Promising diagnostic biomarkers of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: From clinical proteomics to microbiome

Figure 1 Although liver biopsy remains as the gold standard for the diagnosis of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, other current imaging studies are shown, along with promising diagnostic and/or monitoring biomarkers that may be present in each of the stages of hepatic pathology, ranging from reversible steatosis and inflammation to irreversible fibrosis and eventually cirrhosis (Figure 1 created with BioRender. com). US: Ultrasound; TE: Transient elastography; BMI: Body mass index­; Hb: Hemoglobin; FGF-21: Fibroblast growth factor 21; RBP4: Retinol binding protein 4; ­CK18Asp396: Caspase cleaved cytokeratin-18 fragment; TMAO: Trimethylamine N-oxide; LDL-c: Low density lipoprotein cholesterol; Fecal SCFAs: Fecal Short chain fatty acids; fCh: Ferrochelatase; IL-17: Interleukin-17; IL-22: Interleukin-22; PPARα: Peroxisome proliferator-activated receptor α; DR5: Death receptor 5; miRNA-122: MicroRNA 122; miR-192: MicroRNA 192; N/L ratio: Neutrophil/lymphocyte ratio; Th17/Treg imbalance: T helper 17/T regulatory cells imbalance; IL-1: Interleukin-1; IL-6: Interleukin-6; TNFα: Tumor necrosis factor alpha; ASGPR1+: Asialoglycoprotein receptor 1; CNN2: Calponin 2; miRNA-214: MicroRNA 214; miR-34a: MicroRNA 34a; Hfib1: Hepatic fibrosis 1; N/L ratio: Neutrophil/lymphocyte ratio; IFNγ: Interferon γ; IL-4: Interleukin-4; IL-13: Interleukin-13.

Figure 2 Potential biomarkers involved in hepatic pathophysiology. Hb: Hemoglobin; FGF-21: Fibroblast growth factor 21; RBP4: Retinol binding protein 4; CK18Asp396: Caspase cleaved cytokeratin-18 fragment (M30); Fuc-Hpt: Fucosylated haptoglobin; Mac2bp: Mac-2-binding protein; DR5: Death receptor 5; miRNA-122: MicroRNA 122; miR-192: MicroRNA 192; ASGPR1+: Asialoglycoprotein receptor 1; CNN2: Calponin 2; miRNA-214: MicroRNA 214; miR-34a: MicroRNA 34a; TMAO: Trimethylamine N-oxide; LDL-c: Low density lipoprotein cholesterol; Fecal SCFAs: Fecal Short chain fatty acids; fCh: Ferrochelatase; 11-HETE: 11-Hydroxyeicosatetraenoic Acid; 11,12-diHETrE: 11,12-dihydroxyicosatrienoic acid; DHEA-S: Dehydroepiandrosterone sulphate; PPAR-γ: Peroxisome proliferator-activated receptor γ; IL-17: Interleukin-17; IL-22: Interleukin-22; N/L ratio: Neutrophil/lymphocyte ratio; Th17/Treg imbalance: T helper 17/T regulatory cells imbalance; IFNγ: Interferon gamma; IL-4: Interleukin-4; IL-13: Interleukin-13; CD4+T: Cluster of differentiation 4, T helper cells; T reg: Regulatory T cells; ILCs: Innate lymphoid cells.