Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis.
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that can lead to cirrhosis, liver transplant, and even hepatocellular carcinoma. While liver biopsy remains the reference standard for disease diagnosis, analytical and clinical development of non-invasive soluble biomarkers of NASH are...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0217263 |
| _version_ | 1797660740207771648 |
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| author | Sumit Kar Sabina Paglialunga Sharon H Jaycox Rafiqul Islam Angelo H Paredes |
| author_facet | Sumit Kar Sabina Paglialunga Sharon H Jaycox Rafiqul Islam Angelo H Paredes |
| author_sort | Sumit Kar |
| collection | DOAJ |
| description | Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that can lead to cirrhosis, liver transplant, and even hepatocellular carcinoma. While liver biopsy remains the reference standard for disease diagnosis, analytical and clinical development of non-invasive soluble biomarkers of NASH are of great importance to advance the field. To this end, we performed analytical and clinical validation on a series of pro-inflammatory cytokines and chemokines implicated hepatic inflammation; IL-6, CRP, TNFα, MCP-1, MIP-1β, eotaxin, VCAM-1. Biomarker assays were validated for accuracy and precision. Clinical performance was evaluated in a random sample of 52 patients with biopsy-proven NAFLD/NASH. Patients were categorized into three groups according to their fibrosis stage; advanced (F3-F4), mild (F1-2) and no (F0) fibrosis. Serum IL-6 was increased in patients with advanced fibrosis (2.71 pg/mL; 1.26 pg/mL; 1.39 pg/mL p<0.01) compared to patients with mild or no fibrosis respectively. While, there was no significant difference noted in CRP, TNFα, MCP-1, MIP-1β, eotaxin among the three groups, VCAM-1 levels were increased by 55% (p<0.01) and 40% (p<0.05) in the advanced cohort compared to the mild and no fibrosis groups respectively. VCAM-1 also displayed good clinical performance as a biomarker of advanced fibrosis with an area under the receiver operating curve of 0.87. The VCAM-1 assay demonstrated robust accuracy and precision, and VCAM-1 outperformed IL-6, CRP, TNFα, and the chemokines MCP-1, MIP-1β, and eotaxin as a biomarker of advanced fibrosis in NASH. Addition of biomarkers such as IL-6 and VCAM-1 to panels may yield increased sensitivity and specificity for staging of NASH. |
| first_indexed | 2024-03-11T18:35:20Z |
| format | Article |
| id | doaj.art-d70a0ea59b034e4fb7487af2d289a4b9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-11T18:35:20Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-d70a0ea59b034e4fb7487af2d289a4b92023-10-13T05:31:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01147e021726310.1371/journal.pone.0217263Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis.Sumit KarSabina PaglialungaSharon H JaycoxRafiqul IslamAngelo H ParedesNonalcoholic steatohepatitis (NASH) is a chronic liver disease that can lead to cirrhosis, liver transplant, and even hepatocellular carcinoma. While liver biopsy remains the reference standard for disease diagnosis, analytical and clinical development of non-invasive soluble biomarkers of NASH are of great importance to advance the field. To this end, we performed analytical and clinical validation on a series of pro-inflammatory cytokines and chemokines implicated hepatic inflammation; IL-6, CRP, TNFα, MCP-1, MIP-1β, eotaxin, VCAM-1. Biomarker assays were validated for accuracy and precision. Clinical performance was evaluated in a random sample of 52 patients with biopsy-proven NAFLD/NASH. Patients were categorized into three groups according to their fibrosis stage; advanced (F3-F4), mild (F1-2) and no (F0) fibrosis. Serum IL-6 was increased in patients with advanced fibrosis (2.71 pg/mL; 1.26 pg/mL; 1.39 pg/mL p<0.01) compared to patients with mild or no fibrosis respectively. While, there was no significant difference noted in CRP, TNFα, MCP-1, MIP-1β, eotaxin among the three groups, VCAM-1 levels were increased by 55% (p<0.01) and 40% (p<0.05) in the advanced cohort compared to the mild and no fibrosis groups respectively. VCAM-1 also displayed good clinical performance as a biomarker of advanced fibrosis with an area under the receiver operating curve of 0.87. The VCAM-1 assay demonstrated robust accuracy and precision, and VCAM-1 outperformed IL-6, CRP, TNFα, and the chemokines MCP-1, MIP-1β, and eotaxin as a biomarker of advanced fibrosis in NASH. Addition of biomarkers such as IL-6 and VCAM-1 to panels may yield increased sensitivity and specificity for staging of NASH.https://doi.org/10.1371/journal.pone.0217263 |
| spellingShingle | Sumit Kar Sabina Paglialunga Sharon H Jaycox Rafiqul Islam Angelo H Paredes Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis. PLoS ONE |
| title | Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis. |
| title_full | Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis. |
| title_fullStr | Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis. |
| title_full_unstemmed | Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis. |
| title_short | Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis. |
| title_sort | assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of nash fibrosis |
| url | https://doi.org/10.1371/journal.pone.0217263 |
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