One-Year Changes in Liver Stiffness Measurement, but Not in Alanine Aminotransferase and Controlled Attenuation Parameter, Predict Long-Term Liver Outcomes in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease

BACKGROUND & AIMS: The availability of new drugs for the treatment of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) underlines the need of early predictors of response to such therapies. This study evaluated the impact of 1-year changes in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), controlled attenuation parameters (CAP), and serum alanine aminotransferase (ALT) on liver outcomes in patients with MASLD. METHODS: A large multicenter cohort of MASLD patients with LSM ≥8 kPa and prospective follow-up was enrolled. Liver-related events (LREs), including hepatocellular carcinoma (HCC) and liver decompensation (LD), were evaluated during follow-up. LSM, CAP, ALT, and Fibrosis-4 Index (FIB-4) were assessed at baseline and at 1-year follow-up. Cause-specific Cox regression analyses were performed to correlate 1-year variation in LSM, CAP, ALT, and FIB-4 with the risk of developing LRE, LD, and HCC, in terms of cause-specific hazard ratios (csHRs). RESULTS: We included 1744 patients with LSM ≥8 kPa (median age, 55 years; 52.1% male; 58.3% obese; 55.8% with diabetes) and 989 with LSM ≥10 kPa (median age, 56 years; 50.2% male; 54.7% obese; 51% with diabetes), followed for a median of 28.2 and 32 months, respectively. LREs occurred in 39 patients with LSM ≥8 kPa (26 LD, 22 HCC) and in 35 with LSM ≥10 kPa (25 LD, 19 HCC). A 1-year variation in LSM, but not in CAP, ALT, or FIB-4, was independently associated with LRE in patients with MASLD and LSM ≥8 kPa (csHR, 1.007; 95% confidence interval [CI], 1.001-1.014). Likewise, 1-year LSM variation (csHR, 1.009; 95% CI, 1.000-1.018) independently predicted LD in this population, whereas no 1-year changes in CAP, ALT, or FIB-4 were associated with LD risk. No independent associations were observed between 1-year changes in LSM, CAP, ALT, or FIB-4 and the risk of HCC. All findings were confirmed in patients with LSM ≥10 kPa and in those at high risk of progression with type 2 diabetes. CONCLUSIONS: In patients with MASLD and LSM ≥8 or ≥10 kPa, the % LSM reduction at 1 year was independently associated with lower risk of LRE and LD.