Hepatic Encephalopathy Disease

BASICS

DESCRIPTION

Altered mental and neuromotor functioning associated with acute or chronic liver disease and/or portal systemic shunting of blood. The prominent features are mild to marked forgetfulness, impaired arousability, and a "flapping tremor" (asterixis).

System(s) affected: Gastrointestinal, Nervous
Genetics: Unknown
Incidence/Prevalence in USA:
- Occurs in 1/3 of cases of cirrhosis
- Occurs in all cases of fulminant hepatic failure
- Present in nearly half of patients who reach the stage of liver disease requiring transplantation
Predominant age: Parallels that of fulminant liver disease with peak in the 40's, and cirrhosis with peak in late 50's. May occur at any age.
Predominant sex: Male = Female (reflecting the underlying liver disease)

SIGNS AND SYMPTOMS

Ages 10-60
- Prominent signs of underlying liver disease (50%); jaundice most common, ascites second most common
- Gastrointestinal hemorrhage with hematemesis or melena (20%)
- Systemic infection (urinary tract or pulmonary) (20%)
- Four stages of confusion and obtundity: (1) Forgetfulness, disturbance in nocturnal sleep, daytime drowsiness (2) Mild confusion but arousable (3) Arousable but markedly confused, limited orientation and thought content (4) Unarousable
- Asterixis prominent in stages 2 and 3
- Handwriting and hand coordination deteriorated in stages 1 and 2
- Tremor prominent in stage 2
- Psychotic thoughts infrequent
- Reflexes symmetrically hyperactive
- Tremor and asterixis not observed in ocular muscles
- Mental and neurological signs change rapidly (over 6 to 12 hours)
Age over 60
- Signs of underlying liver disease diminished (25%)
- Confusion more prominent
- Precipitating gastrointestinal hemorrhage or infection less often identified
- Remains in stage 1 or 2 for many days
- Progression slower
Age under 10
- Signs of underlying liver disease prominent, usually fulminant hepatic failure or extremely advanced cirrhosis
- Progression through the stages very rapid, often 6 to 12 hours
- Precipitating cause frequently not identified

CAUSES

Shunting of intestinal blood through the severely diseased liver without the intervention of viable liver cells. TIPS (transjugular intrahepatic portacaval shunt), a widely used radiologically inserted shunt to lower portal pressure, produces liver encephalopathy.
Shunting of such blood through collateral circulation or surgically constructed portacaval shunts.
Thus hepatic coma may occur in extremely advanced acute liver disease (fulminant hepatic failure) or following portacaval shunting or transjugular intrahepatic portal shunt (TIPS). However, it is most common in long standing cirrhosis of the liver with spontaneous shunting of intestinal blood through collaterals.
Failure of liver to detoxify agents noxious to CNS, e.g., ammonia, mercaptans, fatty acids.
Increased aromatic and reduced branched chain amino acids in blood.
Precipitation of acute event, search for:
- New overt or occult infection including spontaneous peritonitis
- Potassium, magnesium or other electrolyte depletion
- Use of opiate, sedative, tranquilizer, drugs
- Gastrointestinal bleeding

RISK FACTORS

Infection
Sedative or opiate drugs
Electrolyte disturbance
Anemia
Gastrointestinal hemorrhage

DIAGNOSIS

LABORATORY

Screening blood, sputum and urine cultures to identify infection
Hematology to identify anemia and signs of infection
Standard biochemistry profile to identify hypokalemia, bilirubinemia, altered calcium status, hypomagnesemia, urea, hypoglycemia
Arterial blood gases
Liver tests to evaluate severity of underlying liver disease
Prothrombin and partial thromboplastin time
Venous ammonia (elevated in 70% of liver coma)
Toxicology screen for illicit drugs
Elevated ammonia often present

Drugs that may alter lab results:

Infusion of amino acid solutions may affect ammonia level
Opiate administration - producing severe constipation may affect ammonia level

Disorders that may alter lab results:

Uremia may affect ammonia level
Rapid and severe tissue breakdown, massive burns, trauma or infection may affect ammonia level

PATHOLOGICAL FINDINGS

Brain edema in 100% of fatal cases
Glial hypertrophy in chronic encephalopathy

SPECIAL TESTS

Electroencephalogram shows symmetrical slowing of basic (alpha) rhythm in common with other forms of metabolic encephalopathy
Visually-evoked potential specific in stages 2, 3 and 4

IMAGING

Useful only to rule out other diagnoses
CT scan of head most useful
Brain MRI shows increased glutamine in basal ganglia

DIAGNOSTIC PROCEDURES

Clinical setting and findings adequate in 80% of cases
Venous ammonia of great aid in patients with chronic liver disease when the clinical findings are confusing
EEG is useful to a limited extent, but findings are similar in other forms of metabolic encephalopathy
Treatment response often confirms diagnosis

TREATMENT

APPROPRIATE HEALTH CARE

Outpatient for stages 1 and 2 when diagnosis is clear and if recurrent can be managed satisfactorily
Stage 3 or 4 requires inpatient management
Stage 3 or 4 in fulminant hepatic failure is a strong indication for evaluation for liver transplantation. Transfer to a transplant center should be considered.

GENERAL MEASURES

Identify and treat vigorously precipitating causes - gastrointestinal bleed, infection, sedative drugs, or electrolyte imbalance are most common
Stage 2 or higher - attention to adequate fluid intake, and at least 1000 kcal (4.19 MJ) of food daily
Give Fleet's enema to all patients without diarrhea
Clumsiness and poor judgment prominent. Be sure patient has the care needed to avoid falls, cuts on broken glass, smoking burns, machinery or auto accidents.
Avoid sedative or opiate medications. Benzodiazepine sedatives and opiate derivatives such as Lomotil have caused liver coma.

SURGICAL MEASURES

N/A

ACTIVITY

As tolerated
Avoid driving and machinery

DIET

Integrate with needs of underlying liver disease
Lower total protein. Stage 1: avoid protein gluttony. Stage 2: limit red meat and consume small portions of all other protein foods, total protein for day 50-60 grams. Stage 3: consume 40 grams protein or vegetable protein diet (about 20 grams). Stage 4: consume 10 or fewer grams of protein. For all stages: at least 1000 kcal (4.19 MJ) ingested daily
As coma improves, increase dietary protein as tolerated

PATIENT EDUCATION

Include family in education
Dietitian instruction in eating lower protein diets, avoid protein bingeing
Avoid unnecessary sedative or antianxiety medications and opiates
Recognition of early signs and to get treatment promptly
Pamphlets (quite good for family) - American Association for the Study of Liver Diseases, 6900 Grove Road, Thorofare, NJ 08086, (609) 848-1000

FOLLOW UP

PREVENTION/AVOIDANCE

Avoid unessential medications, particularly opiates, sedatives
Avoid protein binges

POSSIBLE COMPLICATIONS

Recurrence
Stable, chronic, impaired status
With many recurrences, permanent basal ganglion injury (non-Wilsonian hepatolenticular degeneration)
Hepatorenal syndrome
Acute tubular necrosis
Bleeding
Disseminated intravascular coagulation
Bacteremia
Shock

EXPECTED COURSE AND PROGNOSIS

In acute or fulminant
- With adequate aggressive treatment, disappears without residue or recurrence
In chronic liver disease
- Coma returns
- With each recurrence it becomes more and more difficult to treat
- Plateau of maximum improvement shows a decrement over several years, such that the degree of improvement with treatment is less and less. Eventual 80% mortality.

MISCELLANEOUS

ASSOCIATED CONDITIONS

Liver disease
Rarely with portacaval shunt with normal liver function

AGE-RELATED FACTORS

See under Signs and symptoms

Pediatric: N/A
Geriatric: N/A
Others: N/A

PREGNANCY

May occur as a complication of pregnancy

OTHER NOTES

N/A

ABBREVIATIONS

N/A

Clinical Investigations

ROLE OF HOMOEOPATHY

Holistic healing that treats the person, not just the disease. Experience gentle, lasting wellness with expert constitutional care.