ArticleImmunology2014
Conjugated bilirubin affects cytokine profiles in hepatitis A virus infection by modulating function of signal transducer and activator of transcription factors.
Article in Immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Missingness-aware machine learning using routine laboratory data for distinguishing hepatitis from cirrhosis.Frontiers in genetics · 2026Article
- Atypical presentation of pediatric acute hepatitis A: Is the situation alarming?World journal of virology · 2025Review
- Human cytomegalovirus reactivation in cirrhosis patients with acute decompensation.Clinical and molecular hepatology · 2025Observational
- Bilirubin metabolism and its application in disease prevention: mechanisms and research advances.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- A Nomogram for Predicting BK Virus Activation in Kidney Transplantation Recipients Using Clinical Risk Factors.Frontiers in medicine · 2022Article
- Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Yinzhihuang Oral Liquid in Treating Neonatal Hyperbilirubinemia.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Bilirubin as a metabolic hormone: the physiological relevance of low levels.American journal of physiology. Endocrinology and metabolism · 2021Review
- Changes in cellular proliferation and plasma products are associated with liver failure.World journal of hepatology · 2016Article
- Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling.Mediators of inflammation · 2016Article
- Rethinking the immune properties of bilirubin in viral hepatitis: from bench to bedside.Clinical & translational immunology · 2015Review
- T-helper 17-related cytokines and IgE antibodies during hepatitis A virus infection in children.Memorias do Instituto Oswaldo Cruz · 2015Article
- Spontaneous hepatitis C viral clearance and hepatitis C chronic infection are associated with distinct cytokine profiles in Mexican patients.Memorias do Instituto Oswaldo Cruz · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis A virus (HAV) infection is the major cause of acute liver failure in paediatric patients. The clinical spectrum of infection is variable, and liver injury is determined by altered hepatic enzyme function and bilirubin concentration. We recently reported differences in cytokine profiles between distinct HAV-induced clinical courses, and bilirubin has been recognized as a potential immune-modulator. However, how bilirubin may affect cytokine profiles underlying the variability in the course of infection has not been determined. Herein, we used a transcription factor (TF) binding site identification approach to retrospectively analyse cytokine expression in HAV-infected children and to predict the entire set of TFs associated with the expression of specific cytokine profiles. The results suggested that modulation of the activity of signal transducers and activators of transcription proteins (STATs) may play a central role during HAV infection. This led us to compare the degree of STAT phosphorylation in peripheral blood lymphoid cells (PBLCs) from paediatric patients with distinct levels of conjugated bilirubin (CB). Low CB levels in sera were associated with increased STAT-1 and STAT-5 phosphorylation. A positive correlation was observed between the serum interleukin-6 (IL-6) content and CB values, whereas higher levels of CB correlated with reduced serum IL-8 values and with a reduction in the proportion of PBLCs positive for STAT-5 phosphorylation. When CB was used to stimulate patients' PBLCs in vitro, the levels of IL-6 and tumour necrosis factor-α were increased. The data showed that bilirubin plays a role in STAT function and affects cytokine profile expression during HAV infection.
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