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Hepatic encephalopathy is one of the complications of liver cirrhosis. There are several pharmacological therapies that can be used to treat hepatic encephalopathy, which are Lactulose and antibiotics, such as Rifaximin. Currently, Lactulose is the standard treatment to reduce the level of ammonia circulating in the blood, however, there is still no enough evidence that Lactulose itself can prevent recurrence of hepatic encephalopathy. Combination therapy of Lactulose with antibiotic is a promising therapy to prevent recurrence of hepatic encephalopathy. Literature searching through four databases (PubMed®, Cochrane Library®, EBSCOHost®, and SCOPUS®) were performed. Using the inclusion and exclusion criteria, there were three journals, which were two randomized control trials and one retrospective cohort study, that were selected and correlated with the clinical cast. All articles were appraised for validity, importance, and applicability. The studies show that giving Lactulose combined with Rifaximin significantly reduced the recurrence of hepatic encephalopathy with HR 0.42 (CI: 0.28 to 0.64, p < .001) and significantly lower readmission rate (p < .05) in 180 days. Giving Rifaximin in combination with Lactulose can prevent recurrence of hepatic encephalopathy and lowering the readmission rate in patients suffering from overt hepatic encephalopathy.