What triggers Hepatic Encephalopathy (HE)?

Precipitating Factors for Hepatic Encephalopathy

Precipitating factors can be identified in nearly all episodes of hepatic encephalopathy and should be actively sought and treated when found. 1

Recognized Precipitating Events

The most common triggers for HE episodes include:

• Infections and sepsis are major precipitants, with neurological symptoms appearing in 21-33% of cirrhotic patients with sepsis and 60-68% of those with septic shock 1, 2

  • Systemic inflammation and hyperammonemia act synergistically to precipitate HE 3, 2

• Gastrointestinal bleeding precipitates HE through two mechanisms: volume loss causing hypotension and increased ammonia production from breakdown of blood proteins in the intestine 1, 2, 4, 5, 6

• Constipation increases intestinal ammonia production and absorption, making it a frequent and easily correctable precipitant 1, 5

• Hyponatremia is an independent risk factor for HE development, causing cerebral edema through extracellular hypo-osmolality 1, 3, 2

  • Severe hyponatremia (<130 mmol/L) significantly increases HE risk 3, 2

• Dehydration and excessive diuretic use lead to volume depletion and electrolyte disturbances that precipitate HE 1, 2, 5

Medication-Related Triggers

• Sedatives, benzodiazepines, neuroleptics, and opioids directly impair consciousness and can precipitate or worsen HE 1, 5, 7

• Proton pump inhibitors should be limited to strictly validated indications, as they worsen intestinal dysbiosis and increase ammonia production 3

Metabolic and Organ Dysfunction Triggers

• Renal dysfunction reduces ammonia excretion, increasing serum levels and contributing to HE development 3, 2, 5

  • In end-stage liver disease, uremic and hepatic encephalopathy may overlap 1, 8

• Hypoglycemia from impaired hepatic gluconeogenesis causes altered mental status that can precipitate or mimic HE 2

Anatomical Factors

• Portosystemic shunts (spontaneous or iatrogenic, including TIPS) allow ammonia-rich portal blood to bypass hepatic metabolism and enter systemic circulation directly 1, 3, 9, 7
  • These shunts facilitate HE occurrence and are associated with more severe forms 1

Clinical Approach to Identifying Precipitants

When evaluating any HE episode, systematically assess for:

• Signs of infection (fever, leukocytosis, positive cultures) 1, 2, 4, 5
• Evidence of GI bleeding (melena, hematemesis, dropping hemoglobin) 1, 2, 4
• Medication review for sedatives, opioids, or excessive diuretics 1, 5, 7
• Electrolyte panel focusing on sodium levels 1, 3, 2
• Renal function assessment 3, 2, 5
• Bowel movement frequency to identify constipation 1, 5

Important Caveats

• Multiple precipitants often coexist in a single HE episode, requiring comprehensive evaluation 9

• Recurrent or persistent HE without identifiable precipitants should prompt investigation for large portosystemic shunts that may require intervention 4, 6, 9

• Diabetes mellitus has been suggested as a risk factor for HE development, particularly in hepatitis C-related cirrhosis 3