The identification of HCV infection-regulated host serum factors allows us to explore predictive biomarkers, and to mechanistically investigate the host response upon infection. In this study, we have shown that the HCV infection is characterized by higher-thannormal GDF15 levels, and elevated GDF15 potentially regulates both HCV replication and host HCC-related signaling pathway and genes. The TGF-b superfamily of ligands plays a pivotal role in the regulation of a wide variety of physiological processes from development to pathogenesis. GDF15 was originally discovered as a factor in immune regulation and was subsequently considered a host responsive factor linked to tissue injury, cardiovascular events and SYR472 succinate inhibitor cancers. However, the correlations between the GDF15 expression level and virus infections are undefined. We observed that 37 of 54 HCV and 50 of 56 HBV patients had a GDF15 level higher than the average GDF15 level in the healthy volunteers in the control group. Notably, the induction of GDF15 in both HCV and HBV infected patients suggests that GDF15 probably is a non-specific liver injury responsive cytokine in viral hepatitis and other hepatic diseases. As a circulating cytokine, GDF15 may function by transducing signals to target cells through the autocrine, paracrine and endocrine systems. So far, a variety of GDF15 biological functions has been reported, such as an anti-apoptotic in cardiomyocytes, metastasis in prostate cancer cells, motoneuron development, osteoclast differentiation, iron overloading and erythropoiesis. Therefore, it is possible that HCV infection might exert a systemic influence on extrahepatic manifestations during disease using GDF15 as a communicator. Previous studies reported that the TGF-b1 level was elevated in chronic hepatitis C liver biopsy samples and urine, but the association of the cytokine level and disease Sodium tartrate inhibitor progression has not yet been clearly concluded. In the HCV-infected patients, we tried to assess the possible relationship between serum GDF15 levels and several disease characteristics, including viral load, genotypes and liver disease progression. Limited by the small number of subjects in the cohorts, we did not observe an accurate correlation, with the exception of 3 HCC patients that had extremely high levels of circulating GDF15.