TABLE 2.
Genetic, Epigenetic, Metabolomic, and Microbiomic Markers in MAFLD
| Genetic Polymorphisms | Risk Modification | Outcomes |
|---|---|---|
| PNPLA3 (G allele, M variants) | ↑ | Steatosis, steatohepatitis, fibrosis, decompensation, hepatocellular cancer, death |
| GCRK (P446L) | ↑ | Steatosis, steatohepatitis, fibrosis, hepatocellular cancer; synergistic effect with PNPLA3 I148M |
| HSD17B13 (inactivating variants) | ↓ | Steatohepatitis, fibrosis, hepatocellular cancer; mitigates risk in patients with PNPLA3 I148M |
| TM6SF2 (E167K) | ↑ | Steatosis, steatohepatitis, fibrosis, hepatocellular cancer |
| MBOAT7 (rs641738) | ↑ | Steatosis, steatohepatitis, fibrosis, hepatocellular cancer |
| Genes with epigenetic changes | ||
| AQP1 (overexpression) | ↑ | Fibrosis |
| FGFR2 (overexpression) | ↑ | Fibrosis |
| MicroRNAs | ||
| miR‐34a (overexpression) | ↑ | Steatosis, steatohepatitis |
| miR‐122 (underexpression) | ↑ | Steatosis, steatohepatitis; in human studies (potentially differing effects in mice) |
| Metabolites | ||
| Branched‐chain amino acids | ↑ or ↓ (depending on disease stage) | Steatosis, steatohepatitis, fibrosis |
| Lipids (triglycerides and fatty acids) | ↑ or ↓ (depending on molecular subtype) | Steatosis, steatohepatitis, fibrosis |
| Carbohydrates (glycolytic products) | ↑ | Steatosis, steatohepatitis |
| Bile acids (total) | ↑ (predominantly) | Steatosis, steatohepatitis, fibrosis; some bile acids reduce risk for steatosis and steatohepatitis |
| Gut microbiome | ||
| Proteobacteria, Enterobacteria | ↑ | Steatosis, steatohepatitis, fibrosis |
| Firmicutes | ↑ or ↓ (depending on bacterial species and disease stage) | Steatosis, steatohepatitis, fibrosis; Firmicutes concentrations may decrease with fibrosis progression |
| Bacteroidetes | ↑ or ↓ (depending on bacterial species and disease stage) | Steatosis, steatohepatitis, fibrosis |