Serum levels of Vitamin D3, Zinc, and Parathyroid Hormone in HCV-induced Hepatocellular Carcinoma. Running Title: Vitamin D3, Zinc, Parathyroid Hormone and HCV-related Hepatocellular Carcinoma

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Abstract Background: The role of the metabolic syndrome in hepatocellular carcinoma (HCC) has been extensively reported, however, the role of other individual metabolic variables in development of HCC in HCV infected patients is still not clear. This study aimed to investigate the possible role of Parathyroid hormone (PTH), calcium, phosphorus, vitamin D3 and Zinc, serum levels as non-traditional metabolic risk factors in development of HCV-related HCC. Methods: Serum levels of vitamin D3, Zinc, PTH, calcium, and phosphorus were determined in HCV infected patients with and without HCC. Results: Our results show significantly higher age, male sex, aspartate transaminase (AST), PTH and corrected serum calcium levels in the HCC patients compared to values in the other two groups, (p<0.001); while significant lower vitamin D3 and zinc levels were detected among the HCC patients compared to patients with non-HCC liver cirrhosis and CHC, (p<0.001). Vitamin D3 deficiency was detected in 96% of the HCC patients, while it was detected in only 22.5% of the cirrhotic patients and in none of the CHC patients, (p<0.001). However, on multiple stepwise regression analysis, only the age, AST, PTH, and corrected calcium levels were the independent predictors for HCC when studied in relation to chronic liver disease. Conclusions: This study indicates the prevalent high PTH and calcium levels along with deficient vitamin D3 and zinc levels in HCV-induced HCC patients. However, a causal relationship between the low levels of Vitamin D3 and Zinc in relation to HCC development is not established in this study.

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