Hepatic Encephalopathy: An Update on the Pathophysiology and Therapeutic Options

Saleh Elwir, Robert S Rahimi, Saleh Elwir, Robert S Rahimi

Abstract

Hepatic encephalopathy is a spectrum of reversible neuropsychiatric abnormalities, seen in patients with liver dysfunction and/or portosystemic shunting. One of the most debilitating complications of cirrhosis, encephalopathy affects 30-45% of cirrhotics. In addition to significantly affecting the lives of patients and their caregivers, it is also associated with increased morbidity and mortality as well as significant utilization of health care resources. In this paper, we provide an overview on the pathophysiology, diagnosis, management and newer therapies of hepatic encephalopathy.

Keywords: Cirrhosis; Hepatic encephalopathy; Lactulose; Rifaximin.

Conflict of interest statement

Rahimi R.S. received research support from Ocera Therapeutics. The others has no conflict of interest related to this publication.

Figures

Fig. 1.. Multiorgan ammonia pathways with specific…
Fig. 1.. Multiorgan ammonia pathways with specific ammonia-lowering medications used in cirrhosis.
Circulating concentrations of ammonia (NH3) are shown with multiorgan involvement in the production of NH3, ultimately resulting in NH3 crossing the blood–brain barrier, contributing to astrocyte swelling and hepatic encephalopathy, as decreased urea cycle capability and reduced liver glutamine synthetase activity is present in cirrhosis. The alternative pathway is also shown at the top, where NH3 binds with glutamate (GLU) forming glutamine (GLN) after enzymatic processing using glutamine synthetase (GS). Both ornithine phenylacetate (OP) and glycerol phenylbutyrate (GPB) are ammonia-lowering medications; they combine GLN and phenylacetate (PAA) to form phenylacetylglutamine (PAGN), which is excreted in the urine. AST-120 is a carbon microsphere adsorbent that binds NH3 in the gut, thus lowering circulating ammonia levels. Polyethylene glycol (PEG) is a cathartic, which causes rapid clearance of gut bacterial synthesizing ammonia to be excreted into the feces. About one-quarter of urea-derived byproducts from the urea cycle is shunted to the colon (not shown; remaining three-fourths of urea excreted in the kidneys), where urease-producing bacterial organisms produce ammonia that enters the portal circulation. Skeletal muscle also contributes to the regulation of NH3 as depicted. Not shown in the figure is the presence of GS and glutaminase in each organ, contributing to NH3 homeostasis. Adapted from publication by Thieme publications. Abbreviation: PBA, Phenylbutyric acid.
Fig. 2.. Approach for addressing a patient…
Fig. 2.. Approach for addressing a patient with suspected HE.

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