What are the diagnostic criteria and treatment options for portosystemic encephalopathy syndrome?

Diagnostic Criteria and Treatment Options for Portosystemic Encephalopathy Syndrome

Portosystemic encephalopathy syndrome should be diagnosed based on clinical features of neuropsychiatric dysfunction in the presence of portosystemic shunting, with elevated ammonia levels, and treated primarily with lactulose and rifaximin to reduce ammonia production and absorption. 1, 2

Diagnostic Criteria

Classification

• Portosystemic encephalopathy (PSE) is classified as Type B hepatic encephalopathy, occurring due to portosystemic shunting without significant liver disease 1
• The syndrome can be distinguished from Type A (acute liver failure) and Type C (cirrhosis with or without portosystemic shunting) 1

Clinical Presentation

• Symptoms include fatigue, cognitive deficits, and recurrent episodes of encephalopathy 1
• Neuropsychological tests reveal cognitive deficits similar to those in cirrhosis with minimal hepatic encephalopathy 1
• Patients may develop symptoms early in life or remain asymptomatic until the sixth or seventh decades 1

Essential Diagnostic Tests

• Unexplained hyperammonemia is a key diagnostic finding 1
• MRI is recommended for diagnosis and classification of portosystemic shunts 1
• Complete blood tests including electrolytes, renal function, and liver function tests are essential 3
• West Haven criteria should be used for grading when temporal disorientation is present (grades ≥2) 1
• Glasgow Coma Scale should be added for patients with grades III-IV encephalopathy 1

Differential Diagnosis

• Other causes of cognitive impairment must be ruled out, including neurodegenerative diseases, vascular dementia, and other alcohol-related neurological conditions 4
• Metabolic causes to consider include uremia, hypercapnia, hypoglycemia, and electrolyte disorders 3

Treatment Options

First-Line Treatments

• Lactulose is the first-line treatment with an initial dosing of 25-45 mL (20-30g) three to four times daily, adjusted to produce 2-3 soft stools daily 2
• For acute episodes, hourly doses of 30-45 mL may be used until rapid laxation is achieved 2
• For comatose patients, lactulose can be administered as a retention enema (300 mL lactulose mixed with 700 mL water or saline) retained for 30-60 minutes, repeatable every 4-6 hours 2

Second-Line and Adjunctive Treatments

• Rifaximin is effective as an add-on therapy when lactulose alone is insufficient 5
• Rifaximin prophylaxis is recommended before non-urgent TIPS procedures to prevent post-TIPS encephalopathy 1

Management of Portosystemic Shunts

• Portosystemic shunt ligation/embolization should not be performed systematically but considered on a case-by-case basis 1
• Radiological embolization or surgical ligation of large portosystemic shunts appears feasible in selected patients with HE, resulting in recovery in 46-100% of cases 1
• MELD score is the strongest predictor of HE recurrence, with a cut-off of 11 used for patient selection 1
• Potential complications include local hematoma, aggravation of ascites, or esophageal varices 1

Definitive Treatment

• Liver transplantation should be offered to patients with disabling symptoms of hepatic encephalopathy refractory to drug and non-drug treatments 1
• Liver transplantation may be the only treatment option when there is an absent portal vein or with intractable portosystemic encephalopathy 1

Special Considerations

Congenital Portosystemic Shunts

• Congenital portosystemic shunting should be investigated in patients with unexplained hyperammonemia, mental retardation, or clinical picture compatible with hepatic encephalopathy in the absence of cirrhosis 1
• Two types exist: extrahepatic and intrahepatic (includes patent ductus venosus) 1
• Shunt diameter may determine clinical course: large shunts cause persistent manifestations from childhood, while small intrahepatic shunts lead to recurrent episodes beginning in adulthood 1

TIPS-Related Encephalopathy

• TIPS-related HE occurs in approximately 35% of cases 1
• A single episode of overt HE is not a formal contraindication to elective TIPS creation, but should be discussed case-by-case 1
• For cases of refractory gastrointestinal bleeding, there is no contraindication to TIPS as there is no therapeutic alternative 1

Clinical Pitfalls

• Mental status changes may be subtle in early stages, requiring formal neuropsychological testing 1
• Avoid benzodiazepines and other sedatives that can worsen symptoms 4, 5
• Always rule out other causes of altered mental status before attributing symptoms to PSE 3
• Recognize that hyponatremia and sepsis can produce encephalopathy independently and precipitate hepatic encephalopathy 3