Understanding the Psychiatric Aspects of Liver Disease

When we hear the word "hepatitis," we tend to associate it with cirrhosis and other disorders affecting the liver. But it's not always the case. As with other persistent, chronic infections, hepatitis can directly impact one organ system (in this case, the liver) while indirectly affecting other organ systems, as well.

One system indirectly impacted by liver disease is the central nervous system, and most specifically the brain. During an acute or chronic hepatitis infection, toxic substances from the liver can accumulate in the bloodstream and spread (or disseminate) throughout the body. When these substances enter the brain, they can cause a neurological condition called hepatic encephalopathy.

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.

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.

Causes of Hepatic Encephalopathy

While hepatic encephalopathy is associated with acute liver failure, there are usually other contributing factors at play. Many of these factors have nothing to do with either the liver or the brain; they simply appear to either trigger an attack or further aggravate an existing episode.

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
• Spontaneous bacterial peritonitis, usually the result of liver cirrhosis
• Urinary tract infection
• Low potassium and/or sodium levels, often caused by diuretics used to treat ascites in later-stage disease
• Benzodiazepines, a sedative often prescribed to treat alcohol withdrawal
• Narcotics and anti-psychotic drugs
• The use of shunts (known at transjugular intrahepatic portosystemic shunt, or TIPS), used to correct blood flow in the liver

By identifying the underlying causes of hepatic encephalopathy, doctors are able to treat the disease more effectively by minimizing the factors that may have precipitated or aggravated an attack.

How Liver Failure Affects the Brain

Hepatic encephalopathy typically occurs when the liver is no longer able to perform its usual metabolic functions.

In persons with a normal liver function, nitrogen-containing compounds from the intestines are transported to the liver, where they are processed and excreted from the body. When liver function is impaired, the nitrogen-containing compounds begin to gradually build up, which causes an increase in ammonia levels.

These ammonia particles then spread throughout the bloodstream and pass through the semi-permeable membrane that that surrounds the brain. There, they cause the swelling of brain cells called astrocytes, which eventually slows the production of neurotransmitters vital to cognitive thinking.

Signs and Symptoms of Hepatic Encephalopathy

Hepatic encephalopathy is often difficult to diagnose in the earliest stages of the disease. Forgetfulness, irritability, anxiety, and confusion are often the first signs, most of which easily missed even in persons with known liver disease.

Perhaps the first obvious symptom would be something called an inverted sleep-wake pattern, in which a person will literally sleep by day and remain awake at night. This is often followed by a range of later-stage symptoms, which can include:

• Lethargy
• Marked personality change
• Increasing confusion
• Problems with writing and fine hand movement
• Shaky hands or involuntary "flapping" of hands
• Involuntary jerking of limbs
• Uninhibited behavior
• Amnesia

Severe cases can lead to a worsening state of consciousness, often progression to violent seizures and coma. Death is usually caused by the severe swelling of the brain (called cerebral edema).

The Stages of Hepatic Encephalopathy

The stages of hepatic encephalopathy are graded on a scale called the West Haven Criteria, which classifies the severity of symptoms based on the level of neurological impairment:

• Minimal: changes in motor speed without signs of mental changes
• Grade 1: trivial lack of awareness, euphoria or anxiety, shortened attention span, altered sleep rhythm
• Grade 2: lethargy or apathy, disorientation, obvious personality change, inappropriate behavior, motor skill problems, tremors with "flapping" of hands
• Grade 3: a semi-stupor state, confusion, severe disorientation, bizarre behavior
• Grade 4: coma

Clinical diagnoses are also made by classifying the underlying cause, whether it be an acute liver failure (Type A), a portosystemic shunt that bypasses the liver (TIPS procedure) (Type B), or cirrhosis (Type C). Each of these classifications assists in determining the appropriate course of action in treating the condition.

Diagnosis

The diagnosis of hepatic encephalopathy can only be made in the presence of confirmed liver disease or in persons who have undergone a TIPS procedure. Diagnosis is made by excluding all other possible causes of neurological impairment.

Clinical expertise is needed in order to make a differential diagnosis; there is no one test that can either fully confirm or exclude the condition. If hepatic encephalopathy is suspected, doctors will typically order a battery of tests, which can include:

• An evaluation of visual, motor and verbal skills
• CT scans to either exclude or confirm brain hemorrhage
• Electroencephalograms (EEG) if seizures are noted
• Blood tests to check for serum ammonia levels
• Fluid samples from the peritoneal cavity (which separates the abdominal cavity from the abdominal wall) to either exclude or confirm a bacterial infection
• Other tests, including chest X-rays and urinalysis, to exclude other possible causes

Treatment

Hepatic encephalopathy is treatable. Treatment is typically focused on resolving any underlying condition which may have triggered or exacerbated an attack. In some cases (such as in persons who have undergone a TIPS procedure), the condition may resolve spontaneously and require no further intervention. At other times, termination of a certain drug or the treatment of constipation can significantly improve neurological symptoms.

In cases where an active infection has been diagnosed, antibiotics will typically be prescribed in the form of rifaximin. Additionally, lactulose is commonly prescribed as first-line therapy to reduce the production of ammonia in the intestines.

The prognosis for a person with hepatic encephalopathy can vary significantly. The diagnosis of encephalopathy, along with a battery of liver tests, will typically be used to determine whether an individual will need a liver transplant. In persons with advanced liver disease, such as decompensated cirrhosis or liver cancer, a liver transplant is most often indicated.