Hepatic encephalopathy: A review of its pathophysiology and treatment

Abstract

Hepatic encephalopathy (HE) is a broad spectrum of neuropsychiatric manifestations usually affecting individuals with end-stage liver disease. The presence of HE is a poor prognostic sign, with 1-year mortality rates of almost 60%. There is much debate about the underlying mechanisms that result in this syndrome; however, elevated plasma and central nervous system ammonia levels are considered key factors in its pathogenesis. Initial evaluation of the patient presenting with overt HE should include a careful search for predisposing factors, including underlying infection, gastrointestinal (GI) bleeding, electrolyte disturbances, hepatocellular carcinoma, dehydration, hypotension, and excessive use of benzodiazepines, psychoactive drugs, or alcohol. The mainstay of treatment for many years has been nonabsorbable disaccharides, particularly lactulose. Alternative treatments, which usually are second line in patients who do not respond to lactulose, include zinc, antibiotics (neomycin, metronidazole, and rifaximin), ornithine aspartate, sodium benzoate, probiotics, and surgical intervention. Accepted treatments for HE are associated with significant unpleasant side effects, including diarrhea, renal failure, neuropathy, and other GI disturbance. Newer therapies are still in development, and most are awaiting human trials in order to confirm their benefit. These include manganese chelators, L-carnitine, N-methyl-d-aspartate receptor antagonists, blood purification dialysis system, and an intravenous combination of sodium benzoate and phenylacetate.

Störungen des angeborenen Immunsystems bei akuten und chronischen Lebererkrankungen

“…In patients with liver cirrhosis, probiotics have been shown to decrease hepatic encephalopathy [125,126], improve liver biochemistry [127] and decrease the rate of infection after liver transplantation [128]. Several meta-analyses have already supported the benefit of probiotics in preventing infection in the general hospital population [129][130][131]; however, the exact mechanism is still largely speculative.…”

Medical comorbidity and alcohol dependence

“…Although there is debate surrounding the mechanisms underlying this syndrome, it can be defined as a broad spectrum of neuropsychiatric manifestations usually affecting patients with liver failure and/or a portal-systemic bypass, possibly as complications of AD (also see "Hepatic disease") [17]. Since 2002, a new nomenclature of HE classifies HE as encephalopathy type A (associated with acute liver failure), type B (associated with portal-systemic bypass), and type C (associated with liver cirrhosis).…”

Evaluation of Relation Between Air Pollution and Hepatic Encephalopathy Exacerbation

“…Although HE is often triggered by an inciting event that results in a rise of the serum ammonia level, the precise underlying pathophysiologic mechanisms are not well understood [5]. A number of factors have been implicated in the development of HE.…”

“…These factors include production of neurotoxins, altered permeability of the blood-brain barrier, and abnormal neurotransmission. The best-described neurotoxin involved in HE is ammonia, which is produced primarily in the colon, where bacteria metabolize proteins and other nitrogenbased products into ammonia [5,21].…”

“…It has been postulated that inadequate hepatic elimination of nitrogenous compounds and neurotoxin byproducts of GI tract metabolism, accumulation of inflammatory cytokines, benzodiazepine-like compounds and manganese deposition result in hepatic encephalopathy [1,4,5].…”