Abstract
Liver fibrosis is a key pathological precondition for hepatocellular carcinoma in which the severity is confidently correlated with liver cancer. Liver fibrosis, characterized by gradual cell loss and excessive extracellular matrix deposition, can be reverted if detected at the early stage. The gold standard for staging and diagnosis of liver fibrosis is undoubtedly biopsy. However, this technique needs careful sample preparation and expert analysis. In the present work, an ex vivo, minimally destructive, label-free characterization of liver biopsies is presented. Through a custom-made experimental setup, liver biopsies of bile-duct-ligated and sham-operated mice were measured at 8, 15, and 21 days after the procedure. Changes in impedance were observed with the progression of fibrosis, and through data fitting, tissue biopsies were approximated to an equivalent RC circuit model. The model was validated by means of 3D hepatic cell culture measurement, in which the capacitive part of impedance was proportionally associated with cell number and the resistive one was proportionally associated with the extracellular matrix. While the sham-operated samples presented a decrease in resistance with time, the bile-duct-ligated ones exhibited an increase in this parameter with the evolution of fibrosis. Moreover, since the largest difference in resistance between healthy and fibrotic tissue, of around 2 k, was found at 8 days, this method presents great potential for the study of fibrotic tissue at early stages. Our data point out the great potential of exploiting the proposed needle setup in clinical applications.
Highlights
2 million deaths occur every year worldwide due to severe liver diseases, imposing a significant burden on healthcare systems [1]
It is known that the degree of liver fibrosis has an effect on the management and prognosis of chronic hepatitis; accurate staging of liver fibrosis is essential in evaluating its evolution to cirrhosis and associated complications such as hepatocellular carcinoma and liver failure
The PicroSirius red (PSR)-based histological evaluation of liver sections of mice subjected to BDL revealed a time-dependent increase in extracellular matrix (ECM) deposition around the periportal area starting from day 8 post-surgery with respect to the sham control
Summary
2 million deaths occur every year worldwide due to severe liver diseases, imposing a significant burden on healthcare systems [1]. Liver diseases have been estimated to be the fifth most common cause of death worldwide, with a rising trend [2]. Liver fibrosis surges as a wound-healing response to chronic injuries. An imbalance in the synthesis and degradation of the extracellular matrix (ECM) alters the hepatic tissue architecture, in which scar tissue replaces liver parenchyma [3]. It is known that the degree of liver fibrosis has an effect on the management and prognosis of chronic hepatitis; accurate staging of liver fibrosis is essential in evaluating its evolution to cirrhosis and associated complications such as hepatocellular carcinoma and liver failure. The earlier liver fibrosis is diagnosed, the faster the causal agent can be removed, resulting in early liver fibrosis reversibility [3]
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