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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)\u2010HBV and REVEAL\u2010HCV cohorts from Taiwan. REVEAL\u2010HBV included 185 cases and 161 matched controls, and REVEAL\u2010HCV 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 coreceptor), and LPS\u2010binding protein (LBP). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarker levels and HCC were calculated using multivariable\u2010adjusted logistic regression. A doubling of the circulating levels of antiflagellin IgA or LBP was associated with a 76% to 93% increased risk of HBV\u2010related HCC (OR per one unit change in log<jats:sub>2<\/jats:sub> antiflagellin IgA\u00a0=\u00a01.76, 95% CI: 1.06\u20102.93; OR for LBP\u00a0=\u00a01.93, 95% CI: 1.10\u20103.38). None of the other markers were associated with an increased risk of HBV\u2010related or HCV\u2010related HCC. Results were similar when cases diagnosed in the first 5\u2009years of follow\u2010up were excluded. Our findings contribute to understanding the interplay of gut barrier dysfunction and primary liver cancer etiology.<\/jats:p>","DOI":"10.1002\/ijc.34492","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T02:17:50Z","timestamp":1678155470000},"page":"44-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Biomarkers of gut barrier dysfunction and risk of hepatocellular carcinoma in the <scp>REVEAL\u2010HBV<\/scp> and <scp>REVEAL\u2010HCV<\/scp> cohort studies"],"prefix":"10.1002","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6580-450X","authenticated-orcid":false,"given":"Jessica L.","family":"Petrick","sequence":"first","affiliation":[{"name":"Slone Epidemiology Center at Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea A.","family":"Florio","sequence":"additional","affiliation":[{"name":"Department of Nutrition Harvard T.H. 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