What are the diagnosis and management options for hepatic encephalopathy?

Diagnosis and Management of Hepatic Encephalopathy

Diagnosis

Hepatic encephalopathy should be diagnosed using the West Haven criteria for grades ≥2 (temporal disorientation or worse), while covert HE requires neuropsychological/neurophysiological testing or the Animal Naming Test for grades 0-1. 1

Clinical Assessment

• Grade severity using West Haven criteria when temporal disorientation is present, and add the Glasgow Coma Scale for grades III-IV 1
• Measure plasma ammonia levels in all patients with suspected HE—a normal ammonia level should prompt reconsideration of the diagnosis and evaluation for alternative causes 1
• Note that ammonia levels do not correlate with HE severity or prognosis, but normal values make HE unlikely 1

Differential Diagnosis

• Perform brain imaging (CT or MRI) when diagnostic doubt exists or when patients fail to respond to treatment 1
• Rule out alternative causes including intracranial hemorrhage, drug intoxication, metabolic encephalopathies, infections, and neurodegenerative diseases 1, 2
• Consider vascular dementia particularly in NAFLD patients with metabolic syndrome, as cognitive impairment patterns may overlap 1

Management of Overt Hepatic Encephalopathy

Lactulose is the first-line treatment for overt HE and should be initiated immediately without delay, targeting 2-3 soft bowel movements daily. 1, 3, 4

Immediate Priorities

• Identify and correct precipitating factors first—this alone resolves symptoms in approximately 90% of cases 1, 3
• Admit patients with grades 3-4 HE to the ICU due to aspiration risk and inability to protect the airway 1
• Screen systematically for all precipitating factors as 100% of ICU-admitted patients have at least one, and 82% have multiple concomitant factors 5

Common Precipitating Factors and Management

Precipitating Factor	Diagnostic Approach	Management
Gastrointestinal bleeding	Endoscopy, CBC, rectal exam, stool blood test [1]	Transfusion, endoscopic therapy, vasoactive drugs [1]
Infection	CBC with differential, CRP, chest X-ray, urinalysis/culture, blood culture, diagnostic paracentesis [1]	Antibiotics [1]
Hyponatremia	Serum sodium—critical threshold <130 mmol/L [1]	Stop/reduce diuretics, maintain sodium >135 mmol/L if possible [1]
Constipation	History, abdominal X-ray [1]	Enema or laxatives [1]
Dehydration/AKI	BUN, creatinine, electrolytes [1]	Stop/reduce diuretics, IV albumin [1]
Benzodiazepines	History [1]	Discontinue immediately, flumazenil if needed [1]

Pharmacological Treatment

Lactulose Dosing:

• Start with 25 mL (or 15-30 mL) orally every 12 hours, titrating to achieve 2-3 soft bowel movements daily 1, 3
• Lactulose reduces blood ammonia by 25-50% and improves mental state in approximately 75% of patients 4
• Avoid excessive dosing that can cause aspiration, dehydration, hypernatremia, and severe perianal irritation 3

Rifaximin:

• Do NOT use rifaximin as monotherapy for initial treatment of overt HE 3
• Rifaximin 550 mg twice daily is FDA-approved but should be reserved for specific indications 3, 6

Prevention of Recurrence (Secondary Prophylaxis)

Lactulose should be continued indefinitely after the first episode of overt HE to prevent recurrence, maintaining 2-3 bowel movements daily. 1, 3

• After a first episode, initiate lactulose for secondary prophylaxis 1
• Add rifaximin 550 mg twice daily only after >1 additional episode within 6 months despite lactulose therapy 1, 3
• Rifaximin reduces recurrence risk by 58% when added to lactulose and can be continued for >24 months safely 3

Covert Hepatic Encephalopathy

• Screen for covert HE using available neuropsychological tests or the Animal Naming Test 1
• Treat covert HE with non-absorbable disaccharides as it is a risk factor for progression to overt HE 1

Prevention Strategies

Monitor and correct modifiable risk factors throughout the course of cirrhosis to prevent HE episodes. 1

Key Preventive Measures

• Monitor serum sodium closely in decompensated cirrhosis, maintaining levels >130 mmol/L (ideally >135 mmol/L) 1
• Contraindicate benzodiazepines in patients with decompensated cirrhosis 1
• Limit proton pump inhibitors to strict validated indications only, as they increase HE risk through dysbiosis 1

Liver Transplantation

• Refer patients to transplant evaluation after the first episode of overt HE 1
• Consider transplantation urgently for recurrent or persistent HE with liver failure 1, 3

Critical Pitfalls to Avoid

• Do not rely solely on ammonia levels for diagnosis or monitoring—they lack prognostic value 1
• Do not delay lactulose while waiting to identify precipitating factors—start both simultaneously 3
• If lactulose fails, search for unrecognized precipitating factors or alternative diagnoses rather than simply increasing the dose 3
• Do not use rifaximin alone for acute overt HE treatment 3
• Recognize that hyponatremia predicts non-response to lactulose therapy 1