Edit concept Question Editor Create issue ticket

Hepatic Encephalopathy

Hepatic Encephalopathy Syndrome

Hepatic encephalopathy (HE) is a pathological condition defined by the spectrum of neuropsychiatric abnormalities which result from a liver dysfunction. It is known in the scientific community with a number of different names, such as portosystemic encephalopathy, liver encephalopathy or hepatic coma.


Presentation

HE presentation can be classified based on the grading of its symptoms with the West Haven classification system. According to this system, there are five different grades of HE described as follows:

Grade 0: No detectable changes in the patient’s personality; minimal changes in memory, coordination, intellectual function and concentration.

Grade 1: Minimal lack of awareness; decreased attention capability; hypersomnia, insomnia, or inverted sleep pattern; depression usually accompanied by alternated moments of euphoria and irritability; slowed mental task performance (especially mathematical operations); mild confusion.

Grade 2: Marked personality changes usually accompanied by inappropriate behavior and slurred speech; heavily reduced mental task performance; recurrent/intermittent time disorientation; frequent lethargy/apathy.

Grade 3: Compromised mental task performance; time and space disorientation; marked personality changes with confusion, incomprehensible speech, fits of rage and amnesia.

Grade 4: Coma frequently accompanied by the absence of painful stimuli response.

In grade zero and one HE is also defined as “covert”, because of the minimal evidence of symptoms. By contrast, in the remaining three grades HE is defined as “overt” because of the marked evidence of these symptoms [12] [13]. The 11th World Congress of Gastroenterology in Vienna (1998) decided to further classify HE based on the underlying cause [14], in a system which includes three types of disease: type A, associated with acute liver failure, type B, associated with portal-systemic shunting, and type C associated with cirrhosis.

Constipation
  • Dehydration due to various causes was the most common precipitant of overt HE, followed by acute kidney injury (AKI), constipation, and infections.[ncbi.nlm.nih.gov]
  • On admission, she had experienced constipation for seven days and exhibited a high serum ammonia level (251 μg/dL). She was diagnosed with liver cirrhosis as a result of autoimmune hepatitis, combined with Sjögren's syndrome.[ncbi.nlm.nih.gov]
  • Common precipitants of hepatic encephalopathy Renal failure Gastrointestinal bleeding Infection Constipation Sedative drugs e.g. opiates, benzodiazepines, antidepressantsand antipsychotic drugs Diuretics High protein intake Presentation of hepatic encephalopathy[oxfordmedicaleducation.com]
  • Among the potential co-factors in people with acute liver failure: Excessive alcohol use Kidney failure Constipation, which increases the intestinal production of ammonia Pneumonia Gastrointestinal bleeding, which often occurs in later-stage liver disease[verywell.com]
  • Etiology Reduced liver function (due to chronic hepatic disease) is a common finding, but are always other factors, which tilt the balance: bleeding in GIT infection high protein intake hypokalaemia drug involvement hypoxia constipation Pathogenesis There[wikilectures.eu]
Asterixis
  • Secondary end points were mortality from HE or any other cause, decrease in mental status grade, asterixis grade, serum Ammonia grade, NCT grade.[ncbi.nlm.nih.gov]
  • Clinical features include lethargy and confusion (frequently progressing to coma); asterixis; nystagmus, pathologic; brisk oculovestibular reflexes; decorticate and decerebrate posturing; muscle spasticity; and bilateral extensor plantar reflexes (see[icd9data.com]
  • There is usually asterixis and difficulty with writing and other fine motor skills. Patients are moderately obtunded, confused, and disoriented. There is accompanying fetor hepaticus and asterixis. Patients are stuporous with marked confusion.[enotes.tripod.com]
  • Asterixis can be detected. 26 27. Grade 2 Lethargy or apathy. Disorientation. Inappropriate behavior. Slurred speech. Obvious asterixis.[slideshare.net]
  • Definition / general A spectrum of neurocognitive abnormalities seen in patients with acute or chronic liver disease or portosystemic shunting Essential features Characterized by neurocognitive abnormalities, including asterixis, in patients with liver[pathologyoutlines.com]
Fetor Hepaticus
  • There is accompanying fetor hepaticus and asterixis. Patients are stuporous with marked confusion. They are barely responsive to painful stimuli. If it can be elicited, asterixis should be present.[enotes.tripod.com]
  • Moderate Confusion Asterixis Fetor hepaticus Hypothermia Hyperventilation Video on the pathophysiology of hepatic encephalopathy Investigations in hepatic encephalopathy Full septic screen Ascitic tap to check for SBP Digital rectal exam (DRE) to check[oxfordmedicaleducation.com]
  • Symptoms There is a disturbance of consciousness that may progress to deep coma (hepatic coma), psychiatric changes of varying degree, flapping tremor, and fetor hepaticus (breath odor associated with hepatic disease).[healthcentral.com]
  • Fetor hepaticus • This is a sour, musty odour in the breath, due to volatile substances normally formed in the stool by bacteria. • These mercaptans if not removed by the liver are excreted through the lungs and appear in the breath. • Fetor hepaticus[slideshare.net]
  • They may also have a flapping tremor (asterixis), fetor hepaticus (a sweet musty aroma of the breath), hyperventilation and hypothermia.[patient.info]
Epistaxis
  • Abstract Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by epistaxis, mucocutaneous telangiectasia with systemic manifestations due to visceral telangiectasia and arterio-venous malformations (AVMs).[ncbi.nlm.nih.gov]
Psychiatric Manifestation
  • HE produces a wide spectrum of nonspecific neurological and psychiatric manifestations. Minimal HE is diagnosed by abnormal psychometric tests.[ncbi.nlm.nih.gov]
Confusion
  • From Wikidata Jump to navigation Jump to search brain disease that is characterized by loss of brain function, the occurrence of confusion, altered level of consciousness, and coma that results when the liver is unable to remove toxins from the blood[wikidata.org]
  • Clinical features include lethargy and confusion (frequently progressing to coma); asterixis; nystagmus, pathologic; brisk oculovestibular reflexes; decorticate and decerebrate posturing; muscle spasticity; and bilateral extensor plantar reflexes (see[icd9data.com]
  • Grade 1 : mild confusion, euphoria or depression, decreased attention, slowing of ability to perform mental tasks, irritability, disorder of sleep pattern such as inverted sleep cycle.[oxfordmedicaleducation.com]
  • 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[ncbi.nlm.nih.gov]
Seizure
  • All told, between 30 and 45 percent of people with cirrhosis will develop some signs of hepatic encephalopathy, whether it be mild forms of forgetfulness or more severe bouts of amnesia or seizures.[verywell.com]
  • A CT scan of the brain may be required to exclude haemorrhage, and if seizure activity is suspected an electroencephalograph (EEG) study may be performed.[en.wikipedia.org]
  • However, sometimes is the brain damage reversible and the seizures recur (so called chronic hepatic encephalopathy). Unfortunatelly, they still progress and after months or years they lead to the irreversible damage.[wikilectures.eu]
  • […] include: Changes in sleep patterns Mild confusion Difficulty thinking Problems with handwriting Forgetfulness Poor judgment or concentration More severe symptoms can include: Tremor or abnormal movements Severe confusion Slurred speech Slowed movement Seizures[medicine.mc.vanderbilt.edu]
  • […] function tests Kidney function tests Imaging tests of the liver Your doctor may also order tests to assess your brain and nervous system such as: Images of the brain with MRI scan or CT scan EEG to look at brain waves for evidence of encephalopathy and/or seizures[uvahealth.com]
Lethargy
  • Clinical features include lethargy and confusion (frequently progressing to coma); asterixis; nystagmus, pathologic; brisk oculovestibular reflexes; decorticate and decerebrate posturing; muscle spasticity; and bilateral extensor plantar reflexes (see[icd9data.com]
  • Hepatic encephalopathy typically presents with confusion, lethargy, and sometimes dramatic changes in behavior and motor skills. If left untreated, the disease could gradually progress to a coma (coma hepaticum) or even death.[verywell.com]
  • View/Print Table West Haven Criteria for Grading of Mental Status Grade Criteria Grade 0 No signs or symptoms Grade 1 Trivial lack of awareness Euphoria or anxiety Shortened attention span Impaired performance of addition Grade 2 Lethargy or apathy Minimal[aafp.org]
  • Grade 2 : drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behaviour, intermittent disorientation.[oxfordmedicaleducation.com]
  • The second stage is marked by lethargy and personality changes. The third stage is marked by worsened confusion.[en.wikipedia.org]
Somnolence
  • Clinically overt HE includes personality changes, alterations in consciousness progressive disorientation in time and space, somnolence, stupor and, finally, coma. Except for clinical studies, no specific tests are required for diagnosis.[ncbi.nlm.nih.gov]
  • […] awareness Euphoria or anxiety Shortened attention span Impaired performance of addition Grade 2 Lethargy or apathy Minimal disorientation for time or place Subtle personality change Inappropriate behavior Impaired performance of subtraction Grade 3 Somnolence[aafp.org]
  • Grade 3 : somnolent but rousable, unable to perform mental tasks, disorientation to time and place, marked confusion, amnesia, occasional fits of rage, speech is present but incomprehensible.[oxfordmedicaleducation.com]
  • In the intermediate stages, a characteristic jerking movement of the limbs is observed (asterixis, "liver flap" due to its flapping character); this disappears as the somnolence worsens.[en.wikipedia.org]
  • Back to the Case Our patient has severe HE manifested by worsening somnolence.[the-hospitalist.org]
Stupor
  • Clinically overt HE includes personality changes, alterations in consciousness progressive disorientation in time and space, somnolence, stupor and, finally, coma. Except for clinical studies, no specific tests are required for diagnosis.[ncbi.nlm.nih.gov]
  • ., Principles of Neurology, 6th ed, pp1117-20; plum & posner, diagnosis of stupor and coma, 3rd ed, p222-5) Syndrome characterized by central nervous system dysfunction in association with liver failure, including portal-systemic shunts; clinical features[icd9data.com]
  • Clinical manifestations vary from confusion, somnolence, and disorientation to stupor and coma. This article describes the diagnosis as well as management of the condition.[medlink.com]
  • Stupor & coma may develop rapidly within several days of onset of symptoms.[enotes.tripod.com]
  • About Hepatic Encephalopathy Hepatic encephalopathy is a debilitating and progressive complication of liver cirrhosis or liver failure, marked by mental changes including confusion, impaired motor skills, disorientation, and in its more severe form, stupor[globenewswire.com]

Workup

Diagnosis of HE is very difficult, as diseases with similar symptoms are many and differential diagnoses is very frequent [15]. Therefore, diagnosis of HE can only be made when the presence of a liver disorder or a portosystemic shunt has been confirmed with a liver function test or ideally a liver biopsy [16] [17].

Hemorrhage and seizures also have symptoms very similar to those of HE, but this conditions can be easily detected with CT scan of the brain or electroencephalography. The presence of HE can be further confirmed with other examinations such as chest X-ray, blood tests or urinalysis. In addition, there are a number of neurological tests [14] [18] [19] which might be very useful to diagnose the disorder, but they are not very frequently employed and the decision to use them should be based on the severity of the patient’s mental dysfunction.

Triphasic Waves
  • Electroencephalography may demonstrate triphasic waves.[icd9data.com]
  • EEG High-amplitude low-frequency waves and triphasic waves – not specific for hepatic encephalopathy.[oxfordmedicaleducation.com]
  • Electroencephalogram (EEG): may show high-amplitude low-frequency waves and triphasic waves but these findings are not specific for hepatic encephalopathy, although recent work suggests EEG may be useful prognostically. [ 6 ] MRI/CT scanning can help[patient.info]
  • Electroencephalography shows no clear abnormalities in stage 0, even if minimal HE is present; in stages I, II and III there are triphasic waves over the frontal lobes that oscillate at 5 Hz, and in stage IV there is slow delta wave activity.[en.wikipedia.org]
  • Electroencephalogram Electroencephalography shows no clear abnormalities in stage 0, even if minimal HE is present; in stages I, II and III there are triphasic waves over the frontal lobes that oscillate at 5 Hz, and in stage IV there is slow delta wave[slideshare.net]
Hyponatremia
  • Risk Factors that increase your chances of developing hepatic encephalopathy include: Certain conditions that affect the levels of fluids and electrolytes such as hyponatremia and hyperkalemia Kidney failure Infections Gastrointestinal bleeding Certain[uvahealth.com]
  • […] most common): 50% 4 excessive nitrogen-containing intestinal load gastrointestinal bleed (e.g. from varices ) dietary intake of large quantities of protein (e.g. meat) reduced nitrogen excretion constipation renal failure metabolic or drug interactions hyponatremia[radiopaedia.org]
  • . • Electrolyte or metabolic disturbance-hypokalaemia, hyponatremia, alkalosis, dehydration, excess vomiting. • Infections- pneumonia, UTI, spontaneous bacterial peritonitis. • Unknown- 20-30% 7 8. PATHOGENESIS 1.[slideshare.net]
Hepatic Necrosis
  • necrosis and coma due to toxic liver disease Hepatitis w hepatic coma Hepatitis with hepatic coma Subacute liver failure w coma Subacute liver failure with coma Toxic liver disease w hepatic necrosis, w coma Toxic liver disease with hepatic necrosis,[icd9data.com]

Treatment

Treatment for patients affected by HE depends on the its underlying cause, be it an acute liver failure (type A), a portal-systemic shunting (type B) or cirrhosis (type C). If necessity requires it, the physician might choose to send the patient to a specialist centre and receive the appropriate procedures, such as liver transplant or shunt occlusion. In regard to the treatments themselves, these can be divided in two groups, those which aim at decreasing intestinal ammonia production and those which aim at increasing ammonia clearance.

Among the treatments which aim at decreasing intestinal ammonia production there is the modification of diet. Risk of HE can be decreased in subjects affected with chronic liver disease by using a diet with adequate protein supply [16] [20], and the addition of suitable substances like lactulose can help treat the disorder when it occurs. In fact, the conversion of disaccharides lactulose to lactic acid causes gut lumen acidification and conversion of NH4 to NH3, which in turn inhibits ammoniagenic coliform bacteria and increases levels of nonammoniagenic lactobacilli. Ammoniagenic bacteria population can also be decreased by using a number of appropriate antibiotics, such as neomycin, metronizadole and especially rifaximin [21].

Among the treatments which aim at decreasing ammonia clearance there is the regimen with LOLA, a stable salt of the two constituent amino acids l-ornithine and l-aspartate. LOLA stimulates the urea cycle and both amino acids are substrates for glutamate transaminase, whose activity increases glutamate levels. Ammonia is then used to convert glutamate to glutamine through the activity of glutamine synthetase.  The urea cycle can be further increased by zinc administration, as zinc improves the activity of  ornithine transcarbamylase, one of the key enzymes of the urea cycle. Other substances with similar effects on ammonia clearance include sodium benzoate, sodium phenylbutyrate, sodium phenylacetate and glycerol phenylbutyrate [22] [23] [24].

Prognosis

HE presents frequent complications which affect daily life activities, like deficits in working memory, psychomotor speed, attention, and response inhibition [5] [6] [7]. These effects significantly decrease the patients quality of life [8] [9] [10] and financial status, which in addition to the high rates of hospital admissions [11] make HE a serious burden for healthcare programs.

Etiology

As previously mentioned, the major function of the liver is to break down the substances in the body and, if these are poisonous, make them harmless. When a liver dysfunction occurs, these toxins begin to build up in the bloodstream, until they reach particularly dangerous high concentrations. A classical example of poisonous compound is ammonia, produced in the body as a protein metabolism waste product. Other examples of putative neurotoxic substances include short-chain fatty acids, mercaptans, false neurotransmitters (like tyramine) or gamma-aminobutyric acid.

At present the exact cause of HE is unknown. A number of theories have been proposed to explain its development, and the scientific consensus in this regard appears to mainly support the idea of HE being a disorder of the astrocytes. Astrocytes are the characteristic star-shaped glial cells in the central nervous system collectively known as astroglia. They perform several supportive functions, including nutrients supply, biochemical support, ion-balance maintenance and repair. The neurotoxins which enter the brain contribute to several morphological changes in astrocytes, such as swelling and the appearance of large pale nuclei, that in the end lead to brain dysfunction. These physiological changes might even involve changes in gene expression, especially for those genes which code for transporter proteins.

Epidemiology

The majority of the epidemiological data comes from the subjects affected by advanced liver diseases. When it comes to understanding the origin of HE, it is often difficult to assess the burden of a chronic liver disease, as this often has an insidious onset and a long period of latency. Therefore, most patients start seeking for medical assistance when the disease is well on its way to reaching its full development.

HE can appear in patients in both a mild form known as minimal hepatic encephalitis (MHE) and a fully symptomatic overt form know as over hepatic encephalopathy (OHE). Data about the incidence and prevalence of HE is still insufficient. Anyway, according to some studies carried out in the United States, of the 150,000 individuals which are annually diagnosed with chronic liver diseases, cirrhosis accounts for 20% of the cases while chronic hepatitis C accounts for almost two-thirds [1]. Furthermore, while the prevalence of hepatitis C is decreasing, that of cirrhosis is expected to increase in the next two decades [2].

It is believed that most of the patients affected by cirrhosis will develop some degree of HE at some point of the course of their liver disease. According to recent data, it appears that MHE occurs in up to 80% of the cirrhotic patients, while OHE occurs in up to 45% of the cases. OHE also appears in up to 50% of the patient with surgical complications and sometime as complication of an acute liver failure [3]. After the first episode of OHE, the probability to survive is 42% in the first year of follow-up and 23% in the third [4].

Sex distribution
Age distribution

Pathophysiology

One of the most important theories used to explain why liver dysfunction and portosystemic shunting lead to HE is the theory of the nitrogen-containing compounds. Nitrogen-containing compounds come from the gastrointestinal system through the portal vein. After getting into the liver, 80-90% of them will then be metabolized through the urea cycle and excreted through the urogenital system. In all the subtypes of HE the nitrogen-compounds disposal mechanism is impaired, either because hepatocytes are no longer capable of metabolizing these substances or because the shunt that bypasses the liver leads the nitrogen-rich compounds right into the systemic circulation. The shunt can be the product of either a collateral circulation or of a surgery.  

One of the most important nitrogen-rich compounds is ammonia (NH3), a substance which crosses the blood-brain barrier and is absorbed by astrocytes. Astrocytes use ammonia to synthesize glutamine from glutamate, through the activity of the glutamine synthetase. However, in contrast to what happens in other types of cells, such as skeletal muscles and kidney cells, astrocytes are not capable of increasing the glutamine synthetase activity in the setting of hyperammonemia, making the brain extremely vulnerable to the high ammonia concentrations. The high ammonia concentration has multiple neurotoxic effects, like altered transits of amino acids, water and other electrolytes across astrocytes and neurons, in addition to reduced amino acid metabolism, modified energy utilization, and impaired capacity to generate excitatory and inhibitory postsynaptic potentials.

Another important hypothesis used to explain why liver dysfunction and portosystemic shunting lead to HE is the GABA theory. GABA is a neuroinhibitory substance produced in the gastrointestinal tract and found in around 25% of the brain nerve endings. It is believed that the increased GABA plasma levels during HE would cause an influx of chloride ions into the postsynaptic neurons and the subsequent generation of inhibitory potentials. However, experimental data shows no change in the brain GABA levels or in the sensitivity of GABA receptor complex in subjects affected by HE [5].

Prevention

Since HE often comes as a complication of a liver disease, the best way to prevent it is to take steps to prevent the liver disease itself. These include avoiding alcohol and high-fat food consumption, losing weight in excess and steps to prevent viral hepatitis, like frequent hand washing and having no contact with infected subjects. 

Summary

This physiological dysfunction prevents the liver from breaking down and removing several toxic substances which begin to flow freely around the body. The main features of hepatic encephalopahty (HE) include intellectual impairment, personality changes and severely reduced consciousness levels, possibly due to the presence of substances with neurotoxic effects. HE usually occurs in subjects affected by liver cirrhosis and in those with either spontaneous or surgically created vascular shunts.

Patient Information

Hepatic encephalopathy (HE) is a pathological condition defined by the spectrum of neuropsychiatric abnormalities which result from a liver dysfunction. This physiological dysfunction prevents liver from breaking down and removing several toxic substances, which begin to flow freely around the body. A classical example of poisonous compound is ammonia, produced in the body as protein metabolism waste product. Ammonia has a number of toxic effects over the brain, which ultimately cause the typical neural impairments of HE. The disease can be classified using a number of systems, the most used of which recognizes three types  of HE according to the underlying cause: type A, associated with acute liver failure, type B, associated with portal-systemic shunting, and type C, associated with cirrhosis.

Treatment of HE is largely based on the integration in the diet of substances which can affect ammonia intestinal production and ammonia clearance. Since it often comes as a complication of a liver disease, the best way to prevent HE is to take steps to prevent the liver disease itself, such as avoiding alcohol consumption and having no contact with subjects affected by viral hepatitis.

References

Article

  1. Bell BP, Manos MM, Zaman A, et al. The epidemiology of newly diagnosed chronic liver disease in gastroenterology practices in the United States: results from population-based surveillance. Am J Gastroenterol. 2008;103(11):2727-2736.
  2. Davis GL, Albright JE, Cook SF, Rosenberg DM. Projecting future complications of chronic hepatitis C in the United States. Liver Transpl 2003;9(4):331-338.
  3. Blei AT, Córdoba J. Practice guidelines: hepatic encephalopathy. Am J Gastroenterol. 2001;96(7):1968-1976.
  4. Bustamante J, Rimola A, Ventura PJ, et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999;30(5):890-895.
  5. Ahboucha S, Butterworth RF. Pathophysiology of hepatic encephalopathy: a new look at GABA from the molecular standpoint. Metab Brain Dis. Dec 2004;19(3-4):331-43.
  6. Stewart CA, Malinchoc M, Kim WR, Kamath PS. Hepatic encephalopathy as a predictor of survival in patients with end-stage liver disease. Liver Transpl. 2007;13:1366-1371.
  7. Bajaj JS, Schubert CM, Heuman DM, et al. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology. 2010;138:2332-2340.
  8. Arguedas MR, DeLawrence TG, McGuire BM. Influence of hepatic encephalopathy on health-related quality of life in patients with cirrhosis. Dig Dis Sci. 2003;48:1622-1626.
  9. Munoz SJ. Hepatic encephalopathy. Med Clin North Am. 2008;92:795-812, viii.
  10. Bajaj JS, Wade JB, Gibson DP, et al. The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol. 2011;106:1646-1653.
  11. HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare Research and Quality, Rockville, MD. 
  12. Kappus MR, Bajaj JS. Covert hepatic encephalopathy: not as minimal as you might think. Clin Gastroenterol Hepatol. Nov 2012;10(11):1208-19.
  13. Bajaj JS, Cordoba J, Mullen KD, Amodio P, Shawcross DL, Butterworth RF, et al. Review article: the design of clinical trials in hepatic encephalopathy--an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Aliment Pharmacol Ther. Apr 2011;33(7):739-47.
  14. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei A. Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 2002 35 (3): 716–21.
  15. Mullen KD, Dasarathy S. Hepatic encephalopathy. In: Schiff ER, Sorrell MF, Maddrey WC, eds. Schiff's Diseases of the Liver. 8th ed. Philadelphia, Pa: Lippincott-Raven; 1999:545-81.
  16. Cash WJ, McConville P, McDermott E, McCormick PA, Callender ME, McDougall NI (January 2010). "Current concepts in the assessment and treatment of hepatic encephalopathy". QJM 103 (1): 9–16.
  17. Chung RT, Podolsky DK. Cirrhosis and its complications. In Kasper DL, Braunwald E, Fauci AS, et al. Harrison's Principles of Internal Medicine (16th ed.). 2005 New York, NY: McGraw-Hill. pp. 1858–69.
  18. Randolph C, Tierney MC, Mohr E, Chase TN. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol 1998 20 (3): 310–9.
  19. Weissenborn K, Ennen JC, Schomerus H, Rückert N, Hecker H. Neuropsychological characterization of hepatic encephalopathy. J. Hepatol. 2001 34 (5): 768–73.
  20. Sundaram V, Shaikh OS. Hepatic encephalopathy: pathophysiology and emerging therapies. Med. Clin. North Am. 2009 93 (4): 819–36, vii.
  21. Bajaj JS. Review article: the modern management of hepatic encephalopathy. Aliment. Pharmacol. Ther. 2010 31 (5): 537–47.
  22. Sushma S, Dasarathy S, Tandon RK, et al. Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology. Jul 1992;16(1):138-44.
  23. Batshaw ML, MacArthur RB, Tuchman M. Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatr. Jan 2001;138(1 Suppl):S46-54; discussion S54-5.
  24. Ghabril M, Zupanets IA, Vierling J et al. Glycerol phenylbutyrate in patients with cirrhosis and episodic hepatic encephalopathy: a pilot study of safety and effect on venous ammonia concentration. Clinical Pharm in Drug Dev. 2013. 

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2018-06-22 00:54