Psychoneuroimmunology of Viral Hepatitis and Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
- 1Laboratory of Psychoneuroimmunology, Selye Lab, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.; Department of Clinical and Toxicological Analyse
Abstract
Hepatocellular carcinoma (HCC) and viral hepatitis (VH) are recognized primarily as hepatic diseases, yet they impose a substantial neuropsychiatric disorders (NPDs) encompassing depression, anxiety, cognitive impairment, and fatigue. Whether these manifestations reflect psychological reactions or biologically grounded psychoneuroimmune dysfunction remains poorly understood. Here, we present a pre-registered systematic review and meta-analysis (PROSPERO 2026 CRD420251081757) synthesizing evidence from 24 studies combining psychosocial outcomes with immune dysregulation markers across HCC and VH populations. Bibliometric and network analyses identified a growing psychoneuroimmunology research hub linking cytokine signaling, microglial activation, blood-brain barrier (BBB) disruption, and gut-liver-brain axis dysregulation to the neuropsychiatric phenotype of these diseases. Meta-analysis revealed a pooled hazard ratio (HR) of 1.92 (95% CI: 1.09-3.39) for adverse outcomes in HCC and a pooled HR of 2.28 (95% CI: 1.48-3.52) for depression associated to genetic variants in VH. TNF-a, but not IL-6, showed a tendency toward lower levels in VH patients with versus without NPDs, suggesting differential inflammatory roles. The literature, however, remains fragmented by heterogeneous designs and a paucity of longitudinal data. A psychoneuroimmunological approach, integrating immune, endocrine, neural, and psychosocial dimensions, is essential for capturing the full systemic impact of HCC and VH and should inform future mechanistic research and multidisciplinary clinical strategies.
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BibTeX
@misc{nobile2026psychoneuroimmunology,
title = {{Psychoneuroimmunology of Viral Hepatitis and Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis}},
author = {A. Leal Nobile and R. G. Nava and R. S. Santos and F. Y. N. d. Vale and J. N. Usuda and A. S. Adri and Y. L. G. Correa and A. R. Valera and L. B. d. S. Gianasi and G. Cabral-Miranda and L. F. S. Marques and R. J. S. Dalmolin and R. Sharma and H. D. Ochs and I. S. Filgueiras and H. D. Dias and O. Cabral-Marques},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.764298},
url = {https://www.biorxiv.org/content/10.64898/2026.11.04.764298v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Psychoneuroimmunology of Viral Hepatitis and Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
AU - A. Leal Nobile
AU - R. G. Nava
AU - R. S. Santos
AU - F. Y. N. d. Vale
AU - J. N. Usuda
AU - A. S. Adri
AU - Y. L. G. Correa
AU - A. R. Valera
AU - L. B. d. S. Gianasi
AU - G. Cabral-Miranda
AU - L. F. S. Marques
AU - R. J. S. Dalmolin
AU - R. Sharma
AU - H. D. Ochs
AU - I. S. Filgueiras
AU - H. D. Dias
AU - O. Cabral-Marques
PY - 2026
DA - 2026/11/04
PB - bioRxiv
DO - 10.64898/2026.11.04.764298
UR - https://www.biorxiv.org/content/10.64898/2026.11.04.764298v1
AB - Hepatocellular carcinoma (HCC) and viral hepatitis (VH) are recognized primarily as hepatic diseases, yet they impose a substantial neuropsychiatric disorders (NPDs) encompassing depression, anxiety, cognitive impairment, and fatigue. Whether these manifestations reflect psychological reactions or biologically grounded psychoneuroimmune dysfunction remains poorly understood. Here, we present a pre-registered systematic review and meta-analysis (PROSPERO 2026 CRD420251081757) synthesizing evidence from 24 studies combining psychosocial outcomes with immune dysregulation markers across HCC and VH populations. Bibliometric and network analyses identified a growing psychoneuroimmunology research hub linking cytokine signaling, microglial activation, blood-brain barrier (BBB) disruption, and gut-liver-brain axis dysregulation to the neuropsychiatric phenotype of these diseases. Meta-analysis revealed a pooled hazard ratio (HR) of 1.92 (95% CI: 1.09-3.39) for adverse outcomes in HCC and a pooled HR of 2.28 (95% CI: 1.48-3.52) for depression associated to genetic variants in VH. TNF-a, but not IL-6, showed a tendency toward lower levels in VH patients with versus without NPDs, suggesting differential inflammatory roles. The literature, however, remains fragmented by heterogeneous designs and a paucity of longitudinal data. A psychoneuroimmunological approach, integrating immune, endocrine, neural, and psychosocial dimensions, is essential for capturing the full systemic impact of HCC and VH and should inform future mechanistic research and multidisciplinary clinical strategies.
ER -