Table 2.

A summary of therapeutic targets and related therapies in the treatment of hepatic encephalopathy in cirrhosis.

Therapeutic target	Therapies
Laxatives to decrease gut absorption of ammonia	Non-absorbable disaccharides (lactulose) Osmotic laxatives (polyethylene glycol)
Gut dysbiosis and gut production of ammonia	Antimicrobials- rifaximin (other antibiotics not favored, eg neomycin, metronidazole or vancomycin) Solid soluble dispersion rifaximin (in clinical trials) Lactulose (putative intraluminal pH effect) Fecal microbiota transplant (clinical protocols) Probiotics (limited success) Engineered bacteria (early-stage clinical trials) Carbon microspheres (early-stage clinical trials)
Nutritional measures	Adequate nutrition and protein intake to mitigate sarcopenia/malnutrition Branched-chain amino acids Avoid and treat hypokalemia and hyponatremia Zinc repletion (primes the urea cycle)
Closure of portosystemic shunts	Interventional radiology embolization of portosystemic shunts, ideally MELD<12
Enhance nitrogen scavenging	Glycerol and sodium phenylbutyrate (used in urea cycle disorders) Sodium benzoate (used in urea cycle disorders) L-Ornithine L-Aspartate (urea cycle substrate and activator of glutamine synthetase in peripheral organs) Ornithine phenylacetate
Ammonia lowering and prevent ammonia-induced neurotoxity	Acetyl L-carnitine (reduce blood/brain ammonia, enhance cellular/mitochondrial energy production)
Toxin binding	Albumin infusion Albumin dialysis
Direct vigilance modulators	Golexanolone (early-stage clinical trials) Caffeine (limited data)