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Serum Cytokine Analysis Reveals Predictors of Progression from Chronic Hepatitis B to Liver Cirrhosis
1Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Insights
Interleukin-9 (IL-9), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2 receptor subunit α (IL-2Rα) may predict the progression of chronic hepatitis B (CHB) to liver cirrhosis (LC). These cytokines could aid in monitoring CHB patients at risk of developing liver disease.
Area of Science:
- Hepatology
- Immunology
- Biomarker Discovery
Background:
- Chronic hepatitis B (CHB) is a significant cause of chronic liver disease, particularly in China.
- Progression from CHB to liver cirrhosis (LC) necessitates reliable predictors for monitoring and intervention.
- Understanding cytokine profiles in CHB and LC is crucial for identifying disease progression markers.
Purpose of the Study:
- To identify cytokine profiles that predict the progression of CHB to LC.
- To investigate the role of specific cytokines, including IL-9, GM-CSF, and IL-2Rα, as potential biomarkers.
- To evaluate the utility of a cytokine panel in differentiating CHB from LC and assessing disease severity.
Main Methods:
- Multiplex biometric ELISA was used to analyze 48 cytokines in serum from healthy controls (HC), CHB patients, and LC patients.
- Partial least squares discriminant analysis (PLS-DA) and random forest were employed to identify significant differentially expressed cytokines.
- Independent cohorts were used for validation, and receiver-operator characteristic (ROC) analysis was performed on identified biomarkers.
Main Results:
- Eighteen cytokines were differentially expressed between CHB and LC patients.
- Interleukin-9 (IL-9), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2 receptor subunit α (IL-2Rα) were identified as key differentiating cytokines.
- A logistic regression panel combining these three cytokines demonstrated significant predictive power for differentiating CHB from LC and correlated with the Child-Pugh score.
Conclusions:
- IL-9, GM-CSF, and IL-2Rα are potential serum biomarkers for predicting CHB progression to LC.
- The identified cytokine panel offers a promising tool for monitoring liver disease progression in CHB patients.
- These findings contribute to better risk stratification and management strategies for chronic hepatitis B.
Abstract:
Hepatitis B virus (HBV) infection is more likely to develop into chronic and persistent infection in China, which is the main cause of chronic liver disease. We examined the cytokine profiles of chronic hepatitis B (CHB) and CHB-caused liver cirrhosis (LC) to look for the predictor of progression from CHB to LC. Serum samples of 15 healthy controls (HC), 15 CHB patients and 15 LC patients were collected to detect the profiles of 48 cytokines by multiplex biometric ELISA-based immunoassay. Partial least squares discriminant analysis (PLS-DA) and random forest were used to analyse significant cytokines, which were further validated by ELISA using an independent cohort of 60 CHB patients, 60 LC patients and 35 HC samples. There were 18 differentially expressed cytokines of CHB and LC. Three cytokines were identified by PLS-DA and random forest, including interleukin (IL)-9, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-2 receptor subunit α (IL-2Rα), which displayed significant changes in serum levels. Differentially expressed cytokine networks between HC, CHB and LC also indicated particular cytokine co-expression network patterns of CHB and LC. The receiver-operator characteristic (ROC) analysis demonstrated that IL-9, GM-CSF, IL-2Rα and their logistic regression panel are potential predictors that significantly differentiate CHB from LC (P < 0.001) and CHB from Child class A LC (P < 0.001). The three cytokines and the panel showed significant correlation with the Child-Pugh score. IL-9, GM-CSF, IL-2Rα and their logistic panel may be predictors for monitoring the progression of CHB to LC.
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