Longitudinal changes in cardiometabolic risk factors are associated with changes in liver stiffness in adults with MASLD

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by cardiometabolic risk factors (CMRFs). Treatment of CMRFs is the cornerstone of MASLD management, yet other than weight loss, the association between changes in CMRFs and changes in liver-related measures is not defined. This study aimed to characterize these longitudinal associations using non-invasive measurements of hepatic fibrosis and steatosis. METHODS: Adult participants from the NASH CRN prospective study with biopsy-proven MASLD and at least two sequential vibration-controlled transient elastography (VCTE) exams (≥1 year apart) were included. Annual changes in CMRF parameters were compared against annual changes in liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) using adjusted mixed-effects multinomial logistic regression. The primary outcome was LSM change ≥25% (compared to a reference group of no change, or <25% LSM change), while secondary outcomes were CAP change ≥30% and changes in histologic grading of steatohepatitis or fibrosis. RESULTS: A total of 1,417 participants were included (mean age 52 years, 38% male, 82% Caucasian). Annual worsening in all CMRFs (except triglycerides and HDL) was associated with LSM worsening (17% greater risk per 1% increase in hemoglobin A1c; 24% greater risk per 5% increase in weight). Improvements in all CMRFs were associated with LSM improvement (32% greater chance per 1% decrease in hemoglobin A1c; 27% greater chance per 5% decrease in weight). Similar associations were observed for changes in CAP. CONCLUSIONS: Annual changes in CMRFs were associated with clinically relevant changes in LSM, CAP, and liver histology. These findings suggest that treatment of metabolic comorbidities is associated with the trajectory of MASLD. IMPACT AND IMPLICATIONS: Guideline-directed treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) is focused on optimal treatment of cardiometabolic comorbidities, but there is limited evidence on the association between outcomes of this treatment and changes in markers of liver health. The results of this study demonstrate that longitudinal changes in these cardiometabolic parameters, particularly those associated with body weight, blood pressure, and glucose intolerance, are associated with both increases and decreases in liver stiffness measurements that represent clinically meaningful changes in liver health. These results are broadly relevant to the care of individuals with MASLD, as these results can provide meaningful treatment targets for guideline development and treating clinicians, as well as provide feasible goals for impacted individuals with MASLD.