Liver fibrosis phenotyping and severity scoring by quantitative image analysis of biopsy slides

Author:

Watson Adam1ORCID,Petitjean Louis2,Petitjean Mathieu2ORCID,Pavlides Michael34ORCID

Affiliation:

1. Medical Sciences Division University of Oxford Oxford UK

2. Pharmanest Princeton New Jersey USA

3. Translational Gastroenterology Unit, Nuffield Department of Medicine University of Oxford Oxford UK

4. Oxford NIHR Biomedical Research Centre University of Oxford Oxford UK

Abstract

AbstractBackground & AimsDigital pathology image analysis can phenotype liver fibrosis using histological traits that reflect collagen content, morphometry and architecture. Here, we aimed to calculate fibrosis severity scores to quantify these traits.MethodsLiver biopsy slides were categorised by Ishak stage and aetiology. We used a digital pathology technique to calculate four fibrosis severity scores: Architecture Composite Score (ACS), Collagen Composite Score (CCS), Morphometric Composite Score (MCS) and Phenotypic Fibrosis Composite Score (PH‐FCS). We compared how these scores varied according to disease stage and aetiology.ResultsWe included 80 patients (40% female, mean age 59.0 years, mean collagen proportionate area 17.1%) with mild (F0‐2, n = 28), moderate (F3‐4, n = 17) or severe (F5‐6, n = 35) fibrosis. All four aetiology independent scores corelated with collagen proportionate area (ACS: rp = .512, CCS: rp = .727, MCS: rp = .777, PFCS: r = .772, p < .01 for all) with significant differences between moderate and severe fibrosis (p < .05). ACS increased primarily between moderate and severe fibrosis (by 95% to 226% depending on underlying aetiology), whereas MCS and CCS accumulation was more varied. We used 28 qFTs that distinguished between autoimmune‐ and alcohol‐related liver disease to generate an MCS that significantly differed between mild and severe fibrosis for these aetiologies (p < .05).ConclusionsWe describe four aetiology‐dependent and ‐independent severity scores that quantify fibrosis architecture, collagen content and fibre morphometry. This approach provides additional insight into how progression of architectural changes and accumulation of collagen may differ depending on underlying disease aetiology.

Publisher

Wiley

Subject

Hepatology

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