Biomarkers in Detection of Hepatitis C Virus Infection
Abstract
1. Introduction
2. Natural History
3. Risk Factors for HCV
4. HCV Replication
5. Pathogenesis of HCV Infection
6. Detection Markers for HCV Infection
7. Host Biomarkers in Acute Hepatitis C
7.1. HCV Infection in Experimentally Infected Chimpanzees
7.2. HCV-Specific T Cell Responses
7.3. NK Cells
7.4. Cytokines and Chemokines
7.5. Other Biomarkers
7.6. microRNAs
7.7. Mitochondrial DNA
8. Biomarkers in Chronic Hepatitis C Virus Infection
- Chronic HCV infection in experimentally infected chimpanzees
- 2.
- HCV-specific T cells
- 3.
- Cytokines and chemokines
- 4.
- microRNAs
9. Biomarkers for Liver Fibrosis/Cirrhosis
10. Biomarkers for HCC
11. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
Disclaimer
References
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Class | Biomarker | Outcome | Reference |
---|---|---|---|
HCV infection in chimpanzees | ↑ RIG-1, TLR3, TLR7, and type I interferon genes | Elevation of ALT activity | [54] |
↑ Caspase 3/6 activity | Activation of NK and T cells | [54] | |
↑ IFNα/β response, CD3e, and MlP-1α expression | Spontaneous clearance | [66,67,68] | |
↑ Intrahepatic IFN-γ and ALT activities | Spontaneous clearance | [69] | |
↑ ILF3, TIA1, and genes associated with CD8+ T cell response | Spontaneous clearance | [70] | |
↑ HCV-specific CD4+ and CD8+ T cell responses | Spontaneous clearance | [71,72] | |
HCV-specific T cell responses | ↑ CD69, CD38, CD86, and HLA-DR expression on HCV-specific CD8+ T cells | Acute HCV infection | [74,75,76,77,78] |
↑ T cell responses to NS3, Th1 helper CD4+ T cell, and natural T cells expressing CD56 | Viral clearance | [39,41,79,80,81] | |
↑ PD-1 on HCV-specific T cells | Persistent infection | [83,84] | |
↑ Viral escape mutants from CD8+ T cell responses | Persistent infection | [87,88] | |
NK cells | ↑ NK cell activity | Spontaneous clearance | [91,92,93] |
↑ CD56bright NK cells | Spontaneous clearance | [94] | |
↓ CD4+ T cells by ↑ NK cell numbers | Persistent infection | [95] | |
Cytokines and chemokines | ↑ Plasma IL-18, IL-29, IP-10, and IFN-λ | Spontaneous clearance | [96,97,99,101] |
↑ Plasma TNF-α, IL-10, and BLyS/BAFF | Persistent infection | [97,100] | |
↑ IP-10 | Persistent infection | [101,103] | |
↑ IL-29 | Spontaneous clearance | [99,102] | |
Other biomarkers | ↓ HCV IgG antibody avidity | Acute HCV infection | [104,105,106] |
↑ HCV IgG antibody avidity | Chronic HCV infection | [104,105,106] | |
IL28B polymorphism | Spontaneous clearance | [109] | |
serum IP-10 levels/IL28B polymorphisms | Spontaneous clearance | [110] | |
CTLA4 polymorphisms | Spontaneous clearance | [111] | |
LVP in early infection | Persistent infection | [112,113] | |
↑ Plasma apolipoprotein C-III | Spontaneous clearance | [114] | |
↓ Apo B, Apo D, Apo H, and α1-AT | Distinguish HCV from HAV and HBV | [115] | |
MicroRNAs | Hepatic miR-122 | Inverse correlation with liver HCV RNA titer | [120,121,122] |
Serum miR-122 | Positive correlation with serum HCV RNA titer | [120] | |
Hepatic miR-122 and miR-126 | Serum HCV load | [121] | |
Hepatic miR-136 and miR-122 | Steatosis | [121] | |
↓ Plasma miR-92a | Viral clearance | [123] | |
Mitochondrial DNA (mtDNA) | nucleotide diversity | Distinguish acute from chronic HCV infection | [124] |
Class | Biomarker | Outcome | Reference |
---|---|---|---|
HCV infection in chimpanzees | ↑ OAS, MxA, ISG15, ISG20, IRF7, STAT1α/β,IFIT4, and ADAR1 | Chronic HCV infection | [129,130] |
↑ IDO, CTLA-4, and PD-1 | Chronic HCV infection | [131] | |
HCV-specific T cells | ↓ HCV-specific CD8+ T cells | Chronic HCV infection | [136,137,138] |
Dysfunction of dendritic cells | Chronic HCV infection | [139,140] | |
↓ HCV-specific CD4+ T cells with PD-1 and CTLA-4 expression | Chronic HCV infection | [143,144] | |
soluble CD163 and soluble mannose receptor (sMR) | Cirrhosis induced by chronic HCV | [145] | |
Cytokines and chemokines | ↑ Th1 cytokine (IFNg, IL-18) | Chronic HCV infection | [149,150,151] |
↑ Th2 (IL-10) | Chronic HCV infection | [152] | |
↓ Th1 cytokine | Chronic HCV infection | [153] | |
↓ Hepatic IL-10 | Chronic HCV infection | [154] | |
↓ HCV-specific Th17 cells by HCV-induced TGF-b | Chronic HCV infection | [156] | |
↑ Hepatic IL-17 and IL-22-producing T cells | Chronic HCV infection | [157] | |
↑ Serum IL-4, IL-10, and IL-18 | Chronic HCV infection | [158,159] | |
↑ Serum IL-26 | Chronic HCV infection with severe liver inflammation | [160] | |
MicroRNAs | ↑ Serum miR-122 with liver injuries | Chronic HCV infection | [162,163,164,165,166,167] |
↓ Serum miR-122 | Chronic HCV infection | [169] | |
Serum miRNA-122 as diagnostic value | Chronic HCV infection | [170] | |
Combination of miR-122, miR-126, miR-129, miR-199a, miR-155, miR-203a, miR-221, and miR-223 | Liver fibrosis | [171] | |
↑ Serum miR-21 | Chronic HCV infection | [172] | |
↑ Hepatic miR-146a-5p | Chronic HCV infection | [173] | |
↑ PBMC miR-16, miR-193b, miR-199a, miR-222, and miR-324 | Chronic HCV infection | [174] | |
↓ Serum miR-196a | Chronic HCV infection | [175] | |
Combination of miR-20a, miR-215-5p, miR-483-5p, miR-193b-3p, miR-34a-5p, miR-885-5p, miR-26b-5p, and miR-197-3p | HCV-induced liver fibrosis | [123,176] | |
Extracellular vesicles (EV) associated miRNA | ↑ miR-122, ↓miR-192, miR-200b, miR-150, and miR-92a | Early-stage fibrosis | [178] |
Class | Biomarker | Outcome | Reference |
---|---|---|---|
FibroTest/FibroScan | Combination of several serum markers (alpha2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase, and bilirubin) | Non-invasive marker for HCV-induced fibrosis | [179,180,181] |
APRI | AST to platelet ratio index | Non-invasive marker for HCV-induced fibrosis/cirrhosis | [182] |
FIB-4 index | Combination of platelets, ALT, AST, and age | HCV-induced fibrosis and cirrhosis | [183] |
Class | Biomarker | Outcome | Reference |
---|---|---|---|
Alpha-fetoprotein (AFP) | Serum AFP | Early detection of HCC | [186] |
Serum AFP-L3 and DCP | Early detection of HCC | [189,190] | |
Extracellular vesicles (EV) | EVs secreted by HCC | Early detection of HCC | [191,192] |
Golgi proteins (GP) | ↑ Serum GP73 | HCC | [193] |
↑ Serum GOLPH2 | HCC | [194] |
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Woo, J.; Choi, Y. Biomarkers in Detection of Hepatitis C Virus Infection. Pathogens 2024, 13, 331. https://doi.org/10.3390/pathogens13040331
Woo J, Choi Y. Biomarkers in Detection of Hepatitis C Virus Infection. Pathogens. 2024; 13(4):331. https://doi.org/10.3390/pathogens13040331
Chicago/Turabian StyleWoo, Jungreem, and Youkyung Choi. 2024. "Biomarkers in Detection of Hepatitis C Virus Infection" Pathogens 13, no. 4: 331. https://doi.org/10.3390/pathogens13040331
APA StyleWoo, J., & Choi, Y. (2024). Biomarkers in Detection of Hepatitis C Virus Infection. Pathogens, 13(4), 331. https://doi.org/10.3390/pathogens13040331