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Abstract Details
Association between Immunologic Markers and Cirrhosis in Individuals from a Prospective Chronic Hepatitis C Cohort
Cancers (Basel). 2022 Oct 27;14(21):5280. doi: 10.3390/cancers14215280.
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
2Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD 20814, USA.
3Slone Epidemiology Center, Boston University, Boston, MA 02215, USA.
4HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Leidos, Biomedical Research, Inc., Frederick, MD 21702, USA.
5Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
6Graduate Institute of Epidemiology and Preventative Medicine, College of Public Health, National Taiwan University, Taipei 10617, Taiwan.
7Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
8Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
9Biomedical Translation Research Center, Academia Sinica, Taipei 11529, Taiwan.
Abstract
Background: Chronic hepatitis C virus (HCV) infection can affect immune response and inflammatory pathways, leading to severe liver diseases such as cirrhosis and hepatocellular carcinoma (HCC).
Methods: In a prospective cohort of chronically HCV-infected individuals, we sampled 68 individuals who developed cirrhosis, 91 controls who did not develop cirrhosis, and 94 individuals who developed HCC. Unconditional odds ratios (ORs) from polytomous logistic regression models and canonical discriminant analyses (CDAs) were used to compare categorical (C) baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to produce receiver operating characteristic curves to assess predictive ability of markers. Lastly, biological pathways were assessed in association with cirrhotic development compared to controls.
Results: After multivariable adjustment, DEFA-1 (OR: C2v.C1 = 7.73; p < 0.0001), ITGAM (OR: C2v.C1 = 4.03; p = 0.0002), SCF (OR: C4v.C1 = 0.19; p-trend = 0.0001), and CCL11 (OR: C4v.C1 = 0.31; p-trend= 0.002) were all associated with development of cirrhosis compared to controls; these markers, together with clinical/demographics variables, improved prediction of cirrhosis from 55.7% (in clinical/demographic-only model) to 74.9% accuracy. A twelve-marker model based on CDA results further increased prediction of cirrhosis to 88.0%. While six biological pathways were found to be associated with cirrhosis, cell adhesion was the only pathway associated with cirrhosis after Bonferroni correction. In contrast to cirrhosis, DEFA-1 and ITGAM levels were inversely associated with HCC risk.
Conclusions: Pending validation, these findings highlight the important role of immunological markers in predicting HCV-related cirrhosis even 11 years post-enrollment.