Journal Article

Quantitative image-based collagen structural features predict the reversibility of hepatitis C virus-induced liver fibrosis post antiviral therapies

Wei, Lai, Gole, Laurent, Li, Longjie, Zhao, Jingmin, Rao, Huiying, Ong, Kok Haur, Wee, Aileen, Marini, Gabriel Pik Liang, Yu, Weimiao, Liu, Feng, Han, Hao, Young, David

2023

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/114 / 631/114/1564 / 631/114/2397 / 631/114/2400 / 692/308/575 / 692/4020/4021/1607/1604 / 692/4020/4021/1607/1605 / 692/4020/4021/1607/234 / 692/4020/4021/1607/234/1995 / 692/4020/4021/1607/234/2513 / 692/699/249/2510 / Antiviral agents / Antiviral Agents - pharmacology / Antiviral Agents - therapeutic use / Antiviral drugs / Biopsy / Cirrhosis / Collagen / Collagen - therapeutic use / Computer applications / Fibrosis / Hepacivirus - physiology / Hepatitis / Hepatitis C / Hepatitis C, Chronic / Humanities and Social Sciences / Humans / Image processing / Liver / Liver Cirrhosis - diagnostic imaging / Liver Cirrhosis - drug therapy / Liver Cirrhosis - etiology / multidisciplinary / Patients / Prediction models / Science / Science (multidisciplinary)