MECHANISTIC PERSPECTIVES ON HEPATIC ENCEPHALOPATHY: THE IMPACT OF AMMONIA ACCUMULATION, NEUROINFLAMMATION AND ASTROCYTE DYSFUNCTION"

Hepatic encephalopathy (HE), a neuropsychiatric disorder mainly caused by liver failure, leading to impaired detoxification of toxins like ammonia. Elevated ammonia crosses the blood-brain barrier, causing astrocyte swelling, brain edema, and disrupted neurotransmission, which impair neuronal function. Disease progression is also driven by oxidative stress, neuroinflammation, and mitochondrial dysfunction that damage neural cells and impair energy production. Experimental models have helped identify key pathogenic pathways and potential treatments, including antioxidants and strategies to preserve mitochondrial health. Central to HE are disturbances in neurotransmitters such as glutamate and GABA, along with activation of microglia and astrocytes that amplify inflammation and neural injury. Astrocyte swelling due to excess glutamine from ammonia detoxification contributes to brain edema and neurological symptoms. Early diagnosis and a comprehensive approach targeting ammonia reduction, neuroprotection, and inflammation are essential, with ongoing research providing optimism for the development of better treatments to enhance patient results. Keywords: Hepatic Encephalopathy, Ammonia, Glutamate, Neuroinflammation, Oxidative Stress