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

Background & Aims: The absence of hepatic fat in advanced fibrosis has been documented in metabolic dysfunction-associated steatotic liver disease ("burnt-out" MASLD). However, whether hepatic fat loss occurs continuously with fibrosis progression is controversial. We proposed a "burning-out" concept to describe this process and analyze the long-term outcomes of "burnt-out" and "burning-out" MASLD.

Methods: We included a MASLD cohort from 16 centers, including 3273 individuals with baseline histology and 5455 with serial vibration-controlled transient elastography measurements during the follow-up. "Burnt-out" MASLD was defined by steatosis grade ≤S1 and fibrosis stage ≥F3. Trajectory analysis identified "burning-out" patients with continuous trends of decreasing controlled attenuation parameter and increasing liver stiffness measurement values.

Results: Of 3273 patients with histologic evaluation included, 435 had "burnt-out" MASLD. Compared with those with pronounced steatosis in advanced fibrosis, patients with "burnt-out" had higher risks of all-cause mortality (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.14-4.02), liver-related events (LREs; HR, 1.77; 95% CI, 1.12-2.78), and hepatic decompensation (HR, 1.83; 95% CI, 1.11-3.01). Of 5455 patients with vibration-controlled transient elastography included for trajectory analysis, 176 were identified as "burning-out" MASLD. The incidence rates of all-cause mortality, LREs, and decompensation were 7.28, 26.47, and 21.92 per 1000 person-years in "burning-out" patients, respectively. The "burning-out" group had higher cumulative incidences of adverse outcomes than patients with consistently high controlled attenuation parameter and moderate/low liver stiffness measurement values (P < .0001).

Conclusions: Continuous hepatic fat loss accompanied by fibrosis progression, referred to as "burning-out," was observed in advanced MASLD and associated with high rates of all-cause mortality, LREs, and hepatic decompensation.