Impact of a lifestyle intervention for weight loss on liver-related outcomes in adults with obesity: a subanalysis of a clinical trial

Abstract Background This study aimed to evaluate the impact of a structured weight-loss intervention on liver steatosis and liver stiffness in adults with obesity. Methods Post hoc analysis of prospectively collected data from a randomized crossover trial (NCT05420311) assessing changes in liver-related outcomes measured from baseline to three months during the overall sequential lifestyle intervention in adults with obesity. Participants sequentially followed a calorie-restricted standard diet, calorie-restricted ketogenic diet (KD), or modified alternate day fasting (mADF)—one month per diet—. Changes in controlled attenuation parameter (CAP), liver stiffness measurement (LSM) and estimated steatosis/LSM-based fibrosis risk categories assessed by vibration-controlled transient elastography were evaluated from baseline to three months during the overall sequential lifestyle intervention. Other assessments included changes in liver enzymes, anthropometric, and cardiometabolic parameters. Results Seventy-six participants were included in this subanalysis. Mean weight loss was 7.6 ± 4.7 kg at the end of the study period. Significant reductions in CAP and LSM from baseline to 3 months were observed (from 286.6 ± 70.7 dB/m to 256.6 ± 57.1, p < 0.001, and from 8.8 ± 6.0 kPa to 6.9 ± 3.5 kPa, p = 0.012, respectively). In addition, a significant reduction in the percentage of patients with liver steatosis and LSM-based fibrosis risk ≥F2 was observed. Significant decreases in serum levels of liver enzymes (aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase) were also detected. Conclusions A structured weight-loss lifestyle intervention may be associated with improvements in non-invasive liver-related outcomes in adults with obesity. Trial registration ClinicalTrials.gov (NCT05420311).