Hepatic Encephalopathy

From Anvita Health Wiki

Contents 1 Etiology 2 Pathology 3 Clinical-manifestations 4 Laboratory 5 Management 6 More General Terms 7 Additional Terms 8 References

Etiology

• underlying disease processes

• acute & chronic liver disease ( cirrhosis)

• precipitating factors

• GI bleeding
• azotemia ( renal failure)
• constipation
• high protein meal
• hypokalemic alkalosis
• CNS depressants

• benzodiazepines
• barbiturates
• opiates

• hypoxia
• hypercarbia
• sepsis

Pathology

• failure of liver to detoxify agents noxious to CNS due to decreased hepatic function & portocaval shunting
• retention of neurotoxins of intestinal origin

• NH3 (intracellular)

• hypokalemic alkalosis

• pardoxical intracellular acidosis shifts NH3 intracellularly

• mercaptans
• short-chain fatty acids
• phenolic compound

• increased GABA activity
• presence of benzodiazepine-like substances in the brain

Clinical-manifestations

• grade 1

• day/night reversal of sleep cycle
• somnolence
• mild confusion
• personality change
• asterixis (flapping tremor)
• abnormal psychometric testing
• disordered handwriting

• grade 2

• drowsiness
• inappropriate behavior

• grade 3

• stupor
• marked confusion
• inarticulate speech

• grade 4

• coma
• extrapyramidal signs (occasional)
• muscle twitching
• hyperventilation

• Fetor hepaticus (breath & urine odor of mercaptans)

Laboratory

• elevated serum ammonia
• EEG abnormalities

Management

• correct precipitating cause
• pharmacologic agents

• lactulose* 30-45 mL PO TID/ QID, or as enema [4]
• neomycin 4-12 g/day PO, divided every 4 hours

• avoid: adverse effects substantial [2]

• metronidazole 250 mg PO TID
• vancomycin 1 g PO BID
• sorbitol 2 mL/kg up to 50 mL of a 70% solution PO
• flumazenil
• rifaximin may improve outcomes, but cost is high [5]
• unproven therapies: branched chain amino acids, levodopa, bromocryptine

• Harris flush to evacuate colonic gases
• low protein diet not useful for prevention [2]
• amino acid formulations high in branched-chain amino acids & low in aromatic amino acids for encephalopathy refractory to lactulose [2]

• * may reduce morbidity, but not mortality [3]

More General Terms

• metabolic encephalopathy; toxic encephalopathy
• liver disease

Additional Terms

• cirrhosis
• liver transplantation

References

1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 538-40
2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, American College of Physicians, Philadelphia 1998, 2006, 2009
3. Journal Watch 24(14):113, 2004 Als-Nielsen B, Gluud LL, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials. BMJ. 2004 May 1;328(7447):1046. Epub 2004 Mar 30. Review. PMID: [1]
   - Als-Nielsen B et al, BMJ. 2004 May 1;328(7447):1046 [2]
4. Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007 Mar;45(3):549-59. PMID: [3]
5. Prescriber's Letter 17(6): 2010 Rifaximin (Xifaxan) for Hepatic Encephalopathy Detail-Document#: [4] (subscription needed) [5]
   - Sidhu SS et al. Rifaximin improves psychometric performance and health-related quality of life in patients with minimal hepatic encephalopathy (The RIME Trial). Am J Gastroenterol 2011 Feb; 106:307. PMID: [6]
   - Bajaj JS et al. Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy. Gastroenterology 2011 Feb; 140:478. PMID: [7]

hepatic encephalopathy