Table 2.
Chemokines as diagnostic and prognostic biomarkers for MASH
| Chemokine | Participants and sample size | Sample types | Approach | Findings | Value | Refs. |
|---|---|---|---|---|---|---|
| CCL2 | 18 MASL, 36 MASH | PBMCs | qPCR | The expression level of CCL2 was positively correlated with the degree of ballooning of hepatocytes but not of steatosis or lobular inflammation | Diagnostic and predictive value | [39] |
| CCL2 | 14 Controls, 14 MASL, 18 MASH | Liver | Expression profiling by array | CCL2 was one of the hub genes | Diagnostic value | [40] |
| CCL2 | 5 Control Children, 35 MASH Children | Plasma | Luminex® assay | CCL2 was also lower in MASH (P = 0.04). CCL2 was higher in children with severe fibrosis (P = 0.008) with an area under the receiver operating characteristic curve (AUROC) of 0.76 | Predictive value | [47] |
| CCL2 | 30 Controls, 32 MASL, 34 MASH | Serum | ELISA | CCL2 was significantly upregulated in MASH patients compared with MASL patients or control. Serum CCL2 was significantly correlated with the degree of hepatocytes ballooning (the diagnostic endpoint for MASH) without any significant correlation with steatosis or lobular inflammation. The ROC curve analysis of CCL2 for MASH diagnosis revealed an area under curve (AUROC) of 0.959 at cutoff ≥ 227 pg/ml | Diagnostic and predictive value | [43] |
| CCL2 | 250 MASLD | Serum | ELISA | Serum CCL2 levels were weakly associated with liver stiffness, but the association was no longer significant after accounting for age, diabetes, and BMI in a multivariable model | Predictive value | [37] |
| CCL2 | 10 Controls, 34 MASL, 41 MASH, 16 MASH with Fibrosis, 15 Cirrhosis | Serum | Meso scale discovery V-plex assays | CCL2 featured a clear correlation with cirrhosis | Predictive value | [55] |
| CCL2 | 15 MASH,7 without fibrosis, 8 with fibrosis | Visceral adipose | Targeted microarrays | CCL2 were differentially expressed in MASH with fibrosis | Predictive value | [131] |
| CCL2 | 16 controls, 48 MASH | Liver | 730 immuno-oncology-related targets | CCL2 were significantly increased in MASH with advanced fibrosis compared to MASH with minimal fibrosis | Diagnostic and predictive value | [129] |
| CCL3 | 10 Controls, 34 MASL, 41 MASH, 16 MASH with Fibrosis, 15 Cirrhosis | Serum | Meso scale discovery V-plex assays | CCL3 was higher in MASH with fibrosis and featured a clear correlation with AST levels and cirrhosis | Diagnostic and predictive value | [55] |
| CCL3 | 4753 Controls, 4059 MASLD | Plasma or serum | ELISA | Concentrations of CCL3 in the MASH group was significantly higher than that in the control group (SMDs of 0.90) | Diagnostic value | [42] |
| CCL4 | 4753 Controls, 4059 MASLD | Plasma or serum | ELISA | Concentrations of CCL4 in the MASH group was significantly higher than that in the control group (SMDs of 2.05) | Diagnostic value | [42] |
| CCL4 | 15 MASH, 7 without fibrosis, 8 with fibrosis | Visceral adipose | Targeted microarrays | CCL4 were differentially expressed in MASH with fibrosis. CCL4 were found in MASH with T2DM as compared to MASH without T2DM | Predictive value | [131] |
| CCL5 | 64 controls, 109 MASL, 60 MASH | Serum | ELISA | CCL5 have been found to be significantly elevated in MASH patients compared to controls | Diagnostic value | [128] |
| CCL5 | 16 controls, 48 MASH | Liver | 730 immuno-oncology-related targets | CCL5 were significantly increased in MASH with advanced fibrosis compared to MASH with minimal fibrosis | Diagnostic and predictive value | [129] |
| CCL11 | 8 Controls, 8 MASH | Liver | qPCR | CCL11 is upregulated in liver from MASH patients and shows positive correlations with serum ALT, TG, TC, and liver inflammation and fibrosis markers such as TNFA and COL1A1 | Diagnostic and predictive value | [65] |
| CCL18 | 15 MASH, 7 without fibrosis, 8 with fibrosis | Visceral adipose | Targeted microarrays | CCL18 were differentially expressed in MASH with fibrosis | Predictive value | [131] |
| CCL20 | 4753 Controls, 4059 MASLD | Plasma or serum | ELISA-Systematic review | Concentrations of CCL20 in the MASH group was significantly higher than that in the control group (SMDs of 2.16). SUCRA probabilities showed that CCL20 had the highest rank in MASH for all chemokines | Diagnostic value | [42] |
| CCL20 | 12 transcriptome datasets | Liver | Whole-genome expression profiles-Robust rank aggregation method | CCL20 was one of the top 10 upregulated genes in MASH patients | Diagnostic value | [71] |
| CCL20 | Liver: 35 Controls, 32 MASH fibrosis, serum:106 Controls, 77 MASH fibrosis | Liver and serum | qPCR and ELISA | CCL20 protein levels are increased in patients with MASH fibrosis | Diagnostic and predictive value | [69] |
| CCL20 | 21 Controls, 23 MASL, 17 MASH | Liver and serum | nCounter® Human Immunology Panel and ELISA | CCL20 was higher in the liver and serum of MASL and MASH | Diagnostic value | [112] |
| CXCL5 | 24 MASL, 53 MASH without fibrosis, 65 MASH with fibrosis | Liver | qPCR | CXCL5 expression is increased in MASH lobular inflammation and advanced fibrosis | Predictive value | [130] |
| CXCL8 | 14 Controls, 14 MASL, 18 MASH | Liver | Expression profiling by array | CXCL8 were identified as hub genes | Diagnostic value | [93] |
| CXCL8 | 10 Controls, 34 MASL, 41 MASH, 16 MASH with fibrosis, 15 Cirrhosis | Serum | Meso Scale Discovery V-plex assays | CXCL8 was higher in MASH and featured a clear correlation with AST levels and the cirrhosis | Diagnostic and predictive value | [55] |
| CXCL8 | 4753 Controls, 4059 MASLD | Plasma or serum | ELISA-systematic review | Concentrations of CXCL8 in the MASL group were significantly higher than that in the control group (SMDs of 1.95). Concentrations of CXCL8 in the MASH group was significantly higher than that in the control group (SMDs of 0.91). SUCRA probabilities showed that CXCL8 had the highest rank in MASL for all chemokines | Diagnostic value | [42] |
| CXCL8 | 15 MASH, 7 without fibrosis, 8 with fibrosis | Visceral adipose | Targeted microarrays | CXCL8 were found in MASH with T2DM as compared to MASH without T2DM | Predictive value | [131] |
| CXCL8 | 29 normal-weight women, 82 women with morbid obesity (subclassified: 29 normal liver, 32 simple steatosis, and 21 MASH) | Serum | ELISA | CXCL8 was significantly higher in morbid obesity with MASH than in normal-weight | Diagnostic value | [95] |
| CXCL9 | 318 adults with obesity (76 normal liver histology, 88 MASL, 72 MASH F0, 82 MASH F1-4) | Liver | NanoString Technologies nCounter assay | CXCL9 was higher in MASL and MASH and featured a clear correlation with fibrosis | Diagnostic and predictive value | [99] |
| CXCL9 | 21 Controls, 23 MASL, 17 MASH | Liver and serum | nCounter® Human Immunology Panel and ELISA | CXCL9 was higher in the liver of MASL and MASH | Diagnostic value | [112] |
| CXCL10 | 4753 Controls, 4059 MASLD | Plasma or serum | ELISA-Systematic review | Concentrations of CXCL10 in the MASH group was significantly higher than that in the control group (SMDs of 1.46) | Diagnostic value | [42] |
| CXCL10 | 12 transcriptome datasets | Liver | Whole-genome expression profiles-Robust rank aggregation method | CXCL10 was one of the top 10 upregulated genes in MASH patients | Diagnostic value | [71] |
| CXCL10 | For MASLD, 58 MASLD and 60 healthy Controls; for MASH, 187 MASH liver biopsies and 154 healthy controls | Liver | Meta-analysis of GEO transcription data | CXCL10 was upregulated genes in MASLD and MASH patients | Diagnostic value | [111] |
| CXCL10 | Liver:15 controls, 11 MASL, 11MASH; Serum: 73 Controls, 78 MASL, 69 MASH | Liver and serum | qPCR and ELISA | Circulating and hepatic CXCL10 levels were significantly higher in human MASH. The Circulating CXCL10 level was correlated with the degree of lobular inflammation and was an independent risk factor for MASH patients | Diagnostic and predictive value | [108] |
| CXCL10 | 21 Controls, 23 MASL, 17 MASH | Liver and serum | nCounter® Human Immunology Panel and ELISA | CXCL10 was higher in the liver and serum of MASL and MASH | Diagnostic value | [112] |
| CXCL11 | 21 Controls, 23 MASL, 17 MASH | Liver and serum | nCounter® Human Immunology Panel and ELISA | CXCL11 was higher in the liver of MASL and MASH | Diagnostic value | [112] |