Hepatic encephalopathy

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Hepatic encephalopathy
Other namesPortosystemic encephalopathy, hepatic coma, [1] coma hepaticum
Alzheimer type II astrocyte high mag.jpg
Micrograph of Alzheimer type II astrocytes, as may be seen in hepatic encephalopathy
Specialty Gastroenterology
Symptoms Altered level of consciousness, mood changes, personality changes, movement problems [2] slurred speech, Sleep problems, Anxiety or irritability, Muscle twitches (myoclonus), Difficulty concentrating or short attention span, Flapping hand motion (asterixis), Reduced alertness, Cognitive impairment (confused thinking or judgment). [3]
Complications hepatic coma. [3]
TypesAcute, recurrent, persistent [4]
Causes Liver failure [2]
Risk factors Infections, GI bleeding, constipation, electrolyte problems, certain medications [5]
Diagnostic method Based on symptoms after ruling out other possible causes [2] [6]
Differential diagnosis Wernicke–Korsakoff syndrome, delirium tremens, hypoglycemia, subdural hematoma, hyponatremia [1]
Treatment Supportive care, treating triggers, lactulose, liver transplant [1] [4]
Prognosis Average life expectancy less than a year in those with severe disease [1]
FrequencyAffects >40% with cirrhosis [7]

Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. [2] Its onset may be gradual or sudden. [2] Other symptoms may include movement problems, changes in mood, or changes in personality. [2] In the advanced stages it can result in a coma. [4]

Contents

Hepatic encephalopathy can occur in those with acute or chronic liver disease. [4] Episodes can be triggered by infections, gastrointestinal bleeding, constipation, electrolyte problems, or certain medications. [5] The underlying mechanism is believed to involve the buildup of ammonia in the blood, a substance that is normally removed by the liver. [2] The diagnosis is typically based on symptoms after ruling out other potential causes. [2] [6] It may be supported by blood ammonia levels, an electroencephalogram, or computer tomography (CT scan) of the brain. [4] [6]

Hepatic encephalopathy is possibly reversible with treatment. [1] This typically involves supportive care and addressing the triggers of the event. [4] Lactulose is frequently used to decrease ammonia levels. [1] Certain antibiotics (such as rifaximin) and probiotics are other potential options. [1] A liver transplant may improve outcomes in those with severe disease. [1]

More than 40% of people with cirrhosis develop hepatic encephalopathy. [7] More than half of those with cirrhosis and significant HE live less than a year. [1] In those who are able to get a liver transplant, the risk of death is less than 30% over the subsequent five years. [1] The condition has been described since at least 1860. [1]

Signs and symptoms

The mildest form of hepatic encephalopathy is difficult to detect clinically, but may be demonstrated on neuropsychological testing. It is experienced as forgetfulness, mild confusion, and irritability. EEG can reveal a slowering of alpha waves. [8] The first stage of hepatic encephalopathy is characterised by an inverted sleep-wake pattern (sleeping by day, being awake at night). The second stage is marked by lethargy and personality changes. The third stage is marked by worsened confusion. The fourth stage is marked by a progression to coma. [4]

More severe forms of hepatic encephalopathy lead to a worsening level of consciousness, from lethargy to somnolence and eventually coma. 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. There is disorientation and amnesia, and uninhibited behaviour may occur. In the third stage, neurological examination may reveal clonus and positive Babinski sign. Coma and seizures represent the most advanced stage; cerebral edema (swelling of the brain tissue) leads to death. [4]

Encephalopathy often occurs together with other symptoms and signs of liver failure. These may include jaundice (yellow discolouration of the skin and the whites of the eyes), ascites (fluid accumulation in the abdominal cavity), and peripheral oedema (swelling of the legs due to fluid build-up in the skin). The tendon reflexes may be exaggerated, and the plantar reflex may be abnormal, namely extending rather than flexing (Babinski's sign) in severe encephalopathy. A particular smell on an affected person's breath ( foetor hepaticus ) may be detected. [9]

Causes

In a small proportion of cases, the encephalopathy is caused directly by liver failure; this is more likely in acute liver failure. More commonly, especially in chronic liver disease, hepatic encephalopathy is triggered by an additional cause, and identifying these triggers can be important to treat the episode effectively. [4]

TypeCauses [4] [9] [10]
Excessive
nitrogen load		Consumption of large amounts of protein, gastrointestinal bleeding e.g. from esophageal varices (blood is high in protein, which is reabsorbed from the bowel), kidney failure (inability to excrete nitrogen-containing waste products such as urea), constipation
Electrolyte or
metabolic disturbance 		Hyponatraemia (low sodium level in the blood) and hypokalaemia (low potassium levels)—these are both common in those taking diuretics, often used for the treatment of ascites; furthermore alkalosis (decreased acid level), hypoxia (insufficient oxygen levels), dehydration
Drugs and
medications		 Sedatives such as benzodiazepines (often used to suppress alcohol withdrawal or anxiety disorder), narcotics (used as painkillers or drugs of abuse), antipsychotics, alcohol intoxication, Valproic Acid (Used for Epilepsy, Bipolar Disorder, Anti-Migranal purposes. Extremely rare.) [11]
Infection Pneumonia, urinary tract infection, spontaneous bacterial peritonitis, other infections
Others Surgery, progression of the liver disease, additional cause for liver damage (e.g. alcoholic hepatitis, hepatitis A)
UnknownIn 20–30% of cases, no clear cause for an attack can be found

Hepatic encephalopathy may also occur after the creation of a transjugular intrahepatic portosystemic shunt (TIPS). This is used in the treatment of refractory ascites, bleeding from esophageal varices and hepatorenal syndrome. [12] [13] TIPS-related encephalopathy occurs in about 30% of cases, with the risk being higher in those with previous episodes of encephalopathy, higher age, female sex, and liver disease due to causes other than alcohol. [10]

Pathogenesis

Ball and stick model of ammonia; one nitrogen atom with three hydrogen atoms. Accumulation of ammonia in the bloodstream is associated with hepatic encephalopathy. Ammonia-3D-balls-A.png
Ball and stick model of ammonia; one nitrogen atom with three hydrogen atoms. Accumulation of ammonia in the bloodstream is associated with hepatic encephalopathy.

There are various explanations why liver dysfunction or portosystemic shunting might lead to encephalopathy. In healthy subjects, nitrogen-containing compounds from the intestine, generated by gut bacteria from food, are transported by the portal vein to the liver, where 80–90% are metabolised through the urea cycle and/or excreted immediately. This process is impaired in all subtypes of hepatic encephalopathy, either because the hepatocytes (liver cells) are incapable of metabolising the waste products or because portal venous blood bypasses the liver through collateral circulation or a medically constructed shunt. Nitrogenous waste products accumulate in the systemic circulation (hence the older term "portosystemic encephalopathy"). The most important waste product is ammonia (NH3). This small molecule crosses the blood–brain barrier and is absorbed and metabolised by the astrocytes, a population of cells in the brain that constitutes 30% of the cerebral cortex. Astrocytes use ammonia when synthesising glutamine from glutamate. The increased levels of glutamine lead to an increase in osmotic pressure in the astrocytes, which become swollen. There is increased activity of the inhibitory γ-aminobutyric acid (GABA) system and the energy supply to other brain cells is decreased. This can be thought of as an example of brain edema of the "cytotoxic" type. [14]

Despite numerous studies demonstrating the central role of ammonia, ammonia levels do not always correlate with the severity of the encephalopathy; it is suspected that this means that more ammonia has already been absorbed into the brain in those with severe symptoms whose serum levels are relatively low. [4] [9] Other waste products implicated in hepatic encephalopathy include mercaptans (substances containing a thiol group), short-chain fatty acids, and phenol. [9]

Numerous other abnormalities have been described in hepatic encephalopathy, although their relative contribution to the disease state is uncertain. Loss of glutamate transporter gene expression (especially EAAT 2) has been attributed to acute liver failure. [15] Benzodiazepine-like compounds have been detected at increased levels as well as abnormalities in the GABA neurotransmission system. An imbalance between aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) has been described; this would lead to the generation of false neurotransmitters (such octopamine and 2-hydroxyphenethylamine). Dysregulation of the serotonin system, too, has been reported. Depletion of zinc and accumulation of manganese may play a role. [4] [9] Inflammation elsewhere in the body may precipitate encephalopathy through the action of cytokines and bacterial lipopolysaccharide on astrocytes. [10]

Diagnosis

Micrograph of Alzheimer type II astrocytes, as may be seen in hepatic encephalopathy Alzheimer type II astrocyte high mag cropped.jpg
Micrograph of Alzheimer type II astrocytes, as may be seen in hepatic encephalopathy

Investigations

The diagnosis of hepatic encephalopathy can only be made in the presence of confirmed liver disease (types A and C) or a portosystemic shunt (type B), as its symptoms are similar to those encountered in other encephalopathies. To make the distinction, abnormal liver function tests and/or ultrasound suggesting liver disease are required, and ideally a liver biopsy. [4] [9] The symptoms of hepatic encephalopathy may also arise from other conditions, such as bleeding in the brain and seizures (both of which are more common in chronic liver disease). A CT scan of the brain may be required to exclude bleeding in the brain, and if seizure activity is suspected an electroencephalograph (EEG) study may be performed. [4] Rarer mimics of encephalopathy are meningitis, encephalitis, Wernicke's encephalopathy and Wilson's disease; these may be suspected on clinical grounds and confirmed with investigations. [9] [16]

The diagnosis of hepatic encephalopathy is a clinical one, once other causes for confusion or coma have been excluded; no test fully diagnoses or excludes it. Serum ammonia levels are elevated in 90% of people, but not all hyperammonaemia (high ammonia levels in the blood) is associated with encephalopathy. [4] [9] A CT scan of the brain usually shows no abnormality except in stage IV encephalopathy, when brain swelling (cerebral oedema) may be visible. [9] Other neuroimaging modalities, such as magnetic resonance imaging (MRI), are not currently regarded as useful, although they may show abnormalities. [16] 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. [4] However, the changes in EEG are not typical enough to be useful in distinguishing hepatic encephalopathy from other conditions. [16]

Once the diagnosis of encephalopathy has been made, efforts are made to exclude underlying causes (such as listed above in "causes"). This requires blood tests (urea and electrolytes, full blood count, liver function tests), usually a chest X-ray, and urinalysis. If there is ascites, a diagnostic paracentesis (removal of a fluid sample with a needle) may be required to identify spontaneous bacterial peritonitis (SBP). [4]

Classification

West Haven criteria

The severity of hepatic encephalopathy is graded with the West Haven Criteria; this is based on the level of impairment of autonomy, changes in consciousness, intellectual function, behavior, and dependence on therapy. [4] [17]

  • Grade 0 - No obvious changes other than a potentially mild decrease in intellectual ability and coordination
  • Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction
  • Grade 2 - Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behaviour
  • Grade 3 - Somnolence to semistupor, but responsive to verbal stimuli; confusion; gross disorientation
  • Grade 4 - Coma

Types

Micrograph showing liver cirrhosis, a condition that often precedes hepatic encephalopathy. Trichrome stain. Cirrhosis high mag.jpg
Micrograph showing liver cirrhosis, a condition that often precedes hepatic encephalopathy. Trichrome stain.

A classification of hepatic encephalopathy was introduced at the World Congress of Gastroenterology 1998 in Vienna. According to this classification, hepatic encephalopathy is subdivided in type A, B and C depending on the underlying cause. [16]

  • Type A (=acute) describes hepatic encephalopathy associated with acute liver failure, typically associated with cerebral oedema
  • Type B (=bypass) is caused by portal-systemic shunting without associated intrinsic liver disease
  • Type C (=cirrhosis ) occurs in people with cirrhosis - this type is subdivided in episodic, persistent and minimal encephalopathy

The term minimal encephalopathy (MHE) is defined as encephalopathy that does not lead to clinically overt cognitive dysfunction, but can be demonstrated with neuropsychological studies. [16] [18] This is still an important finding, as minimal encephalopathy has been demonstrated to impair quality of life and increase the risk of involvement in road traffic accidents. [19]

Minimal HE

The diagnosis of minimal hepatic encephalopathy requires neuropsychological testing by definition. Older tests include the "numbers connecting test" A and B (measuring the speed at which one could connect randomly dispersed numbers 1–20), the "block design test" and the "digit-symbol test". [16] In 2009 an expert panel concluded that neuropsychological test batteries aimed at measuring multiple domains of cognitive function are generally more reliable than single tests, and tend to be more strongly correlated with functional status. Both the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [20] and PSE-Syndrom-Test [21] may be used for this purpose. [18] The PSE-Syndrom-Test, developed in Germany and validated in several other European countries, incorporates older assessment tools such as the number connection test. [16] [18] [19] [21]

Treatment

Those with severe encephalopathy (stages 3 and 4) are at risk of obstructing their airway due to decreased protective reflexes such as the gag reflex. This can lead to respiratory arrest. Transferring the person to a higher level of nursing care, such as an intensive care unit, is required, and intubation of the airway is often necessary to prevent life-threatening complications (e.g., aspiration or respiratory failure). [9] [22] Placement of a nasogastric tube permits the safe administration of nutrients and medication. [4]

The treatment of hepatic encephalopathy depends on the suspected underlying cause (types A, B, or C) and the presence or absence of underlying causes. If encephalopathy develops in acute liver failure (type A), even in a mild form (grade 1–2), it indicates that a liver transplant may be required, and transfer to a specialist centre is advised. [22] Hepatic encephalopathy type B may arise in those who have undergone a TIPS procedure; in most cases this resolves spontaneously or with the medical treatments discussed below, but in a small proportion of about 5%, occlusion of the shunt is required to address the symptoms. [10]

In hepatic encephalopathy type C, the identification and treatment of alternative or underlying causes is central to the initial management. [4] [9] [10] [19] Given the frequency of infection as the underlying cause, antibiotics are often administered empirically (without knowledge of the exact source and nature of the infection). [4] [10] Once an episode of encephalopathy has been effectively treated, a decision may need to be made on whether to prepare for a liver transplant. [19]

Diet

In the past, it was thought that consumption of protein even at normal levels increased the risk of hepatic encephalopathy. This has been shown to be incorrect. Furthermore, many people with chronic liver disease are malnourished and require adequate protein to maintain a stable body weight. A diet with adequate protein and energy is therefore recommended. [4] [10]

Dietary supplementation with branched-chain amino acids has shown improvement of encephalopathy and other complications of cirrhosis. [4] [10]

Some studies have shown benefit of administration of probiotics ("healthy bacteria"). [10]

Lactulose/lactitol

Lactulose and lactitol are disaccharides that are not absorbed from the digestive tract. They are thought to decrease the generation of ammonia by bacteria, render the ammonia inabsorbable by converting it to ammonium (NH4+) ions, and increase transit of bowel content through the gut. Doses of 15-30 mL are typically administered three times a day; the result is aimed to be 3–5 soft stools a day, or (in some settings) a stool pH of <6.0. [4] [9] [10] [19] Lactulose may also be given by enema, especially if encephalopathy is severe. [19] More commonly, phosphate enemas are used. This may relieve constipation, one of the causes of encephalopathy, and increase bowel transit. [4]

Lactulose and lactitol are beneficial for treating hepatic encephalopathy, and are the recommended first-line treatment. [4] [23] Lactulose does not appear to be more effective than lactitol for treating people with hepatic encephalopathy. [23] Side effects of lactulose and lactitol include the possibility of diarrhea, abdominal bloating, gassiness, and nausea. [23] In acute liver failure, it is unclear whether lactulose is beneficial. The possible side effect of bloating may interfere with a liver transplant procedure if required. [22]

Antibiotics

The antibiotic rifaximin may be recommended in addition to lactulose for those with recurrent disease. [1] It is a nonabsorbable antibiotic from the rifamycin class. This is thought to work in a similar way to other antibiotics but without the complications attached to neomycin or metronidazole. Due to the long history and lower cost of lactulose use, rifaximin is generally only used as a second-line treatment if lactulose is poorly tolerated or not effective. When rifaximin is added to lactulose, the combination of the two may be more effective than each component separately. [4] Rifaximin is more expensive than lactulose, but the cost may be offset by fewer hospital admissions for encephalopathy. [19]

The antibiotics neomycin and metronidazole are other antibiotics used to treat hepatic encephalopathy. [24] The rationale of their use was the fact that ammonia and other waste products are generated and converted by intestinal bacteria, and killing these bacteria would reduce the generation of these waste products. Neomycin was chosen because of its low intestinal absorption, as neomycin and similar aminoglycoside antibiotics may cause hearing loss and kidney failure if used by injection. Later studies showed that neomycin was indeed absorbed when taken by mouth, with resultant complications. Metronidazole, similarly, is less commonly used because prolonged use can cause nerve damage, in addition to gastrointestinal side effects. [4]

L-Ornithine and L-aspartate

The combination of L-ornithine and L-aspartate (LOLA) lowers the level of ammonia in a person's blood. [25] Very weak evidence from clinical trials indicates that LOLA treatment may benefit people with hepatic encephalopathy. [25] LOLA lowers ammonia levels by increasing the generation of urea through the urea cycle, a metabolic pathway that removes ammonia by turning it into the neutral substance urea. [26] LOLA may be combined with lactulose and/or rifaximin if these alone are ineffective at controlling symptoms. [4]

Epidemiology and prognosis

In those with cirrhosis, the risk of developing hepatic encephalopathy is 20% per year, and at any time about 30–45% of people with cirrhosis exhibit evidence of overt encephalopathy. The prevalence of minimal hepatic encephalopathy detectable on formal neuropsychological testing is 60–80%; this increases the likelihood of developing overt encephalopathy in the future. [19] Once hepatic encephalopathy has developed, the prognosis is determined largely by other markers of liver failure, such as the levels of albumin (a protein produced by the liver), the prothrombin time (a test of coagulation, which relies on proteins produced in the liver), the presence of ascites and the level of bilirubin (a breakdown product of hemoglobin which is conjugated and excreted by the liver). Together with the severity of encephalopathy, these markers have been incorporated into the Child–Pugh score; this score determines the one- and two-year survival and may assist in a decision to offer liver transplantation. [16]

In acute liver failure, the development of severe encephalopathy strongly predicts short-term mortality and is almost as important as the nature of the underlying cause of the liver failure in determining the prognosis. Historically, widely used criteria for offering liver transplantation, such as King's College Criteria, are of limited use and recent guidelines discourage excessive reliance on these criteria. The occurrence of hepatic encephalopathy in people with Wilson's disease (hereditary copper accumulation) and mushroom poisoning indicates an urgent need for a liver transplant. [22]

History

The occurrence of disturbed behaviour in people with jaundice may have been described in antiquity by Hippocrates of Cos (c. 460–370 BCE). [21] [27] Celsus and Galen (first and third century respectively) both recognised the condition. Many modern descriptions of the link between liver disease and neuropsychiatric symptoms were made in the eighteenth and nineteenth century; for instance, Giovanni Battista Morgagni (1682–1771) reported in 1761 that it was a progressive condition. [27]

In the 1950s, several reports enumerated the numerous abnormalities reported previously, and confirmed the previously enunciated theory that metabolic impairment and portosystemic shunting are the underlying mechanisms behind hepatic encephalopathy, and that the nitrogen-rich compounds originate from the intestine. [21] [28] Professor Dame Sheila Sherlock (1918–2001) performed many of these studies at the Royal Postgraduate Medical School in London and subsequently at the Royal Free Hospital. The same group investigated protein restriction [27] and neomycin. [29]

The West Haven classification was formulated by Professor Harold Conn (1925–2011) and colleagues at Yale University while investigating the therapeutic efficacy of lactulose. [16] [30] [31]

Related Research Articles

<span class="mw-page-title-main">Wilson's disease</span> Genetic multisystem copper-transport disease

Wilson's disease is a genetic disorder characterized by the excess build-up of copper in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build-up in the abdomen, swelling of the legs, yellowish skin, and itchiness. Brain-related symptoms include tremors, muscle stiffness, trouble in speaking, personality changes, anxiety, and psychosis.

<span class="mw-page-title-main">Ascites</span> Abnormal build-up of fluid in the abdomen

Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, abdominal discomfort, and shortness of breath. Complications can include spontaneous bacterial peritonitis.

<span class="mw-page-title-main">Hyperammonemia</span> Medical condition

Hyperammonemia, or high ammonia levels, is a metabolic disturbance characterised by an excess of ammonia in the blood. Severe hyperammonemia is a dangerous condition that may lead to brain injury and death. It may be primary or secondary.

<span class="mw-page-title-main">Budd–Chiari syndrome</span> Blockage of the hepatic veins that drain the liver

Budd–Chiari syndrome is a very rare condition, affecting one in a million adults. The condition is caused by occlusion of the hepatic veins that drain the liver.

<span class="mw-page-title-main">Alcoholic hepatitis</span> Medical condition

Alcoholic hepatitis is hepatitis due to excessive intake of alcohol. Patients typically have a history of at least 10 years of heavy alcohol intake, typically 8–10 drinks per day. It is usually found in association with fatty liver, an early stage of alcoholic liver disease, and may contribute to the progression of fibrosis, leading to cirrhosis. Symptoms may present acutely after a large amount of alcoholic intake in a short time period, or after years of excess alcohol intake. Signs and symptoms of alcoholic hepatitis include jaundice, ascites, fatigue and hepatic encephalopathy. Mild cases are self-limiting, but severe cases have a high risk of death. Severity in alcoholic hepatitis is determined several clinical prediction models such as the Maddrey's Discriminant Function and the MELD score.

<span class="mw-page-title-main">Portal hypertension</span> Abnormally increased portal venous pressure

Portal hypertension is defined as increased portal venous pressure, with a hepatic venous pressure gradient greater than 5 mmHg. Normal portal pressure is 1–4 mmHg; clinically insignificant portal hypertension is present at portal pressures 5–9 mmHg; clinically significant portal hypertension is present at portal pressures greater than 10 mmHg. The portal vein and its branches supply most of the blood and nutrients from the intestine to the liver.

<span class="mw-page-title-main">Acute liver failure</span> Medical condition

Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease, and indicates that the liver has sustained severe damage. The complications are hepatic encephalopathy and impaired protein synthesis. The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes.

<span class="mw-page-title-main">Lactulose</span> Treatment for constipation and hepatic encephalopathy

Lactulose is a non-absorbable sugar used in the treatment of constipation and hepatic encephalopathy. It is administered orally for constipation, and either orally or rectally for hepatic encephalopathy. It generally begins working after 8–12 hours, but may take up to 2 days to improve constipation.

Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease of the liver which lasts over a period of six months. It consists of a wide range of liver pathologies which include inflammation, liver cirrhosis, and hepatocellular carcinoma. The entire spectrum need not be experienced.

<span class="mw-page-title-main">Transjugular intrahepatic portosystemic shunt</span> Artificial channel within the liver

Transjugular intrahepatic portosystemic shunt is an artificial channel within the liver that establishes communication between the inflow portal vein and the outflow hepatic vein. It is used to treat portal hypertension which frequently leads to intestinal bleeding, life-threatening esophageal bleeding and the buildup of fluid within the abdomen (ascites).

<span class="mw-page-title-main">Gastric antral vascular ectasia</span> Intestinal bleeding due to widening of blood vessels in the stomach

Gastric antral vascular ectasia (GAVE) is an uncommon cause of chronic gastrointestinal bleeding or iron deficiency anemia. The condition is associated with dilated small blood vessels in the gastric antrum, which is a distal part of the stomach. The dilated vessels result in intestinal bleeding. It is also called watermelon stomach because streaky long red areas that are present in the stomach may resemble the markings on watermelon.

<span class="mw-page-title-main">Rifaximin</span> Antibiotic medication

Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription. It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.

<span class="mw-page-title-main">Liver failure</span> Inability of the liver to perform its normal functions

Liver failure is the inability of the liver to perform its normal synthetic and metabolic functions as part of normal physiology. Two forms are recognised, acute and chronic (cirrhosis). Recently, a third form of liver failure known as acute-on-chronic liver failure (ACLF) is increasingly being recognized.

<span class="mw-page-title-main">Portacaval shunt</span> Surgical shunt to divert blood away from liver

A portacaval shunt, portocaval shunt, or portal-caval shunt is a surgical procedure where a connection is made between the portal vein and the inferior vena cava.

Hepatic microvascular dysplasia or portal atresia is a disorder where mixing of venous blood and arterial blood in the liver occurs at the microscopic level. It occurs most commonly in certain dog breeds such as the Cairn and Yorkshire terriers although any dog breed may be at risk.

<span class="mw-page-title-main">Cirrhosis</span> Chronic disease of the liver, characterized by fibrosis

Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a condition of the liver in which the normal functioning tissue, or parenchyma, is replaced with scar tissue (fibrosis) and regenerative nodules as a result of chronic liver disease. Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue and nodules of regenerating hepatocytes can replace the parenchyma, causing increased resistance to blood flow in the liver's capillaries—the hepatic sinusoids—and consequently portal hypertension, as well as impairment in other aspects of liver function. The disease typically develops slowly over months or years.

A liver support system or diachysis is a type of therapeutic device to assist in performing the functions of the liver. Such systems focus either on removing the accumulating toxins, or providing additional replacement of the metabolic functions of the liver through the inclusion of hepatocytes to the device. A diachysis machine is used for acute care i.e. emergency care, as opposed to a dialysis machine which are typically used over the longer term. These systems are being trialed to help people with acute liver failure (ALF) or acute-on-chronic liver failure.

<span class="mw-page-title-main">Hepatic hydrothorax</span> Medical condition

Hepatic hydrothorax is a rare form of pleural effusion that occurs in people with liver cirrhosis. It is defined as an effusion of over 500 mL in people with liver cirrhosis that is not caused by heart, lung, or pleural disease. It is found in 5–10% of people with liver cirrhosis and 2–3% of people with pleural effusions. In cases of decompensated liver cirrhosis, prevalence rises significantly up to 90%. Over 85% of cases occurring on the right, 13% on the left, and 2% on both. Although it is most common in people with severe ascites, it can also occur in people with mild or no ascites. Symptoms are not specific and mostly involve the respiratory system.

Portosystemic shunts are a type of vascular abnormality that causes blood to be emptied into the circulation, without passing through the liver. This prevents the liver from detoxifying the blood. The condition may be either congenital or acquired.

Debbie Lindsay Shawcross is a British physician and clinician who is a professor at King's College London. Her research looks to better understand the cellular and molecular mechanisms that underpin chronic liver disease, with a focus on the gut-liver-brain axis.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 Wijdicks, EF (27 October 2016). "Hepatic Encephalopathy". The New England Journal of Medicine. 375 (17): 1660–1670. doi:10.1056/NEJMra1600561. PMID   27783916.
  2. 1 2 3 4 5 6 7 8 "Hepatic encephalopathy". GARD. 2016. Archived from the original on 5 July 2017. Retrieved 30 July 2017.
  3. 1 2 "Hepatic encephalopathy". Clevelandclinic. Retrieved 9 June 2022.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 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. doi: 10.1093/qjmed/hcp152 . PMID   19903725.
  5. 1 2 Starr, SP; Raines, D (15 December 2011). "Cirrhosis: diagnosis, management, and prevention". American Family Physician. 84 (12): 1353–9. PMID   22230269.
  6. 1 2 3 "Portosystemic Encephalopathy - Hepatic and Biliary Disorders". Merck Manuals Professional Edition. Retrieved 25 September 2019.
  7. 1 2 Ferri, Fred F. (2017). Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 577. ISBN   9780323529570. Archived from the original on 2017-07-30.
  8. ↑ Baumgarten, Thomas J.; Neugebauer, Julia; Oeltzschner, Georg; Füllenbach, Nur-Deniz; Kircheis, Gerald; Häussinger, Dieter; Lange, Joachim; Wittsack, Hans-Jörg; Butz, Markus; Schnitzler, Alfons (2018). "Connecting occipital alpha band peak frequency, visual temporal resolution, and occipital GABA levels in healthy participants and hepatic encephalopathy patients". NeuroImage: Clinical. 20: 347–356. doi:10.1016/j.nicl.2018.08.013. PMC   6090010 . PMID   30109194.
  9. 1 2 3 4 5 6 7 8 9 10 11 12 Chung RT, Podolsky DK (2005). "Cirrhosis and its complications". In Kasper DL, Braunwald E, Fauci AS, et al. (eds.). Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp.  1858–69. ISBN   978-0-07-139140-5.
  10. 1 2 3 4 5 6 7 8 9 10 Sundaram V, Shaikh OS (July 2009). "Hepatic encephalopathy: pathophysiology and emerging therapies". Med. Clin. North Am. 93 (4): 819–36, vii. doi:10.1016/j.mcna.2009.03.009. PMID   19577116.
  11. ↑ Farooq, Faiza; Din, Javiera Sahib; Khan, Ali M; Naqvi, Syeda; Shagufta, Shanila; Mohit, Abdul (August 22, 2017). "Valproate-Induced Hyperammonemic Encephalopathy". Cureus. 9 (8): e1593. doi: 10.7759/cureus.1593 . PMC   5650254 . PMID   29062625.
  12. ↑ Khan S, Tudur Smith C, Williamson P, Sutton R (2006). "Portosystemic shunts versus endoscopic therapy for variceal rebleeding in patients with cirrhosis". Cochrane Database Syst Rev. 2006 (4): CD000553. doi:10.1002/14651858.CD000553.pub2. PMC   7045742 . PMID   17054131.
  13. ↑ Saab S, Nieto JM, Lewis SK, Runyon BA (2006). "TIPS versus paracentesis for cirrhotic patients with refractory ascites". Cochrane Database Syst Rev. 2010 (4): CD004889. doi:10.1002/14651858.CD004889.pub2. PMC   8855742 . PMID   17054221.
  14. ↑ Ryan JM, Shawcross DL (2011). "Hepatic encephalopathy". Medicine. 39 (10): 617–620. doi:10.1016/j.mpmed.2011.07.008.
  15. ↑ Thumburu, KK; Dhiman, RK; Vasishta, RK; Chakraborti, A; Butterworth, RF; Beauchesne, E; Desjardins, P; Goyal, S; Sharma, N; Duseja, A; Chawla, Y (Mar 2014). "Expression of astrocytic genes coding for proteins implicated in neural excitation and brain edema is altered after acute liver failure". Journal of Neurochemistry. 128 (5): 617–27. doi: 10.1111/jnc.12511 . PMID   24164438. S2CID   21367707.
  16. 1 2 3 4 5 6 7 8 9 Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei A (2002). "Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998". Hepatology. 35 (3): 716–21. doi: 10.1053/jhep.2002.31250 . PMID   11870389. S2CID   7929620.[ dead link ]
  17. ↑ "Hepatic Encephalopathy". The Lecturio Medical Concept Library. Retrieved 9 July 2021.
  18. 1 2 3 Randolph C, Hilsabeck R, Kato A, et al. (May 2009). "Neuropsychological assessment of hepatic encephalopathy: ISHEN practice guidelines". Liver Int. 29 (5): 629–35. doi: 10.1111/j.1478-3231.2009.02009.x . PMID   19302444. S2CID   30313260.
  19. 1 2 3 4 5 6 7 8 Bajaj JS (March 2010). "Review article: the modern management of hepatic encephalopathy". Aliment. Pharmacol. Ther. 31 (5): 537–47. doi:10.1111/j.1365-2036.2009.04211.x. PMID   20002027. S2CID   10976362.
  20. ↑ Randolph C, Tierney MC, Mohr E, Chase TN (June 1998). "The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity". J Clin Exp Neuropsychol. 20 (3): 310–9. doi:10.1076/jcen.20.3.310.823. PMID   9845158.
  21. 1 2 3 4 Weissenborn K, Ennen JC, Schomerus H, Rückert N, Hecker H (May 2001). "Neuropsychological characterization of hepatic encephalopathy". J. Hepatol. 34 (5): 768–73. doi: 10.1016/S0168-8278(01)00026-5 . PMID   11434627.
  22. 1 2 3 4 Polson J, Lee WM (May 2005). "AASLD position paper: the management of acute liver failure". Hepatology. 41 (5): 1179–97. doi: 10.1002/hep.20703 . PMID   15841455. S2CID   6216605.
  23. 1 2 3 Gluud, Lise Lotte; Vilstrup, Hendrik; Morgan, Marsha Y. (2016-05-06). "Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis". The Cochrane Database of Systematic Reviews. 2016 (5): CD003044. doi:10.1002/14651858.CD003044.pub4. ISSN   1469-493X. PMC   7004252 . PMID   27153247.
  24. ↑ Ferenci, P (May 2017). "Hepatic encephalopathy". Gastroenterology Report. 5 (2): 138–147. doi:10.1093/gastro/gox013. PMC   5421503 . PMID   28533911.
  25. 1 2 Goh, Ee Teng; Stokes, Caroline S.; Sidhu, Sandeep S.; Vilstrup, Hendrik; Gluud, Lise Lotte; Morgan, Marsha Y. (2018-05-15). "L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis" (PDF). The Cochrane Database of Systematic Reviews. 5 (6): CD012410. doi:10.1002/14651858.CD012410.pub2. ISSN   1469-493X. PMC   6494563 . PMID   29762873.
  26. ↑ Kircheiscorresponding, G; Lüth, S (2019). "Pharmacokinetic and Pharmacodynamic Properties of l-Ornithine l-Aspartate (LOLA) in Hepatic Encephalopathy". Drugs. 79 (1): 23–29. doi:10.1007/s40265-018-1023-2. PMC   6416235 . PMID   30706424.
  27. 1 2 3 Summerskill WH, Davidson EA, Sherlock S, Steiner RE (April 1956). "The neuropsychiatric syndrome associated with hepatic cirrhosis and an extensive portal collateral circulation". Q. J. Med. 25 (98): 245–66. PMID   13323252.
  28. ↑ Sherlock S, Summerskill WH, White LP, Phear EA (September 1954). "Portal-systemic encephalopathy; neurological complications of liver disease". Lancet. 264 (6836): 453–7. doi:10.1016/S0140-6736(54)91874-7. PMID   13193045.
  29. ↑ Last PM, Sherlock S (February 1960). "Systemic absorption of orally administered neomycin in liver disease". N. Engl. J. Med. 262 (8): 385–9. doi:10.1056/NEJM196002252620803. PMID   14414396.
  30. ↑ Conn HO, Leevy CM, Vlahcevic ZR, et al. (1977). "Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial". Gastroenterology. 72 (4 Pt 1): 573–83. doi: 10.1016/S0016-5085(77)80135-2 . PMID   14049.
  31. ↑ Boyer JL, Garcia-Tsao G, Groszmann RJ (February 2012). "In Memoriam: Harold O. Conn, M.D." Hepatology. 55 (2): 658–9. doi: 10.1002/hep.25550 . S2CID   85090164.

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