Current advances in the management of hepatic encephalopathy: an updated and critical review

Hepatic encephalopathy (HE) is a serious and potentially reversible neuropsychiatric syndrome resulting from severe liver insufficiency. HE is primarily considered a gliopathy in which astrocyte dysfunction is the main neuropathological hallmark, while recently microglia and neuronal alterations have been reported. It is believed that reversible factors trigger more than 80% of the cases. Several causative factors, including ammonia, inflammation, neuroinflammation, and oxidative stress, contribute to its pathogenesis, ultimately leading to abnormalities in neurotransmission and altered neuronal integrity. Current treatment strategies for managing HE include the primary use of rifaximin and lactulose, along with other pharmacological therapies that aim to reduce inflammation, neuroinflammation, and oxidative stress. However, liver transplantation remains the definitive curative treatment for end-stage liver diseases and associated encephalopathy. Recently, probiotics and fecal microbiota transplantation, as well as cell-based therapies, have shown promising results in both experimental studies and clinical trials. This review article highlights advances in understanding the complex pathophysiology of HE and assesses recent treatment strategies that aim to promote liver regeneration, target ammonia toxicity, and modulate immune responses.