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Article

Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease

by
David Marti-Aguado
1,2,*,
Matías Fernández-Patón
2,
Clara Alfaro-Cervello
3,4,
Claudia Mestre-Alagarda
3,
Mónica Bauza
5,
Ana Gallen-Peris
6,
Víctor Merino
1,
Salvador Benlloch
6,7,
Judith Pérez-Rojas
5,
Antonio Ferrández
3,4,
Víctor Puglia
8,
Marta Gimeno-Torres
9,
Victoria Aguilera
7,9,
Cristina Monton
1,
Desamparados Escudero-García
1,4,
Ángel Alberich-Bayarri
2,10,
Miguel A. Serra
4 and
Luis Marti-Bonmati
2,11
1
Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, 46010 Valencia, Spain
2
Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, 46026 Valencia, Spain
3
Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, 46010 Valencia, Spain
4
Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
5
Pathology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain
6
Digestive Disease Department, Hospital Arnau de Vilanova, 46015 Valencia, Spain
7
CIBERehd, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain
8
Pathology Department, Hospital Arnau de Vilanova, 46015 Valencia, Spain
9
Hepatology and Liver Transplantation Unit, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain
10
Quantitative Imaging Biomarkers in Medicine, QUIBIM SL, 46021 Valencia, Spain
11
Radiology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain
 
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*
Author to whom correspondence should be addressed.
Biomolecules 2021, 11(12), 1808; https://doi.org/10.3390/biom11121808
Submission received: 30 September 2021 / Revised: 22 November 2021 / Accepted: 29 November 2021 / Published: 2 December 2021
(This article belongs to the Special Issue Digital Pathology)
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Abstract

Traditional histological evaluation for grading liver disease severity is based on subjective and semi-quantitative scores. We examined the relationship between digital pathology analysis and corresponding scoring systems for the assessment of hepatic necroinflammatory activity. A prospective, multicenter study including 156 patients with chronic liver disease (74% nonalcoholic fatty liver disease-NAFLD, 26% chronic hepatitis-CH etiologies) was performed. Inflammation was graded according to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network system and METAVIR score. Whole-slide digital image analysis based on quantitative (I-score: inflammation ratio) and morphometric (C-score: proportionate area of staining intensities clusters) measurements were independently performed. Our data show that I-scores and C-scores increase with inflammation grades (p < 0.001). High correlation was seen for CH (ρ = 0.85–0.88), but only moderate for NAFLD (ρ = 0.5–0.53). I-score (p = 0.008) and C-score (p = 0.002) were higher for CH than NAFLD. Our MATLAB algorithm performed better than QuPath software for the diagnosis of low-moderate inflammation (p < 0.05). C-score AUC for classifying NASH was 0.75 (95%CI, 0.65–0.84) and for moderate/severe CH was 0.99 (95%CI, 0.97–1.00). Digital pathology measurements increased with fibrosis stages (p < 0.001). In conclusion, quantitative and morphometric metrics of inflammatory burden obtained by digital pathology correlate well with pathologists’ scores, showing a higher accuracy for the evaluation of CH than NAFLD.
Keywords: digital pathology; inflammation; nonalcoholic fatty liver disease; chronic hepatitis digital pathology; inflammation; nonalcoholic fatty liver disease; chronic hepatitis
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MDPI and ACS Style

Marti-Aguado, D.; Fernández-Patón, M.; Alfaro-Cervello, C.; Mestre-Alagarda, C.; Bauza, M.; Gallen-Peris, A.; Merino, V.; Benlloch, S.; Pérez-Rojas, J.; Ferrández, A.; et al. Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease. Biomolecules 2021, 11, 1808. https://doi.org/10.3390/biom11121808

AMA Style

Marti-Aguado D, Fernández-Patón M, Alfaro-Cervello C, Mestre-Alagarda C, Bauza M, Gallen-Peris A, Merino V, Benlloch S, Pérez-Rojas J, Ferrández A, et al. Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease. Biomolecules. 2021; 11(12):1808. https://doi.org/10.3390/biom11121808

Chicago/Turabian Style

Marti-Aguado, David, Matías Fernández-Patón, Clara Alfaro-Cervello, Claudia Mestre-Alagarda, Mónica Bauza, Ana Gallen-Peris, Víctor Merino, Salvador Benlloch, Judith Pérez-Rojas, Antonio Ferrández, and et al. 2021. "Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease" Biomolecules 11, no. 12: 1808. https://doi.org/10.3390/biom11121808

APA Style

Marti-Aguado, D., Fernández-Patón, M., Alfaro-Cervello, C., Mestre-Alagarda, C., Bauza, M., Gallen-Peris, A., Merino, V., Benlloch, S., Pérez-Rojas, J., Ferrández, A., Puglia, V., Gimeno-Torres, M., Aguilera, V., Monton, C., Escudero-García, D., Alberich-Bayarri, Á., Serra, M. A., & Marti-Bonmati, L. (2021). Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease. Biomolecules, 11(12), 1808. https://doi.org/10.3390/biom11121808

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