Gender-based investigation of 17 β hydroxysteroid dehydrogenase 13 in HCV-induced cirrhosis and hepatocellular carcinoma

Introduction/Objectives: Hepatitis C virus (HCV) infection- related inflammation, liver fibrosis and cirrhosis often lead to development of hepatocellular carcinoma (HCC). In the United States, 4.6 million people are infected with HCV. Studies show that chronic HCV infections are more prevalent in males and progress more rapidly to cirrhosis and cancer development as compared to females. In contrast, premenopausal females and women on hormone replacement therapy have been associated with lesssevere disease through all stages of HCV infection. Estrogen Receptor signaling is known to regulate inflammation and immunity. We have previously identified sex-based differences in the expression of estrogen receptors (ERs) in normal livers and dysregulated mRNA and protein expression of ER subtypes in both HCV-related cirrhosis and HCC suggesting a possible role in its pathogenesis. Given the United States opioid epidemic and high rates of intravenous drug use, Hepatitis C is an emerging disease among women of child-bearing age (and subsequently, pregnant women). Therefore, HCV-positive pregnant women with high levels estrogen may also be affected by modified behavior of HSDs. As such, our studies can apply to a broad group of people and demand further investigation. Our current study investigates the hydroxysteroid dehydrogenase enzyme family (HSD). HSDs contribute largely to the synthesis and degradation of steroid hormones such as testosterone and estrogen sex-hormones, as well as cholesterol and fatty acid metabolism. They have also been shown to confer involvement in carcinogenesis of extra-hepatic cancers affecting structures such as prostate, breast, and pancreas. Estrogen Receptor signaling is known to regulate inflammation and immunity. Chronic inflammation due to HCV infection in the liver may alter HSD enzyme regulation and alter hormone metabolism. Further, this pro-inflammatory state may contribute to the development of HCC which may be modulated by altered HSDs.