Hepatic encephalopathy

Spectrum of reversible neuropsychiatric abnormalities due to advanced liver dysfunction or portosystemic shunting, leading to accumulation of neurotoxins (especially ammonia).

• Common in cirrhosis (~30–40% of patients) and signifies decompensation of liver disease. Overt HE portends poor prognosis (median survival ~2 years after onset). High-yield on exams as a classic complication of cirrhosis requiring prompt recognition and treatment (e.g., lactulose).

• Occurs in patients with chronic liver disease (e.g., cirrhosis from hepatitis or alcohol) who develop altered mental status. Early signs are subtle (inverted sleep-wake cycle, mild confusion, forgetfulness); as it progresses, patients show asterixis (flapping hand tremor), slurred speech, and can become lethargic or even comatose.
• Common precipitating factors: infection (especially spontaneous bacterial peritonitis), gastrointestinal bleeding (increased ammonia from blood in gut), dehydration or volume loss (e.g., over-diuresis), electrolyte disturbances (notably hypokalemia, which increases ammonia production), sedative drugs (benzodiazepines, opioids), and TIPS (shunting blood past liver). Even constipation can precipitate HE by increasing ammonia absorption.

1. Exclude other causes of altered mental status: check glucose, consider head CT (if trauma or focal deficit), and screen for infections or toxins (don't assume every confused cirrhotic is "just HE").
2. Identify and address precipitating causes: perform diagnostic paracentesis to rule out SBP, review medications (stop sedatives), check electrolytes (correct hypokalemia), and treat any GI hemorrhage or infection.
3. Measure serum ammonia to support the diagnosis (typically elevated), but remember normal ammonia does not rule out HE and level often poorly correlates with severity. Don't rely on serial ammonia levels to guide therapy.
4. Grade the severity using West Haven criteria: Grade I – mild confusion, mood changes, sleep disturbance; Grade II – lethargy, disorientation, asterixis; Grade III – somnolence, incoherent speech, marked confusion; Grade IV – coma. Severe HE (Grade III–IV) requires ICU care and airway protection.

1. Stabilize and treat precipitants first: ensure adequate airway (Grade III/IV HE may require intubation for coma/aspiration risk) and address the cause (e.g., start antibiotics for SBP, control any GI bleeding, rehydrate and correct electrolytes).
2. Give lactulose promptly – it's the first-line therapy. Titrate this nonabsorbable disaccharide to produce 2–3 soft bowel movements per day. It acidifies the colon, trapping ammonia as ammonium (NH4+) and expelling it with laxation.
3. Add rifaximin (nonabsorbable antibiotic) for persistent or recurrent HE. Rifaximin reduces ammonia-producing gut bacteria and is often used alongside lactulose, especially after a second HE episode (neomycin is an older alternative if rifaximin is unavailable).
4. Avoid or correct precipitating factors: discontinue sedatives (no benzodiazepines in cirrhosis), adjust diuretics to prevent dehydration, and replace potassium if low. Ensure adequate nutrition – do not severely restrict protein; provide enough protein to avoid muscle breakdown.
5. For refractory HE, consider additional measures (e.g., zinc supplementation) and evaluate for liver transplantation as definitive therapy once other causes are ruled out and medical management is optimized.

• The classic asterixis ("flapping tremor") is not specific to HE – it also appears in uremia and CO2 retention, but its presence in a cirrhotic patient is a big clue for HE.
• Do not chronically restrict dietary protein in cirrhosis – malnutrition worsens outcomes. Patients need ~1.2–1.5 g/kg of protein daily (small frequent meals and a bedtime snack).
• Serum ammonia often is high in HE, but levels do not reliably correlate with encephalopathy severity – manage the patient, not the number.

• Acute liver failure with any encephalopathy (Type A HE) is very high risk – even Grade I–II can progress rapidly to cerebral edema and herniation. Advanced grades (III–IV) in acute liver failure warrant ICU care with intracranial pressure monitoring and urgent transplant evaluation.
• Lack of improvement with standard HE therapy → reconsider the diagnosis. A cirrhotic patient not responding to lactulose/rifaximin may have another cause of AMS (e.g., intracranial hemorrhage, infection) requiring separate intervention.

1. Cirrhotic patient with altered mental status → suspect hepatic encephalopathy.
2. Initial steps: check ABCs (protect airway if needed) and fingerstick glucose; begin empiric HE treatment (e.g., lactulose) while investigating triggers.
3. Concurrent evaluation: perform necessary tests (labs for electrolytes, ammonia, infection; ascites tap for SBP; imaging like head CT if focal neuro signs) to identify precipitating factors or alternate diagnoses.
4. Treat identified precipitants (antibiotics for infection, endoscopy for variceal bleed, IV fluids for dehydration, etc.) and continue ammonia-lowering therapy (lactulose; add rifaximin if needed).
5. Monitor mental status closely. For severe HE (coma or stupor), admit to ICU and consider intubation. Once stabilized, implement secondary prophylaxis (daily lactulose ± rifaximin) and address underlying liver disease (e.g., referral for transplant in appropriate candidates).

• Patient with long-standing cirrhosis (ascites, varices) develops confusion, inverted sleep schedule, and a flapping hand tremor → hepatic encephalopathy (likely precipitated by a trigger such as infection or dehydration).
• After a large variceal bleed, a cirrhotic patient becomes lethargic with asterixis and confusion → HE caused by increased ammonia from GI bleeding.
• Cirrhotic who recently had a TIPS procedure now presents with confusion and irritability → suspect HE due to portosystemic shunting.