MASLD, At‐Risk MASH and Increased Liver Stiffness Are Associated With Young Adulthood Obesity Without Residual Risk After Losing Obesity

ABSTRACT Background Obesity can result in persistent metabolic changes despite weight loss, which may affect liver health. We aimed to investigate associations between young adulthood obesity and metabolic dysfunction‐associated steatotic liver disease (MASLD), at‐risk steatohepatitis and increased liver stiffness measurement (LSM) in a general population setting. Methods We studied NHANES 2017–2020 community‐dwelling participants aged > 40 years with BMI ≥ 18.5 and no heart failure. Weight at age 25 was obtained through questionnaires and compared to current weight. Assessment included controlled attenuation parameter (CAP) and LSM. Associations between obesity status change with MASLD or at‐risk metabolic dysfunction‐associated steatohepatitis (MASH) and increased LSM were investigated and adjusted for demographics and metabolic health. Results The cohort comprised 4,580 participants (57% stable non‐obesity, 33% gained obesity, 2% lost obesity and 8% stable obesity). Compared to stable no‐obesity, stable obesity was strongly associated with MASLD (odds ratio [OR]: 5.47, 95% confidence interval [95%CI]: 3.97–7.66) as was gained obesity (OR: 4.68, 95% CI: 3.93–5.59), whereas no increased risk was demonstrated for lost obesity (OR: 1.26, 95% CI: 0.76–2.10). Similar associations for stable obesity and gained obesity with at‐risk MASH and LSM ≥ 8 kPa were demonstrated. No residual risk was found for lost obesity (MASH–OR: 1.05 95% CI: 0.36–2.49; LSM ≥ 8 kPa–OR: 0.85, 95% CI: 0.29–1.97). Results were consistent in sensitivity analysis where obesity change was calculated over the past 10 years and weight change was stratified in normal weight/overweight/obesity. Conclusion Young adulthood obesity is an important risk factor for MASLD, at‐risk MASH and increased LSM among the general population aged 40–80 years. Losing obesity resulted in normalisation of odds for MASLD, at‐risk MASH and increased LSM. These findings underline the importance of preventing and treating young adulthood obesity to maintain liver health.