Article, 2023

Validation of computed tomography as a diagnostic tool in guinea pigs with non-alcoholic fatty liver disease

Laboratory Animals, ISSN 1758-1117, 0023-6772, Volume 58, 2, Pages 127-137, 10.1177/00236772231182511

Contributors

Lintrup, Kristine [1] Ipsen, David Højland 0000-0002-2065-8497 [1] Skat-Rørdam, Josephine 0000-0002-8160-9330 [1] Lykkesfeldt, Jens Ole Plum 0000-0002-6514-8407 [1] Tveden-Nyborg, Pernille 0000-0002-5574-5742 [1] Buelund, Lene Elisabeth 0000-0002-4730-4111 (Corresponding author) [1]

Affiliations

  1. [1] University of Copenhagen
    2. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD]

Abstract

Non-alcoholic fatty liver disease (NAFLD) and subsequent steatohepatitis (NASH) is the most common cause of liver disease and liver transplantation in humans. Affecting millions of patients worldwide, diagnosis relies on a biopsy, not without risk to the patient, and emphasises the need for improved diagnostic measures to determine and monitor disease progression. Despite intensive research, approved pharmacological treatment modalities are few, underlining that animal models with increased translational validity are important to advance preclinical drug development. This study validates the applicability of computed tomography (CT) as a non-invasive diagnostic tool for the assessment of liver steatosis in a guinea pig model of NAFLD/NASH. Guinea pigs with induced NAFLD or NASH were compared to healthy controls at two separate time points: week 16, serving as baseline measure, and week 25 to monitor disease progression over time. The animals were subsequently euthanised, and samples were collected to confirm disease stage. The data showed a strong negative correlation between liver triglycerides and Hounsfield unit (HU) values (R2 = 0.8157; p < 0.0001). A significant difference in histopathological scoring and HU values between grade 0 and more advanced stages of steatosis was recorded (p < 0.001), although the degree of liver fibrosis could not be accurately evaluated by differences in HU. In conclusion, the present study validates CT scanning for the determination of hepatic steatosis in guinea pigs, and it strongly supports the technique as a relevant non-invasive diagnostic tool in this species.

Keywords

CT, CT scan, HU values, Hounsfield, Hounsfield units, NAFLD/NASH, Nash, advanced stage, affecting millions, animal models, animals, application of computed tomography, applications, assessment, assessment of liver steatosis, baseline, baseline measurements, biopsy, cause, cause of liver disease, control, correlation, data, degree, degree of liver fibrosis, determination, development, diagnosis, diagnostic measures, diagnostic tool, disease, disease progression, disease stage, drug development, fatty liver disease, fibrosis, guinea, guinea pig model, guinea pigs, healthy controls, hepatic steatosis, histopathological scores, humans, induce non-alcoholic fatty liver disease, intensive research, liver, liver disease, liver fibrosis, liver steatosis, liver transplantation, liver triglycerides, measurements, millions, modalities, model, models of NAFLD/NASH, monitoring disease progression, negative correlation, non-alcoholic fatty liver disease, non-invasive diagnostic tool, patients, pharmacological treatment modalities, pigs, point, preclinical drug development, progression, research, risk, samples, scanning, scores, species, stage, stage of steatosis, steatohepatitis, steatosis, study, technique, time, time points, tomography, tools, translational validity, transplantation, treatment modalities, triglycerides, units, validity, values, weeks

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