Working principle of liquid biopsy- When hepatitis progresses to fibrosis, cirrhosis, and liver failure, the stressed/damaged hepatocyte elements associated with liver inflammation accumulates. The hepatocyte injury may occur due to viral hepatitis infections, alcoholic hepatitis, and non-alcoholic fatty liver disease. Hepatocyte-derived extracellular vesicles (Hep-EVs) which are released from stressed/damaged hepatocytes may be held partly responsible for liver disease progression and liver damage since they activate non-parenchymal cells and infiltrate inflammatory cells within the liver, which are again an important source of EVs. 

This cell-to-cell signalling is important and progresses during inflammation in many liver diseases. 

Liquid biopsies include the utilization of cell-free DNA (cfDNA), long non-coding RNA (lncRNA), and the proteins in EVs as potential diagnostic tools and novel therapeutic targets in patients with viral hepatitis, fatty liver steatosis, and alcoholic liver diseases. So, liquid biopsy methods stamp their importance in the long-term monitoring of chronic liver diseases. 

KEY POINTS-

• Liquid biopsies utilize virus-related cell-free DNA (cfDNA), long non-coding RNA (lncRNA), and the proteins in EVs/EPs and exosomes for the diagnosis of chronic liver diseases.
• EVs are important as they have various actions in different target cells including HSCs, MSCs, and macrophages. They have an important role in complex networks of cell-to-cell communication in liver disease development and progression. 
• EVs can also be utilized to provide therapeutic targets in the near future as they carry specific proteins or genes involved in the biogenesis of diseases.
• The biomarkers expression can be helpful not only to monitor the disease process but can also be used for drug design, drug testing and therapeutic efficiency in the future.
• Thus liquid biopsy has a promising future as a non-invasive and accurately diagnosing and monitoring tool for chronic liver disease.

Source: Shabangu, CS, Huang, JF, Hsiao, HH, Yu, ML, Chuang, WL, Wang, SC. Liquid Biopsy for the Diagnosis of Viral Hepatitis, Fatty Liver Steatosis, and Alcoholic Liver Diseases. Int. J. Mol. Sci. 2020, 21(10), 3732; https://doi.org/10.3390/ijms21103732