BackgroundMetabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end stage liver disease following liver transplantation. However, the influence of immunosuppressive regimens on it has not been explored. MethodsA retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease. ResultsA total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of post-transplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P < 0.05), whereas the other preoperative and postoperative parameters showed no significant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence intervals: 0.15∼0.90, P = 0.021) and a combination of tacrolimus and sirolimus-based immunosuppressive regimen (95% confidence intervals: 1.01∼2.77, P = 0.046) were associated with lower risk of post-transplant metabolic dysfunction-associated fatty liver disease. ConclusionsOur study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus and sirolimus-based immunosuppressive regimen can effectively lower the risk of post-transplant metabolic dysfunction-associated fatty liver disease following liver transplantation.