Economic Value and Clinical Impact Association of a Supervised Lifestyle-improving Program for MASLD

Maurizio Gaetano Polignano^*Antonella BiancoDavide GuidoPietro TrisoliniIsabella FrancoCaterina BonfiglioGianluigi Giannelli

• National Institute of Gastroenterology S. de Bellis Research Hospital (IRCCS), Bari, Italy

Background Metabolic dysfunction–associated steatotic liver disease (MASLD) is common and progressive, . Pharmacological options for selected subgroups are emerging (e.g., resmetirom for MASH with fibrosis; GLP‑1 receptor agonists for obesity/diabetes with metabolic benefits), yet structured lifestyle programs remain foundational in routine care. progressive, and still lacks effective pharmacological therapies. Lifestyle modification is recommended, yet evidence about clinical outcomes and cost-utility from real-world programs remains scarce. Objective To assess the cost-effectiveness utility of a multidisciplinary, kinesiology-supervised lifestyle-improving program for patients with MASLD, supported by clinical evidence. Methods We analysed 27 adults with MASLD, a cohort from an initial group of 43 participants, who participated in a structured program of supervised exercise and dietary counselling. Health-related quality of life (SF-36 mapped to EQ-5D) and associated clinical outcomesmarkers, including hepatic steatosis (ultrasound), blood pressure, serum aminotransferases, were evaluated at baseline and after the program. Cost-utility analysis was conducted from the healthcare system perspective, estimating incremental cost-effectiveness ratios (ICERs, €/QALY) with deterministic and probabilistic sensitivity analyses. Pharmaceutical expenditure and projected disease progression costs were additionally explored using administrative data and literature-based models. Results Health-related quality of life improved after the program, with a QALY gain of 0.081 (95% CI: 0.001–0.161). The base‑case ICER was €17,778/QALY. The probability of cost‑effectiveness was 71% at €25,000/QALY, 84% at €30,000/QALY, and 95% at €40,000/QALY. Ultrasound steatosis showed a distributional shift toward lower grades with unchanged median (Wilcoxon p=0.007). Systolic/diastolic blood pressure decreased by −5.6/−3.7 mmHg (p=0.05 and p=0.03), and AST/ALT declined (both p<0.01).The base-case ICER was €17,778 per QALY, with an 82% probability of cost-effectiveness at a €30,000 threshold. The program also significantly reduced steatosis grade (–0.96 units; p < 0.01), systolic blood pressure (–5.6 mmHg; p = 0.05), diastolic blood pressure (–3.7 mmHg; p = 0.03), as well as AST and ALT (p < 0.01). At two-year follow-up, 55.6% of patients reported maintaining regular physical activity. Outpatient pharmaceutical expenditure showed a decline from €74 to €50 per patient/year between 2018 and 2021, with a reduced variability. Conclusions In this pre–post observational study, the supervised program was associated with favourable cost‑utility and distributional improvements in selected clinical markers.