Abstract 2144: Retinoid and carotenoid depletion in patients at high-risk for liver cancer

Abstract

Abstract Approximately 3.2 million Americans are chronically infected with hepatitis C (HCV), forming the largest group at high-risk for hepatocellular carcinoma (HCC). Oxidative stress due to chronic inflammation impels the progression of chronic liver disease (CLD) & subsequent HCC. Deficiencies in dietary antioxidants such as retinoids and carotenoids may represent a modifiable risk factor for HCC progression. This study aims to identify key predictors of serum antioxidant levels in patients with CLD, to quantify the association between systemic measures of oxidative stress and antioxidant status, and to examine the relationship between retinoid/carotenoid concentrations in serum and hepatic tissue. Patients with HCV undergoing liver biopsy (n=69) provided fasting blood, fresh tissue, urine, and responses to a diet history questionnaire (DHQ). We also collected serum and questionnaire data from healthy volunteers (n=11), and normal liver tissue from public repositories and patients without liver disease (n=11). Serum and tissue retinoid concentrations were obtained by mass spectroscopy. Serum retinol binding protein 4 (RBP4) was quantified by ELISA. Urine 8OHdG and F2α-isoprostanes were determined by mass spectroscopy. Dietary retinoid intake was estimated by DHQ. Associations between diet, serum and tissue retinoids, and urinary oxidative stress markers were assessed by Spearman correlation coefficients. Dietary β-carotene and lutein were associated with their respective serum concentrations (r = 0.24, p = 0.05; r = 0.33, p < 0.01). There was a significant downward trend for serum retinol, lycopene and RBP4 concentrations with progressive fibrosis; mean serum concentrations were lower in subjects with chronic HCV but no fibrosis compared to controls. Urinary isoprostanes levels were inversely correlated with serum retinol (r= -0.22, p = 0.05), β-carotene (r= -0.22 p = 0.05), and RBP4 (r= -0.25 p = 0.03). Urinary 8OHDG did not correlate with any serum retinoids or carotenoids. Serum β-carotene and lycopene were strongly associated with the respective tissue concentrations (r = 0.56, p<.01; r= 0.76 p< 0.01); however, serum retinol and tissue retinyl palmitate did not correlate in this population (r = -0.08 p = 0.55). There was a suggestive downward trend of tissue retinyl palmitate with increasing levels of fibrosis. Depletion of serum retinol, β-carotene, and RBP4 worsens with liver fibrosis severity. RBP4 might be a better marker for vitamin A status due to its stronger association with disease severity. Retinoid and carotenoid levels decline as disease progresses, and our data suggest that this decline occurs early in the disease process, even before fibrosis is apparent. In HCV patients, decreases in retinoid/carotenoid levels are accompanied by an increase in urinary F2α-isoprostanes, an indicator of lipid peroxidation due to oxidative stress. Dietary or chemopreventive strategies for replenishing antioxidant levels should be studied further. Citation Format: Yachana Kataria, Erika Enk Rueter, Ryan Deaton, Donald Jensen, Scott Cotler, Peter Gann. Retinoid and carotenoid depletion in patients at high-risk for liver cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2144. doi:10.1158/1538-7445.AM2014-2144