S2796 Clinical Efficacy of Combined Rifaximin and Lactulose vs Lactulose Monotherapy in the Treatment of Hepatic Encephalopathy: A Systematic Review and Meta-Analysis

Introduction: Hepatic encephalopathy (HE) is a debilitating neuropsychiatric complication of advanced liver disease, with lactulose being the long-term standard of care for management. However, recurrent episodes and incomplete response rates persist. Rifaximin, a gut-selective antibiotic, has been shown to reduce ammonia-producing gut flora, thereby lowering recurrence risk. Recent trials and guidelines suggest that combining rifaximin with lactulose may offer superior efficacy compared to lactulose alone, particularly in preventing recurrent overt HE episodes. This meta-analysis evaluates the comparative effectiveness of combination therapy versus lactulose monotherapy in improving clinical outcomes in the patients. Methods: The review conducted follows the PRISMA guidelines. PUBMED, Google Scholar and Science-Direct, were searched using a comprehensive search term to retrieve available articles. The articles that included the assessment of the detection of adenoma and polyp by AI-assisted colonoscopy and traditional colonoscopy were included in the final analysis. The data was analyzed using the Meta, Metadata and the Metafor packages of R Studio. The odds ratio (OR) of improvement of hepatic encephalopathy in rifaximin and lactulose combination therapy in comparison to lactulose monotherapy was assessed as the primary outcome. Secondary outcomes included mortality rates and the mean difference in hospital stay. The Mantel-Haenszel method and the Inverse variance method were utilised to analyze the odds ratio. Results: The conducted meta-analysis included a total of 7 articles where 583 patients with hepatic encephalopathy received rifaximin and lactulose as combination therapy and 508 patients received Lactulose-only therapy. The clinical efficacy of both the groups were similar in terms of all the outcomes ie; improvement/Reversal of Hepatic Encephalopathy (OR = 1.62 (0.76; 3.48, I2 = 86.4% , P < 0.0001) , Mean difference in hospital stay (MDS = -1.15 (-12.67;10.36), I2 = 0%, P = 0.793) and relative risk of morality. (RR = 0.82 (0.45; 1.50), I2 = 77.6%, P = 0.0039). Conclusion: Our study suggests that lactulose monotherapy in comparison with rifaxmin and lactulose combination therapy for hepatic encephalopathy show similar clinical efficacy in terms of reversal of hepatic encephalopathy, difference in hospital stay and relative risk of mortality, This suggests that lactulose and rifaximin combination therapy do not confer any additional benefits in comparison with lactulose monotherapy.