Novel metabolic classification for extrahepatic complication of metabolic associated fatty liver disease: A data-driven cluster analysis with international validation

Metabolism. 2022 Nov:136:155294. doi: 10.1016/j.metabol.2022.155294. Epub 2022 Aug 20.

Abstract

Background: Traditional classification systems of metabolic-associated fatty liver disease (MAFLD) do not account for the high rate of extrahepatic complications. To create a new classification of MAFLD using metabolic parameters to identify risks of complications more accurately.

Methods: The retrospective study included MAFLD patients from the First Affiliated Hospital of Sun Yat-sen University for model development, and the model was validated respectively using Chinese cohort and UK Biobank database. Cluster analysis with k-means cluster was built using age, body mass index (BMI), glycosylated hemoglobin (HbA1c), total cholesterol/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride, and lipoprotein(a) [Lp(a)] levels. Cox regression models were used to compare the risk of type 2 diabetes (T2DM), chronic heart disease (CHD), stroke and mortality between the clusters.

Results: 1038 MAFLD patients from cross-sectional population were recruited for the model derivation, with 10,451 cases (33.4 % of MAFLD) from Chinese cohort and 304,141 cases (34.9 % of MAFLD, 1010 cases with magnetic resonance imaging proton density fat fraction measurement [MRI-PDFF]) from the international cohort validated. Five replicable clusters of MAFLD patients were identified: Cluster 1(mild obesity and dyslipidemia-related), Cluster 2 (age related), Cluster 3 (severe insulin resistance-related), Cluster 4[high Lp(a)-related], and Cluster 5 (severe mixed hyperlipidemia-related). Patients in different clusters exhibited differences in the development of T2DM, CHD, stroke and all-causes mortality. Patients in Cluster 3 had significantly worst survival outcomes and higher risks of T2DM and CVD than those in other clusters.

Conclusion: The novel classification offers improved discrimination of new-onset MAFLD patients with different metabolic complications.

Keywords: Apolipoproteins; Classification; Cluster; Lipids; Metabolic associated fatty liver disease; Prognosis; Risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholesterol, HDL
  • Cluster Analysis
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2* / complications
  • Glycated Hemoglobin
  • Humans
  • Lipoprotein(a)
  • Liver Diseases*
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Protons
  • Retrospective Studies
  • Stroke*
  • Triglycerides / metabolism

Substances

  • Cholesterol, HDL
  • Glycated Hemoglobin A
  • Lipoprotein(a)
  • Protons
  • Triglycerides