BACKGROUND: Hepatic encephalopathy (HE) in cirrhosis is an extremely challenging complication for patients and care partners. To identify potentially modifiable factors to enhance HE self-management strategies, we conducted a synthesis of quantitative and qualitative research about real-world HE behaviours, knowledge, and experiences. METHODS: Using the EPPI-Centre's mixed methods synthesis procedure, a systematic literature search in five databases was completed; methods of selected articles underwent critical appraisal followed by descriptive analysis and coded line-by-line of content. Through refutational translation, the findings from the quantitative and qualitative syntheses were juxtaposed to highlight congruencies, incongruencies, or gaps. These findings informed generation of cross-analytical themes that were transformed into action statements. RESULTS: The quantitative narrative review of synthesis ( = 17) generated four themes (patients had low awareness of HE and low treatment adherence rates, physicians had a non-uniform approach to non-pharmaceutical therapies). Meta-aggregation of qualitative data from six articles yielded three themes (patients and care partners had low levels of HE awareness, were unfamiliar with HE self-management, and were adherent to treatments). Comparison of findings revealed three congruencies, two gaps, and one incongruency. The combined synthesis yielded two self-management themes: universal patient-oriented cirrhosis HE education and ensuring each health care encounter systematically addresses HE to guarantee health care is continuously modified to meet their needs. CONCLUSIONS: By drawing on elements of Bloom's Taxonomy and distributed knowledge networks, deliberate patient-oriented HE messaging at all health care encounters is greatly needed to improve health outcomes and reduce care burdens related to HE.