The Most Serious Sign of Hepatic Encephalopathy

Hepatic encephalopathy (HE) often starts slowly, and the patient may not be aware of it.

Hepatic encephalopathy (HE) is a condition in which brain function is severely compromised because of liver failure due to severe liver disease. It can be short-term or long-standing.

HE often starts slowly, and at first, the patient may not be aware of it. Below are the most serious signs of HE:

• Becoming unresponsive, unconscious, and entering into a coma (hepatic coma or coma hepatic) are the most serious signs of HE. 

Other serious signs and symptoms include:

• Worsening confusion or disorientation
• Memory loss
• Unable to walk normally, swaying gait
• Difficulty in speech or slurring
• Extreme sleepiness
• Reduced mental alertness and motor activity 
• Presence of involuntary abnormal movements such as tremors and increased muscle tone (shaking of hands or arms called “flapping”)
• Musty or sweet odor breath

Hepatic encephalopathy (HE), or portosystemic encephalopathy or PSE, is a condition that causes the worsening of brain function in people with advanced liver disease. When the liver is damaged, it can no longer remove toxic substances from the blood. These toxins may reach the brain and cause the brain cells to swell. This hampers brain function.

HE is classified into three types:

• Type A: It is associated with acute liver failure.
• Type B: It occurs when there is no primary liver damage, and encephalopathy occurs due to the portosystemic shunting of the blood (an abnormal vein that bypasses blood purification by liver bypassing called shunting). Portosystemic shunts can be either congenital (present at birth) or acquired.
• Type C: It is an encephalopathy associated with severe liver disease or severe liver damage. Encephalopathy can either be episodic (acute) or persistent (chronic).

The stages of HE include the following: 

• Grade 0 (Minimal): Difficult to detect clinically; subtle impairment in memory, concentration, and intellectual functions. Slight impairment of coordination such as poor work performance or ability to drive (incidences of traffic violations while driving)
• Grade 1 (Mild): Presence of mood changes, depression, irritability, a decreased attention span, and sleep issues
• Grade 2 (Moderate): Associated with increasing forgetfulness, slurred speech, inappropriate behavior, inability to do simple mental tasks such as basic math, shaking of hands, and writing difficulties
• Grade 3 (Severe): Characterized by marked sleepiness, disoriented in space and time, extreme anxiety, and strange behavior
• Grade 4 (Coma): The patient loses consciousness and passes into a comatose state.

Patients may not have a definite cause of hepatic encephalopathy (HE), but the most common causes of HE include:

• Excessive alcohol intake
• Intake of large amounts of protein in persons with a damaged liver
• Liver cirrhosis (a condition where there is scarring of the liver tissue) due to various causes
• Fulminant hepatitis due to hepatitis viruses
• Overdosing of drugs such as paracetamol, painkillers, water pills, or sleeping drugs
• Severe infections called sepsis
• Multiple organ failure

Understanding the cause of hepatic encephalopathy (HE) paves the way to treating HE. If pre-existing conditions are treated, the occurrence of HE may be reduced. The doctor may suggest a few drugs and therapies that may reduce the toxins in the body:

• Lactulose: This helps cut down ammonia formation from the stools. Less ammonia means fewer toxic products in the brain.
• Antibiotics: Drugs such as rifaximin, neomycin/paromomycin/metronidazole, or vancomycin may help. They curb the gut bacteria that create toxins when they digest food.
• Patients may be started on zinc therapy: As per some research, zinc deficiency has been shown to cause a disturbance in the levels of neurotransmitters such as GABA and norepinephrine. Zinc might increase the key enzymes in the urea cycle, which favors the conversion of ammonia to urea and subsequent excretion in the urine.
• Patients with alcoholic cirrhosis and HE may be given thiamine (Vitamin B1 supplements).
• L-ornithine and L-aspartate preparation (LOLA) increases the use of ammonia in the urea cycle to produce urea.
• Probiotics or friendly bacteria can change the balance of bacteria in the intestines, increasing the proportion of friendly bacteria. This can result in decreased levels of ammonia production and other toxic substances.
• The definitive form of management includes liver transplant to reverse liver dysfunction and the symptoms of HE.

• The outlook of hepatic encephalopathy (HE) is poor with or without treatment.
• None of the current treatments are curative, and liver transplant is not readily available for most patients.
• The current day treatments are to ease symptoms and improve the quality of life.
• Early identification may be a key because it allows for expeditious identification and management of any precipitating factors.