Mental health diseases are associated with active hepatitis C and partly drive HCC trends in Veterans.

Pham NV, Singh R, Leng M, Han SB, May FP, Singh J, Benhammou JN. Mental health diseases are associated with active hepatitis C and partly drive HCC trends in Veterans. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2025 Nov 29 DOI: 10.1016/j.cgh.2025.11.026.

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Abstract:

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) incidence is on the rise. While biological factors have been studied extensively, how Mental Health Diseases (MHD) affect the risk of HCC remains unexplored. In this study, we aimed to determine whether MHD are associated with HCC incidence among at-risk Veterans. METHODS: We conducted a retrospective cohort study of Veterans with cirrhosis (2000-2021). MHD were defined by ICDs and mental health surveys and were categorized into individual MHDs or, alcohol/substance use disorders (AUD/SUD), non-AUD/SUD (anxiety, depression, PTSD, schizophrenia and bipolar), and any MHD, based on clinical relevance and correlations ( > 0.7). Cirrhosis was defined by 2-consecutives FIB-4 > 3.25 or validated ICDs. The Census Bureau and RUCAC geospatial codes were used to define rurality. The association between incident HCC, MHD, rurality and HCV (per direct acting antiviral-DAA-era) was analyzed using multivariable Cox logistic regression. RESULTS: We identified 221,721 Veterans, 7% (n = 15,710) of whom developed HCC. AUD/SUD was the most prevalent MHD (n = 44,140; 19.6%). AUD (6.74%) was the most common individual MHD, with large overlaps between MHD. DAAs improved but did not eliminate the risk of HCC in Veterans (adj.HR = 1.32, 95%CI 1.26-1.38 vs. adj.HR = 1.59, 95%CI1.89-2.14). AUD/SUD was a significant risk for HCC in the pre-DAA era (adj.HR = 1.42, 95%CI1.28-1.59). In the post-DAA era, AUD/SUD significantly interacted with HCV (adj.HR = 1.98, 95%CI1.54-2.55). CONCLUSION: In a large cohort of Veterans with cirrhosis, any MHD significantly increased incident HCC risk and associated with active HCV, even in the post-DAA era, with AUD and ALD having the largest effects. Multidisciplinary management of vulnerable, at-risk Veterans is needed to mitigate the risk of HCC.