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Published on: February 10, 2015
Early inflammatory markers for prediction of cholestasis in very-low-birth-weight infants
Sara B DeMauro1, Laurie E Kilpatrick, Jeffrey S Gerdes
1Department of Pediatrics, The Children's Hospital of Philadelphia, Pennsylvania Hospital and the University of Pennsylvania, Philadelphia, PA 19104, USA. demauro@email.chop.edu
Insights
Neonatal cholestasis in very-low-birth-weight infants is linked to elevated inflammatory markers like C-reactive protein (CRP) and cytokines. These markers may help predict which infants are at risk for developing cholestasis.
Area of Science:
- Neonatology
- Pediatric Gastroenterology
- Immunology
Background:
- Neonatal cholestasis presents a significant risk for mortality and adverse outcomes in infants.
- Current diagnostic tools lack the ability to predict infants at risk for developing cholestasis.
- Very-low-birth-weight (VLBW) infants are particularly vulnerable to cholestasis, often requiring prolonged parenteral nutrition.
Purpose of the Study:
- To investigate the association between cholestasis in VLBW infants and alterations in cytokine levels and C-reactive protein (CRP).
- To determine if specific inflammatory markers can predict the development of cholestasis in VLBW infants.
- To explore the potential of inflammatory markers in understanding the pathogenesis and prediction of neonatal cholestasis.
Main Methods:
- A prospective cohort study involving VLBW infants requiring parenteral nutrition for over 7 days.
- Infants were categorized based on direct bilirubin levels (≥1.0 mg/dl for high-risk group).
- Biomarkers including cytokines and CRP were measured over time and analyzed using descriptive statistics and multivariable models.
Main Results:
- Of 63 infants, 29 were identified as high-risk for cholestasis.
- C-reactive protein (CRP) demonstrated a strong correlation with direct bilirubin levels.
- Infants at high risk exhibited significantly elevated levels of IL-1β, IL-6, IL-8, and IL-10 at 2, 4, and 6 weeks, and CRP at 2 and 6 weeks.
- Early measurements of CRP or IL-1β at 2 weeks predicted cholestasis development (logistic models).
- CRP, IL-6, and IL-8 levels were predictive of cholestasis in linear mixed-effects models.
Conclusions:
- Elevated levels of CRP and specific cytokines are significantly associated with cholestasis in VLBW infants.
- These inflammatory markers show promise as predictors for cholestasis in this vulnerable population.
- Further research into these markers is warranted for understanding pathogenesis, improving prediction, and developing prevention strategies for neonatal cholestasis.
Background:
Neonatal cholestasis is associated with increased mortality and other adverse outcomes. There are no tools for prediction of infants at risk for cholestasis.
Objective:
To determine if cholestasis in very-low-birth-weight (VLBW) infants is associated with alterations in cytokines or C-reactive protein (CRP) and, if so, whether inflammatory markers predict which infants will develop cholestasis.
Methods:
VLBW infants expected to be on parenteral nutrition for >7 days were enrolled in this prospective cohort study. Infants with direct bilirubin ≥1.0 mg/dl were considered to have a high risk for cholestasis and were compared to infants who never developed direct bilirubin ≥1.0 mg/dl. Standard descriptive statistics were used to compare biomarkers over time. Multivariable models were used to estimate associations between early inflammatory markers and cholestasis.
Results:
Of 63 infants enrolled, 29 were at risk for cholestasis. CRP was highly correlated with direct bilirubin. Infants in the high-risk group had significantly higher IL-1β, IL-6, IL-8, and IL-10 at 2, 4, and 6 weeks and CRP at 2 and 6 weeks. In logistic models, CRP (OR = 4.97, p = 0.02) or IL-1β (OR = 1.11, p = 0.008) at 2 weeks of age was predictive of cholestasis. In linear mixed-effects models, CRP (p < 0.001) or IL-6 (p = 0.02) and IL-8 (p < 0.001) were predictive of cholestasis.
Conclusion:
Elevated CRP and cytokines are associated with cholestasis in VLBW infants. These inflammatory markers are candidates for further research into the pathogenesis, prediction, and prevention of cholestasis.
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