Hepatitis C virus is an important human pathogen affecting an estimated 170 million people worldwide. There is no HCV vaccine available, and the existing pegylated interferon/ ribavirin standard-of-care antiviral therapy is only about 50% effective in genotype 1 HCV and poorly tolerated. Chronic HCV infection is often clinically asymptomatic but can frequently progress to liver fibrosis, cirrhosis and hepatocellular carcinomas. Although both viral proteins and dysregulated immunocytes have been implicated for causing liver diseases, the knowledge about HCV infection induced hepatopathogenesis is still limited. Therefore, non-invasive serum predictors of HCV infection and knowledge of their potential roles during disease progression are urgently needed to help adjust treatment regimens and understand pathogenic mechanisms. Our previous work DDD00107587 screened the possible involvement of growth differentiation factor 15 during HCV infection. GDF15, also known as macrophage inhibitory cytokine 1, is a member of the transforming growth factor beta cytokine superfamily. GDF15 was first cloned from human monocytoid cell line U937 and identified for inhibiting TNF-a production by macrophages. As a circulating cytokine, the function of GDF15 may be systemic and complicated. Recent studies suggest that GDF15 might be involved in cell survival, cancer cell invasiveness, tumor-induced anorexia and weight loss. Association studies suggest that GDF15 is dramatically induced in liver injury, cancers, cardiovascular diseases, thalassemia and HPV-mediated cervical cancer. However, an association between GDF15 and viral hepatitis has not been SHP099 hydrochloride reported, so far. In the present study, we identified the up-regulation of GDF15 in HCV-infected hepatoma cells and evaluated serum levels of GDF15 in cohorts of patients with chronic hepatitis C or hepatitis B. Additionally, we investigated the biological impact of increased GDF15 on hepatoma cells. We demonstrate that GDF15 is an HCV induced host circulating biomarker and may play important roles during liver pathogenesis by regulating specific pathways and HCC-related genes. Different mechanisms have been proposed to explain HCV pathogenesis, including fibrogenesis and HCC. Among these mechanisms, an involvement of the virus-host interactions has been suggested by a number of in vitro and in vivo studies.