Quantitative image-based collagen structural features predict the reversibility of hepatitis C virus-induced liver fibrosis post antiviral therapies
Gole, L ; Liu, F ; Ong, KH ; Li, L ; Han, H ; Young, D ; Marini, GPL ; Wee, A ; Zhao, J ; Rao, H ... show 2 more
Liu, F
Ong, KH
Li, L
Marini, GPL
Zhao, J
Rao, H
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Alternative Title
Abstract
The novel targeted therapeutics for hepatitis C virus (HCV) in last decade solved most of the clinical needs for this disease. However, despite antiviral therapies resulting in sustained virologic response (SVR), a challenge remains where the stage of liver fibrosis in some patients remains unchanged or even worsens, with a higher risk of cirrhosis, known as the irreversible group. In this study, we provided novel tissue level collagen structural insight into early prediction of irreversible cases via image based computational analysis with a paired data cohort (of pre- and post-SVR) following direct-acting-antiviral (DAA)-based treatment. Two Photon Excitation and Second Harmonic Generation microscopy was used to image paired biopsies from 57 HCV patients and a fully automated digital collagen profiling platform was developed. In total, 41 digital image-based features were profiled where four key features were discovered to be strongly associated with fibrosis reversibility. The data was validated for prognostic value by prototyping predictive models based on two selected features: Collagen Area Ratio and Collagen Fiber Straightness. We concluded that collagen aggregation pattern and collagen thickness are strong indicators of liver fibrosis reversibility. These findings provide the potential implications of collagen structural features from DAA-based treatment and paves the way for a more comprehensive early prediction of reversibility using pre-SVR biopsy samples to enhance timely medical interventions and therapeutic strategies. Our findings on DAA-based treatment further contribute to the understanding of underline governing mechanism and knowledge base of structural morphology in which the future non-invasive prediction solution can be built upon.
Keywords
Humans, Antiviral Agents, Hepacivirus, Hepatitis C, Liver Cirrhosis, Collagen, Hepatitis C, Chronic
Source Title
Scientific Reports
Publisher
Springer Science and Business Media LLC
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Date
2023-12-01
DOI
10.1038/s41598-023-33567-4
Type
Article