Recent epidemiological studies suggest that profound alterations in glucose homeostasis, as occurs in type 2 diabetes mellitus or metabolic syndrome, increase the risk of fatty liver disease as well as of hepatocellular carcinoma (HCC). In fact, many clinical and experimental data have demonstrated that type 2 diabetes is more common among patients with chronic hepatitis C virus than in those with hepatitis B virus or in the general population and that CHC infection is associated with increased risk of developing insulin resistance and its major late feature, type 2 diabetes.
In general, CHC infection itself also increases the risk of HCC, leading to complications such as chronic hepatitis, hepatocellular necrosis and inflammation, fibrosis, cirrhosis and HCC. For patients with CHC-related cirrhosis the risk for development of HCC is 0.54 to 2.0% per year.
Recently type 2 diabetes has been recognized as a cofactor that can modify the course of CHC infection and can be used as an independent predictor of HCC. Recent studies have shown that type 2 diabetes was associated with hepatocarcinogenesis in patients with CHC infection without liver cirrhosis. Therefore, there has been a great interest in the search of possible specific immunological markers able to follow the progression of CHC to cirrhosis and HCC also in association with type 2 diabetes.
It is well known that cytokines and chemokines are signaling molecules involved in the inflammatory as well as in cancer-related processes. Hence, understanding in patients affected from cancers the dynamics of the complex interaction network of cytokines, defined “cytokinome", should be very useful to follow the disease progression and evolution from its early stages as well as to define therapeutic strategies by using systems biology approaches. However, many data on cytokines have been reported in the literature and sometimes their correlation appears to be difficult. In fact, in the most part of these papers, the researchers have evaluated only few cytokines by single measurements and, therefore, both the global inflammation mechanism and the cytokine relationships are understandable with difficulty.
In our approach, the serum levels of a panel of numerous cytokines, chemokines, adipokines and growth factors were evaluated at the same time by BioPlex assay in patients with chronic hepatitis C (CHC), CHC-related cirrhosis (LC), type 2 diabetes (T2D), CHC hepatitis and type 2 diabetes (CHD), CHC-related cirrhosis and type 2 diabetes (LCD) and in healthy controls, to identify those molecules that might be useful for discriminating the various stages of these diseases. In other hands, the simultaneous quantitative determination of a large panel of cytokines, able to report the correct ratios and dynamics between highly and poorly represented molecules, has emerged as an accurate, simple, specific, noninvasive, reproducible and less expensive method that, in future, could be included in routine clinical practice to monitor the association of type 2 diabetes and/or CHC to liver cirrhosis and, possibly, to cancer, and to improve the prognosis of these diseases.