Classifying Metabolic-Associated Fatty Liver Disease Subtypes Benefits Risk Stratification

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MAFLD-lean and MAFLD-diabetes subgroups recorded a higher risk of all-cause and disease-specific mortality compared to the MAFLD-overweight/obese group.

The classification of metabolic-associated fatty liver disease (MAFLD) based on metabolic phenotypes might benefit the risk stratification of patients with MAFLD, according to new research.

The large, nationwide study indicated the MAFLD-diabetes and MAFLD-lean subgroups had a higher risk of all-cause and disease-specific mortality compared to the MAFLD-overweight/obese group.

“The results of this study showing that MAFLD-diabetes can be a strong predictor of all-cause and disease-specific mortality are in line with previous literature,” wrote corresponding authors Kyungdo Han, Department of Statistics and Actuarial Science, Soongsil University and Eun Ju Cho, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine.

The investigator team sought the differential risk of all-cause and disease-specific mortality according to the identified MAFLD subgroups divided by metabolic risk factors and overweight/obesity status using the Korean National Health Insurance Service database. The study identified 10,585,844 adults aged ≥20 years who underwent health screening examinations between January – December 2009. Participants with incomplete information were excluded, leaving 9,935,314 subjects for the analysis.

The study population was separated into four subgroups: no MAFLD, MAFLD-diabetes, MAFLD-overweight/obese, and MAFLD-lean. Cox proportional hazards models analyzed hazard ratios (HRs) and 95% confidence intervals (CI) values for all-cause and disease-specific mortality according to these subgroups.

Participants had a mean age of 47.2 years and were 56.0% female, with a MAFLD prevalence of 35.8%. The prevalence of each MAFLD subtype was 5.5% (MAFLD-diabetes), 28.4% (MAFLD-overweight/obese), and 1.9% (MAFLD-lean).

Investigators found the individuals in the MAFLD-diabetes group had the highest all-cause mortality among the four evaluated groups (HR, 1.43; 95% CI, 1.42 - 1.45) in the age- and sex-adjusted model.

The multivariable model additionally reported individuals with MAFLD-diabetes had the highest increased risk of all-cause mortality (HR, 1.61; 95% CI, 1.59 - 1.63) followed by the MAFLD-lean (HR, 1.36; 95% CI, 1.34 - 1.38) and MAFLD-overweight/obese groups (HR, 1.19; 95% CI, 1.18 - 1.20).

Investigators noted the magnitude of cardiovascular disease (CVD) and cancer-related risk showed the same pattern. Individuals in the MAFLD-diabetes group had the highest CVD-specific mortality (HR, 1.61; 95% CI, 1.58 - 1.65) and the highest cancer-specific mortality (HR, 1.31; 95% CI, 1.29 - 1.33).

Moreover, individuals in the MAFLD-diabetes group had a 2.85-fold higher liver disease-related mortality (HR, 2.85; 95% CI, 2.75 - 2.95) with similar risk observed for those in the MAFLD-lean group (HR, 2.84; 95% CI, 2.72 - 2.97).

Secondary analyses stratified by body mass index (BMI) determined the increased risk for all-cause, cardiovascular, cancer, and liver-related mortality in the MAFLD-diabetes group was most prominent in patients with underweight (P for interaction <0.05). Liver-related mortality was the highest in MAFLD-lean individuals in the underweight group (HR, 5.03; 95% CI, 4.23 - 5.97).

“Further replicative research is warranted to validate and elucidate our results- underlying mechanisms,” authors wrote.

The study, “Lean or diabetic subtypes predict increased all-cause and disease-specific mortality in metabolic-associated fatty liver disease,” was published in BMC Medicine.