New insight on hepatic encephalopathy: a comprehensive review

Hepatic encephalopathy (HE) encompasses a wide spectrum of neuropsychiatric disturbances that arise as a consequence of acute or chronic liver dysfunction. It represents a critical event in the natural history of cirrhosis and serves as an independent predictor of morbidity and mortality in affected patients worldwide. The clinical manifestations of HE range from subtle cognitive impairments, such as poor concentration, memory deficits, anxiety, depression, and insomnia, to severe psychomotor abnormalities, disorientation, and coma. Hyperammonemia is widely regarded as the central hallmark of HE pathogenesis and remains a cornerstone in both diagnosis and therapeutic monitoring. However, elevated ammonia levels do not always correlate with clinical severity, and some patients may present with significant neurological impairment despite near-normal ammonia concentrations. This discrepancy highlights the multifactorial mechanisms underlying HE, including neuroinflammation, oxidative stress, alterations in neurotransmission, and gut-liver-brain axis dysregulation. In this review, we provide a comprehensive overview of the pathogenesis, clinical spectrum, diagnostic approaches, and current as well as emerging therapeutic strategies for hepatic encephalopathy, with a focus on recent advances that may improve patient outcomes.