the first application. Furthermore, if it is difficult to decide whether the catheter tip is in the right location, confirmation with US can be considered.

  5. Treatment of hepatic encephalopathy by retrograde transcaval coil embolization of an ileal vein-to-right gonadal vein portosystemic shunt

    SciTech Connect

    Nishie, Akihiro; Yoshimitsu, Kengo; Honda, Hiroshi; Kaneko, Kuniyuki; Kuroiwa, Toshiro; Fukuya, Tatsuro; Irie, Hiroyuki; Ninomiya, Toshiharu; Yoshimitsu, Takahiro; Hirakata, Hideki; Okuda, Seiya; Masuda, Kouji

    1997-05-15

    A 43-year-old non-cirrhotic woman suffered from encephalopathy caused by an extrahepatic portosystemic shunt between the ileal vein and inferior vena cava via the right gonadal vein. Percutaneous transcatheter embolization with stainless steel coils was performed by the retrograde systemic venous approach. Encephalopathy improved dramatically.

  6. Comparison of once a day rifaximin to twice a day dosage in the prevention of recurrence of hepatic encephalopathy in patients with chronic liver disease.

    PubMed

    Khokhar, Nasir; Qureshi, Muhammad Omar; Ahmad, Shafiq; Ahmad, Aiza; Khan, Hamza Hassan; Shafqat, Farzana; Salih, Muhammad

    2015-09-01

    Rifaximin has been used for prevention of recurrence of hepatic encephalopathy in twice a day dosage. The drug is expensive and lower dising may be possible. To determine the efficacy of rifaximin once a day dose in the prevention of hepatic encephalopathy (HE) in patients with liver cirrhosis as compared with twice daily dose of rifaximin. This Randomized control trial was carried out at the Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan from November 2012 to February 2014. Patients with known chronic liver disease with at least one episode of HE in the past were randomized to group A (rifaximin 550 mg OD) and group B (rifaximin 550 mg BD), after fulfilling the inclusion criteria. Each patient was followed for 6 months for any episode of HE. Patients in each group were identified for any breakthrough episode of encephalopathy during this period. Data were analyzed using SPSS version 16. Chi-squared test and t-test were applied where required to determine the significant difference between the two groups. There were a total of 306 patients: 128 patients in Group A while 178 in group B. Majority of patients (75.81%) had hepatitis C virus with mean age of 52.30 ± 9.92, MELD score 13.58 ± 8.3, and 55.22% were in Child-Pugh B. Eighty-one patients had an episode of HE during the study period. There were 27 patients in group A and 54 patients in group B with breakthrough episode of HE (P = 0.088). This study suggests that there is no significant difference in rifaximin once a day or twice daily dose in preventing HE. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  7. Liver Retransplantation for Hepatic Abscess Due to Hepatic Artery Thrombosis: A Case Report.

    PubMed

    Zanus, G; Romano, M; Finotti, M; Dalla Bona, E; Sgarabotto, D; Bassi, D; Mescoli, C; Angeli, P; Burra, P; Gringeri, E; Vitale, A; D'Amico, F; Feltracco, P; Cillo, U

    2017-05-01

    Hepatic artery thrombosis (HAT) is a well-recognized complication of liver transplantation (LT). HAT is an important risk factor for infectious, in particular hepatic abscess, which can cause graft loss and increasing morbidity and mortality. We present a case report of complicated LT in a 52-year-old Caucasian man with primary sclerosing cholangitis. In 2007 the patient was included on the waiting list in Padua for LT. In 2012 the patient underwent percutaneous transhepatic biliary drainage for bile duct stricture, complicated with acute pancreatitis. A diagnostic laparoscopy was performed with choledochotomy and Kehr's T tube drainage. On February 14, 2012, the patient underwent LT with arterial reconstruction and choledochojejunostomy. The postoperative course was complicated with HAT, multiple liver abscesses, and sepsis associated with bacteremia due to Enterococcus faecium despite massive intravenous antibiotic therapy and percutaneous drainages. On November 28, 2012, the patient underwent retransplantation. Four years after transplantation the patient is still in good general condition. Hepatic abscess formation secondary to HAT following LT is a major complication associated with important morbidity and mortality. In selected cases retransplantation should be considered as our case demonstrates. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Probiotic and lactulose: influence on gastrointestinal flora and pH value in minimal hepatic encephalopathy rats.

    PubMed

    Jiang, Shu-Man; Jia, Lin; Zhang, Mei-Hua

    2015-01-01

    The present study was conducted to investigate the influence on gastrointestinal flora, counts of bifidobacteria and Enterobacterceae in colon and pH value of gastrointestinal after lactulose and probiotic treatment on rat experimental minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA). MHE was induced by intraperitoneal injection of TAA. 48 male MHE models were then randomly divided into 4 groups: control group (n = 12); MHE group (n = 12) received tap water ad libitum only; lactulose group (n = 12) and probiotics group (n = 12) gavaged respectively with 8 ml/kg of lactulose and 1.5 g/kg of probiotic preparation Golden Bifid (highly concentrated combination probiotic) dissolved in 2 ml of normal saline, once a day for 8 days. The latency of Brainstem auditory evoked potentials (BAEP) I was used as objective index of MHE. Counts of gastrointestinal flora, counts of bifidobacteria and Enterobacterceae in colon and pH value of gastrointestinal were examined respectively. Compared to MHE group, counts of gastrointestinal flora has greatly decreased, ratio of bifidobacteria and Enterobacterceae has greatly increased, pH value of colon has greatly descended (P < 0.05). However, there was no significant difference between lactulose group and probiotic group (P > 0.05). Both lactulose and probiotics can effectively prevent bacteria translocation and overgrowth, intensify CR, improved value of B/E, and acidify intestinal, decreased pH value of colon. Probiotic compound Golden Bifid is as useful as lactulose for the prevention and treatment of MHE. Probiotic therapy may be a safe, natural, well-tolerated therapy appropriate for the long-term treatment of MHE.

  9. Probiotic and lactulose: influence on gastrointestinal flora and pH value in minimal hepatic encephalopathy rats

    PubMed Central

    Jiang, Shu-Man; Jia, Lin; Zhang, Mei-Hua

    2015-01-01

    Aim: The present study was conducted to investigate the influence on gastrointestinal flora, counts of bifidobacteria and Enterobacterceae in colon and pH value of gastrointestinal after lactulose and probiotic treatment on rat experimental minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA). Methods: MHE was induced by intraperitoneal injection of TAA. 48 male MHE models were then randomly divided into 4 groups: control group (n = 12); MHE group (n = 12) received tap water ad libitum only; lactulose group (n = 12) and probiotics group (n = 12) gavaged respectively with 8 ml/kg of lactulose and 1.5 g/kg of probiotic preparation Golden Bifid (highly concentrated combination probiotic) dissolved in 2 ml of normal saline, once a day for 8 days. The latency of Brainstem auditory evoked potentials (BAEP) I was used as objective index of MHE. Counts of gastrointestinal flora, counts of bifidobacteria and Enterobacterceae in colon and pH value of gastrointestinal were examined respectively. Results: Compared to MHE group, counts of gastrointestinal flora has greatly decreased, ratio of bifidobacteria and Enterobacterceae has greatly increased, pH value of colon has greatly descended (P < 0.05). However, there was no significant difference between lactulose group and probiotic group (P > 0.05). Both lactulose and probiotics can effectively prevent bacteria translocation and overgrowth, intensify CR, improved value of B/E, and acidify intestinal, decreased pH value of colon. Conclusion: Probiotic compound Golden Bifid is as useful as lactulose for the prevention and treatment of MHE. Probiotic therapy may be a safe, natural, well-tolerated therapy appropriate for the long-term treatment of MHE. PMID:26309689

  10. Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy.

    PubMed

    Laleman, Wim; Simon-Talero, Macarena; Maleux, Geert; Perez, Mercedes; Ameloot, Koen; Soriano, German; Villalba, Jordi; Garcia-Pagan, Juan-Carlos; Barrufet, Marta; Jalan, Rajiv; Brookes, Jocelyn; Thalassinos, Evangelos; Burroughs, Andrew K; Cordoba, Juan; Nevens, Frederik

    2013-06-01

    Refractory hepatic encephalopathy (HE) remains a major cause of morbidity in cirrhosis patients. Large spontaneous portosystemic shunts (SPSSs) have been previously suggested to sustain HE in these patients. We aimed to retrospectively assess the efficacy and safety of patients treated with embolization of large SPSSs for the treatment of chronic therapy-refractory HE in a European multicentric working group and to identify patients who may benefit from this procedure. Between July 1998 and January 2012, 37 patients (Child A6-C13, MELD [Model of Endstage Liver Disease] 5-28) with refractory HE were diagnosed with single large SPSSs that were considered eligible for embolization. On a short-term basis (i.e., within 100 days after embolization), 22 out of 37 patients (59.4%) were free of HE (P < 0.001 versus before embolization) of which 18 (48.6% of patients overall) remained HE-free over a mean follow-up period of 697 ± 157 days (P < 0.001 versus before embolization). Overall, we noted improved autonomy, decreased number of hospitalizations, and severity of the worst HE episode after embolization in three-quarters of the patients. Logistic regression identified the MELD score as strongest positive predictive factor of HE recurrence with a cutoff of 11 for patient selection. As to safety, we noted one major nonlethal procedure-related complication. There was no significant increase in de novo development or aggravation of preexisting varices, portal hypertensive gastropathy, or ascites. This multicenter European cohort study demonstrated a role for large SPSSs in chronic protracted or recurrent HE and substantiated the effectiveness and safety of embolization of these shunts, provided there is sufficient functional liver reserve. Copyright © 2013 American Association for the Study of Liver Diseases.

  11. Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis.

    PubMed

    Kawaguchi, Takumi; Taniguchi, Eitaro; Sata, Michio

    2013-10-01

    Branched-chain amino acids (BCAAs) constituting of valine, leucine, and isoleucine act as both substrates of proteins and as key regulators for various nutrient metabolisms. Patients with liver cirrhosis frequently lack sufficient BCAAs and therefore suffer from various metabolic disorders. Hepatic encephalopathy (HE) is a severe metabolic disorder with neurologic manifestations such as flapping tremors and coma in patients with liver cirrhosis. In addition, a mild form of HE known as minimal HE (MHE) is an important social issue because it occurs in up to 80% of patients with chronic liver disease and affects prognosis and activities of daily living, possibly resulting in falls and motor vehicle accidents. Although HE/MHE can be caused by various pathological conditions, including in an accumulation of mercaptans, short-chain fatty acids, and alterations in the gut flora, hyperammonemia has also been implicated in an important pathogenesis of HE/MHE. Besides urea cycle of liver, ammonia can be detoxified in the skeletal muscles by the amidation process for glutamine synthesis using BCAAs. Thus, BCAA supplementation may enhance detoxification of ammonia in skeletal muscle and may be a possible therapeutic strategy for HE/MHE. In this review, we summarize the clinical impacts of BCAA supplementation on HE/MHE and discuss possible mechanisms for a BCAA-induced improvement of HE/MHE. Furthermore, we present some modifications of oral BCAA therapy for improvement of efficacy in HE treatment. We also briefly describe pleiotropic benefits of BCAAs on life-threatening events and overall prognosis in patients with liver cirrhosis.

  12. The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand

    SciTech Connect

    Basile, A.S.; Ostrowski, N.L.; Gammal, S.H.; Jones, E.A.; Skolnick, P. )

    1990-02-01

    Autoradiographic analysis was used to examine radioligand binding to benzodiazepine (BZ) and GABAA receptors in the brains of rabbits with hepatic encephalopathy (HE). Thin sections of whole brain from normal rabbits and rabbits with HE were mounted on slides and subdivided into two groups. One group was washed before incubation with radioligand, while the second group was not prewashed. (3H)Flunitrazepam binding to BZ receptors was decreased by 22% to 42% (p less than 0.05) in the cerebral cortex, superior and inferior colliculi, and cerebellum of unwashed sections from rabbits with HE compared to all other groups. The binding of (3H)Ro 15-1788 to unwashed sections from rabbits with HE was reduced by a similar degree (18% to 37%, p less than 0.05) in the cerebral cortex, hippocampus, superior colliculus, and cerebellar cortex. Incubation of sections with the GABA-mimetic muscimol and NaCl produced an additional decrease in (3H)flunitrazepam binding to the cortex and hippocampus (25% to 31%, p less than 0.05) in unwashed HE rabbit brain, but increased radioligand binding (27% to 71%, p less than 0.05) to several regions in control rabbits. No changes in radioligand binding to either GABAA or peripheral benzodiazepine receptors was observed between HE and control rabbit sections. These findings are consistent with previous electrophysiologic and neurochemical observations indicating no significant changes in either the function or density of GABAA or BZ receptors in this model of HE. Further, they indicate that a reversible BZ receptor ligand with agonist properties is present in the brain in HE. This substance may contribute to the enhancement of GABAergic tone observed in this syndrome.

  13. Validation of a Paper and Pencil Test Battery for the Diagnosis of Minimal Hepatic Encephalopathy in Korea.

    PubMed

    Jeong, Jae Yoon; Jun, Dae Won; Bai, Daiseg; Kim, Ji Yean; Sohn, Joo Hyun; Ahn, Sang Bong; Kim, Sang Gyune; Kim, Tae Yeob; Kim, Hyoung Su; Jeong, Soung Won; Cho, Yong Kyun; Song, Do Seon; Kim, Hee Yeon; Jung, Young Kul; Yoon, Eileen L

    2017-09-01

    The aim of this study was to validate a new paper and pencil test battery to diagnose minimal hepatic encephalopathy (MHE) in Korea. A new paper and pencil test battery was composed of number connection test-A (NCT-A), number connection test-B (NCT-B), digit span test (DST), and symbol digit modality test (SDMT). The norm of the new test was based on 315 healthy individuals between the ages of 20 and 70 years old. Another 63 healthy subjects (n = 31) and cirrhosis patients (n = 32) were included as a validation cohort. All participants completed the new paper and pencil test, a critical flicker frequency (CFF) test and computerized cognitive function test (visual continuous performance test [CPT]). The scores on the NCT-A and NCT-B increased but those of DST and SDMT decreased according to age. Twelve of the cirrhotic patients (37.5%) were diagnosed with MHE based on the new paper and pencil test battery. The total score of the paper and pencil test battery showed good positive correlation with the CFF (r = 0.551, P < 0.001) and computerized cognitive function test. Also, this score was lower in patients with MHE compared to those without MHE (P < 0.001). Scores on the CFF (32.0 vs. 28.7 Hz, P = 0.028) and the computer base cognitive test decreased significantly in patients with MHE compared to those without MHE. Test-retest reliability was comparable. In conclusion, the new paper and pencil test battery including NCT-A, NCT-B, DST, and SDMT showed good correlation with neuropsychological tests. This new paper and pencil test battery could help to discriminate patients with impaired cognitive function in cirrhosis (registered at Clinical Research Information Service [CRIS], https://cris.nih.go.kr/cris, KCT0000955). © 2017 The Korean Academy of Medical Sciences.

  14. Incidence of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS) according to its severity and temporal grading classification.

    PubMed

    Fonio, Paolo; Discalzi, Andrea; Calandri, Marco; Doriguzzi Breatta, Andrea; Bergamasco, Laura; Martini, Silvia; Ottobrelli, Antonio; Righi, Dorico; Gandini, Giovanni

    2017-05-16

    To evaluate hepatic encephalopathy (HE) incidence after transjugular intrahepatic portosystemic shunt (TIPS) and classify by gravity and frequency. This is a retrospective study of 75 patients with no previous episodes of HE who underwent TIPS between 2008 and 2014 with clinical follow-up after 6 and 12 months. Patient risk factors evaluated include age, INR (international normalized ratio), creatinine, bilirubin, and MELD score (Model for End-of-stage Liver Disease). HE was reported using two classifications: (1) gravity divided in moderate (West-Haven grades I-II) and severe (III-IV); (2) frequency divided in episodic and recurrent/persistent. Overall HE incidence was 36% at 6 months, with 12 month incidence significantly decreased to 27% (p = 0.02). 13/75 (17%) patients had one episode of moderate HE, while 3/75 (4%) patients had severe recurrent/persistent HE. Age was the only pre-TIPS risk predictor. Post-TIPS bilirubin and INR showed variations from basal values only in the presence of diagnosed HE. Bilirubin significantly increased (p = 0.03) in correlation to HE severity, whereas INR changes correlated with temporal frequency (p = 0.04). HE distribution classified for severity is similar at 6 and 12 months, whereas when classified for frequency shows significant differences (p = 0.04). A classification by gravity and frequency attests post-TIPS HE as a manageable risk. Monitoring of bilirubin and INR may help on clinical management risk stratification.

  15. Validation of a Paper and Pencil Test Battery for the Diagnosis of Minimal Hepatic Encephalopathy in Korea

    PubMed Central

    2017-01-01

    The aim of this study was to validate a new paper and pencil test battery to diagnose minimal hepatic encephalopathy (MHE) in Korea. A new paper and pencil test battery was composed of number connection test-A (NCT-A), number connection test-B (NCT-B), digit span test (DST), and symbol digit modality test (SDMT). The norm of the new test was based on 315 healthy individuals between the ages of 20 and 70 years old. Another 63 healthy subjects (n = 31) and cirrhosis patients (n = 32) were included as a validation cohort. All participants completed the new paper and pencil test, a critical flicker frequency (CFF) test and computerized cognitive function test (visual continuous performance test [CPT]). The scores on the NCT-A and NCT-B increased but those of DST and SDMT decreased according to age. Twelve of the cirrhotic patients (37.5%) were diagnosed with MHE based on the new paper and pencil test battery. The total score of the paper and pencil test battery showed good positive correlation with the CFF (r = 0.551, P < 0.001) and computerized cognitive function test. Also, this score was lower in patients with MHE compared to those without MHE (P < 0.001). Scores on the CFF (32.0 vs. 28.7 Hz, P = 0.028) and the computer base cognitive test decreased significantly in patients with MHE compared to those without MHE. Test-retest reliability was comparable. In conclusion, the new paper and pencil test battery including NCT-A, NCT-B, DST, and SDMT showed good correlation with neuropsychological tests. This new paper and pencil test battery could help to discriminate patients with impaired cognitive function in cirrhosis (registered at Clinical Research Information Service [CRIS], https://cris.nih.go.kr/cris, KCT0000955). PMID:28776344

  16. Vascular Plug-Assisted Retrograde Transvenous Obliteration for the Treatment of Gastric Varices and Hepatic Encephalopathy: A Prospective Multicenter Study.

    PubMed

    Gwon, Dong Il; Kim, Young Hwan; Ko, Gi-Young; Kim, Jong Woo; Ko, Heung Kyu; Kim, Jin Hyoung; Shin, Ji Hoon; Yoon, Hyun-Ki; Sung, Kyu-Bo

    2015-11-01

    To evaluate technical and clinical outcomes of vascular plug-assisted retrograde transvenous obliteration (PARTO) for the treatment of gastric varices (GVs) and hepatic encephalopathy (HE). From March 2012 to June 2014, 73 consecutive patients (47 men, 26 women; mean age, 59 y; range, 28-79 y) who had undergone PARTO were evaluated in a prospective multicenter study. Among 57 patients with GVs, 28 had GVs in danger of rupture, 23 had experienced recent bleeding, and 6 had active variceal bleeding. The 16 patients with HE had been treated unsuccessfully with medical therapies. Placement of the vascular plug and subsequent gelatin sponge embolization were technically successful in all 73 patients. There were no procedure-related complications. Follow-up CT obtained within 1 wk after PARTO showed complete thrombosis of GVs and portosystemic shunts in 72 of 73 patients (98.6%). Sixty patients who underwent follow-up longer than 3 mo showed complete obliteration of GVs and portosystemic shunts. There were no cases of variceal bleeding or HE at the end of follow-up (mean, 544 d). Improvement in Child-Pugh score was observed in 24 patients (40%) at 1-mo follow-up. Worsening of ascites and esophageal varices was observed in 14 (23.3%) and 16 (26.7%) patients at 3-mo follow-up. The present results of PARTO indicate that it can be rapidly performed with high technical success and durable clinical efficacy for the treatment of GVs and HE in the presence of a portosystemic shunt. Therefore, PARTO might be considered a first-line treatment in appropriate patients. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

  17. Glycosylation patterns and PHA-E-associated glycoprotein profiling associated with early hepatic encephalopathy in Chinese hepatocellular carcinoma patients

    PubMed Central

    Liu, Tian-Hua; Liu, Deng-He; Mo, Cui-Ju; Sun, Lu; Liu, Xiao-Xia; Li, Wei; Zhang, Shu; Liu, Yin-Kun; Guo, Kun

    2016-01-01

    Hepatic encephalopathy (HE) as a severe neuropsychiatric complication is commonly present in the end stage of Hepatocellular Carcinoma (HCC). However, widely accepted biomarkers for diagnosing early HE are still absent. Here, we screened glycosylation patterns of serum proteins from Chinese HCC patients with or without early HE by lectin microarray. Then, phaseolus vulgaris erythroagglutinin (PHA-E) as a lectin binding with bisecting GlcNAc structure which was significantly decreased in sera from Chinese HCC patients with early HE, was chosen to perform lectin affinity chromatography, following by in-gel digestion, Mass Spectrometry (MS) analysis and bioinformatics analysis. Here we found, 13 lectins showed statistically significant reduction suggesting GalNAc, terminal α-1,3 Man, bisecting GlcNAc, (GlcNAc)n, O-GlcNAc, Neu5Ac, tetra-antennary complex-type N-glycan and GalNAc α/β1-3/6 Gal were decreased in serum glycoproteins from Chinese HCC patients with early HE. Furthermore, a total of 141 PHA-E-associated glycoproteins were identified in MS, of which 12 serum glycoproteins only in Chinese HCC patients without early HE and 26 serum glycoproteins only in Chinese HCC patients with early HE. In addition, bioinformatics analysis revealed the PHA-E-associated serum glycoproteins only in Chinese HCC patients with early HE might be related to early HE occurrence through p38 MAPK signaling pathway and MAPK/ERK signaling pathway. Collectively, this was the first glycomics study of serum proteins in HCC patients with early HE and it could provide a database for discovering and developing serum biomarkers to identify and predict early HE in HCC patients. PMID:27830009

  18. Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy.

    PubMed

    Mullen, Kevin D; Sanyal, Arun J; Bass, Nathan M; Poordad, Fred F; Sheikh, Muhammad Y; Frederick, R Todd; Bortey, Enoch; Forbes, William P

    2014-08-01

    Rifaximin is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month, randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use. We conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, N = 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n = 140). In the all-rifaximin population, the median exposure to rifaximin was 427.0 days (range, 2-1427 d), with 510.5 person-years of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72). Long-term treatment (≥24 mo) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. Improvement of sleep architecture parameters in cirrhotic patients with recurrent hepatic encephalopathy with the use of rifaximin.

    PubMed

    Bruyneel, Marie; Sersté, Thomas; Libert, Walter; van den Broecke, Sandra; Ameye, Lieveke; Dachy, Bernard; Mulkay, Jean-Pierre; Moreno, Christophe; Gustot, Thierry

    2017-03-01

    Sleep disorders are frequently reported in patients with cirrhosis and hepatic encephalopathy (HE). This study assessed the effect of rifaximin on sleep architecture parameters in patients with recurrent HE. This sequential, prospective, and exploratory study involved all patients with cirrhosis and recurrent HE admitted between June 2014 and September 2015. HE was assessed according to the West-Haven Classification. Patients underwent 24-h polysomnography (PSG) and 7-day actigraphy. Rapid eye movement (REM) sleep was considered to be an indicator of good sleep quality. Patients completed questionnaires assessing the quality of sleep and sleepiness. After a 28-day course of rifaximin, the same assessment was repeated. Fifteen patients were included (nine men, mean age: 57±11 years). Child-Pugh scores ranged from B7 to C15. Before rifaximin, the mean HE score was 2.7±0.7. Data from PSG analysis indicated long total sleep time (TST): 571±288 min, and limited REM sleep: 2.5% TST (0-19). Seven-day actigraphy showed an impaired number of steps: 1690/24 h (176-6945). Questionnaires indicated that patients experienced impaired sleep quality and excessive daytime sleepiness. After rifaximin, HE scores decreased to 1.7±0.6 (P<0.001). REM sleep increased to 8.5% TST (0-25) (P=0.003). No changes were observed for TST, number of steps, and on questionnaires. Patients with recurrent HE suffer from poor sleep quality and excessive daytime sleepiness. On 24-h PSG, rifaximin improves objective sleep architecture parameters with no changes in the subjective quality of sleep and sleepiness.

  20. [A Case of Clinically Mild Encephalitis/encephalopathy with a Reversible Splenial Lesion due to Dengue Fever].

    PubMed

    Saito, Nobuo; Kitashouji, Emi; Kojiro, Maiko; Furumoto, Akitugu; Morimoto, Konosuke; Morita, Kouichi; Ariyoshi, Koya

    2015-07-01

    Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been recently proposed as a clinical-radiological syndrome. Several causes of MERS have been reported including infectious diseases. We present herein on a case of MERS induced by dengue fever in a Japanese traveler. A 48-year-old male returning from Thailand and Cambodia was admitted for an unknown fever. Following admission, the dengue virus was diagnosed with a positive RT-PCR result. On day 5 of the illness, regardless of reduced fever, weakness suddenly developed in both upper limbs. A cerebral MRI showed hyperintensities in the splenium of the corpus callosum on T2-weighted and diffusion-weighted images. The symptoms resolved completely within two days of onset. The patient was diagnosed as having MERS due to the MRI features and the mild clinical course. Although only a few cases of MERS caused by dengue fever have been reported, the condition is possibly underdiagnosed. It is hypothesized that dengue fever can induce MERS as dengue fever can cause increased endothelium permeability and hypo-sodium which have been proposed in the pathogenesis of MERS. However, there is currently limited evidence for this. Further research is recommended to demonstrate a causal association between dengue fever and MERS.

  1. Kidney Injury due to Ureteral Obstruction Caused by Compression from Infected Simple Hepatic Cyst.

    PubMed

    Sawada, Naoya; Endo, Tetsu; Mikami, Kenichiro; Igarashi, Go; Sakamoto, Juichi; Tono, Hiroshi; Fukuda, Shinsaku

    2017-01-01

    Simple hepatic cysts are common and most often asymptomatic. In symptomatic cases, hemorrhage, rupture, and infection are major complications. However, urinary tract obstruction caused by a simple hepatic cyst is rare. We treated an 82-year-old Japanese man with an infected giant hepatic cyst causing right hydronephrosis who had a past history of left nephrectomy for renal cell carcinoma. The patient underwent ultrasound-guided percutaneous drainage and sclerotherapy with minocycline hydrochloride for the infected hepatic cyst. Right hydronephrosis was relieved, and renal dysfunction improved with regression of the hepatic cyst after treatment. This is the first report of hydronephrosis due to ureteral obstruction caused by compression from a hepatic cyst.

  2. Traumatic common hepatic artery injury causing isolated right hepatic ischemia due to a left accessory artery. A case report.

    PubMed

    Fernandes, Eduardo; Pedrazzani, Corrado; Gerena, Marielia; Omi, Ellen

    2017-08-08

    Hepatic arterial liver flow is renowned for its redundancy. Previous studies have demonstrated that the common hepatic artery is not essential for liver survival. We present a case of a 31year-old involved in a high-speed motor vehicle accident whose liver survived thanks to the presence of an accessory hepatic artery. We present the case of a 31year-old male who sustained a traumatic injury of the proper hepatic artery following a motor vehicle accident. The patient suffered temporary right liver lobe ischemia due to the presence of an accessory left hepatic artery. This resulted in the selective formation of 'biliary lakes' distinctively within the territory of the right hepatic artery supply. Simultaneously the patient developed a pseudo-aneurysm of the proper hepatic artery which required radiology intervention. At the time of pseudo-aneurysm embolisation, a rich network of arterial collaterals had formed between the accessory left hepatic and the inferior phrenic artery. On follow up the biliary lakes to the right lobe had resolved, but a small area at the periphery of the right lobe had encountered atrophy. This case report is an 'in vivo' demonstration of liver resilience to arterial flow re-distribution and demonstrates the ability of the biliary epithelium to recover from and ischemic injury. Parenchymal liver survival is mostly independent from flow within the common hepatic artery. Acute and chronic liver parenchyma changes following interruption of hepatic artery flow can still occur. Copyright © 2017. Published by Elsevier Ltd.

  3. Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue

    PubMed Central

    Plinston, Chris; Hart, Patricia; Hunter, Nora; Manson, Jean C.

    2014-01-01

    Bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt–Jakob disease in humans have previously been shown to be caused by the same strain of transmissible spongiform encephalopathy agent. It is hypothesized that the agent spread to humans following consumption of food products prepared from infected cattle. Despite evidence supporting zoonotic transmission, mouse models expressing human prion protein (HuTg) have consistently shown poor transmission rates when inoculated with cattle BSE. Higher rates of transmission have however been observed when these mice are exposed to BSE that has been experimentally transmitted through sheep or goats, indicating that humans may potentially be more susceptible to BSE from small ruminants. Here we demonstrate that increased transmissibility of small ruminant BSE to HuTg mice was not due to replication of higher levels of infectivity in sheep brain tissue, and is instead due to other specific changes in the infectious agent. PMID:24828334

  4. Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue.

    PubMed

    Plinston, Chris; Hart, Patricia; Hunter, Nora; Manson, Jean C; Barron, Rona M

    2014-08-01

    Bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt-Jakob disease in humans have previously been shown to be caused by the same strain of transmissible spongiform encephalopathy agent. It is hypothesized that the agent spread to humans following consumption of food products prepared from infected cattle. Despite evidence supporting zoonotic transmission, mouse models expressing human prion protein (HuTg) have consistently shown poor transmission rates when inoculated with cattle BSE. Higher rates of transmission have however been observed when these mice are exposed to BSE that has been experimentally transmitted through sheep or goats, indicating that humans may potentially be more susceptible to BSE from small ruminants. Here we demonstrate that increased transmissibility of small ruminant BSE to HuTg mice was not due to replication of higher levels of infectivity in sheep brain tissue, and is instead due to other specific changes in the infectious agent. © 2014 The Authors.

  5. The continuous reaction time test for minimal hepatic encephalopathy validated by a randomized controlled multi-modal intervention-A pilot study.

    PubMed

    Lauridsen, M M; Mikkelsen, S; Svensson, T; Holm, J; Klüver, C; Gram, J; Vilstrup, H; Schaffalitzky de Muckadell, O B

    2017-01-01

    Minimal hepatic encephalopathy (MHE) is clinically undetectable and the diagnosis requires psychometric tests. However, a lack of clarity exists as to whether the tests are in fact able to detect changes in cognition. To examine if the continuous reaction time test (CRT) can detect changes in cognition with anti-HE intervention in patients with cirrhosis and without clinically manifest hepatic encephalopathy (HE). Firstly, we conducted a reproducibility analysis and secondly measured change in CRT induced by anti-HE treatment in a randomized controlled pilot study: We stratified 44 patients with liver cirrhosis and without clinically manifest HE according to a normal (n = 22) or abnormal (n = 22) CRT. Each stratum was then block randomized to receive multimodal anti-HE intervention (lactulose+branched-chain amino acids+rifaximin) or triple placebos for 3 months in a double-blinded fashion. The CRT is a simple PC-based test and the test result, the CRT index (normal threshold > 1.9), describes the patient's stability of alertness during the 10-minute test. Our study outcome was the change in CRT index in each group at study exit. The portosystemic encephalopathy (PSE) test, a paper-and-pencil test battery (normal threshold above -5), was used as a comparator test according to international guidelines. The patients with an abnormal CRT index who were randomized to receive the active intervention normalized or improved their CRT index (mean change 0.92 ± 0.29, p = 0.01). Additionally, their PSE improved (change 3.85 ± 1.83, p = 0.03). There was no such effect in any of the other study groups. In this cohort of patients with liver cirrhosis and no manifest HE, the CRT identified a group in whom cognition improved with intensive anti-HE intervention. This finding infers that the CRT can detect a response to treatment and might help in selecting patients for treatment.

  6. Increased toll-like receptor 4 in cerebral endothelial cells contributes to the astrocyte swelling and brain edema in acute hepatic encephalopathy.

    PubMed

    Jayakumar, Arumugam R; Tong, Xiao Y; Curtis, Kevin M; Ruiz-Cordero, Roberto; Abreu, Maria T; Norenberg, Michael D

    2014-03-01

    Astrocyte swelling and the subsequent increase in intracranial pressure and brain herniation are major clinical consequences in patients with acute hepatic encephalopathy. We recently reported that conditioned media from brain endothelial cells (ECs) exposed to ammonia, a mixture of cytokines (CKs) or lipopolysaccharide (LPS), when added to astrocytes caused cell swelling. In this study, we investigated the possibility that ammonia and inflammatory agents activate the toll-like receptor 4 (TLR4) in ECs, resulting in the release of factors that ultimately cause astrocyte swelling. We found a significant increase in TLR4 protein expression when ECs were exposed to ammonia, CKs or LPS alone, while exposure of ECs to a combination of these agents potentiate such effects. In addition, astrocytes exposed to conditioned media from TLR4-silenced ECs that were treated with ammonia, CKs or LPS, resulted in a significant reduction in astrocyte swelling. TLR4 protein up-regulation was also detected in rat brain ECs after treatment with the liver toxin thioacetamide, and that thioacetamide-treated TLR4 knock-out mice exhibited a reduction in brain edema. These studies strongly suggest that ECs significantly contribute to the astrocyte swelling/brain edema in acute hepatic encephalopathy, likely as a consequence of increased TLR4 protein expression by blood-borne noxious agents.

  7. Role of Cerebral Endothelial Cells in the Astrocyte Swelling and Brain Edema Associated with Acute Hepatic Encephalopathy

    PubMed Central

    Jayakumar, A.R.; Tong, X.Y.; Ospel, J.; Norenberg, M.D.

    2012-01-01

    Brain edema is an important complication of acute hepatic encephalopathy (AHE), and astrocyte swelling is largely responsible for its development. Elevated blood and brain ammonia levels have been considered as major etiological factors in this edema. In addition to ammonia, recent studies have suggested that systemic infection, inflammation (and associated cytokines), as well as endotoxin (lipopolysaccharide, LPS) are also involved in AHE-associated brain edema. As endothelial cells (ECs) are the first resident brain cells exposed to blood-borne “noxious agents” (i.e., ammonia, cytokines, LPS) that are present in AHE, these cells may be in a critical position to react to these agents and trigger a process resulting in astrocyte swelling/brain edema. We therefore examined the effect of conditioned media (CM) from ammonia, LPS and cytokine-treated cultured brain ECs on cell swelling in cultured astrocytes. CM from ammonia-treated ECs when added to astrocytes caused significant cell swelling, and such swelling was potentiated when astrocytes were exposed to CM from ECs-treated with a combination of ammonia, LPS and CKs. We also found an additive effect when astrocytes were exposed to ammonia along with CM from ammonia-treated ECs. Additionally, ECs treated with ammonia showed a significant increase in the production of oxy-radicals, nitric oxide, as well as evidence of oxidative/nitrative stress and activation of the transcription factor NF-κ B. CM derived from ECs treated with ammonia, along with antioxidants or the NF-κB inhibitor BAY 11-7082, when added to astrocytes resulted in a significant reduction in cell swelling, as compared to the effect of CM from ECs-treated only with ammonia. We also identified increased nuclear NF-κB expression in rat brain cortical ECs in the thioacetamide model of AHE. These studies suggest that endothelial cells significantly contribute to the astrocyte swelling/brain edema in AHE, likely as a consequence of oxidative

  8. A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy.

    PubMed

    Sharma, Barjesh Chander; Sharma, Praveen; Lunia, Manish Kumar; Srivastava, Siddharth; Goyal, Rohit; Sarin, S K

    2013-09-01

    Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Drugs used in the treatment of HE are primarily directed at the reduction of the blood ammonia levels. Rifaximin and lactulose have shown to be effective in HE. We evaluated the efficacy and safety of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE. In this prospective double-blind randomized controlled trial, 120 patients with overt HE were randomized into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63) and group B (lactulose (n=57) plus placebo). The primary end point was complete reversal of HE and the secondary end points were mortality and hospital stay. A total of 120 patients (mean age 39.4±9.6 years; male/female ratio 89:31) were included in the study. 37 (30.8%) patients were in Child-Turcotte-Pugh (CTP) class B and 83 (69.2%) were in CTP class C. Mean CTP score was 9.7±2.8 and the MELD (model for end-stage liver disease) score was 24.6±4.2. At the time of admission, 22 patients (18.3%) had grade 2, 40 (33.3%) had grade 3, and 58 (48.3%) had grade 4 HE. Of the patients, 48 (76%) in group A compared with 29 (50.8%) in group B had complete reversal of HE (P<0.004). There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8% vs. 49.1%, P<0.05). There were significantly more deaths in group B because of sepsis (group A vs. group B: 7:17, P=0.01), whereas there were no differences because of gastrointestinal bleed (group A vs. group B: 4:4, P=nonsignificant (NS)) and hepatorenal syndrome (group A vs. group B: 4:7, P=NS). Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8±3.4 vs. 8.2±4.6 days, P=0.001). Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.

  9. Altered Regional Homogeneity in the Development of Minimal Hepatic Encephalopathy: A Resting-State Functional MRI Study

    PubMed Central

    Zhang, Long Jiang; Zhong, Jianhui; Zheng, Gang; Zhang, Zhiqiang; Zhong, Yuan; Xu, Qiang; Liao, Wei; Jiao, Qing; Wu, Xingjiang; Fan, Xinxin; Lu, Guang Ming

    2012-01-01

    Background Little is known about how spontaneous brain activity progresses from non-hepatic encephalopathy (non-HE) to minimal HE (MHE). The purpose of this study was to evaluate the evolution pattern of spontaneous brain activities in cirrhotic patients using resting-state fMRI with a regional homogeneity (ReHo) method. Methodology/Principal Findings Resting-state fMRI data were acquired in 47 cirrhotic patients (minimal HE [MHE], n = 20, and non-HE, n = 27) and 25 age-and sex-matched healthy controls. The Kendall’s coefficient of concordance (KCC) was used to measure the regional homogeneity. The regional homogeneity maps were compared with ANOVA tests among MHE, non-HE, and healthy control groups and t-tests between each pair in a voxel-wise way. Correlation analyses were performed to explore the relationships between regional ReHo values and Child-Pugh scores, number connection test type A (NCT-A), digit symbol test (DST) scores, venous blood ammonia levels. Compared with healthy controls, both MHE and non-HE patients showed decreased ReHo in the bilateral frontal, parietal and temporal lobes and increased ReHo in the bilateral caudate. Compared with the non-HE, MHE patients showed decreased ReHo in the bilateral precuneus, cuneus and supplementary motor area (SMA). The NCT-A of cirrhotic patients negatively correlated with ReHo values in the precuneus, cuneus and lingual gyrus. DST scores positively correlated with ReHo values in the cuneus, precuneus and lingual gyrus, and negatively correlated with ReHo values in the bilateral caudate (P<0.05, AlphaSim corrected). Conclusions/Significance Diffused abnormal homogeneity of baseline brain activity was nonspecific for MHE, and only the progressively decreased ReHo in the SMA and the cuneus, especially for the latter, might be associated with the development of MHE. The ReHo analysis may be potentially valuable for detecting the development from non-HE to MHE. PMID:22848692

  10. Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis.

    PubMed

    Gluud, Lise Lotte; Vilstrup, Hendrik; Morgan, Marsha Y

    2016-05-06

    Non-absorbable disaccharides (lactulose and lactitol) are recommended as first-line treatment for hepatic encephalopathy. The previous (second) version of this review included 10 randomised clinical trials (RCTs) evaluating non-absorbable disaccharides versus placebo/no intervention and eight RCTs evaluating lactulose versus lactitol for people with cirrhosis and hepatic encephalopathy. The review found no evidence to either support or refute the use of the non-absorbable disaccharides and no differences between lactulose versus lactitol. To assess the beneficial and harmful effects of i) non-absorbable disaccharides versus placebo/no intervention and ii) lactulose versus lactitol in people with cirrhosis and hepatic encephalopathy. We carried out electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 10), MEDLINE, EMBASE, and Science Citation Index Expanded to 19 October 2015; manual searches of meetings and conference proceedings; checks of bibliographies; and correspondence with investigators and pharmaceutical companies. We included RCTs, irrespective of publication status, language, or blinding. Two review authors, working independently, retrieved data from published reports and correspondence with investigators. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We presented the results of meta-analyses as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed the quality of the evidence using 'Grading of Recommendations Assessment Development and Evaluation' (GRADE) and bias control using the Cochrane Hepato-Biliary Group domains. Our analyses included regression analyses of publication bias and other small study effects, Trial Sequential Analyses to detect type 1 and type 2 errors, and subgroup and sensitivity analyses. We included 38 RCTs with a total of 1828 participants. Eight RCTs

  11. Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis.

    PubMed

    Gluud, Lise Lotte; Vilstrup, Hendrik; Morgan, Marsha Y

    2016-04-18

    Non-absorbable disaccharides (lactulose and lactitol) are recommended as first-line treatment for hepatic encephalopathy. The previous (second) version of this review included 10 randomised clinical trials (RCTs) evaluating non-absorbable disaccharides versus placebo/no intervention and eight RCTs evaluating lactulose versus lactitol for people with cirrhosis and hepatic encephalopathy. The review found no evidence to either support or refute the use of the non-absorbable disaccharides and no differences between lactulose versus lactitol. To assess the beneficial and harmful effects of i) non-absorbable disaccharides versus placebo/no intervention and ii) lactulose versus lactitol in people with cirrhosis and hepatic encephalopathy. We carried out electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 10), MEDLINE, EMBASE, and Science Citation Index Expanded to 19 October 2015; manual searches of meetings and conference proceedings; checks of bibliographies; and correspondence with investigators and pharmaceutical companies. We included RCTs, irrespective of publication status, language, or blinding. Two review authors, working independently, retrieved data from published reports and correspondence with investigators. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We presented the results of meta-analyses as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed the quality of the evidence using 'Grading of Recommendations Assessment Development and Evaluation' (GRADE) and bias control using the Cochrane Hepato-Biliary Group domains. Our analyses included regression analyses of publication bias and other small study effects, Trial Sequential Analyses to detect type 1 and type 2 errors, and subgroup and sensitivity analyses. We included 38 RCTs with a total of 1828 participants. Eight RCTs

  12. Vascular Plug-Assisted Retrograde Transvenous Obliteration of Portosystemic Shunts for Refractory Hepatic Encephalopathy: A Case Report

    PubMed Central

    Park, Jonathan K.; Cho, Sung-Ki; Kee, Stephen; Lee, Edward W.

    2014-01-01

    While balloon-assisted retrograde transvenous obliteration (BRTO) has been used for two decades in Asia for the management of gastric variceal bleeding, it is still an emerging therapy elsewhere. Given the shunt closure brought about by the procedure, BRTO has also been used for the management of portosystemic encephalopathy with promising results. Modified versions of BRTO have been developed, including plug-assisted retrograde transvenous obliteration (PARTO), where a vascular plug is deployed within a portosystemic shunt. To our knowledge, we present the first North American case of PARTO in the setting of a large splenorenal shunt for the management of portosystemic encephalopathy. PMID:24744943

  13. Vascular plug-assisted retrograde transvenous obliteration of portosystemic shunts for refractory hepatic encephalopathy: a case report.

    PubMed

    Park, Jonathan K; Cho, Sung-Ki; Kee, Stephen; Lee, Edward W

    2014-01-01

    While balloon-assisted retrograde transvenous obliteration (BRTO) has been used for two decades in Asia for the management of gastric variceal bleeding, it is still an emerging therapy elsewhere. Given the shunt closure brought about by the procedure, BRTO has also been used for the management of portosystemic encephalopathy with promising results. Modified versions of BRTO have been developed, including plug-assisted retrograde transvenous obliteration (PARTO), where a vascular plug is deployed within a portosystemic shunt. To our knowledge, we present the first North American case of PARTO in the setting of a large splenorenal shunt for the management of portosystemic encephalopathy.

  14. [EEG manifestations in metabolic encephalopathy].

    PubMed

    Lin, Chou-Ching K

    2005-09-01

    Normal brain function depends on normal neuronal metabolism, which is closely related to systemic homeostasis of metabolites, such as glucose, electrolytes, amino acids and ammonia. "Metabolic encephalopathy" indicates diffuse brain dysfunction caused by various systemic derangements. Electroencephalogram (EEG) is widely used to evaluate metabolic encephalopathy since 1937, when Berger first observed slow brain activity induced by hypoglycemia. EEG is most useful in differentiating organic from psychiatric conditions, identifying epileptogenicity, and providing information about the degree of cortical or subcortical dysfunction. In metabolic encephalopathy, EEG evolution generally correlates well with the severity of encephalopathy. However, EEG has little specificity in differentiating etiologies in metabolic encephalopathy. For example, though triphasic waves are most frequently mentioned in hepatic encephalopathy, they can also be seen in uremic encephalopathy, or even in aged psychiatric patients treated with lithium. Spike-and-waves may appear in hyper- or hypo-glycemia, uremic encephalopathy, or vitamin deficiencies, etc. Common principles of EEG changes in metabolic encephalopathy are (1) varied degrees of slowing, (2) assorted mixtures of epileptic discharge, (3) high incidence of triphasic waves, and (4), as a rule, reversibility after treatment of underlying causes. There are some exceptions to the above descriptions in specific metabolic disorders and EEG manifestations are highly individualized.

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

    PubMed

    Sharma, Praveen; Sharma, Barjesh Chander; Agrawal, Amit; Sarin, Shiv Kumar

    2012-08-01

    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. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  16. Development of quantitative neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter collaborative study in Japanese.

    PubMed

    Kato, Akinobu; Kato, Motoichiro; Ishii, Hiromasa; Ichimiya, Yosuke; Suzuki, Kazuyuki; Kawasaki, Hironaka; Yamamoto, Shin-Ichiro; Kumashiro, Ryukichi; Yamamoto, Kyosuke; Kawamura, Naohiro; Hayashi, Naoaki; Matsuzaki, Shohei; Terano, Akira; Okita, Kiwamu; Watanabe, Akiharu

    2004-10-01

    At present, there are no generally accepted diagnostic criteria or methods for subclinical hepatic encephalopathy (SHE) associated with liver cirrhosis. We therefore developed an easily conducted computer-aided quantitative neuropsychiatric function test system for use in routine medical practice. We established normal values in healthy Japanese subjects and determined differences between healthy persons and liver cirrhosis patients without clinical encephalopathy in a multi-center clinical trial. The test system consists of eight tests: number connection tests A and B, a figure position test, a digit symbol test, a block design test, and reaction time tests A, B and C. The test results were affected by age, but not by gender or facility. No learning effect was noted. The results were therefore reported by 5-year quartile ranges and differences were evaluated between 542 healthy subjects and 292 cirrhotic patients. When the cut-off value was set at the 10th/90th percentile of the results in healthy subjects, the results of each of the 8 tests were abnormal in about 25% of cirrhotic patients, and at least 1 of the 8 tests gave values greater than the 10th/90th percentile cut-off value in 58.2% of the 292 liver cirrhosis patients. SHE patients were thought to be included in these 58.2% of patients. The developed test makes it possible to quantitatively assess neuropsychiatric function, and the results obtained can be used as a basis for the diagnosis of SHE.

  17. Hepatitis Due to Equine Abortion Virus. Comparison Between the Liver Histology in Human, Canine, Duckling, and Equine Viral Hepatitis1

    PubMed Central

    Corrêa, W. M.; Nilsson, M. R.

    1966-01-01

    Five livers of equine fetuses, aborted due to the action of equine abortion virus, five livers from men, two of whom died of epidemic hepatitis and three obtained by needle biopsies, 5 livers of dogs with infectious canine hepatitis and 7 livers of ducklings that had hepatitis, were studied histopathologically. The foals' livers were studied by several staining methods and the others by H. E. only. The results indicate that the lesions are quite similar in the four species with the appearance of nuclear inclusion bodies only in foals and dogs. The strong staining properties of the nuclear inclusion bodies in infectious canine hepatitis and the weak staining properties of the equine virus abortion reveal that the protein-DNA association is different resulting in a different electropolarity. The lesions in foals are of two main types, one a Necrotic-Mosaic Type in which the hepatocyte degeneration is irregularly distributed within the hepatic lobules and the other an Hyperplastic Type in which marked regeneration occurs. In the Hyperplastic Type the practical absence of plasmocytes in foals' livers might suggest that if the newborn is a female, abortions may occur later in life because the virus remained alive in colts which were born in an immune tolerance state. Histologically the picture in the livers of aborted foals assume features of a viral hepatitis similar to the viral hepatitis in men, dogs and ducklings. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8.Fig. 9. PMID:4225286

  18. Cognitive performance as a predictor of hepatic encephalopathy in pretransplant patients with cirrhosis receiving psychoactive medications: a prospective study.

    PubMed

    Bajaj, Jasmohan S; Thacker, Leroy R; Heuman, Douglas M; Sterling, Richard K; Stravitz, R Todd; Sanyal, Arun J; Luketic, Velimir; Fuchs, Michael; Gilles, Ho Chong S; Wade, James B

    2012-10-01

    Psychiatric disorders and medications may affect the cognitive performance of patients with cirrhosis and complicate the diagnosis and prediction of hepatic encephalopathy (HE). The aim of this study was to study the association of psychoactive medications with cognitive performance and their effects on the ability of tests to predict HE development in patients with cirrhosis referred for transplant evaluation. Cirrhosis details, psychiatric disorders, psychoactive medications, and any history of prior HE were recorded for patients with cirrhosis at 2 transplant centers. Patients were followed until the development of HE. Five cognitive tests--number connection test A (NCT-A), number connection test B, the digit symbol test (DST), the block design test, and the inhibitory control test (ICT)--were administered. A high lure score and a low ICT target score indicated poor performance. The cognitive performances of patients with psychiatric disorders/medications and patients without them were compared. A proportional hazards model was created with the time to HE as the outcome, and it was based on demographics, psychoactive medications, cirrhosis details, and individual cognitive scores. Patients with prior HE and patients without prior HE were then studied separately. One hundred fifty-five patients with a mean age of 57.5 ± 6.2 years and a mean Model for End-Stage Liver Disease (MELD) score of 15.1 ± 6.2 were included [prior HE, 48%; diabetes, 34%; selective serotonin reuptake inhibitors (SSRIs), 32%; opioids, 19%; and antipsychotics, 10%]. Prior HE and antipsychotics (but not opioids or diabetes) were associated with worse cognition. SSRI users had better NCT-A and DST performance. One hundred forty-eight patients were followed for a median of 182.5 days; 58 developed HE at a median of 99 days after inclusion. In the entire group, the model showed that prior HE (hazard ratio = 4.13), the MELD score (hazard ratio = 1.07), and a high lure score (hazard ratio = 1

  19. Portosystemic hepatic encephalopathy model shows reversal learning impairment and dysfunction of neural activity in the prefrontal cortex and regions involved in motivated behavior.

    PubMed

    Méndez, M; Méndez-López, M; López, L; Aller, M A; Arias, J; Arias, J L

    2011-05-01

    Hepatic encephalopathy (HE) is a neurological complication that affects attention and memory. Experimental animal models have been used to study HE, the most frequent being the portacaval shunt (PCS). In order to investigate learning impairment and brain functional alterations in this model, we assessed reversal learning and neural metabolic activity in a PCS rat model. PCS and sham-operated rats were tested for reversal learning in the Morris water maze. Brains were then processed for cytochrome oxidase (CO) histochemistry. The PCS group had reversal learning impairment and a reduction in CO activity in the prefrontal cortex, ventral tegmental area and accumbens shell nucleus. These results suggest that this model of portosystemic HE shows learning impairments that could be linked to dysfunction in neural activity in the prefrontal cortex and regions involved in motivated behavior.

  20. Regional cerebral blood flow assessed by single photon emission computed tomography (SPECT) in dogs with congenital portosystemic shunt and hepatic encephalopathy.

    PubMed

    Or, Matan; Peremans, Kathelijne; Martlé, Valentine; Vandermeulen, Eva; Bosmans, Tim; Devriendt, Nausikaa; de Rooster, Hilde

    2017-02-01

    Regional cerebral blood flow (rCBF) in eight dogs with congenital portosystemic shunt (PSS) and hepatic encephalopathy (HE) was compared with rCBF in eight healthy control dogs using single photon emission computed tomography (SPECT) with a (99m)technetium-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) tracer. SPECT scans were abnormal in all PSS dogs. Compared to the control group, rCBF in PSS dogs was significantly decreased in the temporal lobes and increased in the subcortical (thalamic and striatal) area. Brain perfusion imaging alterations observed in the dogs with PSS and HE are similar to those in human patients with HE. These findings suggest that dogs with HE and PSS have altered perfusion of mainly the subcortical and the temporal regions of the brain.

  1. Use of ImPACT to diagnose minimal hepatic encephalopathy: an accurate, practical, user-friendly internet-based neuropsychological test battery.

    PubMed

    Tsushima, Matthew; Tsushima, William; Tsushima, Vincent; Lim, Nelson; Madrigal, Erika; Jackson, Christian; Mendler, Michel Henry

    2013-09-01

    An effective, user-friendly neurocognitive test to diagnose minimal hepatic encephalopathy (MHE) is needed. Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) is a brief, validated, Web-based, neuropsychological test battery resulting in four composite scores [Verbal Memory (VrbM), Visual Memory, Visual Motor Speed (VMS), Reaction Time (RT)]. We compared ImPACT to traditional paper-and-pencil tests in patients at risk for MHE versus controls. Ninety cirrhotic patients with no history of overt hepatic encephalopathy were compared with 131 controls on standard psychometric tests (SPT) [Trail Making Test-A, Trail Making Test-B, Digit Symbol Test], 4 ImPACT composite scores, and the Sickness Impact Profile (SIP). MHE+ was defined by a score 2 SD below the normative mean on at least one of the SPT. ImPACT (ImP+) scores of patients were defined as 2 SD from the control mean. Cirrhotic patients scored more poorly than controls on 3/4 of ImPACT scores: VrbM (78.88 vs. 71.37, p<0.001), VMS (26.47 vs. 22.68, p<0.001) and RT (0.89 vs. 1.00, p<0.01), as well as on all 3 SPT. Of the 90 cirrhotics, 16 (18%) were MHE+, who performed more poorly (p<0.001) than patients without MHE on VrbM (58.13 vs. 74.19), VMS (16.77 vs. 23.95) and RT (1.24 vs. 0.95). Of the 90 cirrhotics, 25 (27.8%) were ImP+. MHE+ and ImP+ patients had increased SIP scores versus controls (p<0.001). Compared to paper-and-pencil testing, ImPACT provides a brief, user-friendly, neuropsychological evaluation of MHE. ImPACT could become a new standard for MHE diagnosis.

  2. Rats with mild bile duct ligation show hepatic encephalopathy with cognitive and motor impairment in the absence of cirrhosis: effects of alcohol ingestion.

    PubMed

    Giménez-Garzó, Carla; Salhi, Dounia; Urios, Amparo; Ruíz-Sauri, Amparo; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2015-02-01

    Studies in animal models allow identifying mechanisms and treatments for cognitive and motor alterations in hepatic encephalopathy (HE). Liver diseases leading to HE in humans have different aetiologies (alcoholic, viral, etc.). The International Society for Hepatic Encephalopathy points out that satisfactory model for HE resulting from alcoholic cirrhosis are lacking. This work aimed to develop and characterize an animal model for HE in alcoholic liver cirrhosis. To potentiate the effects of alcohol on liver we administered it (5, 8 or 10% in drinking water) to rats showing mild liver damage induced by "mild" bile duct ligation (MBDL), obtained by sectioning 3 out of 5 bile ducts. MBDL rats show increased markers of cholestasis and liver damage, hyperammonemia and inflammation. MBDL rats also show motor in-coordination, hypokinesia, impaired learning ability in a Y maze and reduced spatial memory in the Morris water maze. Ingesting 10% ethanol does not induce relevant liver damage in control rats but potentiates liver damage in MBDL rats. In contrast, ethanol did not enhance the biochemical or neurological alterations in MBDL rats. This supports that the combination of certain levels of hyperammonemia and inflammation is enough to induce mild cognitive impairment, even in the absence of liver cirrhosis. Rats with MBDL and MBDL-OH survived more than 3 months, allowing performing long-term studies on cognitive and motor alterations and on underlying mechanisms. MBDL-OH rats are a good model to study the mechanisms of ethanol-induced liver cirrhosis and the factors making the liver susceptible to ethanol damage.

  3. Activation of neuronal nitric oxide synthase in cerebellum of chronic hepatic encephalopathy rats is associated with up-regulation of NADPH-producing pathway.

    PubMed

    Singh, Santosh; Trigun, Surendra K

    2010-09-01

    Cerebellum-associated functions get affected during mild hepatic encephalopathy (MHE) in patients with chronic liver failure (CLF). Involvement of nitrosative and antioxidant factors in the pathogenesis of chronic hepatic encephalopathy is an evolving concept and needs to be defined in a true CLF animal model. This article describes profiles of NADPH-dependent neuronal nitric oxide synthase (nNOS) and those of glutathione peroxidase and glutathione reductase (GR) vis-a-vis regulation of NADPH-producing pathway in the cerebellum of CLF rats induced by administration of thioacetamide (100 mg kg⁻¹ b.w., i.p.) up to 10 days and confirming MHE on Morris water maze tests. Significant increases in the expression of nNOS protein and nitric oxide (NOx) level coincided with a similar increment in NADPH-diaphorase activity in the cerebellum of CLF rats. Glutathione peroxidase and GR utilize NADPH to regenerate reduced glutathione (GSH) in the cells. Both these enzymes and GSH level were found to be static and thus suggested efficient turnover of GSH in the cerebellum of MHE rats. Relative levels of glucose-6-phosphate dehydrogenase (G6PD) vs. phosphofructokinase 2 (PFK2) determine the rate of pentose phosphate pathway (PPP) responsible to synthesize NADPH. The cerebellum of CLF rats showed overactivation of G6PD with a significant decline in the expression of PFK2 and thus suggested activation of PPP in the cerebellum during MHE. It is concluded that concordant activations of PPP and nNOS in cerebellum of MHE rats could be associated with the implication of NOx in the pathogenesis of MHE.

  4. Approach to clinical syndrome of jaundice and encephalopathy in tropics.

    PubMed

    Anand, Anil C; Garg, Hitendra K

    2015-03-01

    A large number of patients present with jaundice and encephalopathy in tropical country like India and acute liver failure is the usual cause. Clinical presentation like ALF is also a complication of many tropical infections, and these conditions may mimic ALF but may have subtle differences from ALF. Moreover, what hepatologists see as acute liver failure in tropics is different from what is commonly described in Western Textbooks. Paracetamol overdose, which is possibly the commonest cause of ALF in UK and USA, is hardly ever seen in India. Most common etiology here is viral hepatitis (hepatitis E > hepatitis B> hepatitis A). Apart from ALF, one may also come across subacute hepatic failure (SAHF) as well as acute-on-chronic liver failure (ACLF) due to viral hepatitis. Interestingly, a host of other conditions can mimic ALF because clinical presentation in these conditions can be dominated by jaundice and encephalopathy. Malarial hepatopathy is possibly the best-known condition out of these and is not an uncommon manifestation of severe malaria. A similar presentation can also be seen in other common infections in tropics such as dengue fever, typhoid fever, leptospirosis, scrub typhus, amoebic liver abscesses, tuberculosis and other bacterial and fungal infections with or without human immunodeficiency virus (HIV) related disease. In many of these conditions, liver failure may not be underlying pathophysiology. Some pregnancy related liver diseases could also present with jaundice and encephalopathy. This review summarizes the commonly seen presentations in tropical country like India, where jaundice and encephalopathy dominate the clinical picture.

  5. Approach to Clinical Syndrome of Jaundice and Encephalopathy in Tropics

    PubMed Central

    Anand, Anil C.; Garg, Hitendra K.

    2015-01-01

    A large number of patients present with jaundice and encephalopathy in tropical country like India and acute liver failure is the usual cause. Clinical presentation like ALF is also a complication of many tropical infections, and these conditions may mimic ALF but may have subtle differences from ALF. Moreover, what hepatologists see as acute liver failure in tropics is different from what is commonly described in Western Textbooks. Paracetamol overdose, which is possibly the commonest cause of ALF in UK and USA, is hardly ever seen in India. Most common etiology here is viral hepatitis (hepatitis E > hepatitis B> hepatitis A). Apart from ALF, one may also come across subacute hepatic failure (SAHF) as well as acute-on-chronic liver failure (ACLF) due to viral hepatitis. Interestingly, a host of other conditions can mimic ALF because clinical presentation in these conditions can be dominated by jaundice and encephalopathy. Malarial hepatopathy is possibly the best-known condition out of these and is not an uncommon manifestation of severe malaria. A similar presentation can also be seen in other common infections in tropics such as dengue fever, typhoid fever, leptospirosis, scrub typhus, amoebic liver abscesses, tuberculosis and other bacterial and fungal infections with or without human immunodeficiency virus (HIV) related disease. In many of these conditions, liver failure may not be underlying pathophysiology. Some pregnancy related liver diseases could also present with jaundice and encephalopathy. This review summarizes the commonly seen presentations in tropical country like India, where jaundice and encephalopathy dominate the clinical picture. PMID:26041951

  6. Toxic Encephalopathy

    PubMed Central

    Kim, Jae Woo

    2012-01-01

    This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

  7. Changes in expression of the chloride homeostasis-regulating genes, KCC2 and NKCC1, in the blood of cirrhotic patients with hepatic encephalopathy.

    PubMed

    Li, Jun-Jie; Ji, Ru; Shi, Yong-Quan; Wang, Ya-Yun; Yang, Yan-Ling; Dou, Ke-Feng

    2012-12-01

    Hepatic encephalopathy (HE), a neuropsychiatric abnormality that commonly accompanies cirrhosis of the liver, is often difficult to treat and manage. Changes in chloride homeostasis are involved in the generation of a number of brain disorders. In this study, we considered whether chloride homeostasis is associated with HE. The mRNA levels of the Cl(-) extrusion system (KCC2) and the Cl(-) intrusion system (NKCC1) were detected by real-time RT-PCR in the plasma of 29 cirrhotic patients with HE of grade I-II, 36 cirrhotic patients with HE of grade III-IV, 20 cirrhotic patients without HE and 15 healthy controls. The mRNA levels of KCC2 in cirrhotic patients with mild and severe HE were significantly lower compared to those in cirrhotic patients without HE or in the healthy controls. However, NKCC1 mRNA levels did not differ between the different groups. In addition, for cirrhotic patients with HE, there were significant negative correlations between KCC2 levels and the levels of blood ammonia and hepatic function scores (Child-Pugh and model for end-stage liver disease scores); there was also a significant positive correlation between KCC2 levels and neurological status (Glasgow scores). In conclusion, our study indicates that an imbalance of KCC2 and NKCC1 may be a novel biomarker for detecting HE and for monitoring disease development.

  8. Biliary obstruction due to a huge simple hepatic cyst treated with laparoscopic resection.

    PubMed

    Kaneya, Yohei; Yoshida, Hiroshi; Matsutani, Takeshi; Hirakata, Atsushi; Matsushita, Akira; Suzuki, Seiji; Yokoyama, Tadashi; Maruyama, Hiroshi; Sasajima, Koji; Uchida, Eiji

    2011-01-01

    Most hepatic cysts are asymptomatic, but complications occasionally occur. We describe a patient with biliary obstruction due to a huge simple hepatic cyst treated with laparoscopic resection. A 60-year-old Japanese woman was admitted to our hospital because of a nontender mass in the right upper quadrant of the abdomen. Laboratory tests revealed the following: serum total bilirubin, 0.6 mg/dL; serum aspartate aminotransferase, 100 IU/L; serum alanine aminotransferase, 78 IU/L; serum alkaline phosphatase, 521 IU/L; and serum gamma glutamic transpeptidase, 298 IU/L. Abdominal computed tomography, ultrasonography, and magnetic resonance cholangiopancreatography revealed a huge hepatic cyst, 13 cm in diameter, at the hepatic hilum, accompanied by dilatation of the intrahepatic bile duct and obstruction of the common bile duct. We diagnosed biliary obstruction due to a huge hepatic cyst at the hepatic hilum, and laparoscopic surgery was performed. A huge hepatic cyst was seen at the hepatic hilum. After needle puncture of the huge cyst, the anterior wall of the cyst was unroofed, and cholecystectomy was done. Intraoperative cholangiography through a cystic duct revealed stenosis of the duct. Subsequent decapsulation of the cyst was performed in front of the common bile duct. After this procedure, cholangiography revealed that the stenosis of the common bile duct had resolved. Histopathological examination of the surgical specimen confirmed the hepatic cyst was benign. The postoperative course was uneventful, and the results of liver function tests normalized. The patient was discharged 7 days after operation. Computed tomography 3 months after operation revealed disappearance of the hepatic cyst and no dilatation of the intrahepatic bile duct.

  9. Encephalopathy in an infant with infantile spasms: possible role of valproate toxicity

    PubMed Central

    Sivathanu, Shobhana; Sampath, Sowmya; Veerasamy, Madhubala; Sunderkumar, Satheeshkumar

    2014-01-01

    An infant presented with global developmental delay and infantile spasms. EEG was suggestive of hypsarrhythmia. She was started on sodium valproate, clonazepam and adrenocorticotropic hormone injection. After an initial improvement the child developed vomiting, altered sensorium and increase in frequency of seizures suggestive of encephalopathy. Valproate-induced hyperammonaemia or hepatic encephalopathy was considered and the drug was withheld following which there was a dramatic improvement. Paradoxically, the liver function tests and serum ammonia were normal. However, a complete reversal of encephalopathy, on withdrawal of the drug, strongly suggested an adverse drug reaction (ADR) due to valproic acid. Marginal elevation of serum valproic acid prompted us to use the Naranjo ADR probability score to confirm the diagnosis. This case highlights the fact that valproate toxicity can manifest with normal liver function and serum ammonia levels. This is the youngest reported case with this rare form of valproate-induced encephalopathy. PMID:24810446

  10. Encephalopathy and death in infants with abusive head trauma is due to hypoxic-ischemic injury following local brain trauma to vital brainstem centers.

    PubMed

    Matschke, Jakob; Büttner, Andreas; Bergmann, Markus; Hagel, Christian; Püschel, Klaus; Glatzel, Markus

    2015-01-01

    Infants with abusive head trauma (AHT) have diffuse brain damage with potentially fatal brain swelling. The pathogenesis of the brain damage remains unclear. We hypothesize that brain damage in AHT is due to hypoxic-ischemic injury with hypoxic-ischemic encephalopathy (HIE) rather than primary traumatic brain injury (TBI) with traumatic diffuse axonal injury (tDAI). We studied brain tissue of AHT victims. Primary outcome measure was the presence of primary traumatic versus hypoxic-ischemic brain injury. The diagnosis of tDAI followed a standardized semiquantitative diagnostic approach yielding a 4-tiered grading scheme (definite, possible, improbable, and none). In addition, results of quantitative immunohistochemical analysis in a subgroup of AHT victims with instant death were compared with matched SIDS controls. In our cohort of 50 AHT victims, none had definite tDAI (no tDAI in 30, tDAI possible in 2, and tDAI improbable in 18). Instead, all AHT victims showed morphological findings indicative of HIE. Furthermore, the subgroup with instant death showed significantly higher counts of damaged axons with accumulation of amyloid precursor protein (APP) in the brainstem adjacent to the central pattern generator of respiratory activity (CPG) (odds ratio adjusted for age, sex, brain weight, and APP-count in other regions = 3.1; 95 % confidence interval = 1.2 to 7.7; p = 0.015). AHT victims in our cohort do not have diffuse TBI or tDAI. Instead, our findings indicate that the encephalopathy in AHT is the due to hypoxic-ischemic injury probably as the result of respiratory arrest due to local damage to parts of the CPG in the brainstem.

  11. Anaphylactic shock due to unruptured hepatic hydatid cyst complicated by multiple intrahospital infections.

    PubMed

    Popovic-Dragonjic, Lidija; Jovanovic, Maja; Vrbic, Miodrag; Kostic, Velimir; Miladinovic-Tasic, Natasa; Kocic, Biljana; Rankovic, Aleksandar; Dragonjic, Ivan

    2014-12-01

    Anaphylactic shock due to unruptured hydatid cyst is a rare complication of hepatic echinococcosis. Here, we present an unusual case of unruptured hydatid cyst causing anaphylactic shock followed by appendicitis, ileus, and complicated by septic condition due to multiple intrahospital infections. Decision of the surgical cyst removal at the right moment and appropriate antimicrobial treatment are key factors for a positive outcome.

  12. Acute amnestic encephalopathy in amyloid-β oligomer-injected mice is due to their widespread diffusion in vivo.

    PubMed

    Epelbaum, Stéphane; Youssef, Ihsen; Lacor, Pascale N; Chaurand, Pierre; Duplus, Eric; Brugg, Bernard; Duyckaerts, Charles; Delatour, Benoît

    2015-06-01

    Amyloid-β (Aβ) oligomers are the suspected culprit as initiators of Alzheimer's disease (AD). However, their diffusion in the brain remains unknown. Here, we studied Aβ oligomers' dissemination and evaluated their in vivo toxicity. Wild-type mice were injected with 50 pmol of synthetic Aβ oligomers (of different size) in the hippocampus. Oligomers diffused largely in the brain as soon as 1 hour and up to 7 days after injection. A transient encephalopathy with memory impairment was induced by this unique injection. The immunoreactivity of the postsynaptic marker PSD95 was diffusely decreased. Similar results (both on memory and PSD95 immunoreactivity) were obtained with delipidated and high molecular weight oligomers (>50 kDa) but not with smaller assemblies. Tau hyperphosphorylation was observed in the oligomer-injected brains. Finally, fos immunostaining was increased in Aβ-derived diffusible ligands-injected mice, suggesting neuronal hyperactivity. Rapid and widespread diffusion of Aβ oligomers was demonstrated in vivo and associated with decreased synaptic markers and memory deficits which gives new insight to the pathogenicity of Aβ.

  13. [Anesthetic Management of a Parturient with Eclampsia, Posterior Reversible Encephalopathy Syndrome and Pulmonary Edema due to Pregnancy-induced Hypertension].

    PubMed

    Aida, Junko; Okutani, Hiroai; Oda, Yutaka; Okutani, Ryu

    2015-08-01

    A 27-year-old woman with mental retardation was admitted to a nearby hospital for an abrupt onset of seizure. Physical examination revealed remarkable hypertension and pregnancy with estimated gestational age of 28th week. Severe pulmonary edema and hypoxia led to a diagnosis of pregnancy-induced hypertension (PIH) accompanied by eclampsia. She was orotracheally intubated because of refractory seizure and hypoxemia, and transferred to our hospital for further treatment. Besides severe hypoxia and hypercapnea, an enhanced lesion was detected in the left posterior cerebrum by brain MRI. No abnormal findings were detected in the fetus, with heart rate of 150 beats x min. She was diagnosed with posterior reversible encephalopathy syndrome (PRES) caused by PIH and emergency cesarean section under general anesthesia was scheduled. A male newborn was delivered with Apgar score of 1/4 (1/5 min), followed by starting continuous infusion of nicardipine for controlling hypertension. Chest X-P on completion of surgery revealed remarkably alleviated pulmonary edema. She received intensive treatment and continued positive pressure ventilation for four days after delivery. She recovered with no neurological deficits and her child was well without any complications.

  14. Epileptic Encephalopathies.

    PubMed

    Germain, Blair; Maria, Bernard L

    2017-01-01

    Epileptic encephalopathies encompass a heterogeneous group of epilepsy syndromes that manifest with cognitive, behavioral, and neurologic deficits, seizures that are often intractable and multiform, aggressive electroencephalographic paroxysmal activity, and sometimes early death. As more is learned about the etiologies and manifestations of epileptic encephalopathies, progress has been made toward better treatment options. However, there is still a great need for further randomized controlled trials and research to help create clinically effective therapies. The 2015 Neurobiology of Disease in Children symposium, held in conjunction with the 44th annual meeting of the Child Neurology Society, aimed to (1) describe the clinical concerns involving diagnosis and treatment, (2) review the current status of understanding in the pathogenesis of epileptic encephalopathy, (3) discuss clinical management and therapies for epileptic encephalopathy, and (4) define future directions of research. This article summarizes the presentations and includes an edited transcript of question-and-answer sessions.

  15. [Wernicke encephalopathy].

    PubMed

    Djelantik, M; Bloemkolk, D; Tijdink, J

    2015-01-01

    Wernicke encephalopathy is an acute neuropsychiatric disease with heterogeneous symptoms, including changes in mental status, ataxia and ocular abnormalities; if left untreated, these symptoms can lead to morbidity and even to mortality. The treatment is thiamine suppletion. Because of the heterogeneity of the symptoms and the high risk of morbidity and mortality if the symptoms are not treated, it is vitally important that on observing a patient's early symptoms the clinician immediately suspects that the symptoms could point to Wernicke encephalopathy.

  16. Minimal hepatic encephalopathy is associated with expansion and activation of CD(4+)CD28(-), Th22 and Tfh and B lymphocytes.

    PubMed

    Mangas-Losada, Alba; García-García, Raquel; Urios, Amparo; Escudero-García, Desamparados; Tosca, Joan; Giner-Durán, Remedios; Serra, Miguel Angel; Montoliu, Carmina; Felipo, Vicente

    2017-07-27

    Peripheral inflammation acts synergistically with hyperammonemia in inducing neurological alterations in cirrhotic patients with minimal hepatic encephalopathy (MHE). We hypothesized that appearance of MHE would be associated to some specific qualitative change in peripheral inflammation. The aim of this work was to characterize the changes in peripheral inflammation associated to appearance of MHE. We analyzed it by immunophenotyping and cytokine profile analysis, in cirrhotic patients without or with MHE and controls. The main alterations associated specifically with MHE are: 1) increased activation of all subtypes of CD4(+) T-lymphocytes, with the increased expression of CD69; 2) increased amount of CD4(+)CD28(-) T lymphocytes, associated with increased levels of CX3CL1 and of IL-15; 3) increased differentiation of CD4(+) T lymphocytes to Th follicular and Th22; 4) increased activation of B lymphocytes and serum IgG. This study has identified some specific alterations of the immune system associated with appearance of the neurological alterations in MHE patients.

  17. Bacopa monnieri Extract (CDRI-08) Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats

    PubMed Central

    Mondal, Papia; Trigun, Surendra Kumar

    2015-01-01

    Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells. Bacopa monnieri (BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE. PMID:26413124

  18. Increased Toll-Like Receptor 4 in Cerebral Endothelial Cells Contributes to the Astrocyte Swelling and Brain Edema in Acute Hepatic Encephalopathy

    PubMed Central

    Jayakumar, A.R.; Tong, X.Y.; Curtis, K.M.; Ruiz-Cordero, R.; Abreu, M.T.; Norenberg, M.D.

    2013-01-01

    Astrocyte swelling and the subsequent increase in intracranial pressure and brain herniation are major clinical consequences in patients with acute hepatic encephalopathy (AHE). We recently reported that conditioned media (CM) from brain endothelial cells (ECs) exposed to ammonia, a mixture of cytokines (CKs) or lipopolysaccharide (LPS), when added to astrocytes caused cell swelling. In the present study we investigated the possibility that ammonia and inflammatory agents activate the toll-like receptor 4 (TLR4) in ECs, resulting in the release of factors that ultimately cause astrocyte swelling. We found a significant increase in TLR4 protein expression when ECs were exposed to ammonia, CKs or LPS alone, while exposure of ECs to a combination of these agents potentiated such effects. Additionally, astrocytes exposed to CM from TLR4-silenced ECs that were treated with ammonia, CKs or LPS, resulted in a significant reduction in astrocyte swelling. TLR4 protein upregulation was also detected in rat brain ECs after treatment with the liver toxin thioacetamide (TAA), and that TAA-treated TLR4 knock-out mice exhibited a reduction in brain edema. These studies strongly suggest that ECs significantly contribute to the astrocyte swelling/brain edema in AHE, likely as a consequence of increased TLR4 protein expression by blood-borne noxious agents. PMID:24261962

  19. DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy

    PubMed Central

    Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

    2017-01-01

    Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95–nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95–nNOS interactions in MHE. PMID:28932186

  20. Neuroprotective effects of guanosine administration on behavioral, brain activity, neurochemical and redox parameters in a rat model of chronic hepatic encephalopathy.

    PubMed

    Paniz, L G; Calcagnotto, M E; Pandolfo, P; Machado, D G; Santos, G F; Hansel, G; Almeida, R F; Bruch, R S; Brum, L M; Torres, F V; de Assis, A M; Rico, E P; Souza, D O

    2014-09-01

    It is well known that glutamatergic excitotoxicity and oxidative stress are implicated in the pathogenesis of hepatic encephalopathy (HE). The nucleoside guanosine exerts neuroprotective effects through the antagonism against glutamate neurotoxicity and antioxidant properties. In this study, we evaluated the neuroprotective effect of guanosine in an animal model of chronic HE. Rats underwent bile duct ligation (BDL) and 2 weeks later they were treated with i.p. injection of guanosine 7.5 mg/kg once a day for 1-week. We evaluated the effects of guanosine in HE studying several aspects: a) animal behavior using open field and Y-maze tasks; b) brain rhythm changes in electroencephalogram (EEG) recordings; c) purines and glutamate levels in the cerebral spinal fluid (CSF); and d) oxidative stress parameters in the brain. BDL rats presented increased levels of glutamate, purines and metabolites in the CSF, as well as increased oxidative damage. Guanosine was able not only to prevent these effects but also to attenuate the behavioral and EEG impairment induced by BDL. Our study shows the neuroprotective effects of systemic administration of guanosine in a rat model of HE and highlights the involvement of purinergic system in the physiopathology of this disease.

  1. Acute hepatitis due to hepatitis A virus subgenotype IA as an imported infectious disease from Indonesia.

    PubMed

    Utsumi, Takako; Yano, Yoshihiko; Amin, Mochamad; Lusida, Maria I; Soetjipto; Hotta, Hak; Hayashi, Yoshitake

    2014-10-01

    A 25-year-old Japanese man was admitted with general malaise and fever, which had developed 12 days after coming back to Japan from Indonesia. Blood examination revealed elevated transaminase levels and positivity for the IgM anti-HAV antibody; therefore, he was diagnosed with acute hepatitis A. HAV-RNA was detected in his serum and phylogenetically classified as subgenotype IA. The partial genome in the VP1/P2A region was consistent with the strain recently isolated from Surabaya, which indicated that he had been infected during his stay in Indonesia. Thus, HAV vaccination is recommended before visiting HAV-endemic countries for a long period of time.

  2. Metronidazole-induced encephalopathy in a patient with liver cirrhosis

    PubMed Central

    Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul

    2011-01-01

    Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis. PMID:21757988

  3. Infantile mitochondrial encephalopathy.

    PubMed

    Uziel, Graziella; Ghezzi, Daniele; Zeviani, Massimo

    2011-08-01

    Individually rare, when taken as a whole, genetic inborn errors of metabolism (IEM) account for a significant proportion of early onset encephalopathy. Prompt diagnosis is crucial to assess appropriate investigation and can sometimes warrant successful therapy. Recent improvements in technology and expansion of knowledge on the biochemical and molecular basis of these disorders allow astute child neurologists and paediatricians to improve the early diagnosis of these genetically determined defects. However, because of rarity and heterogeneity of these disorders, IEM encephalopathies are still a formidable challenge for most physicians. The most frequent cause of childhood IEM encephalopathy is mitochondrial disease, whose biochemical 'signature' is faulty energy supply due to defects of the last component of the oxidative pathways residing within mitochondria, i.e. the mitochondrial respiratory chain. Copyright © 2011. Published by Elsevier Ltd.

  4. Hot Topics in Primary Care: Diagnosis of Cirrhosis and Evaluation of Hepatic Encephalopathy: Common Errors and Their Significance for the PCP.

    PubMed

    Flamm, Steven L

    2017-04-01

    Cirrhosis has become the focus of greater attention in recent years largely because of the increasing prevalence of 2 of its most common causes: chronic viral hepatitis and steatohepatitis (a subset of nonalcoholic fatty liver disease [NAFLD]). Cirrhosis is the result of progressive destruction and regeneration of the liver parenchyma due to chronic liver disease (CLD).

  5. Hashimoto's Encephalopathy Presenting with Acute Cognitive Dysfunction and Convulsion.

    PubMed

    Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo

    2013-12-01

    Hashimoto's encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto's encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto's encephalopathy is very rare. We report a 65-year-old man who developed acute onset of cognitive decline and convulsion due to Hashimoto's encephalopathy.

  6. Cerebral glucose metabolism after portacaval shunting in the rat. Patterns of metabolism and implications for the pathogenesis of hepatic encephalopathy.

    PubMed Central

    Lockwood, A H; Ginsberg, M D; Rhoades, H M; Gutierrez, M T

    1986-01-01

    The regional cerebral metabolic rate for glucose was measured in normal and portacaval shunted rats and the effects of unilateral carotid infusions of "threshold" amounts of ammonia were assessed. 8 wk after shunting the glucose metabolic rate was increased in all 20 brain regions sampled. Effects on subcortical and phylogenetically older regions of the brain were most pronounced with a 74% increase observed in the reticular formation at the collicular level. Increases in the cerebral cortex ranged from 12 to 18%. Unilateral infusions of ammonia did not affect behavior but altered the electroencephalogram and selectively increased the glucose metabolic rate in the thalamus, hypothalamus, and substantia nigra in half of the animals, a pattern similar to that seen after a portacaval shunt, suggesting hyperammonemia as the cause of postshunt increases in glucose metabolism. Visual inspection of autoradiograms, computed correlation coefficients relating interregional metabolism, and principal component analysis suggest that normal cerebral metabolic and functional interrelationships are altered by shunting. Ammonia stimulation of the hypothalamic satiety centers may suppress appetite and lead to cachexia. Reductions in the ammonia detoxification capacity of skeletal muscle may increase the probability of developing future episodes of hyperammonemia, perpetuating the process. Direct effects of ammonia on specific brain centers such as the dorsomedial hypothalamus and reticular activating system may combine with global disruptions of cerebral metabolic-functional relationships to produce the protean manifestations of portal-systemic encephalopathy. Images PMID:3722388

  7. Acute enteral manganese intoxication with hepatic failure due to ingestion of a joint supplement overdose.

    PubMed

    Borchers, Angela; Epstein, Steven E; Gindiciosi, Blaz; Cartoceti, Andrew; Puschner, Birgit

    2014-09-01

    Manganese is a ubiquitous, essential trace element and a common ingredient of joint supplement tablets. Little information is known about the inherent toxic potential if ingested at higher doses. A 5-year-old female spayed Pug dog presented for evaluation of vomiting and ataxia after accidental ingestion of approximately 100 joint supplement tablets. The dog developed acute hepatic failure and was euthanized 6 days after presentation due to progression of the disease. Necropsy showed severe acute hepatic necrosis. Liver and kidney samples were submitted for toxicology analysis, results of which showed severely elevated manganese concentrations in the liver and kidneys.

  8. Oral mucosa alterations in chronic hepatitis and cirrhosis due to HBV or HCV infection.

    PubMed

    Sulka, Agnieszka; Simon, Krzysztof; Piszko, Paweł; Kalecińska, Ewa; Dominiak, Marzena

    2006-03-01

    The aim of the study was to evaluate the character of lesions within oral mucosa in patients suffering from chronic hepatitis and cirrhosis of the liver due to either HBV or HCV infection. A total of 74 patients treated at the Clinic of Infectious Diseases in Wrocław for chronic hepatitis B (20 patients, group I) and for chronic hepatitis C (23 patients group III) and cirrhosis of the liver due to HBV (15 patients , group II) and HCV (16 patients, group IV) infection. The control group comprised 29 healthy subjects. Lesions within the oral mucosa found on clinical examinations were confirmed with a histopathological evaluation. Patients suffering from chronic hepatitis B revealed leukoplakia (1/20), melanoplakia (1/20), petechiae (1/20), 17 patients from this group did not show any changes. Patients suffering from chronic hepatitis C revealed leukoplakia (6/23), Delbanco's disease (2/23), melanoplakia (1/23), lichen planus (1/23), petechiae (1/23), 12 patients from this group did not show any changes. Patients suffering from cirrhosis of the liver due of HBV infection revealed leukoplakia (3/15) petechiae (2/15), Delbanco's disease (1/15), angular cheilitis (1/15), aphthae (1/15), 7 patients from this group did not reveal any changes. Patients suffering from cirrhosis of the liver due of HCV infection revealed petechiae (2/16), melanoplakia (1/16), candidosis (1/16), labial herpes (1/16), 11 patients from this group did not reveal any changes. In control group we observed leukoplakia (3/29), Delbanco's disease (1/29), labial herpes (1/29), petechiae (1/29), and 23 subjects did not present pathological lesions within the oral mucosa. Results indicate the lack of connection between chronic HBV and HCV infection as well as the stage of the disease with the incidence and character of oral lesions in oral mucosa.

  9. Treatment of portal systemic encephalopathy: standard and new treatments.

    PubMed

    Marín, E; Uribe, M

    1990-07-01

    The management of hepatic encephalopathy should be considered accordingly with the precipitating factor and the type of encephalopathy. Ideally the therapeutic approach must be useful for both acute and chronic forms of encephalopathy. Current treatment of hepatic encephalopathy consists of certain well-established measures attempting to identify and treat the precipitating factors, and to reduce the intestinal nitrogenous compounds formation and absorption by dietary restriction or bowel-cleansing with catartics or antibiotics such as neomycin, metronidazol, etc. This review describes briefly several therapeutic modalities.

  10. Chinese herbal medicine formula Jieduhuayu granules improves cognitive and neurophysiological functions in patients with cirrhosis who have minimal hepatic encephalopathy: a randomized controlled trial.

    PubMed

    Yao, Chun; Huang, Guochu; Wang, Meng; Xia, Meng; Yao, Fan; Niu, Dengfeng; Zhang, Yuer; Li, Shan; Zhong, Yu

    2014-12-01

    Minimal hepatic encephalopathy (MHE) impairs patients' cognitive and neurophysiological functions. In this study, we investigated the effect of treatment-related improvement in cognitive and neurophysiological functions. We measured psychometric performance by number connection tests part A (NCT-A), digit symbol test (DST), mini-mental state examination (MMSE) and event related potential P300 wave of 80 patients with cirrhosis who have minimal hepatic encephalopathy on inclusion into the study and 15 days later. They were randomly assigned in a 1:1:1:1 ratio to four groups, to receive treatment of Chinese herbal medicine formula (HMG) or lactulose (LG) or Chinese herbal medicine formula combined with lactulose (HMCLG) for 15 days (n=20) or no treatment (CG) (n=20). This study was not blind. The mean number of NCT-A and MMSE scores improved significantly in patients in the HMG (0 day, 102.00±24.49 for NCT-A, 18.55±2.89 for MMSE; 15 days, 78.30±22.55 for NCT-A, 24.20±2.78 for MMSE) compared with patients in the CG after 15 days of follow-up (0 day, 103.00±24.98 for NCT-A, 17.90±2.99 for MMSE; 15 days, 95.65±24.34 for NCT-A, 18.85±3.12 for MMSE), P<0.05; the mean number of P300 latency (ms) and wave amplitude (μV) improved significantly among patients in the HMG after 15 days of treatment (0 day, 341.90±14.04 for latency, 8.40±1.73 for wave amplitude; 15 days, 305.45±23.95 for latency, 13.00±3.80 for wave amplitude) compared with patients in the CG after 15 days of follow-up (0 day, 343.85±14.88 for latency, 8.29±1.77 for wave amplitude; 15 days, 340.40±13.06 for latency, 8.50±1.82 for wave amplitude), P<0.05. Similar improvement were also found among patients in the LG and HMCLG; improvements among patients in the HMG were significantly greater than they were in the LG (P<0.05). Synergistic action were shown among patients in the HMCLG (P<0.05). Treatment with Chinese herbal medicine formula Jieduhuayu granules and lactulose may improve cognitive and

  11. Carnitine, acylcarnitine and amino acid profiles analyzed by tandem mass spectrometry in a surfactant/virus mouse model of acute hepatic encephalopathy.

    PubMed

    Murphy, M G; Crocker, J F S; O'Regan, P; Lee, S H S; Geldenhuys, L; Dooley, K; Al-Khalidi, M; Acott, P D

    2007-08-01

    Tandem mass spectrometry (MS/MS) was used to analyze multiple serum metabolites for the first time in a surfactant/virus mouse model of acute hepatic encephalopathy (AHE). AHE is characterized by acute liver failure that can lead to potentially lethal increases in intracranial pressure. We have reproduced AHE in young CD-1 mice exposed from postnatal day (P) 2-13 to the industrial surfactant, Toximul 3409F (Tox), and then infected intranasally on P14 with sublethal doses (LD(10-30)) of mouse-adapted human influenza B (Lee) virus (FluB). The sera analyzed by MS/MS were from mice exhibiting typical markers of Tox-mediated potentiation of viral illness, including reduced weights and blood glucose levels. Most metabolite abnormalities were not evident until five days after viral infection (P19), the time corresponding to the onset of weight loss and mortality. Values for fatty acylcarnitines and amino acids in the Tox+FluB-treated mice were either additive or supra-additive relative to the effects of either treatment alone. Amino acid profiles were consistent with those reported for human AHE. None of the treated mice exhibited signs of carnitine deficiency, and propionylcarnitine levels were normal. On P19, mice given combined Tox+FluB treatment had significant increases in levels of both medium- and long-chain acylcarnitines (C6:0-C12:0 and C14:0-C20:0, respectively), including their monounsaturated metabolites. Levels of medium-chain dicarboxylic and long-chain hydroxy-acylcarnitines were also elevated in the combined treatment group. The results of this study indicate a diffuse mitochondrial dysfunction in Tox+FluB-treated mice that results in a serum metabolite profile unique from those observed in classic inherited metabolic disorders.

  12. Nano optical sensor binuclear Pt-2-pyrazinecarboxylic acid -bipyridine for enhancement of the efficiency of 3-nitrotyrosine biomarker for early diagnosis of liver cirrhosis with minimal hepatic encephalopathy.

    PubMed

    Attia, M S; Al-Radadi, Najlaa S

    2016-12-15

    A new, precise, and very selective method for increasing the impact and assessment of 3-nitrotyrosine (3-Nty) as a biomarker for early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE) disease was developed. The method depends on the formation of the ion pair associate between 3-nitrotyrosine and the optical sensor binuclear Pt-2-pyrazinecarboxylic acid (pca)-Bipyridine (bpy) complex doped in sol-gel matrix in buffer solution of pH 7.3. The binuclear Pt (pca)(bpy) has +II net charge which is very selective and sensitive for [3-Nty](-2) at pH 7.3 in serum sample of liver cirrhosis with MHE diseases. 3-nitrotyrosine (3-Nty) quenches the luminescence intensity of the nano optical sensor binuclear Pt(pca) (bpy) at 528nm after excitation at 370nm, pH 7.3. The remarkable quenching of the luminescence intensity at 528nm of nano binuclear Pt(pca) (bpy) doped in sol-gel matrix by various concentrations of the 3-Nty was successfully used as an optical sensor for the assessment of 3-Nty in different serum samples of (MHE) in patients with liver cirrhosis. The calibration plot was achieved over the concentration range 1.85×10(-5) - 7.95×10(-10)molL(-1) 3-Nty with a correlation coefficient of (0.999) and a detection limit of (4.7×10(-10)molL(-1)). The method increases the sensitivity (93.75%) and specificity (96.45%) of 3-Nty as a biomarker for early diagnosis of liver cirrhosis with MHE in patients.

  13. Management of Transjugular Intrahepatic Portosystemic Shunt (TIPS)-associated Refractory Hepatic Encephalopathy by Shunt Reduction Using the Parallel Technique: Outcomes of a Retrospective Case Series

    SciTech Connect

    Cookson, Daniel T. Zaman, Zubayr; Gordon-Smith, James; Ireland, Hamish M.; Hayes, Peter C.

    2011-02-15

    Purpose: To investigate the reproducibility and technical and clinical success of the parallel technique of transjugular intrahepatic portosystemic shunt (TIPS) reduction in the management of refractory hepatic encephalopathy (HE). Materials and Methods: A 10-mm-diameter self-expanding stent graft and a 5-6-mm-diameter balloon-expandable stent were placed in parallel inside the existing TIPS in 8 patients via a dual unilateral transjugular approach. Changes in portosystemic pressure gradient and HE grade were used as primary end points. Results: TIPS reduction was technically successful in all patients. Mean {+-} standard deviation portosystemic pressure gradient before and after shunt reduction was 4.9 {+-} 3.6 mmHg (range, 0-12 mmHg) and 10.5 {+-} 3.9 mmHg (range, 6-18 mmHg). Duration of follow-up was 137 {+-} 117.8 days (range, 18-326 days). Clinical improvement of HE occurred in 5 patients (62.5%) with resolution of HE in 4 patients (50%). Single episodes of recurrent gastrointestinal hemorrhage occurred in 3 patients (37.5%). These were self-limiting in 2 cases and successfully managed in 1 case by correction of coagulopathy and blood transfusion. Two of these patients (25%) died, one each of renal failure and hepatorenal failure. Conclusion: The parallel technique of TIPS reduction is reproducible and has a high technical success rate. A dual unilateral transjugular approach is advantageous when performing this procedure. The parallel technique allows repeat bidirectional TIPS adjustment and may be of significant clinical benefit in the management of refractory HE.

  14. (1)H and (31)P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism.

    PubMed

    Rackayova, Veronika; Braissant, Olivier; McLin, Valérie A; Berset, Corina; Lanz, Bernard; Cudalbu, Cristina

    2016-12-01

    Chronic liver disease (CLD) leads to a spectrum of neuropsychiatric disorders named hepatic encephalopathy (HE). Even though brain energy metabolism is believed to be altered in chronic HE, few studies have explored energy metabolism in CLD-induced HE, and their findings were inconsistent. The aim of this study was to characterize for the first time in vivo and longitudinally brain metabolic changes in a rat model of CLD-induced HE with a focus on energy metabolism, using the methodological advantages of high field proton and phosphorus Magnetic Resonance Spectroscopy ((1)H- and (31)P-MRS). Wistar rats were bile duct ligated (BDL) and studied before BDL and at post-operative weeks 4 and 8. Glutamine increased linearly over time (+146 %) together with plasma ammonium (+159 %). As a compensatory effect, other brain osmolytes decreased: myo-inositol (-36 %), followed by total choline and creatine. A decrease in the neurotransmitters glutamate (-17 %) and aspartate (-28 %) was measured only at week 8, while no significant changes were observed for lactate and phosphocreatine. Among the other energy metabolites measured by (31)P-MRS, we observed a non-significant decrease in ATP together with a significant decrease in ADP (-28 %), but only at week 8 after ligation. Finally, brain glutamine showed the strongest correlations with changes in other brain metabolites, indicating its importance in type C HE. In conclusion, mild alterations in some metabolites involved in energy metabolism were observed but only at the end stage of the disease when edema and neurological changes are already present. Therefore, our data indicate that impaired energy metabolism is not one of the major causes of early HE symptoms in the established model of type C HE.

  15. pH-sensitive microemulsion-based gels for removal of colonic ammonia: a novel preventative oral preparation for hepatic encephalopathy in rats.

    PubMed

    Zhang, Chun-Le; Duan, Zhi-Jun; Tian, Ge; Tian, Yan; He, Gao-Hong; Bian, Teng-Fei; Jin, Xue; Sun, Xiao-Yu; Liu, Zhen; Chang, Qing-Yong

    2015-05-01

    Microemulsions with limited stability in mimetic gastrointestinal environments have previously demonstrated potential for the effective removal of ammonia from artificial colonic fluid. Specialized pH‑sensitive microemulsion‑based gels for the removal of colonic ammonia (MBG‑RCA), however, possess relative stability in the gastrointestinal (GI) tract of normal rats, indicating potential use in in vivo applications. An investigation of the effects of oral MBG‑RCA was conducted in order to evaluate the reduction of intestinal ammonia and the prevention of hepatic encephalopathy (HE) in rat models. Eighty rats were allocated into eight 4‑day treatment groups: The HE model (intraperitoneal injection of thioacetamide) group; the high‑, medium‑ and low‑dose MBG‑RCA therapeutic groups (15, 10 and 5 ml/kg MBG‑RCA, respectively); and the normal, blank, lactulose and acetic acid control groups, each of which received daily treatment administration. Oral MBG‑RCA effects were identified using behavioral monitoring observed by an infrared night vision supervisory control system, electroencephalograms, blood ammonia levels, intestinal ammonia levels, liver functionality and pathological observation. High‑ and medium‑dose oral administrations of MBG‑RCA significantly decreased the blood and intestinal ammonia levels (P<0.05), improved liver functionality and reduced the clinical manifestations of HE in rats. MBG‑RCA demonstrated high clearance of rat colonic ammonia while maintaining sufficient stability in the GI tract, indicating the potential for the development of new clinically relevant oral preparations for the prevention of HE. Additionally, such preparations are advantageous in that ammonia is eliminated without the production of potentially harmful metabolic byproducts.

  16. Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy.

    PubMed

    Nasehi, Mohammad; Mafi, Fatemeh; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2016-10-15

    Liver disease has been known for a long time to affect brain function. We now report the function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced by hepatic encephalopathy (HE) following bile duct ligation (BDL), a model of chronic liver disease. Assessment of spatial and object novelty detection memories was carried out in the non-associative task. It consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). Both spatial and object novelty detection memories were impaired by BDL after 4 weeks. In the BDL mice, pre-test intraperitoneal administration of naloxone (μ-opioidergic receptor antagonist) at dose of 0.9mg/kg restored while sulpiride (D2-like dopamine receptor antagonist) at dose of 40mg/kg potentiated object novelty detection memory deficit. However, SCH23390 (D1-like dopamine receptor antagonist) at dose of 0.04mg/kg or sulpiride (20mg/kg) restored spatial novelty detection memory deficit. Moreover, SCH23390 or sulpiride impaired while naloxone did not alter both memories in sham-operated mice. Furthermore, subthreshold dose co-administration of dopaminergic antagonists together or each one plus naloxone did not alter both memory impairments in BDL mice, while all of three co-administration groups impaired object novelty detection and co-administration of naloxone plus sulpiride impaired spatial detection memory in sham-operated mice. In conclusion, we suggest that opioidergic and dopaminergic systems through separate pathways may contribute in memory impairments induced by BDL in the non-associative task. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations.

    PubMed

    Felipo, Vicente; Piedrafita, Blanca; Barios, Juan A; Agustí, Ana; Ahabrach, Hanan; Romero-Vives, María; Barrio, Luis C; Rey, Beatriz; Gaztelu, Jose M; Llansola, Marta

    2015-01-01

    Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light.

  18. Cost-effectiveness analysis of rifaximin-α administration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France.

    PubMed

    Kabeshova, Anastasiia; Ben Hariz, Soumaia; Tsakeu, Elyonore; Benamouzig, Robert; Launois, Robert

    2016-07-01

    Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs most often in a context of acute or chronic liver disease. Despite the seriousness of the pathology, only a few treatments have been developed for improving its management. Rifaximin-α is the first treatment that has been clinically developed for overt HE (OHE) episodes. Recent results of clinical studies demonstrated its significant improvement in the health-related quality of life. The objective of the current study was to estimate the long-term cost-effectiveness of rifaximin-α used in combination with lactulose compared with lactulose monotherapy in cirrhotic patients, who have experienced at least two prior OHE events. A Markov model was used to estimate rifaximin-α cost-effectiveness, evaluating it from the perspective of all contributors as recommended by French health technology assessment guidelines. Costs were based on current French treatment practices. The transition between health states was based on the reanalysis of the rifaximin-α pivotal clinical trials RFHE3001 and RFHE3002. The main outcome of the model was cost per quality adjusted life year (QALY). The results indicate that rifaximin-α is a cost-effective treatment option with an incremental cost per QALY gained of €19,187 and €18,517 over two different time horizons (2 and 5 years). The robustness of the model was studied using probabilistic sensitivity analysis. For the societal willingness to pay threshold of €27,000 per QALY gained, rifaximin-α in combination with lactulose is a cost-effective and affordable treatment for patients who have experienced at least two prior overt HE episodes.

  19. The Influence of Finasteride on Mean and Relative Spectral Density of EEG Bands in Rat Model of Thioacetamide-Induced Hepatic Encephalopathy.

    PubMed

    Mladenović, D; Hrnčić, D; Rašić-Marković, A; Macut, Dj; Stanojlović, O

    Liver failure is associated with a neuropsychiatric syndrome, known as hepatic encephalopathy (HE). Finasteride, inhibitor of neurosteroid synthesis, may improve the course of HE. The aim of our study was to investigate the influence of finasteride on mean and relative power density of EEG bands, determined by spectral analysis, in rat model of thioacetamide-induced HE. Male Wistar rats were divided into groups: (1) control; (2) thioacetamide-treated group, TAA (900 mg/kg); (3) finasteride-treated group, FIN (150 mg/kg); and (4) group treated with finasteride (150 mg/kg) and thioacetamide (900 mg/kg), FIN + TAA. Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered during 3 subsequent days, and in FIN + TAA group FIN was administered 2 h before every dose of TAA. EEG was recorded 22-24 h after treatment and analyzed by fast Fourier transformation. While TAA did not induce significant changes in the beta band, mean and relative power in this band were significantly higher in FIN + TAA versus control group (p < 0.01). TAA caused a significant decline in mean power in alpha, theta, and delta band, and in FIN + TAA group the mean power in these bands was significantly higher compared with control. While in TAA group relative power was significantly decreased in theta (p < 0.01) and increased in delta band (p < 0.01) versus control, the opposite changes were found in FIN + TAA group: an increase in theta (p < 0.01) and a decrease in delta relative power (p < 0.01). In this study, finasteride pretreatment caused EEG changes that correspond to mild TAA-induced HE.

  20. Pancreatic encephalopathy

    PubMed Central

    Sharf, B.; Bental, E.

    1971-01-01

    A 58 year old woman presenting with abdominal distress and a neuropsychiatric disturbance with evidence of focal neurological deficit is described. A diagnosis of pancreatic encephalopathy was made, and the patient was treated accordingly with pancreatic anti-enzymes. A survey of the literature is presented. Images PMID:5315218

  1. Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

    PubMed

    Sonthalia, Nikhil; Pawar, Sunil V; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Rathi, Pravin M; Contractor, Qais

    2016-10-01

    Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Prolonged course of hepatic granulomatous disease due to Bartonella henselae infection.

    PubMed

    De Keukeleire, S; Geldof, J; De Clerck, F; Vandecasteele, S; Reynders, M; Orlent, M

    2016-01-01

    Cat-scratch disease (CSD) is an emerging zoonosis caused by Bartonella henselae. The disease is usually self-limiting and typically presents in about 90% of all cases as a subacute regional lymphadenopathy. We present a case report of an unusual CSD presentation, persistent hepatic granulomatous disease due to Bartonella henselae infection despite combination therapy with doxycycline and rifampicin. Furthermore, a review of literature was conducted. (Acta gastroenterol. belg., 2016, 79, 497-499). © Acta Gastro-Enterologica Belgica.

  3. Down-regulation of Kir4.1 in the cerebral cortex of rats with liver failure and in cultured astrocytes treated with glutamine: Implications for astrocytic dysfunction in hepatic encephalopathy.

    PubMed

    Obara-Michlewska, Marta; Pannicke, Thomas; Karl, Anett; Bringmann, Andreas; Reichenbach, Andreas; Szeliga, Monika; Hilgier, Wojciech; Wrzosek, Antoni; Szewczyk, Adam; Albrecht, Jan

    2011-12-01

    Brain edema in acute hepatic encephalopathy (HE) is due mainly to swelling of astrocytes. Efflux of potassium is implicated in the prevention of glial swelling under hypoosmotic conditions. We investigated whether pathogenic factors of HE, glutamine (Gln) and/or ammonia, induce alterations in the expression of glial potassium channels (Kir4.1, Kir2.1) and Na(+) -K(+) -2Cl(-) cotransporter-1 (NKCC1) in rat cerebral cortex and cultured rat cortical astrocytes and whether these alterations have consequences for potassium efflux and astrocytic swelling. Thioacetamide-induced acute liver failure in rats resulted in significant decreases in the Kir4.1 mRNA and protein contents of cerebral cortex, whereas expression of Kir2.1 and NKCC1 remained unaltered. Incubation of primary cortical astrocytes for 72 hr in the presence of Gln (5 mM), but not of ammonia (5 mM or 10 mM), induced a decrease in the levels of Kir4.1 mRNA and protein. Similarly to incubation with Gln, reduction of Kir4.1 mRNA expression by RNA interference caused swelling of astrocytes as shown by confocal imaging followed by 3D computational analysis. Gln reduced the astrocytic uptake of D-[(3) H]aspartate, but, in contrast to the earlier reported effect of ammonia, this reduction was not accompanied by decreased expression of the astrocytic glutamate transporter GLT-1 mRNA. Both Gln and ammonia decreased hypoosmolarity-induced (86) Rb efflux from the cells, but the effect was more pronounced with Gln. The results indicate that down-regulation of Kir4.1 may mediate distinct aspects of Gln-induced astrocytic dysfunction in HE.

  4. Wernicke encephalopathy and ethanol-related syndromes.

    PubMed

    Kim, Tae Eun; Lee, Eun Ja; Young, Jeong Bo; Shin, Dong Jae; Kim, Ji Hoon

    2014-04-01

    Ethanol causes diverse neurologic conditions caused by acute and chronic brain damage. This review provides an overview of Wernicke encephalopathy and other ethanol-related brain changes, such as chronic brain atrophy, Marchiafava-Bignami disease, osmotic demyelination syndrome, chronic hepatic encephalopathy, and acute alcohol withdrawal. As clinical symptoms of this spectrum of diseases have nonspecific neurologic alterations, radiologists should have current radiologic information and understand the imaging findings pertaining to the pathophysiology to support diagnosis.

  5. Gasoline sniffing and lead encephalopathy.

    PubMed Central

    Ross, C. A.

    1982-01-01

    Gasoline sniffing is endemic in northern Manitoba and perhaps throughout much of northern Canada. Its most serious complication is lead encephalopathy, which can be fatal. Most of the toxic effects are thought to be due to tetraethyl lead and its metabolites. The specific treatment is chelation therapy, for which a protocol has been developed at the Health Sciences Centre, Winnipeg. Lead encephalopathy, however, is a manifestation of social, cultural and psychologic malaise. PMID:7139470

  6. [Hashimoto encephalopathy].

    PubMed

    Pocsay, Gábor; Gazdag, Andrea; Engelhardt, József; Szaniszló, István; Szolnoki, Zoltán; Forczek, Gabriella; Mikló, László

    2013-08-18

    The authors present a case report and review the literature on Hashimoto encephalopathy. The onset of the disease may be marked by focal and then progressively generalized seizures or other neurological symptoms, but a cognitive decline or various psychiatric symptoms may also emerge. High levels of anti-thyroid peroxidase antibodies and/or anti-thyroglobulin antibodies are present in the serum. Corticosteroid treatment usually results in an improvement of symptoms. The syndrome is frequently overlooked and, therefore, the authors strongly recommend testing serum thyroid autoantibodies in cases with encephalopathy of unknown origin independently on the presence of thyroid disease in the patient or family history. The importance of long-term immunosuppressive treatment should also be stressed.

  7. KCNQ2 encephalopathy

    PubMed Central

    Millichap, John J.; Park, Kristen L.; Tsuchida, Tammy; Ben-Zeev, Bruria; Carmant, Lionel; Flamini, Robert; Joshi, Nishtha; Levisohn, Paul M.; Marsh, Eric; Nangia, Srishti; Narayanan, Vinodh; Ortiz-Gonzalez, Xilma R.; Patterson, Marc C.; Pearl, Phillip L.; Porter, Brenda; Ramsey, Keri; McGinnis, Emily L.; Taglialatela, Maurizio; Tracy, Molly; Tran, Baouyen; Venkatesan, Charu; Weckhuysen, Sarah

    2016-01-01

    Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments. Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients. Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures persisted in 9 patients. Development was delayed in all, severely in 14. The KCNQ2 variants identified introduced amino acid missense changes or, in one instance, a single residue deletion. They were clustered in 4 protein subdomains predicted to poison tetrameric channel functions. EZO use (assessed by the treating physicians and parents) was associated with improvement in seizures and/or development in 3 of the 4 treated before 6 months of age, and 2 of the 7 treated later; no serious side effects were observed. Conclusions: KCNQ2 variants cause neonatal-onset epileptic encephalopathy of widely varying severity. Pathogenic variants in epileptic encephalopathy are clustered in “hot spots” known to be critical for channel activity. For variants causing KCNQ2 channel loss of function, EZO appeared well tolerated and potentially beneficial against refractory seizures when started early. Larger, prospective studies are needed to enable better definition of prognostic categories and more robust testing of novel interventions. Classification of evidence: This study provides Class IV evidence that EZO is effective for refractory seizures in patients with epilepsy due to KCNQ2 encephalopathy. PMID:27602407

  8. Pulmonary and hepatic granulomatous disorders due to the inhalation of cement and mica dusts.

    PubMed Central

    Cortex Pimentel, J; Peixoto Menezes, A

    1978-01-01

    Hepatic and pulmonary granulomas were recognised in two workers exposed respectively to Portland cement and to muscovite dusts. The pulmonary lesions in the patient exposed to cement consisted of histiocytic granulomas and irregular fibrohyaline scars, and in the patient exposed to mica of a diffuse thickening of all interalveolar septa due to new formation of reticulin and collagen fibres and proliferation of fibroblasts and histiocytes. In the liver the following pathological findings were observed: focal or diffuse swelling of sinusoidal lining cells, sarcoid-type granulomas, and, in the case of mica exposure, perisinusoidal and portal tract fibrosis. Abundant inclusions of the inhaled material were identified within the pulmonary and hepatic lesions by histochemical and x-ray diffraction techniques. Images PMID:663882

  9. Severe early-onset epileptic encephalopathy due to mutations in the KCNA2 gene: Expansion of the genotypic and phenotypic spectrum.

    PubMed

    Hundallah, Khaled; Alenizi, Asma'a; AlHashem, Amal; Tabarki, Brahim

    2016-07-01

    Recently, de novo loss- or gain-of-function mutations in the KCNA2 gene; have been described in individuals with epileptic encephalopathy, ataxia or intellectual disability. In this report, we describe a further case of KCNA2-early-onset epileptic encephalopathy. The patient presented since birth with intractable seizures, progressive microcephaly, developmental delay, and progressive brain atrophy. Whole-exome sequencing showed a novel de novo mutation in the KCNA2 gene: c.1120A > G (p.Thr374Ala). This case expands the genotypic and phenotypic disease spectrum of this genetic form of KCNA2-early onset epileptic encephalopathy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  10. Hepatitis

    MedlinePlus

    ... CPR: A Real Lifesaver Kids Talk About: Coaches Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... have liver damage because of it. What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  11. Cognitive Reserve is a Determinant of Health-Related Quality of Life in Patients with Cirrhosis, Independent of Covert Hepatic Encephalopathy and MELD Score

    PubMed Central

    Patel, Ankit V; Wade, James B.; Thacker, Leroy R.; Sterling, Richard K; Siddiqui, Muhammad S; Stravitz, R Todd; Sanyal, Arun J; Luketic, Velimir; Puri, Puneet; Fuchs, Michael; Matherly, Scott; White, Melanie B.; Unser, Ariel; Heuman, Douglas M.; Bajaj, Jasmohan S.

    2014-01-01

    Background & Aims Covert hepatic encephalopathy (CHE) is associated with cognitive dysfunction, which affects daily function and health-related quality of life (HRQOL) in patients with cirrhosis. The effects of CHE and liver disease are determined by cognitive reserve—the ability of the brain to cope with increasing damage while continuing to function—and are assessed by composite intelligence quotient (IQ) scores. We examined cognitive reserve as a determinant of HRQOL in patients with cirrhosis. Methods We performed a prospective study of 118 outpatients with cirrhosis without overt HE (age, 56 years). We studied cognition using the standard paper-pencil battery; patients with below-normal results from more than 2 tests were considered to have CHE. We also assessed HRQOL (using the sickness impact profile, sickness impact profile (SIP), psychosocial and physical scores (a high score indicates reduced HRQOL), model for end-stage liver disease (MELD) scores, and cognitive reserve (using the Barona Index, a validated IQ analysis, based on age, race, education, residence area, and occupation). Cognitive reserve was divided into average and high groups (below or above 109), and MELD and SIP scores were compared. We performed regression analyses, using total SIP score and psychosocial and physical dimensions as outcomes, with cognitive reserve, CHE, and MELD score as predictors. Results Study participants had average MELD scores of 9, and 14 years of education; 81% were white, 63% were urban residents, their mean IQ was 108±8, and 54% had average cognitive reserve (the remaining 46% had high reserves). CHE was diagnosed in 49% of patients. Cognitive reserve was lower in patients with than CHE (109) than without (105, P=.02). Cognitive reserve correlated with total SIP and psychosocial score (both r= −0.4; P<.001) and physical score (r= −0.3; P=.01), but not MELD score (P=.8). Patients with high cognitive reserve had better HRQOL, despite similar MELD scores

  12. Lactulose is highly potential in prophylaxis of hepatic encephalopathy in patients with cirrhosis and upper gastrointestinal bleeding: results of a controlled randomized trial.

    PubMed

    Wen, Jing; Liu, Qingsen; Song, Jie; Tong, Muhong; Peng, Lihua; Liang, Hao

    2013-01-01

    Upper gastrointestinal bleeding (UGB) is an important precipitating factor for the development of hepatic encephalopathy (HE) in cirrhotic patients. The aim of this study was to evaluate the efficacy of lactulose in a controlled randomized trial for prophylaxis of HE after UGB. 128 cirrhotic patients with UGB were consecutively classified according to Child-Pugh criteria and randomized to receive lactulose (group A, n = 63) or no lactulose (group B, n = 65) treatment after the symptoms of active bleeding disappeared. Curative effects were observed for 6 days. Two patients in group A and 11 in group B had developed HE; the incidence rates were 3.2 and 16.9% (χ(2) 5.2061, p < 0.05). After treatment, a significant increase in ammonia level and higher number connection test (NCT) in the non-lactulose group, median blood ammonia levels (60.0 vs. 52.0), p < 0.05, and median NCT (43 vs. 38), p < 0.05, were observed. Patients who had developed HE had a significantly higher baseline Child-Turcotte-Pugh score (10.15 ±1.82 vs. 6.35 ± 1.60, p < 0.05), alanine aminotransferase (111.25 ± 91.62 vs. 48.32 ± 47.45, p < 0.05), aspartate aminotransferase (171.42 ± 142.68 vs. 46.33 ± 42.68, p < 0.05), total bilirubin (73.44 ± 47.20 vs. 29.75 ± 22.08, p < 0.05), serum albumin (24.65 ± 5.04 vs. 33.43 ± 6.49, p < 0.05), plasma prothrombin time (22.18 ± 4.60 vs. 17.12 ± 4.62, p < 0.05), and lower hemoglobin level (72.31 ± 15.15 vs. 87.45 ± 19.79, p < 0.05) as compared to patients who did not develop HE. On unconditional logistic regression analysis, patients who had developed HE were significantly associated with a higher baseline Child-Turcotte-Pugh score (OR 9.92, 95% CI 1.94-50.63, p < 0.05) and lactulose therapy (OR 0.02, 95% CI 0-0.74, p < 0.05) but were not associated with other parameters. Lactulose is an effective prophylaxis agent of HE for cirrhotic patients who had developed UGB. Copyright © 2013 S. Karger AG, Basel.

  13. Hepatic structural enhancement and insulin resistance amelioration due to AT1 receptor blockade.

    PubMed

    Souza-Mello, Vanessa

    2017-01-18

    Over the last decade, the role of renin-angiotensin system (RAS) on the development of obesity and its comorbidities has been extensively addressed. Both circulating and local RAS components are up-regulated in obesity and involved in non-alcoholic fatty liver disease onset. Pharmacological manipulations of RAS are viable strategies to tackle metabolic impairments caused by the excessive body fat mass. Renin inhibitors rescue insulin resistance, but do not have marked effects on hepatic steatosis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) yield beneficial hepatic remodeling. ARBs elicit body mass loss and normalize insulin levels, tackling insulin resistance. Also, this drug class increases adiponectin levels, besides countering interleukin-6, tumoral necrosis factor-alpha, and transforming growth factor-beta 1. The latter is essential to prevent from liver fibrosis. When conjugated with peroxisome proliferator-activated receptor (PPAR)-alpha activation, ARB fully rescues fatty liver. These effects might be orchestrated by an indirect up-regulation of MAS receptor due to angiotensin II receptor type 1 (AT1R) blockade. These associations of ARB with PPAR activation and ACE2-angiotensin (ANG) (1-7)-MAS receptor axis deserve a better understanding. This editorial provides a brief overview of the current knowledge regarding AT1R blockade effects on sensitivity to insulin and hepatic structural alterations as well as the intersections of AT1R blockade with peroxisome proliferator-activated receptor activation and ACE2-ANG (1-7) - MAS receptor axis.

  14. Hepatic structural enhancement and insulin resistance amelioration due to AT1 receptor blockade

    PubMed Central

    Souza-Mello, Vanessa

    2017-01-01

    Over the last decade, the role of renin-angiotensin system (RAS) on the development of obesity and its comorbidities has been extensively addressed. Both circulating and local RAS components are up-regulated in obesity and involved in non-alcoholic fatty liver disease onset. Pharmacological manipulations of RAS are viable strategies to tackle metabolic impairments caused by the excessive body fat mass. Renin inhibitors rescue insulin resistance, but do not have marked effects on hepatic steatosis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) yield beneficial hepatic remodeling. ARBs elicit body mass loss and normalize insulin levels, tackling insulin resistance. Also, this drug class increases adiponectin levels, besides countering interleukin-6, tumoral necrosis factor-alpha, and transforming growth factor-beta 1. The latter is essential to prevent from liver fibrosis. When conjugated with peroxisome proliferator-activated receptor (PPAR)-alpha activation, ARB fully rescues fatty liver. These effects might be orchestrated by an indirect up-regulation of MAS receptor due to angiotensin II receptor type 1 (AT1R) blockade. These associations of ARB with PPAR activation and ACE2-angiotensin (ANG) (1-7)-MAS receptor axis deserve a better understanding. This editorial provides a brief overview of the current knowledge regarding AT1R blockade effects on sensitivity to insulin and hepatic structural alterations as well as the intersections of AT1R blockade with peroxisome proliferator-activated receptor activation and ACE2-ANG (1-7) - MAS receptor axis. PMID:28144388

  15. [Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse reactions due to nimesulide in a case].

    PubMed

    Tejos, S; Torrejón, N; Reyes, H; Meneses, M

    2000-12-01

    A 66 year-old obese woman with arthrosis, self-medicated with oral nimesulide, 200 mg daily. After 6 weeks she developed nausea, jaundice and dark urine. Two weeks later she had recurrent hematemesis and was hospitalized. Besides obesity and anemia her physical examination was unremarkable. An upper GI endoscopy revealed 3 acute gastric ulcers and a 4th one in the pyloric channel. Abdominal ultrasonogram showed a slightly enlarged liver with diffuse reduction in ecogenicity; the gallbladder and biliary tract were normal. Blood tests demonstrated a conjugated hyperbilirubinemia (maximal total value: 18.4 mg/dl), ALAT 960 U/l, ASAT 850 U/l, GGT 420 U/l, alkaline phosphatases mildly elevated, pro-time 49% and albumin 2.7 mg/dl. Serum markers for hepatitis A, B and C viruses were negative. ANA, AMA, anti-SmA, were negative. Ceruloplasmin was normal. A liver biopsy showed bridging necrosis and other signs of acute toxic liver damage. Gastric ulcers healed after conventional treatment and hepatitis subsided after 2 months leaving no signs of chronic liver damage. The diagnosis of toxic hepatitis due to nimesulide was supported by the time-course of drug usage, sex, age, absence of other causes of liver disease, a compatible liver biopsy and the improvement after drug withdrawal. Peptic ulcers or toxic hepatitis have been previously described as independent adverse reactions in patients taking nimesulide or other NSAIDs but their simultaneous occurrence in a single patient is a unique event that deserves to be reported.

  16. Canine congenital portosystemic encephalopathy.

    PubMed

    Maddison, J E

    1988-08-01

    The case records of 21 dogs with congenital portosystemic encephalopathy are reviewed. The disorder was most common in Australian cattledogs (blue heelers; 8 cases), Old English sheepdogs (3 cases) and Maltese terriers (3 cases). Extra-hepatic shunts occurred in small breeds, with the exception of 1 cattledog, while intra-hepatic shunts occurred in the medium to large breeds. The most common clinical pathology abnormalities were abnormal ammonia tolerance, mild to moderate increases in plasma alanine aminotransferase or alkaline phosphatase concentrations, decreased total serum protein concentrations, increased fasting ammonia concentrations and ammonium biurate crystalluria. Radiological examination revealed that all the dogs had a small liver. The kidneys were enlarged in 5 of 10 dogs in which kidney size could be estimated. Surgical ligation of an extra-hepatic shunt was successful in 2 of 4 dogs in which it was attempted. Medical management resulted in alleviation of clinical signs in 5 of 8 dogs. The period of successful treatment ranged from a few months to over a year.

  17. Hashimoto encephalopathy: literature review.

    PubMed

    Zhou, J Y; Xu, B; Lopes, J; Blamoun, J; Li, L

    2017-03-01

    Hashimoto encephalopathy (HE) presents as an encephalopathy without central nervous system infection or tumor. HE is associated with autoimmune thyroiditis and is thus considered to be an autoimmune disorder. The prevalence of HE is low, but death and status epilepticus have been reported. HE manifests with a wide range of symptoms that include behavioral changes and confusion. Elevated thyroid antibodies are present in the majority of cases and are required for the diagnosis of HE. Normal brain MRI findings are found in the majority of patients diagnosed with HE. The most consistent CSF abnormality noted in HE patients is the presence of elevated protein. Most HE patients respond well to steroid therapy. Clinical improvements are also observed with IV immunoglobulin and plasmapheresis. In conclusion, it is now generally accepted that the diagnosis of HE must include encephalopathy characterized by cognitive impairment associated with psychiatric features, such as hallucinations, delusions, and paranoia. Autoimmune encephalitis and prion disease should be considered in the differential diagnosis due to the similarity of the clinical features of these conditions to those of HE. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Hepatitis

    MedlinePlus

    ... clotting problems or chronic liver disease. previous continue Hepatitis B and Hepatitis C Although hep A is a ... does — through direct contact with infected body fluids. Hepatitis B and C are even more easily passed in ...

  19. Hepatitis

    MedlinePlus

    ... A if they've been vaccinated against it. Hepatitis B Hepatitis B is a more serious infection. It may lead ... of which cause severe illness and even death. Hepatitis B virus (HBV) is transmitted from person to person ...

  20. Hepatitis

    MedlinePlus

    ... a problem with the liver itself What Is Hepatitis A? Hepatitis A virus (HAV) is contagious, usually spreading to others ... objects contaminated by feces (poop) containing HAV. The hepatitis A vaccine has helped to make the infection rare ...

  1. Affinities and densities of high-affinity (/sup 3/H)muscimol (GABA-A) binding sites and of central benzodiazepine receptors are unchanged in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy

    SciTech Connect

    Butterworth, R.F.; Lavoie, J.; Giguere, J.F.; Pomier-Layrargues, G.

    1988-09-01

    The integrity of GABA-A receptors and of central benzodiazepine receptors was evaluated in membrane preparations from prefrontal cortex and caudate nuclei obtained at autopsy from nine cirrhotic patients who died in hepatic coma and an equal number of age-matched control subjects. Histopathological studies revealed Alzheimer Type II astrocytosis in all cases in the cirrhotic group; controls were free from neurological, psychiatric or hepatic diseases. Binding to GABA-A receptors was studied using (/sup 3/H)muscimol as radioligand. The integrity of central benzodiazepine receptors was evaluated using (/sup 3/H)flunitrazepam and (/sup 3/H)Ro15-1788. Data from saturation binding assays was analyzed by Scatchard plot. No modifications of either affinities (Kd) or densities (Bmax) of (/sup 3/H)muscimol of central benzodiazepine binding sites were observed. These findings do not support recent suggestions that alterations of either high-affinity GABA or benzodiazepine receptors play a significant role in the pathogenesis of hepatic encephalopathy.

  2. Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B

    PubMed Central

    Lee, Yoon-Suk; Kim, Byung-Kook; Lee, Ho-Jae

    2016-01-01

    In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved. PMID:27247753

  3. HEPATIC VISCERAL LARVA MIGRANS DUE TO TOXOCARA CANIS IN A 72-YEAR-OLD MAN.

    PubMed

    Ko, Ki Dong; Lee, Jae Joon; Kim, Kyoung Kon; Suh, Heuy Sun; Hwang, In Cheol; Choi, Seung Joon

    2015-03-01

    Hepatic toxocariasis is visceral larva migrans caused by Toxocara. We report a case of hepatic toxocariasis detected incidentally during a health checkup. The patient had elevated levels of eosinophils, total IgE, and anti-Toxocara IgG antibodies. On contrast-enhanced computed tomography (CT) imaging he had a single, 2.16 cm, oval, ill-defined, low-attenuation hepatic nodule which was best appreciated during the portal venous phase of the scan. Clinicians should consider hepatic toxocariasis as a possible diagnosis in any individual who presents with eosinophilia of unknown etiology and an ill-defined hepatic lesion on CT imaging.

  4. Hepatic steatosis in hepatitis C is a storage disease due to HCV interaction with microsomal triglyceride transfer protein (MTP).

    PubMed

    Mirandola, Silvia; Bowman, David; Hussain, Mahmood M; Alberti, Alfredo

    2010-02-23

    Liver steatosis is a frequent histological feature in patients chronically infected with hepatitis C virus (HCV). The relationship between HCV and hepatic steatosis seems to be the result of both epigenetic and genetic factors. In vivo and in vitro studies have shown that HCV can alter intrahepatic lipid metabolism by affecting lipid synthesis, oxidative stress, lipid peroxidation, insulin resistance and the assembly and secretion of VLDL. Many studies suggest that HCV-related steatosis might be the result of a direct interaction between the virus and MTP. It has been demonstrated that MTP is critical for the secretion of HCV particles and that inhibition of its lipid transfer activity reduces HCV production. However, higher degrees of hepatic steatosis were found in chronic hepatitis C patients carrying the T allele of MTP -493G/T polymorphism that seems to be associated with increased MTP transcription. We propose here that liver steatosis in hepatitis C could be a storage disease induced by the effects of the virus and of its proteins on the intracellular lipid machinery and on MTP. Available data support the hypothesis that HCV may modulate MTP expression and activity through a number of mechanisms such as inhibition of its activity and transcriptional control. Initial up regulation could favour propagation of HCV while down regulation in chronic phase could cause impairment of triglyceride secretion and excessive lipid accumulation, with abnormal lipid droplets facilitating the "storage" of virus particles for persistent infection.

  5. Multicenter clinical study on Fuzhenghuayu capsule against liver fibrosis due to chronic hepatitis B

    PubMed Central

    Liu, Ping; Hu, Yi-Yang; Liu, Cheng; Xu, Lie-Ming; Liu, Cheng-Hai; Sun, Ke-Wei; Hu, De-Chang; Yin, You-Kuan; Zhou, Xia-Qiu; Wan, Mo-Bin; Cai, Xiong; Zhang, Zhi-Qing; Ye, Jun; Zhou, Ren-Xing; He, Jia; Tang, Bao-Zhang

    2005-01-01

    AIM: To study the efficacy and safety of Fuzhenghuayu capsule (FZHY capsule, a capsule for strengthening body resistance to remove blood stasis) against liver fibrosis due to chronic hepatitis B. METHODS: Multicenter, randomized, double blinded and parallel control experiment was conducted in patients (aged from 18 to 65 years) with liver fibrosis due to chronic hepatitis B. Hepatic histologic changes and HBV markers were examined at wk 0 and 24 during treatment. Serologic parameters (HA, LM, P-III-P, IV-C) were determined and B ultrasound examination of the spleen and liver was performed at wk 0, 12 and 24. Liver function (liver function and serologic parameters for liver fibrosis) was observed at wk 0, 6, 12, 18 and 24. Blood and urine routine test, renal function and ECG were examined before and after treatment. RESULTS: There was no significant difference between experimental group (110 cases) and control group (106 cases) in demographic features, vital signs, course of illness, history for drug anaphylaxis and previous therapy, liver function, serologic parameters for liver fibrosis, liver histologic examination (99 cases in experimental group, 96 cases in control group), HBV markers, and renal function. According to the criteria for liver fibrosis staging, mean score of fibrotic stage(s) in experimental group after treatment (1.80) decreased significantly compared to the previous treatment (2.33, P<0.05), but there was no significant difference in mean score of fibrotic stage(s) (2.11 and 2.14 respectively). There was a significant difference in reverse rate between experimental group (52%) and control group (23.3%) in liver biopsy. With marked effect on decreasing the mean value of inflammatory activity and score of inflammation (P<0.05), Fuzhenghuayu capsule had rather good effects on inhibiting inflammatory activity and was superior to that of Heluoshugan capsule. Compared to that of pretreatment, there was a significant decrease in HA, LM, P-III-P and IV

  6. [A Case of Renal Cell Carcinoma with High Everolimus Blood Concentrations and Hyperglycemia Due to Everolimus-Induced Hepatic Dysfunction].

    PubMed

    Takasaki, Shinya; Kikuchi, Masafumi; Kawasaki, Yoshihide; Ito, Akihiro; Arai, Yoichi; Yamaguchi, Hiroaki; Mano, Nariyasu

    2017-01-01

    We report the case of a patient who had renal cell carcinoma with high everolimus blood concentrations and hyperglycemia due to everolimus-induced hepatic dysfunction. A 74-year-old man who underwent right nephrectomy for renal cell carcinoma was administered everolimus for multiple lung metastases. Everolimus caused grade 3 hepatic dysfunction and hyperglycemia; hence, high blood levels of everolimus were observed. Although the patient was re-administrated everolimus after recovering from hepatic dysfunction, hepatic function test values worsened again. Everolimus was discontinued before its blood concentration increased, and the patient was switched to axitinib treatment. Therefore, the measurement of everolimus blood level is considered useful for the management of adverse events in renal cell carcinoma.

  7. Autoimmune encephalopathies

    PubMed Central

    Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

    2014-01-01

    Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

  8. [Posterior reversible encephalopathy syndrome].

    PubMed

    Petrović, Branko; Kostić, Vladimir; Sternić, Nadezda; Kolar, Jovo; Tasić, Nebojsa

    2003-01-01

    Reversible Posterior Leukoencephalopathy Syndrome was introduced into clinical practice in 1996 in order to describe unique syndrome, clinically expressed during hypertensive and uremic encephalopathy, eclampsia and during immunosuppressive therapy [1]. First clinical investigations showed that leucoencephalopathy is major characteristic of the syndrome, but further investigations showed no significant destruction in white cerebral tissue [2, 3, 4]. In majority of cases changes are localise in posterior irrigation area of the brain and in the most severe cases anterior region is also involved. Taking into consideration all above mentioned facts, the suggested term was Posterior Reversible Encephalopathy Syndrome (PRES) for the syndrome clinically expressed by neurological manifestations derived from cortical and subcortical changes localised in posterior regions of cerebral hemispheres, cerebral trunk and cerebellum [5]. Patient, aged 53 years, was re-hospitalized in Cardiovascular Institute "Dediwe" two months after successful aorto-coronary bypass performed in June 2001 due to the chest bone infection. During the treatment of the infection (according to the antibiogram) in September 2001, patient in evening hours developed headache and blurred vision. The recorded blood pressure was 210/120 mmHg so antihypertensive treatment was applied (Nifedipin and Furosemid). After this therapy there was no improvement and intensive headache with fatigue and loss of vision developed. Neurological examination revealed cortical blindness and left hemiparesis. Manitol (20%, 60 ccm every 3 hours) and i.v. Nytroglicerin (high blood pressure). Brain CT revealed oedema of parieto-occipital regions of both hemispheres, more emphasized on the right. (Figure 1a, b, c). There was no sign of focal ischemia even in deeper sections (Figure 1d, e, f). Following three days enormous high blood pressure values were registered. On the fourth day the significant clinical improvement occurred

  9. A global amnesia associated with the specific variant of posterior reversible encephalopathy syndrome (PRES) that developed due to severe preeclampsia and malignant hypertension

    PubMed Central

    Borovac, Josip Anđelo; Božić, Joško; Žaja, Nikola; Kolić, Krešimir; Hrboka, Vedran

    2016-01-01

    A case is reported of a 26-year-old primiparous woman in the 32nd week of gestation who presented to the emergency department with the symptoms of a severe headache, nausea and vomiting. The patient was diagnosed with preeclampsia that later progressed to eclampsia. This state was characterized by a sudden onset of a headache and diplopia that advanced to cortical blindness and precipitated significant alterations in mental status, most notable being global amnesia that resolved within 48 h. A post-partum magnetic resonance imaging of the brain in FLAIR mode revealed multiple cortico-subcortical areas of hyperintense signals suggestive of edematous lesions that chiefly involved occipital and parietal lobes with additional atypical manifestations. Such radiologic findings suggested a posterior reversible encephalopathy syndrome variant with the global amnesia as an extraordinary constituent. This unique feature should be acknowledged when treating a preeclamptic or hypertensive patient that exhibits neurological symptomatology and vision disturbances. PMID:27099774

  10. Analysis of hepatic gene expression during fatty liver change due to chronic ethanol administration in mice

    SciTech Connect

    Yin, H.-Q.; Je, Young-Tae; Kim, Mingoo; Kim, Ju-Han; Kong, Gu; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-IL; Lee, Mi-Ock; Lee, Byung-Hoon

    2009-03-15

    Chronic consumption of ethanol can cause cumulative liver damage that can ultimately lead to cirrhosis. To explore the mechanisms of alcoholic steatosis, we investigated the global intrahepatic gene expression profiles of livers from mice administered alcohol. Ethanol was administered by feeding the standard Lieber-DeCarli diet, of which 36% (high dose) and 3.6% (low dose) of the total calories were supplied from ethanol for 1, 2, or 4 weeks. Histopathological evaluation of the liver samples revealed fatty changes and punctate necrosis in the high-dose group and ballooning degeneration in the low-dose group. In total, 292 genes were identified as ethanol responsive, and several of these differed significantly in expression compared to those of control mice (two-way ANOVA; p < 0.05). Specifically, the expression levels of genes involved in hepatic lipid transport and metabolism were examined. An overall net increase in gene expression was observed for genes involved in (i) glucose transport and glycolysis, (ii) fatty acid influx and de novo synthesis, (iii) fatty acid esterification to triglycerides, and (iv) cholesterol transport, de novo cholesterol synthesis, and bile acid synthesis. Collectively, these data provide useful information concerning the global gene expression changes that occur due to alcohol intake and provide important insights into the comprehensive mechanisms of chronic alcoholic steatosis.

  11. Wernicke encephalopathy in alcoholics with diabetic ketoacidosis.

    PubMed

    Chamorro, Antonio J; Marcos-Martin, Miguel; Martin-Polo, Jorge; Garcia-Diez, Luis Carlos; Luna, Guillermo

    2009-01-01

    Wernicke encephalopathy is caused by thiamine deficiency in the central nervous system, and is defined by the triad of confusional symptoms, ocular alterations and ataxia. Some other factors may also predispose alcoholic patients to this deficiency. We report two patients with hyperglicaemia and ketoacidosis due to diabetes mellitus decompensation and chronic alcoholism who developed Wernicke encephalopathy before their hospital admission. The outcome was successful after intravenous thiamine administration and insulinotherapy. The presence of Wernicke encephalopathy in alcoholics with diabetic ketoacidosis, suggests that metabolic decompensation is essential in the onset of the disease.

  12. First case of anti-ganglioside GM1-positive Guillain-Barré syndrome due to hepatitis E virus infection.

    PubMed

    Maurissen, I; Jeurissen, A; Strauven, T; Sprengers, D; De Schepper, B

    2012-06-01

    A 51-year-old previously healthy woman presented with Guillain-Barré syndrome (GBS) and elevated liver enzymes. Further diagnostic investigations showed the presence of an acute hepatitis E infection associated with anti-ganglioside GM1 antibodies. After treatment with intravenous immunoglobulins, the patient made a rapid recovery. Here, we report the first case of GBS due to acute hepatitis E virus (HEV) infection associated with the presence of anti-ganglioside GM1 antibodies. We also review available literature on the association between acute HEV infection and GBS.

  13. Liver abscess developed after cadaveric liver transplantation due to ligation of an accessory right hepatic artery of the donor graft.

    PubMed

    Yu, Young-Dong; Kim, Dong-Sik; Byun, Geon-Young; Suh, Sung-Ock

    2012-10-01

    It is important that extrahepatic arteries are identified precisely at the time of graft procurement. We present a case where the accessory right hepatic artery of the liver was ligated leading to postoperative liver abscess formation in the liver graft. A forty-seven-year-old female patient diagnosed with liver cirrhosis underwent orthotopic cadaveric liver transplantation due to altered mentality. The donor graft showed a variant of the hepatic artery anatomy where an accessory right hepatic artery arose from the superior mesenteric artery. This artery was accidentally transected during procurement. Since the back bleeding test using perfusion fluid was good, the artery was ligated. Postoperative abdominal computed tomography scan revealed a 6 cm low attenuating lesion in the liver. The patient underwent conservative treatment. We believe that even small accessory arteries (1 to 2 mm) should be reconstructed whenever possible to avoid postoperative complications such as liver abscess.

  14. RiMINI - the influence of rifaximin on minimal hepatic encephalopathy (MHE) and on the intestinal microbiome in patients with liver cirrhosis: study protocol for a randomized controlled trial.

    PubMed

    Schulz, Christian; Schütte, Kerstin; Kropf, Siegfried; Schmitt, Friedhelm C; Vasapolli, Riccardo; Kliegis, Leon M; Riegger, Antonia; Malfertheiner, Peter

    2016-02-29

    Hepatic encephalopathy (HE) is a clinically significant complication of liver cirrhosis impacting on the patients' quality of life. Minimal hepatic encephalopathy (MHE) is diagnosed by psychometric tests, found in up to 80 % of patients with liver cirrhosis and carries a high risk of progression to overt HE. Continuous therapy with rifaximin in combination with lactulose significantly reduces the risk of overt HE, recurrence of HE and HE-related hospitalizations in randomized, double-blind, placebo-controlled clinical trials. Rifaximin is approved for the therapy of overt HE in Germany. Treatment with lactulose has been shown to improve cognitive functions in patients with liver cirrhosis. Data from prospective clinical trials comparing the efficacy of rifaximin alone against a combination of rifaximin and lactulose in the treatment of MHE are scarce. Changes in the microbiome of the upper and lower gastrointestinal tract as a result of therapy with rifaximin have not yet been addressed in clinical studies. RiMINI is a monocentric exploratory pilot study on 60 patients with MHE as assessed by critical flicker frequency (CFF). Additionally, visual evoked potentials' (VEP) testing, electroencephalography (EEG) and psychometric testing (NCT-A) will be carried out. Patients will be randomized to treatment either with rifaximin alone (550 mg twice daily (bid) continuously for a period of 3 months) or with rifaximin (550 mg bid continuously) in combination with lactulose (30-60 ml daily) for 3 months. An esophagogastroduodenoscopy (EGD) will be performed at baseline, at the end of treatment and 6 and 12 weeks after the end of treatment to obtain gastric and duodenal biopsies and aspirates. The samples will be analyzed for their content of specific bacterial taxae by applying next generation sequencing (NGS) after rRNA isolation to identify the microbiome of the stomach and duodenum, and of the gut, in patients with liver cirrhosis and MHE before and after therapy

  15. Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis: A randomized, double blind, placebo-controlled, multicenter clinical study

    PubMed Central

    Mao, Yi-Min; Zeng, Min-De; Lu, Lun-Gen; Wan, Mo-Bin; Li, Cheng-Zhong; Chen, Cheng-Wei; Fu, Qing-Chuen; Wang, Ji-Yao; She, Wei-Min; Cai, Xiong; Ye, Jun; Zhou, Xia-Qiu; Wang, Hui; Wu, Shan-Ming; Tang, Mei-Fang; Zhu, Jin-Shui; Chen, Wei-Xiong; Zhang, Hui-Quan

    2004-01-01

    AIM: To evaluate the efficacy and safety of oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: It was a randomized, double blind, placebo-controlled, multicenter clinical study. One hundred and forty-four patients were divided into oxymatrine capsule group(group A) and placebo group (group B).The course was 52 wk. Patients were visited once every 12 wk and the last visit was at 12 wk after cessation of the treatment. All patients had liver biopsy before treatment. part of them had a second biopsy at the end of therapy. Clinical symptoms, liver function test, serum markers of hepatic fibrosis were tested. Ultrasound evaluation was performed before, during and at the end of therapy. RESULTS: One hundred and forty-four patients enrolled in the study. Of them 132 patients completed the study according to the protocol,49 patients had liver biopsy twice (25 patients in group A and 24 in group B). At the end of therapy, significant improvements in hepatic fibrosis and inflammatory activity based on Semi-quantitative scoring system (SSS) were achieved in group A. The total effective rate of the treatment was 48.00%, much higher than that of 4.17% in group B (P < 0.05). Significant improvement in serum markers of hepatic fibrosis such as hyaluronic acid (HA) and type III procollagenic peptide (P III P) in group A was seen (P < 0.05). The total effective rate of serum markers at the end of therapy in group A was 68.19%, much higher than that of 34.85% in group B (P < 0.05). The total effective rate of noninvasive markers at the end of therapy in group A was 66.67%, much higher than that of 30.30% in group B (P < 0.05). The rate of adverse events was similar in two groups. CONCLUSION: Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis. PMID:15484298

  16. Wernicke encephalopathy in a patient with liver failure

    PubMed Central

    Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

    2016-01-01

    Abstract Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice. A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1. To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians’ awareness of its possible onset. PMID:27399058

  17. [Interferon-alpha and liver fibrosis in patients with chronic damage due to hepatitis C virus].

    PubMed

    Gonzalez-Huezo, María Sarai; Gallegos-Orozco, Juan Fernando

    2003-01-01

    The present review focuses on the published information published regarding the effects of interferon alpha therapy on liver fibrosis in patients with chronic liver damage secondary to hepatitis C infection. Data reviewed included results of the in vitro effects of interferon on hepatic cell line cultures with regards to indirect markers of fibrosis, activation of hepatic stellate cells and oxidative stress response. In the clinical arena, there is current clear evidence of a favorable histological outcome in patients with sustained viral response to interferon therapy. For this reason, the current review focuses more on the histological outcomes regarding liver fibrosis in patients who have not attained viral response to therapy (non-responders) or who already have biopsy defined cirrhosis. Data in these patients were analyzed according to the results of objective testing of fibrosis through the assessment of liver biopsy and its change during time, specially because the morbidity and mortality of this disease is directly related to the complications of liver cirrhosis and not necessarily to the persistence of the hepatitis C virus. Lastly, it is concluded that the process of liver fibrosis/cirrhosis is a dynamic one and that there is some evidence to support the usefulness of interferon alpha therapy as a means to halt or retard the progression of hepatic fibrosis. The result of current clinical trials in which interferon therapy is being used to modify the progression of fibrosis in non-responders or cirrhotic patients is eagerly awaited.

  18. Acute hepatitis due to shen-min: a herbal product derived from Polygonum multiflorum.

    PubMed

    Cárdenas, Andrés; Restrepo, Juan Carlos; Sierra, Fernando; Correa, Gonzalo

    2006-08-01

    Shen-Min is a herbal product sold as a supplement for women to enhance hair growth. It is widely available across Asia, Europe, and the United States and sold without prescription as a hair nutritional supplement. We describe a case of acute liver injury in a 28-year-old white woman who developed symptomatic hepatitis 8 weeks after starting Shen-Min. All other potential causes of acute hepatitis including viral, hypoxic/ischemic, metabolic, and autoimmune etiologies were excluded. The liver injury slowly resolved over 3 weeks after discontinuing the herbal product. Although the mechanism of Shen-Min hepatotoxicity is unknown, we suspect an idiosyncratic reaction because the patient developed a fine maculopapular rash, mild eosinophilia, and did not overdose. Shen-Min is a Chinese herbal product with a mixture of several plants and vitamins including Polygonum multiflorum, a root that has been previously associated with hepatotoxicity. Nonetheless to our knowledge this is the first reported case of herbal-induced hepatotoxicity in a patient taking Shen-Min per se. Clinicians taking care of patients with acute hepatitis of unclear etiology should be aware that the consumption of Shen-Min, a hair supplement widely available in the United States and Western countries might cause acute hepatitis.

  19. Hepatitis B reactivation in a long-term nonprogressor due to nivolumab therapy.

    PubMed

    Lake, Adam C

    2017-09-24

    : Hepatitis B virus (HBV) reactivation has been documented in association with multiple immunotherapy regimens . These reactivations can be life-threatening and result in fulminant hepatic failure. There are currently no reports of HBV reactivation on nivolumab treatment. This is a case of a patient with known HIV infection and previous HBV workup that revealed him to be anti-hepatitis B core antibody positive, hepatitis B surface antigen negative, and HBV DNA negative. He experienced a HBV reactivation while on therapy with nivolumab for stage IIIa poorly differentiated carcinoma of the lung, which was a recurrence from a prior surgically resected stage Ia well differentiated adenocarcinoma of the lung. He is a long-term nonprogressor in regards to his HIV and had previously had a negative HBV DNA level and had declined antiretroviral therapy until just prior to starting nivolumab. This case is also of interest as antiprogrammed death-1 receptors are involved in CD4-related HIV control , and the effects of nivolumab in a patient who was an HIV long-term nonprogressor are unknown. There was concern that he would develop increased HIV viremia and CD4-related immune dysfunction without antiretroviral therapy, and thus, he agreed to treatment prior to starting antineoplastic immunotherapy.

  20. Hepatitis A virus genotype IA-infected patient with marked elevation of aspartate aminotransferase levels.

    PubMed

    Miura, Yoshifumi; Kanda, Tatsuo; Yasui, Shin; Takahashi, Koji; Haga, Yuki; Sasaki, Reina; Nakamura, Masato; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Nishizawa, Tsutomu; Okamoto, Hiroaki; Yokosuka, Osamu

    2017-02-01

    We describe a case of acute liver failure (ALF) without hepatic encephalopathy with marked elevation of aminotransferase due to hepatitis A, according to the revised Japanese criteria of ALF. This liver biopsy of the patient showed compatible to acute viral hepatitis and she immediately recovered without intensive care. She had no comorbid disorders. Of interest, phylogenetic tree analysis using almost complete genomes of hepatitis A virus (HAV) demonstrated that the HAV isolate from her belonged to the HAV subgenotype IA strain and was similar to the HAJFF-Kan12 strain (99% nucleotide identity) or FH1 strain (98% nucleotide identity), which is associated with severe or fulminant hepatitis A. Careful interpretation of the association between HAV genome variations and severity of hepatitis A is needed and the mechanism of the severe hepatitis should be explored.

  1. Hepatitis

    MedlinePlus

    ... low because of routine testing of donated blood. Sexual transmission and transmission among family members through close contact ... associated with drinking contaminated water. Hepatitis Viruses ... B Blood, needles, sexual 10% of older children develop chronic infection. 90% ...

  2. Bovine Spongiform Encephalopathy

    USDA-ARS?s Scientific Manuscript database

    Bovine spongiform encephalopathy (BSE), also referred to as “mad cow disease” is a chronic, non-febrile, neuro-degenerative disease affecting the central nervous system. The transmissible spongiform encephalopathies (TSEs) of domestic animals, of which BSE is a member includes scrapie of sheep...

  3. Modification in CSF specific gravity in acutely decompensated cirrhosis and acute on chronic liver failure independent of encephalopathy, evidences for an early blood-CSF barrier dysfunction in cirrhosis.

    PubMed

    Weiss, Nicolas; Rosselli, Matteo; Mouri, Sarah; Galanaud, Damien; Puybasset, Louis; Agarwal, Banwari; Thabut, Dominique; Jalan, Rajiv

    2017-04-01

    Although hepatic encephalopathy (HE) on the background of acute on chronic liver failure (ACLF) is associated with high mortality rates, it is unknown whether this is due to increased blood-brain barrier permeability. Specific gravity of cerebrospinal fluid measured by CT is able to estimate blood-cerebrospinal fluid-barrier permeability. This study aimed to assess cerebrospinal fluid specific gravity in acutely decompensated cirrhosis and to compare it in patients with or without ACLF and with or without hepatic encephalopathy. We identified all the patients admitted for acute decompensation of cirrhosis who underwent a brain CT-scan. Those patients could present acute decompensation with or without ACLF. The presence of hepatic encephalopathy was noted. They were compared to a group of stable cirrhotic patients and healthy controls. Quantitative brain CT analysis used the Brainview software that gives the weight, the volume and the specific gravity of each determined brain regions. Results are given as median and interquartile ranges and as relative variation compared to the control/baseline group. 36 patients presented an acute decompensation of cirrhosis. Among them, 25 presented with ACLF and 11 without ACLF; 20 presented with hepatic encephalopathy grade ≥ 2. They were compared to 31 stable cirrhosis patients and 61 healthy controls. Cirrhotic patients had increased cerebrospinal fluid specific gravity (CSF-SG) compared to healthy controls (+0.4 %, p < 0.0001). Cirrhotic patients with ACLF have decreased CSF-SG as compared to cirrhotic patients without ACLF (-0.2 %, p = 0.0030) that remained higher than in healthy controls. The presence of hepatic encephalopathy did not modify CSF-SG (-0.09 %, p = 0.1757). Specific gravity did not differ between different brain regions according to the presence or absence of either ACLF or HE. In patients with acute decompensation of cirrhosis, and those with ACLF, CSF specific gravity is modified compared to

  4. The posterior reversible encephalopathy syndrome.

    PubMed

    Sanjay, K Mandal; Partha, P Chakraborty

    2008-09-01

    The posterior/potentially reversible encephalopathy syndrome is a unique syndrome encountered commonly in hypertensive encephalopathy. A 13-year-old boy presented with of intermittent high grade fever, throbbing headache and non-projective vomiting for 5 days. The patient had a blood pressure of 120/80 mmHg but fundoscopy documented grade 3 hypertensive retinopathy. The patient improved symptomatically following conservative management. However, on the 5(th) post-admission day headache reappeared, and blood pressure measured at that time was 240/120 mmHg. Neuroimaging suggested white matter abnormalities. Search for the etiology of secondary hypertension led to the diagnosis of pheochromocytoma. Repeated MRI after successful surgical excision of the tumor patient showed reversal of white matter abnormalities. Reversible leucoencephalopathy due to pheochromocytoma have not been documented in literature previously.

  5. Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment.

    PubMed

    Xu, Jingming; Sun, Shichun; Wei, Wei; Fu, Jianmin; Qi, Wenbo; Manchester, Lucien C; Tan, Dun-Xian; Reiter, Russel J

    2007-03-01

    The bipyridyl herbicide, diquat, is a potent prooxidant that generates superoxide anions through redox cycling in vivo. Exposure to elevated levels of this compound causes acute hepatic and renal toxicity as well as death in rodents. In the present study, we investigated whether melatonin, a free radical scavenger and antioxidant, could protect against diquat-induced hepatic and renal damage and whether the indole would improve survival of Kunming mice given a lethal dose of diquat. When mice were intraperitoneally (i.p.) given a single dose of diquat (50 mg/kg body weight), liver and kidney injuries were observed at 6 hr as indicated by elevated serum levels of both alanine aminotransferase (ALT) activity and blood urea nitrogen (BUN). In addition, lipid peroxidation levels in both liver and kidney showed significant increases as shown by elevated concentrations of F(2)-isoprostanes. The administration of melatonin (20 mg/kg) 30 min before the diquat injection resulted in a significant reduction in serum levels of ALT and BUN as well as hepatic and renal F(2)-isoprostanes levels. For the survival study, 75 mg/kg diquat was administered i.p. into mice to induce acute death. Without melatonin treatment, 10 of 23 (43.5%) mice died within 24 hr after diquat injection. Pretreatment with melatonin (20 mg/kg) 30 min prior to the injection of diquat and thereafter at 4-hr intervals until the end of the observation period (24 hr), reduced the death rate to two of 22 (9.1%) mice. Chi-squared test revealed a significant difference with P < or = 0.05. In conclusion, melatonin, a broad spectrum antioxidant, reduces hepatic and renal damage and lowers the death rate in diquat-treated mice.

  6. Metronidazole-induced encephalopathy: not always a reversible situation.

    PubMed

    Hobbs, Kyle; Stern-Nezer, Sara; Buckwalter, Marion S; Fischbein, Nancy; Finley Caulfield, Anna

    2015-06-01

    Metronidazole is a nitroimidazole antimicrobial drug prescribed to treat infections caused by anaerobic bacteria and protozoa. Uncommonly, it causes central nervous system (CNS) toxicity manifesting as metronidazole-induced encephalopathy (MIE). Case report. A 65-year-old woman with hepatitis B cirrhosis (Child-Pugh class C, MELD 21) developed progressive encephalopathy to GCS 4 during a 3-week course of metronidazole for cholecystitis. Initial MRI was consistent with CNS metronidazole toxicity, with symmetrical T2 hyperintensity and generally restricted diffusion in bilateral dentate nuclei, corpus callosum, midbrain, superior cerebellar peduncles, internal capsules, and cerebral white matter. Laboratory values did not demonstrate significant electrolyte shifts, and continuous EEG was without seizure. High-dose thiamine was empirically administered. Lumbar puncture was not performed due to coagulopathy and thrombocytopenia. Despite discontinuation of metronidazole and keeping ammonia levels near normal, the patient did not improve. MRI was repeated 1 week after discontinuation of metronidazole. Although there was decreased DWI hyperintensity in the dentate nuclei, diffuse T2 hyperintensity persisted and even progressed in the brainstem, basal ganglia, and subcortical white matter. Petechial hemorrhages developed in bilateral corticospinal tracts and subcortical white matter. T1 hypointensity appeared in the corpus callosum. She was transitioned to comfort measures only and died 12 days later. MIE is an uncommon adverse effect of treatment with metronidazole that characteristically affects the dentate nuclei but may also involve the brainstem, corpus callosum, subcortical white matter, and basal ganglia. While the clinical symptoms and neuroimaging changes are usually reversible, persistent encephalopathy with poor outcome may occur.

  7. Metabolic encephalopathy in Egyptian children.

    PubMed

    Hindawy, A; Gouda, A; El-Ayyadi, A; Megahed, H; Bazaraa, H

    2007-01-01

    Fatty Acid Oxidation disorders represent an expanding group of inborn errors of metabolism. Clinical manifestations include episodic encephalopathy, hypoketotic hypoglycemia, Reye like episodes, hepatic, muscular, cardiac affection and sudden death. Analysis of urinary organic acids and plasma fatty acids of 44 clinically suspected patients by Gas Chromatography Mass spectrometry revealed 4 cases of Medium chain acyl-CoA dehydrogenase deficiency (MCADD), 3 cases of Very long chain acyl-CoA dehydrogenase deficiency, 9 cases of multiple defects of acyl-CoA dehydrogenation in addition to 3 patients with other metabolic disorders. Timely detection of these disorders including screening for MCADD can have a favorable impact on the outcome of these patients (Tab. 11, Fig. 3, Ref. 24) Full Text (Free, PDF).

  8. Decreased exposure of atorvastatin in diabetic rats partly due to induction of hepatic Cyp3a and Oatp2.

    PubMed

    Shu, Nan; Hu, Mengyue; Liu, Can; Zhang, Mian; Ling, Zhaoli; Zhang, Ji; Xu, Ping; Zhong, Zeyu; Chen, Yang; Liu, Li; Liu, Xiaodong

    2016-10-01

    1. Atorvastatin is frequently prescribed for lowering blood cholesterol and for prevention of events associated with cardiovascular disease. The aim of this study was to investigate the pharmacokinetics of atorvastatin in diabetic rats. 2. Diabetes was induced in rats by combination of high-fat diet and low-dose streptozotocin (35 mg/kg). Plasma concentrations of atorvastatin following oral (10 mg/kg) and intravenous (2 mg/kg) administrations to rats were measured by LC-MS. Metabolism and uptake of atorvastatin in primary hepatocytes of experimental rats were assessed. Protein expressions and activities of hepatic Cyp3a and Oatp2 were further investigated. 3. Clearances of atorvastatin in diabetic rats following oral and intravenous administrations were remarkably increased, leading to marked decreases in area-under-the-plasma concentration-time curve (AUC). The estimated oral and systematic clearances of atorvastatin in diabetic rats were 4.5-fold and 2.0-fold of control rats, respectively. Metabolism and uptake of atorvastatin in primary hepatocytes isolated from diabetic rats were significantly increased, which were consistent with the up-regulated protein expressions and activities of hepatic Cyp3a and Oatp2. 4. All these results demonstrated that the plasma exposure of atorvastatin was significantly decreased in diabetic rats, which was partly due to the up-regulated activities and expressions of both hepatic Cyp3a and Oatp2.

  9. Metabolic Causes of Epileptic Encephalopathy

    PubMed Central

    Pearl, Phillip L.

    2013-01-01

    Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. Selected diseases are organized by the defective molecule or mechanism and categorized as small molecule disorders (involving amino and organic acids, fatty acids, neurotransmitters, urea cycle, vitamers and cofactors, and mitochondria) and large molecule disorders (including lysosomal storage disorders, peroxisomal disorders, glycosylation disorders, and leukodystrophies). Details including key clinical features, salient electrophysiological and neuroradiological findings, biochemical findings, and treatment options are summarized for prominent disorders in each category. PMID:23762547

  10. Noncirrhotic hyperammonaemic encephalopathy.

    PubMed

    Laish, Ido; Ben Ari, Ziv

    2011-10-01

    Adult hyperammonaemia is associated with severe liver disease in 90% of cases. In the remainder, noncirrhotic causes should be considered. Measurements of serum ammonia level must be part of the basic work-up in all patients presenting with encephalopathy of unknown origin, even when liver function is normal. Clinician awareness of noncirrhotic hyperammonaemic encephalopathy can contribute to early diagnosis and the initiation of sometimes life-saving treatment. This review focuses on the physiology, aetiology and underlying mechanisms of noncirrhotic hyperammonaemic encephalopathy and discusses the available treatment modalities.

  11. Hepatitis and splenitis due to systemic tetratrichomoniasis in an American white pelican (Pelecanus erythrorhynchos).

    PubMed

    Burns, Rachel E; Braun, Josephine; Armién, Aníbal G; Rideout, Bruce A

    2013-07-01

    A free-ranging, young adult, female American white pelican (Pelecanus erythrorhynchos), found dead on the grounds of the San Diego Zoo Safari Park in Southern California, had severe multifocal to coalescing necrotizing hepatitis and splenitis on postmortem examination. Histologically, within the large areas of necrosis were myriad pleomorphic, 5-20 µm in diameter, protozoal organisms with 1 to multiple nuclei. Ultrastructurally, the organisms were consistent with a trichomonad flagellate. Polymerase chain reaction and sequencing of the small subunit ribosomal RNA gene identified nucleotide sequences with 99% identity to Tetratrichomonas gallinarum, which is a common inhabitant of the intestinal tract of galliform and anseriform birds that has occasionally been associated with disease, including typhlitis and hepatitis. Damage to the cecal mucosa in the pelican from trematodes and secondary bacterial infection could have allowed invasion and systemic dissemination of the organism. Exposure of the pelican to a variety of native and exotic anseriform and galliform birds at the zoological institution could have led to cross-species infection and severe manifestation of disease in a novel host.

  12. The influence of hepatic insufficiency due to alcoholic cirrhosis on the erythrocyte transketolase activity (ETKA).

    PubMed

    Graudal, N; Torp-Pedersen, K; Bonde, J; Hanel, H K; Kristensen, M; Milman, N; Thomsen, A C

    1987-04-01

    The erythrocyte transketolase activity (ETKA), the stimulated erythrocyte transketolase activity (ETKAS), and the thiaminepyrophosphate effect (TPPE) were measured in 21 alcoholic patients with cirrhosis and hepatic insufficiency, 13 alcoholic patients without cirrhosis and 21 non-alcoholic persons before and after oral treatment with 100 mg of thiamine daily for 2 weeks in order to investigate the influence of hepatic insufficiency on these variables. A statistically significant rise in ETKA and fall in TPPE were found in all three groups. ETKA, ETKAS and TPPE did not differ from each other in alcoholic patients with and without cirrhosis, but TPPE was significantly higher in these patients than in the non-alcoholic persons. The conclusions are that severe cirrhosis does not affect the erythrocyte transketolase apoenzyme, the ability of the tissues to convert thiamine to thiaminepyrophosphate for use in the erythrocytes or the absorption of thiamine from the gastrointestinal tract. Besides alcoholism seems to dispose to thiamine deficiency to a higher degree than cirrhosis, and the role of the liver as a thiamine store appears to be of minor importance in the development of thiamine deficiency. Finally, ETKA, ETKAS, and TPPE are considered to be usable as thiamine deficiency indicators in patients with cirrhosis as well as in patients without cirrhosis.

  13. Natural History of Patients Taking Rifaximin-α for Recurrent Hepatic Encephalopathy and Risk of Future Overt Episodes and Mortality: A Post-hoc Analysis of Clinical Trials Data.

    PubMed

    Bannister, Christian A; Orr, James G; Reynolds, Alan V; Hudson, Mark; Conway, Peter; Radwan, Amr; Morgan, Christopher Ll; Currie, Craig J

    2016-05-01

    Hepatic encephalopathy (HE) is a complication of cirrhosis signaling decompensation and is associated with mortality. There has been little characterization of HE once an incident episode has occurred and of what effect the transition to overt HE might have on outcomes. We characterized the relationships between the number of previous HE episodes and risk of subsequent episodes and mortality to better understand the natural history of HE. Data on 321 patients from a 24-month, open-label, nonrandomized trial evaluating the long-term safety profile and tolerability of twice-daily rifaximin-α 550 mg were analyzed. Patients were followed for a mean of 1.5 years (total follow-up of 467 years). There were a total of 334 HE episodes and 75 deaths, corresponding to unadjusted event rates of 715 HE episodes and 161 deaths per 1000 years. There was a direct association between rate of subsequent HE episodes and number of prior HE episodes; the risk of subsequent HE episodes was elevated for each additional HE episode (hazard ratio = 1.23; 95% CI, 1.19-1.29). There was a nonlinear, nonmonotonic relationship between risk of death and number of prior HE episodes; risk initially increased, then decreased, and finally plateaued as the number of prior HE episodes increased. Patients with a larger number of previous, overt HE episodes had a greater risk for subsequent episodes. However, mortality risk decreased after the third episode of HE. A plausible hypothesis to explain this finding is that risk of mortality may be reduced in patients receiving long-term rifaximin-α therapy. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  14. Liver transplantation for acute hepatic failure due to chemotherapy-induced HBV reactivation in lymphoma patients

    PubMed Central

    Noterdaeme, Timothée; Longrée, Luc; Bataille, Christian; Deroover, Arnaud; Lamproye, Anne; Delwaide, Jean; Beguin, Yves; Honoré, Pierre; Detry, Olivier

    2011-01-01

    Hepatitis B (HBV) reactivation induced by chemotherapy is problem encountered recently in the management of malignant diseases. Chemotherapy-induced HBV reactivation may ultimately lead to terminal acute liver failure. Liver transplantation (LT) currently remains the only definitive treatment option for such cases, but is generally denied to patients suffering from malignancy. Here, the authors describe 2 cases of cancer-free and HBV graft re-infection-free survival after LT performed for terminal liver failure arising from HBV reactivation induced by chemotherapy for advanced stage lymphoma. These 2 cases, and some other reports in the literature, may suggest that patients suffering from hematologic malignancies and terminal liver disease can be considered for LT if the prognosis of their hematologic malignancy is good. PMID:21799656

  15. [Cerebral manifestations in the hepatic coma syndrome (author's transl)].

    PubMed

    Funovics, J

    1975-01-01

    The pathogenesis of hepatic encephalopathy has been investigated in a two-stage devascularization model in the rat with portavacal shunt and hepatic artery ligation. There is a significant increase in brain octopamine and phenylethanolamine and a decrease in brain norepinephrine (NE) 6 to 9 hours after hepatic artery ligation. The depletion of NE seems the sequel of diminished synthesis in the presence of an unaltered turnover rate, due to a blockade of tyrosine hydroxylase either by accumulation of false neurochemical transmitters or by phenylalanine. It is most marked in the cortex and midbrain. The high-energy phosphate compounds, ATP, phosphocreatine and glucose-6-phosphate are not diminished in hepatic coma, nor is glucose, indicating that other mechanism are involved in the pathogenesis of metabolic state by the increased ammonia level. "intestinal sterilization" and total colectomy have no significant effect on the ammonia level, but cause a decrease in the level or aromatic precursor amino acids in the plasma and brain, with normalization of the level of cerebral transmitters. These results permit the formulation of a unified concept of the hepatic coma syndrome and its clinical manifestations such as flapping tremor, the hyperdynamic cardiovascular state and the hepatorenal syndrome. Moreover, they form the basis for the introduction of a new therapeutic principle in the management of hepatic encephalopathy by L-dopa or modified amino acid solutions, which act by altering the central and peripheral neurotransmitters.

  16. Hypertensive brain stem encephalopathy.

    PubMed

    Liao, Pen-Yuan; Lee, Chien-Chang; Chen, Cheng-Yu

    2015-01-01

    A 48-year-old man presented with headache and extreme hypertension. Computed tomography showed diffuse brain stem hypodensity. Magnetic resonance imaging revealed diffuse brain stem vasogenic edema. Hypertensive brain stem encephalopathy is an uncommon manifestation of hypertensive encephalopathy, which classically occurs at parietooccipital white matter. Because of its atypical location, the diagnosis can be challenging. Moreover, the coexistence of hypertension and brain stem edema could also direct clinicians toward a diagnosis of ischemic infarction, leading to a completely contradictory treatment goal.

  17. Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight.

    PubMed

    Grunt, Sebastian; Steinlin, Maja; Weisstanner, Christian; Schöning, Martin; Mullis, Primus E; Flück, Christa E

    2013-01-01

    Prenatal glucocorticoid (GC) treatment of the female fetus with 21-hydroxylase deficiency (21-OHD) may prevent genital virilization and androgen effects on the brain, but prenatal GC therapy is controversial because of possible adverse effects on fetal programming, the cardiovascular system and the brain. We report 2 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD who were treated prenatally with dexamethasone, suffered from an acute encephalopathy and showed focal and multifocal cortical and subcortical diffusion restrictions in early MRI and signs of permanent alterations in the follow-up neuroimaging studies. Both patients recovered from the acute episode. Whereas the first patient recovered without neurological sequelae the second patient showed hemianopsia and spastic hemiplegia in the neurological follow-up examination. These are 2 children with CAH, both treated prenatally with high doses of dexamethasone to prevent virilization. The question arises whether prenatal high-dose GC treatment in patients with CAH might represent a risk factor for brain lesions in later life. Adverse effects/events should be reported systematically in patients undergoing prenatal GC treatment and long-term follow-up studies involving risk factors for cerebrovascular disease should be performed. Copyright © 2013 S. Karger AG, Basel.

  18. Portal-systemic encephalopathy in two patients without liver cirrhosis and portal hypertension.

    PubMed

    K C, Sudhamshu; Matsutani, Shoichi; Maruyama, Hitoshi; Fukamachi, Tadahiro; Nomoto, Hiromasa; Akiike, Taro; Ebara, Masaaki; Saisho, Hiromitsu

    2002-06-01

    The portal-systemic venous shunt is uncommon in patients without portal hypertension. We present two cases of portal-systemic encephalopathy due to extrahepatic shunt without liver cirrhosis and portal hypertension. Two women in their seventies were admitted to our hospital because of recurrent episodes of altered sensorium, drowsiness, slurred speech, disorientation, asterexis and high blood ammonia levels. There was no history of abdominal surgery or abdominal trauma. Clinical examination revealed no signs of portal hypertension or stigmata of chronic liver diseases. Brain CT and MRI scanning were unremarkable except for a high intensity signal in the basal ganglia on T1 weighted MRI images. Laboratory tests were almost normal except for the hyperammonemia occurring on several occasions. There was no evidence of liver cirrhosis by imaging. However, color Doppler showed an extra-hepatic shunt in both patients and pulsed Doppler showed decreased velocity and volume of the portal venous flow. These sonographic findings were confirmed during percutaneous transhepatic portography (PTP). Portal pressures measured during PTP were 9 and 11 mm