Hepatic Encephalopathy


What is Hepatic Encephalopathy?

Hepatic encephalopathy (HE) refers to the impairment in the brain function that occurs in certain patients with liver disease.

Its severity ranges from a mild condition with no externally apparent abnormalities to a severe form that leads ultimately to serious, life-threatening complications. In the terminal stage, it is also referred to as hepatic coma or coma hepaticum.

What are the Possible Factors That Play a Role In Hepatic Encephalopathy?

The exact way in which hepatic encephalopathy occurs is poorly understood. An important factor in its development is the entry of portal blood into the systemic circulation through portosystemic shunts. Normally blood from the digestive tract first goes to the liver via the portal vein so that any toxins can be removed. In the presence of a portosystemic shunt, the blood bypasses the liver and reaches the general circulation without getting detoxified. Thus, the toxins in the blood can affect the brain resulting in encephalopathy.

Two possible factors that have been suggested to play a role include:

1. Gut derived neurotoxins such as ammonia

  • Under physiological conditions, ammonia enters the portal blood from the digestive tract. It is mainly derived from the colonic bacteria and additionally from deamination (removal of amino group) of the amino acid glutamine in the small intestine.
  • When the function of liver is intact, the liver is able to clear most of the ammonia entering the portal venous blood, converting it into urea and glutamine, and thus preventing the entry of ammonia into the systemic circulation.
  • However, in the presence of liver damage, the ammonia is shunted into the systemic circulation and reaches the brain, thereby affecting it.

2. Alterations in astrocyte structure and function

  • The astrocytes are supporting cells found in the brain. They protect and nourish the neurons or nerve cells and protect them from the harmful effects of ammonia by converting it to glutamine.
  • In liver failure, the astrocytes become overwhelmed with the huge quantities of ammonia entering the brain and are unable to metabolize it. There is resultant astrocyte swelling and edema of the brain, which can result in some of the neurological symptoms of hepatic encephalopathy.

Other Possible Factors

  • Other effects of increased ammonia levels in brain include impaired function of both excitatory and inhibitory neurotransmitters with overall inhibitory effect. There is a disturbance in the ratio of branched chain amino acids to aromatic amino acids (BCAA/AAA) with enhanced brain uptake of AAA leading to disturbance in neurotransmission.
  • Many toxic chemicals formed by the colonic bacteria have been shown to enhance the toxicity of ammonia. These include phenols, short chain fatty acids, mercaptans and oxindole.
  • Additional factors that might contribute to elevated blood ammonia levels include impaired kidney function affecting the excretion of ammonia, and muscle wasting which is commonly found in persons with cirrhosis; muscle plays an important role in extrahepatic ammonia elimination.
  • Sepsis and inflammation in a previously stable cirrhosis patient has been found to precipitate hepatic encephalopathy (HE). The suggested mechanism is the effect of inflammatory mediators such as cytokines and tumor necrosis factor (TNF) in increasing the brain uptake of ammonia by increasing blood vessel permeability.

What are the Causes of Hepatic Encephalopathy?

Hepatic encephalopathy (HE) can be precipitated by a variety of factors in an otherwise stable cirrhotic patient. These include:

  • Excess nitrogen burden – Intake of large amounts of protein, bleeding from esophageal varices, kidney failure with impaired excretion of nitrogenous waste
  • Fluid and electrolyte imbalance – Dehydration, hyponatremia (low blood sodium levels), hypokalemia (low blood potassium levels), alkalosis (decreased acid level), hypoxia (lack of oxygen)
  • MedicationsBenzodiazepines, alcohol, narcotics, antipsychotics
  • InfectionsPneumonia, spontaneous bacterial peritonitis, urinary tract infections
  • Constipation – Constipation enhances intestinal ammonia production
  • Idiopathic – In about a quarter of patients, no precipitating cause can be found

Causes of Hepatic Encephalopathy

What are the Types of Hepatic Encephalopathy?

Hepatic encephalopathy is sub-classified into three types based on the status of the liver.

  • Type A: Associated with acute liver failure.
  • Type B: Occurs when there is no primary liver damage and encephalopathy occurs due to portosystemic shunting of blood.
  • Type C: Encephalopathy associated with chronic liver disease such as cirrhosis and portal hypertension. The encephalopathy can either be episodic (acute) or persistent (chronic). In some cases, the encephalopathy is subclinical, and the term ‘minimal’ encephalopathy is used to describe such cases.

What are the Stages of Hepatic Encephalopathy?

HE is assessed according to the severity of the symptoms. The most commonly used grading system is the West Haven grading system, which is as follows:

  • Grade 0 (Minimal HE or MHE) – Difficult to detect clinically; subtle impairment in memory, concentration and intellectual functions. Slight impairment of coordination that may manifest as poor work performance or ability to drive (incidences of traffic violations while driving). If such occurrences are brought to the physician’s notice, the patient may be referred for neuropsychiatric evaluation and followed up regularly to monitor the condition. At present, there are no drugs to treat minimal HE.
  • Grade 1 (Mild HE)Presence of mood changes, depression, irritability, a decreased attention span and sleep issues
  • Grade 2 (Moderate HE) -Associated with increasing forgetfulness, slurred speech, inappropriate behavior, inability to do simple mental tasks like basic math, shaking of hands and writing difficulties
  • Grade 3 (Severe HE) –Characterized by marked sleepiness, disoriented in space and time, extreme anxiety and strange behaviour
  • Grade 4 (Coma) – Patient loses consciousness and passes into a comatose state