Liquid biopsy: Fundamental principles and clinical value in hepatocellular carcinoma

The incidence and mortality related to Hepatocellular carcinoma (HCC) is steadily rising. Moreover, there is a paradigm shift in the epidemiology of this malignancy with metabolism onset fatty liver disease gradually becoming the predominant underlying liver disease. However, prognostication of these patients is not straight forward as the disease is heterogeneous. Tumor markers like alfa-fetoprotein (AFP) and des-gammacarboxy prothrombin (DCP) are commonly used prognostic markers though both of these may be normal in patients with HCC. Conversely, the levels of AFP and DCP may be elevated in patients with out HCC. Tumor biopsy can also be used to characterize the lesion which is of great value in prognostication of these patients. However, liver biopsy is invasive and is not always feasible in these patients due to underlying coagulopathy and ascites. In such a scenario liquid biopsy represent a non-invasive modality to extract tumor products like DNAs, RNAs or extracellular vesicles from blood stream. These cellular products can easily be used for early diagnosis and prognostication of patients with HCC. This review aims to provide insight in to fundamental principles of liquid biopsy and their current clinical application in context of HCC. The incidence and mortality related to Hepatocellular carcinoma (HCC) is steadily rising. Moreover, there is a paradigm shift in the epidemiology of this malignancy with metabolism onset fatty liver disease gradually becoming the predominant underlying liver disease. However, prognostication of these patients is not straight forward as the disease is heterogeneous. Tumor markers like alfa-fetoprotein (AFP) and des-gammacarboxy prothrombin (DCP) are commonly used prognostic markers though both of these may be normal in patients with HCC. Conversely, the levels of AFP and DCP may be elevated in patients with out HCC. Tumor biopsy can also be used to characterize the lesion which is of great value in prognostication of these patients. However, liver biopsy is invasive and is not always feasible in these patients due to underlying coagulopathy and ascites. In such a scenario liquid biopsy represent a non-invasive modality to extract tumor products like DNAs, RNAs or extracellular vesicles from blood stream. These cellular products can easily be used for early diagnosis and prognostication of patients with HCC. This review aims to provide insight in to fundamental principles of liquid biopsy and their current clinical application in context of HCC.