From "Burnt-Out" to "Burning-Out": Capturing Liver Fat Loss in Patients With Advanced Metabolic Dysfunction-Associated Steatotic Liver Disease From a Dynamic Perspective.

Summary

In a 16-center cohort (n=3273 histology; n=5455 serial VCTE), ‘burnt-out’ MASLD (≤S1 steatosis, ≥F3 fibrosis) carried significantly higher risks of mortality, liver-related events, and decompensation. Trajectory-defined ‘burning-out’ MASLD, with progressive CAP decline and LSM rise, also showed elevated adverse outcome rates, underscoring that fat loss in advanced disease signals worse prognosis.

Key Findings

• Defined ‘burnt-out’ MASLD (≤S1 steatosis, ≥F3 fibrosis) in 435/3273 histology cases with higher mortality (HR 2.14), LREs (HR 1.77), and decompensation (HR 1.83).
• Identified 176 ‘burning-out’ patients via trajectory analysis (falling CAP, rising LSM) with elevated incidence of adverse outcomes.
• Burning-out group had higher cumulative incidence of events than patients with consistently high CAP and lower LSM (P < .0001).

Clinical Implications

Patients with advanced MASLD and low/declining steatosis merit aggressive surveillance for decompensation and liver-related events; dynamic CAP/LSM trajectories can refine prognosis and therapeutic prioritization.

Limitations

• Observational design susceptible to residual confounding.
• Definitions rely on CAP/LSM thresholds which may vary by device/setting.

Future Directions

Prospective validation of burning-out trajectories across platforms and integration into risk models; evaluate whether targeted antifibrotic or metabolic therapies alter burning-out course.