From "burnt-out" to "burning-out": capturing liver fat loss in patients with advanced metabolic dysfunction-associated steatotic liver disease from a dynamic perspective

Abstract

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 there has been a continuous process of fat loss is controversial. We proposed a "burning-out" concept to describe this process and analyze the long-term outcomes of "burnt-out" and "burning-out".

Methods: we included a MASLD cohort from 16 centers, including 3273 individuals with baseline histology and 5455 with serial vibration-controlled transient elastography (VCTE) measurements during follow-up. "Burnt-out" was defined by steatosis grade ≤ S1 and fibrosis stage ≥ F3. Trajectory analysis identified "burning-out" patients with decreasing liver fat [decreasing controlled attenuation parameter (CAP)] and fibrosis progression [increasing liver stiffness measurement (LSM)].

Results: of 3273 patients with histological evaluation included, 435 were presumed to have "burnt-out" MASLD. Compared to those with pronounced steatosis in advanced fibrosis, patients with "burnt-out" had higher risks of all-cause mortality (HR, 2.14; 95% CI, 1.14 to 4.02), liver-related events (LREs) (HR, 1.77; 95% CI, 1.12 to 2.78), and hepatic decompensation (HR, 1.83, 95% CI, 1.11 to 3.01). Of 5455 patients with VCTEs 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 CAP and moderate/low LSM values (P <0.0001).

Conclusion: continuous process of fat loss, referred to as "burning-out", was observed in advanced MASLD and is associated with high rates of all-cause mortality, LREs and hepatic decompensation.

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Identifiers

ORCID for Chris Byrne: orcid.org/0000-0001-6322-7753

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