Association between longitudinal weight change and clinical outcome in individuals with MASLD

BACKGROUND AND AIMS: Weight control remains the cornerstone for metabolic dysfunction-associated steatotic liver disease (MASLD) management. We assessed the relationships between dynamic weight change and the risk of liver-related events (LREs) and liver stiffness changes in MASLD. APPROACH AND RESULTS: By enrolling adult MASLD individuals with ≥2 weight measurements from 16 tertiary referral centers, we assessed how longitude weight change, including the following categories (stable ≤5% change, weight loss >5% decrease, weight gain >5% increase) and changing status of obesity (persistent non-obesity, persistent obesity, transition from non-obesity to obesity, transition from obesity to non-obesity), were associated with LREs. Analyses were undertaken with multivariable linear regressions, Cox proportional hazards regression, and logistic regression, adjusting for age, sex, ethnicity, baseline BMI, hypertension, T2D, LSM, CAP, and SGLT-2i/GLP-1RAs usage. Analyses between weight change and liver stiffness change were also undertaken. A total of 10,014 MASLD individuals with ≥2 weight measurements were included. Over a measurement interval of 29.2 months, 123 LREs occurred during 12.4 months of follow-up after the final weight assessment. Weight gain >5% was associated with increased risk of LREs [aHR=1.84 (95% CI: 1.01-3.09), p =0.020] and liver stiffness progression [aOR=2.07 (95% CI: 1.55-2.74), p <0.001], while weight loss >5% exhibited liver stiffness improvement. Although those who progressed to or persisted with obesity had a higher LREs risk, obesity reversal had a comparable LREs risk [aHR=1.44 (95% CI: 0.57-3.61), p =0.435] to the persistent non-obese. CONCLUSIONS: In MASLD, weight gain is associated with increased LREs risks and liver stiffness progression. Conversely, weight loss confers benefits for liver stiffness improvement and modifies LREs risk in those who achieve obesity reversal.