Weight Regain after Lifestyle Interventions is Associated with Higher Risk of Liver Inflammation: A Retrospective Observational Study

Background: Lifestyle-induced weight loss improves metabolic health, but weight regain is common. Its hepatic consequences, particularly in relation to metabolic dysfunction-associated steatotic liver disease (MASLD), remain insufficiently characterized. Methods: This retrospective observational study included 213 patients categorized as weight regain (≥5% lifestyle-induced weight loss followed by return to or exceeding baseline weight) or weight sustain (weight change within ±5% of baseline) over 3 years. Propensity score matching (PSM) balanced age, sex, weight, and body mass index. Clinical, biochemical, and noninvasive liver indices were compared. In a bariatric surgery subset, liver histology, transcriptomics, quantitative PCR, and immunohistochemistry were performed. Results: No significant differences were found in metabolic parameters between groups. After PSM, the weight regain group showed higher alanine aminotransferase (ALT) (median 59.00 vs 41.00 IU/L, P=0.007) and aspartate aminotransferase (AST) (33.50 vs 26.00 IU/L, P=0.041). In males, ALT (88.00 vs 47.00 IU/L, P