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Hepatic encephalopathy is a complication of decompensated liver disease that consumes considerable health care resources and has a negative impact on quality of life. For several decades, maintenance therapy with lactulose has been considered the standard of care, but emerging data from clinical trials demonstrate that other therapeutic options may be available and could have a better tolerability profile than lactulose. This brief review will discuss the pathophysiology of hepatic encephalopathy and proposed mechanisms of action of zinc and probiotics in this context, discussing the findings of key trials.