Hepatic Encephalopathy: From Pathophysiology to Treatment

Abstract

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome due to hepatic dysfunction and porto-systemic shunting of the intestinal blood. Cirrhosis is the most frequent liver disease causing HE. On most occasions, HE appears due to a superimposed precipitating factor (gastrointestinal bleeding, infections, renal and electrolyte disturbances, etc.). Ammonia produced in colon by intestinal bacteria is the main toxic substance implicated in the pathogenesis of HE. Other mechanisms, such as changes in the GABA-benzodiazepine system, accumulation of manganese into the basal ganglia of the brain, changes in blood-brain barrier and neurotransmission disturbances are also present. Clinical manifestations of HE may vary widely, from minimal neurologic changes, only detected with specific tests, to deep coma. Treatment of HE should be directed to controlling the precipitating factors, as well as therapies aimed at correcting the above-mentioned pathophysiological changes, mainly reduction of blood ammonia levels. Artificial liver support systems may play a role in the future. Liver transplantation should be evaluated as a definitive therapy in all cases of HE.

Equine Hepatic Encephalopathy

“…Another pathogenetic mechanism has been suggested where an accumulation of manganese into the basal ganglia contributes to the clinical manifestation of cognitive dysfunction. 22 Swapna et al (2006) demonstrated that in rats, given a potent hepatotoxin (thioacetamide), myelin phospholipid, cholesterol, sphingomyelin, phosphatidylserine and phosphatidylethanolamine were significantly decreased. The suggestion is that these changes were observed as a consequence of neuronal oxidative damage.…”

“…Therapeutic trials aimed at reducing ammonia production and absorption do ameliorate the clinical signs referable to encephalopathy in these patients. 22,28 Conversely, however, there appears to be a poor correlation between detectable serum ammonia concentrations and the severity of clinical signs observed in equine patients with HE. 16 Furthermore, when ammonia is administered, the electroencephalographic (EEG) findings are not consistent with the encephalopathy associated with liver disease.…”

Surgical attenuation of spontaneous congenital portosystemic shunts in dogs resolves hepatic encephalopathy but not hypermanganesemia

“…The pathogenesis of HE is multifactorial with ammonia and inflammation currently considered to be the main causes of neurological disturbances in patients with liver disease. However, other metabolic disturbances, notably in sodium homeostasis, have been linked to the development of HE (McPhail et al 2010;Mas 2006).…”

Is Oral l-Acyl-Carnitine an Effective Therapy for Hepatic Encephalopathy? Review of the Literature

“…HE is common in patients with advanced cirrhosis, and symptoms range from subclinical impairment of memory and concentration to frank coma. The most widely accepted pathophysiological mechanism is that endogenous and gut-derived ammonia crosses the bloodbrain barrier and alters neurotransmission via glutamatergic, serotoninergic, g-aminobutyric acid (GABA)-ergic mechanisms [1]. Based on this concept of pathogenesis, current therapies of HE focus on a reduction in serum ammonia levels as a surrogate for decreased central nervous system ammonia exposure.…”