Covert and Overt Hepatic Encephalopathy: Diagnosis and Management

Abstract

Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into 2 broad categories based on severity: covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE). CHE has a significant impact on a patient's quality of life, driving performance, and recently has been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, early diagnosis and management are imperative. In addition, focus also should be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of nonabsorbable disaccharides, antibiotics (ie, rifaximin), and, potentially, probiotics. Other therapies currently under further investigation include L-ornithine-L-aspartate, ornithine phenylacetate, glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion.

Keywords: Ammonia; Cirrhosis; Covert Hepatic Encephalopathy; Hepatic Encephalopathy; Lactulose; Overt Hepatic Encephalopathy; Rifaximin.

Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1. Pathophysiology and Potential Therapeutic Targets of Hepatic Encephalopathy

*Experimental therapy ** In the brain, astrocytes metabolize ammonia through glutamine synthetase, converting glutamate and ammonia to glutamine which is osmotically active. Increased levels of ammonia leads to an increased production of glutamine which changes the osmotic gradient and causes intracellular swelling and edema. In addition, neurons may be affected by increased “GABAergic tone” from synthesis of benzodiazepine like compounds from the intestinal flora. ***Microbiota may be responsible for the formation or release of products such as ammonia, endotoxins, indoles, oxindoles, and other gut derived toxins that may lead to cognitive impairment. ^Flumazenil (not currently used) +Contributing factors LOLA, L-ornithine L-aspartate; OP, Ornithine –phenylacetate; GP, Glycerol – phenylbutyrate; TNF, tumor necrosis factor; IL, interleukin; BZD, benzodiazepine receptor antagonist

FIGURE 2. Management of Covert and Overt Hepatic Encephalopathy

* if suspicious based on history ** Potential reasons for refractory HE: worsening of liver disease only, failure to identify infection and dehydration, ileus, long acting sedative drug use, concomitant central nervous system diseases or metabolic diseases (i.e. hypothyroidism), transjugular intrahepatic portosystemic shunt dysfunction or supra-therapeutic shunt diameter (if present), profound zinc deficiency, and spontaneous portosystemic shunts. ***Zinc supplementation, LOLA (if available), IV albumin and albumin dialysis, Ornithine phenylacetate, Glycerol phenylbutyrate, spontaneous porto-systemic shunts ^Maintenance therapy: 1) lactulose titrated to 2–3 soft BM a day; if intolerant of lactulose start rifaximin 550mg PO BID 2) If > 2 overt episodes start both lactulose and rifaximin; ensure compliance with lactulose along with education (an re-education). AMS, altered mental status; GI, gastrointestinal; BM, bowel movement; CBC, complete blood count; BMP, basic metabolic panel; OG, oral gastric; CHE, covert hepatic encephalopathy; OHE, overt hepatic encephalopathy