Bronchopulmonary dysplasia

Disease Description (Causes and Symptoms)

Hepatic encephalopathy is a condition in which brain function becomes impaired due to the accumulation of toxic substances that should be removed by the liver—particularly toxic substances from the gut–liver axis, such as ammonia—because of reduced liver function or a portosystemic shunt. It includes acute cerebral edema in acute liver failure and recurrent, reversible cognitive impairment in chronic cirrhosis.

Major pathophysiological factors

• Increased blood ammonia produced by the breakdown of proteins in the intestines and its accumulation in the brain
• Inflammation (infection) and electrolyte abnormalities (such as hyponatremia) enhance the neurotoxic effects of ammonia
• Reduced detoxification function of the liver and diversion of portal-systemic blood flow

Major symptoms and course (refer to the West Haven classification)

• Early stage: changes in the sleep–wake rhythm, reduced concentration, and changes in personality and emotions (irritability, apathy)
• Moderate stage: impaired orientation, bradycardia and dysarthria, abnormal movements (asterixis, hand flapping when the arms are extended)
• Severe stage: confusion, reduced response to stimuli, clouding of consciousness → in severe cases, coma and respiratory failure or increased intracranial pressure
• Symptoms may occur acutely or chronically and may be reversible when precipitating factors (gastrointestinal bleeding, infection, electrolyte imbalance, medications, etc.) are corrected

Diagnostic clues

• Clinical symptoms and physical examination (including asterixis) and medical history (presence or absence of liver disease or cirrhosis)
• Blood ammonia testing (does not completely correlate with clinical severity)
• Nonspecific changes on electroencephalography (EEG), sometimes including triphasic waves
• Exclusion of other brain diseases (CT/MRI if necessary)

Treatment and Precautions

Principle: Identify and correct precipitating factors → remove ammonia and intestinal toxins → provide intensive care such as management of cerebral edema and airway protection in severe cases → consider definitive treatment (liver transplantation)

Non-drug and general care

• Treatment of precipitating factors: infection (antibiotics), gastrointestinal bleeding (endoscopy, transfusion, hemostasis), discontinuation or adjustment of medications (sedatives, analgesics, diuretics, etc.), correction of electrolyte abnormalities and dehydration, and treatment of constipation
• Severe cases (coma): secure the airway (intubation), intensive care unit management, and management of intracranial pressure if cerebral edema is suspected (head elevation to 30°, osmotherapy, etc.)

Drug treatment

• Lactulose: first-line treatment that promotes the excretion of ammonia from the intestines. It is administered orally or as an enema, with a target of 2–3 loose stools per day. Take care to avoid dehydration caused by diarrhea.
• Nonabsorbable antibiotics (e.g., rifaximin): added when lactulose alone is insufficient or for maintenance treatment of recurrent hepatic encephalopathy. Generally used as outpatient maintenance therapy.
• Supplementary treatment: Zinc supplementation may be helpful when zinc deficiency is confirmed.
• Other: L-ornithine L-aspartate (LOLA) or probiotics have been reported to be helpful in some situations, but their use depends on guidelines and country-specific insurance coverage.

Special procedures/surgery

• When a persistent or refractory portosystemic shunt is the cause: shunt embolization may be considered
• Definitive treatment: liver transplantation (for recurrent or refractory hepatic encephalopathy caused by acute liver failure or end-stage cirrhosis)

Precautions (including self-management)

• Complete protein restriction is not recommended. Ensure an appropriate protein intake considering nutritional status (generally about 1.0–1.5 g/kg/day is recommended, adjusted individually)
• If excessive diarrhea caused by lactulose leads to dehydration or electrolyte abnormalities, the condition may worsen; dose adjustment is therefore necessary
• Avoid central nervous system depressants such as benzodiazepines, sedatives, and some analgesics (opioids)
• Do not take folk remedies or herbal preparations (risk of hepatotoxicity)
• Evaluation for liver transplantation eligibility is necessary in cases of recurrent hepatic encephalopathy or worsening liver function

Prognosis

• Varies greatly depending on the cause: hepatic encephalopathy caused by acute liver failure carries a high risk of cerebral edema and death, and emergency liver transplantation may be necessary
• In patients with chronic cirrhosis, the condition may improve when precipitating factors are corrected and medications are used, but the prognosis is poor in recurrent or refractory cases, and liver transplantation should be considered

Complications

• Acute cerebral edema and brain injury, aspiration pneumonia, falls and trauma, recurrent cognitive decline (long-term cognitive impairment), and electrolyte abnormalities

Prevention

• Patients with liver disease should receive regular liver function monitoring, avoid alcohol, promptly treat infections, bleeding, and constipation, and use caution with medications (including over-the-counter drugs)

Checklist Before an Outpatient Visit (Including Items to Bring and Sample Questions)

Items to bring

• A list of all medications currently being taken (including prescription drugs, nonprescription drugs, herbal medicines, and health functional foods)
• Copies or a summary of recent test results (liver function tests, INR, electrolytes, creatinine, serum ammonia, etc.)
• History of previous episodes of hepatic encephalopathy (number of episodes, severity, treatment, and response)
• A record of recent symptom changes (sleep changes, memory or personality changes, changes in bowel movement frequency, and whether bleeding or fever occurred)
• A record of meals and alcohol consumption, and notation of bowel movement frequency
• A caregiver or family member to accompany the patient (in cases of cognitive or communication impairment)

Examples of items and questions to show or ask the doctor during an outpatient visit (items for patients and caregivers to prepare)

• Recent blood test results (ALT/AST, bilirubin, INR, electrolytes, ammonia)
• Medication list and dosing times
• Differences between the symptoms at onset and current symptoms (changes over time)
• Previous hospitalizations, endoscopies, liver surgeries, and transplantation history

Examples of General Questions to Ask the Doctor

• What is the cause of this condition, and what immediate action should I (or the caregiver) take now?
• What are the expected effects and common side effects of the prescribed medications (lactulose and rifaximin)?
• What lifestyle measures should be followed to reduce recurrence (protein intake, alcohol, and medications)?
• How is eligibility for or the need for liver transplantation determined? When should an evaluation be performed?
• Is it safe to drive or carry out daily activities? (Restrictions are necessary when cognitive decline or confusion is present.)

Examples of Condition-Specific Questions

• What do you think is the precipitating cause of my hepatic encephalopathy? (For example, infection, bleeding, medications, or electrolyte abnormalities.)
• If it recurs repeatedly, would I be eligible for interventional treatment such as liver transplantation or shunt embolization?