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Biomarkers of gut barrier dysfunction and risk of hepatocellular carcinoma in the REVEAL-HBV and REVEAL-HCV Cohort Studies

  1. Author:
    Petrick, Jessica L [ORCID]
    Florio, Andrea A
    Zen, Jane
    Wang, Yanyu
    Gewirtz, Andrew T
    Pfeiffer, Ruth M [ORCID]
    Loftus,Sarah
    Inglefield,Jon
    Koshiol, Jill [ORCID]
    Yang, Baiyu [ORCID]
    Yu, Kelly [ORCID]
    Hildesheim, Allan
    Chen, Chien-Jen [ORCID]
    Yang, Hwai-I
    Lee, Mei-Hsuan
    McGlynn, Katherine A [ORCID]

  2. Author Address

    Slone Epidemiology Center at Boston University, Boston, Massachusetts, USA., Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA., Applied Developmental Research Directorate, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland, USA., Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA., Genomics Research Center, Academia Sinica, Taipei, Taiwan., Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan.,
    1. Year: 2023
    2. Date: Mar 06
    3. Epub Date: 2023 03 06
  2. Journal: International Journal of Cancer
  4. Type of Article: Article
  1. Abstract:

    Gut barrier dysfunction can result in the liver being exposed to an elevated level of gut-derived bacterial products via portal circulation. Growing evidence suggests that systemic exposure to these bacterial products promotes liver diseases including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). However, prospective studies have not examined the association between biomarkers of gut barrier dysfunction and HCC risk in a population of hepatitis B or C viral (HBV/HCV) carriers. We investigated whether prediagnostic, circulating biomarkers of gut barrier dysfunction were associated with HCC risk, using the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL)-HBV and REVEAL-HCV cohorts from Taiwan. REVEAL-HBV included 185 cases and 161 matched controls, and REVEAL-HCV 96 cases and 96 matched controls. The biomarkers quantitated were immunoglobulin A (IgA), IgG, and IgM against lipopolysaccharide (LPS) and flagellin, soluble CD14 (an LPS co-receptor), and LPS-binding protein (LBP). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarker levels and HCC were calculated using multivariable-adjusted logistic regression. A doubling of the circulating levels of anti-flagellin IgA or LBP was associated with a 76-93% increased risk of HBV-related HCC (OR per one unit change in log2 anti-flagellin IgA = 1.76, 95%CI: 1.06-2.93; OR for LBP = 1.93, 95%CI: 1.10-3.38). None of the other markers were associated with an increased risk of HBV-related or HCV-related HCC. Results were similar when cases diagnosed in the first five years of follow-up were excluded. Our findings contribute to understanding the interplay of gut barrier dysfunction and primary liver cancer etiology. This article is protected by copyright. All rights reserved.

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  2. DOI: 10.1002/ijc.34492
  3. PMID: 36878686

Library Notes

  1. Fiscal Year: FY2022-2023
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