Key result
Metabolically healthy obesity masks liver risk with ~96% showing MASLD despite low FIB-4 scores.
Why the study?
Although FIB-4 predicts all-cause mortality in heart failure and assesses liver fibrosis in MASLD, it is unknown how it relates to metabolically healthy vs unhealthy obese phenotypes.
A large proportion of obese patients classified as metabolically healthy actually have metabolic dysfunction-associated steatotic liver disease (MASLD) and advanced fibrosis, highlighting the need for deeper metabolic risk stratification to prevent cardiovascular events.
Answers are grounded in this paper and cite their sources.
MHO classification may mask high MASLD and fibrosis prevalence; this cohort finding challenges current definitions and leaves open need for prospective validation.
Background/Introduction The liver-heart axis has increasingly been valued, with the fibrosis-4 index score (FIB-4) recently considered a predictor of death from all causes in patients with Heart Failure (HF). This score is used to assess the degree of liver fibrosis in patients with metabolic dysfunction-associated steatosis liver disease (MASLD), a population at high risk of HF. It is recognized that obese individuals vary in their metabolic profile and risk of cardiovascular events. However, it is unknown how FIB-4 relates to metabolic phenotypes, that is, metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Purpose Identify, in obese patients, the relationship between Fib-4, FLI and metabolic profiles (healthy and unhealthy) classified according to Khan et al. Methods Retrospective analysis of a cohort of obese patients who underwent bariatric surgery in a University Hospital. Data were collected using electronic records: T0 (pre-op) and T1 (1 year after surgery). MASLD and liver fibrosis were classified by calculating Fatty Liver Index (FLI) and FIB-4 index, respectively. Results 265 patients were included, 86% women, mean age of 43 ± 10.7 years. At T0 median FIB-4 index was 0.7141, FLI was > 60 in 217 (82%) patients, in which the diagnosis of MASLD was assumed. At T0, 82% patients were considered MHO, however, within this group, 96% had MASLD, with FLI>60 (p<0.001). Fib-4 was considered low (<1.30) in 79% and high in 6% of MHO (p = 0.5). At T1, 38% of MHO were considered non-MASLD, with FLI<60 (p 0.72). The fib-4 were low in 83% of MHO 1 year after surgery (p=0.58). Conclusions Despite being classified as metabolically healthy, the majority of obese patients had MASLD and 6% had advanced fibrosis. More data is needed, but it may be useful to identify obese patients within the MHO group who are at higher metabolic risk (such as those with MASLD and fibrosis) in order to intervene early to prevent cardiovascular events.
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Leitao et al. (2025) studied this question. Among metabolically healthy obese patients, 96% had MASLD and 6% showed advanced fibrosis, despite low Fib-4 in most; indicating hidden liver risks in MHO.
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