Understanding Hepatic Encephalopathy and Its Treatment

Contributor: Alec Coston, MD

Educational Pearls:

• Hepatic encephalopathy (HE) is defined as a disruption in brain function that results from impaired liver function or portosystemic shunting.
  • Manifests as various neurologic and psychiatric symptoms such as confusion, inattention, and cognitive dysfunction
• Although ammonia levels have historically been recognized as important criteria for HE, the diagnosis is ultimately made clinically.
  • An elevated ammonia level lacks sensitivity and specificity for HE
  • Trends in ammonia levels do not correlate with disease improvement or resolution
  • A 2020 study published in the American Journal of Gastroenterology evaluated 551 patients diagnosed with hepatic encephalopathy and treated with standard therapy
    • Only 60% of patients had an elevated ammonia level, demonstrating the limitations of ammonia levels
  • However, a normal ammonia level in a patient with concern for HE should raise suspicion for other pathology.
• In patients with cirrhosis presenting with neuropsychiatric symptoms, consider HE as the diagnosis after excluding other potential causes of altered mental status (i.e., Seizure, infection, intracranial hemorrhage)
• The primary treatment is lactulose
  • Works by acidifying the gastrointestinal tract.
  • Ammonia (NH₃) is converted into ammonium (NH₄⁺), which is poorly absorbed and subsequently eliminated from the body
  • Also exerts a laxative effect, further enhancing elimination

References:

1. Haj M, Rockey DC. Ammonia Levels Do Not Guide Clinical Management of Patients With Hepatic Encephalopathy Caused by Cirrhosis. Am J Gastroenterol. 2020 May;115(5):723-728. doi: 10.14309/ajg.0000000000000343. PMID: 31658104.\
2. Lee F, Frederick RT. Hepatic Encephalopathy-A Guide to Laboratory Testing. Clin Liver Dis. 2024 May;28(2):225-236. doi: 10.1016/j.cld.2024.01.003. Epub 2024 Jan 30. PMID: 38548435.
3. Vilstrup, Hendrik1; Amodio, Piero2; Bajaj, Jasmohan3,4; Cordoba, Juan1,5; Ferenci, Peter6; Mullen, Kevin D.7; Weissenborn, Karin8; Wong, Philip9. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study Of Liver Diseases and the European Association for the Study of the Liver. Hepatology 60(2):p 715-735, August 2014. | DOI: 10.1002/hep.27210
4. Weissenborn K. Hepatic Encephalopathy: Definition, Clinical Grading and Diagnostic Principles. Drugs. 2019 Feb;79(Suppl 1):5-9. doi: 10.1007/s40265-018-1018-z. PMID: 30706420; PMCID: PMC6416238.

Summarized by Ashley Lyons, OMS3 | Edited by Ashley Lyons & Jorge Chalit, OMS4

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