Reducing the Risk of Overt Hepatic Encephalopathy Recurrence: A Narrative Review

Hepatic encephalopathy (HE) is a neurologic complication of advanced liver disease (e.g., cirrhosis) resulting in impaired functioning and reduced quality of life. This condition is associated with a substantial burden for patients and their caregivers and carries a poor prognosis and increased risk of hospitalization and mortality. This narrative review discusses the burden of HE, precipitating risk factors, and clinical considerations for reducing the risk of overt HE (OHE) recurrence in adults with cirrhosis. Key precipitating factors include certain medications, constipation, dehydration, uncontrolled diabetes mellitus, electrolyte imbalances, gastrointestinal bleeding, infection, and sarcopenia, among others. Identification and treatment of precipitating factors are critical steps in the management of HE. Components of ongoing care include patient and caregiver education, nutritional supplementation and sleep management, pharmacotherapy, and nonpharmacologic interventions (e.g., spontaneous portosystemic shunt embolization and liver transplantation in appropriate patients). Clinical guidelines recommend lactulose therapy as secondary prophylaxis after an initial episode of OHE. Rifaximin is recommended as add-on therapy to lactulose when an additional OHE episode occurs. Polyethylene glycol has been investigated as an alternative to lactulose in patients with acute HE and in those with chronic HE and a poor response to lactulose. Oral L-ornithine-L-aspartate may reduce the risk of OHE recurrence in patients with cirrhosis. Investigational agents include nitazoxanide, fecal microbiota transplantation, and the use of artificial intelligence, app-based technology, and wearable devices to facilitate acute and prophylactic management of HE.