Covert hepatic encephalopathy in cirrhosis: implications for early diagnosis and appropriate management

Covert hepatic encephalopathy (CHE) is a frequent and clinically relevant complication of liver cirrhosis, affecting approximately 30-70% of patients. Despite the absence of overt neurological symptoms, CHE is associated with impaired quality of life and increased risks of falls, traffic accidents, hospitalization, progression to overt HE (OHE), and mortality. The pathophysiology of HE, including CHE and OHE, is multifactorial and involves complex interactions among hyperammonemia, systemic inflammation, oxidative stress, gut dysbiosis, bile acid dysregulation, and sarcopenia along the gut-liver-brain axis. Several diagnostic tools are available, including psychometric batteries, computerized neuropsychological assessments, the Stroop test, critical flicker frequency, and the inhibitory control test. However, time and resource constraints hinder their routine implementation in real-world clinical settings, leading to substantial underdiagnosis of CHE. Although treatment strategies for CHE have not yet been fully established, non-absorbable disaccharides and rifaximin have emerged as promising ammonia-lowering therapies and microbiota-targeted interventions for improving cognitive function and reducing the risk of progression to overt HE. Early recognition and multidisciplinary intervention for CHE are essential to prevent disease progression and improve clinical outcomes. This review summarizes the current evidence on the epidemiology, pathophysiology, diagnosis, clinical significance, and therapeutic approaches for CHE in cirrhosis, with the aim of enhancing its recognition and optimizing patient management.