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Review Article Open Access
Volume 5 | Issue 1 | DOI: https://doi.org/10.46439/toxicology.5.022

Conceptualizing the use of the clinical index of liver fibrosis, FIB-4 index, in in vivo preclinical toxicological studies

  • 1Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Science, Kwame Nkrumah University of Science and Technology, Ghana
+ Affiliations - Affiliations

Corresponding Author

Kwesi Boadu Mensah, kbmensah.pharm@knust.edu.gh

Received Date: July 07, 2023

Accepted Date: July 26, 2023

Abstract

Background: Evaluation of the effects of chemicals on the liver in vivo, is an essential part of drug development. Here, it is hypothesized that a clinical index of liver fibrosis i.e. FIB-4 could be used as a simple, objective tool in preclinical in vivo studies for detection of hepato-active chemicals. The aim is to determine the sensitivity, specificity, and applicability of FIB-4 index in preclinical hepatic studies.

Method: Online research databases were searched to identify published safety pharmacological/toxicological studies with tabulated hepatograms and hematograms from 2008-2019. The relationship between the parameters used in computing Liver Fibrosis-4 index (FIB-4) were analyzed by linear regression. The sensitivity and specificity of FIB-4 index in preclinical hepatic studies were estimated using Area Under the Receiver Operating Characteristic curve (AUROC).

Results: Twenty five (25) published preclinical safety pharmacological/toxicological studies were selected. In the preclinical studies, the relationship between FIB-4 index and its independent variables was linear. This relationship was independent of the hepatotoxicant, or the experimental animal used. Using the Run’s test, none of the studies deviated from linearity. For sensitivity and specificity, Area Under the Receiver Operating Characteristic Curve (AUROC) was 0.9698 ± 0.008989 (95% Cl 0.9522 to 0.9874 at p < 0.0001 ****). The separability or discriminatory performance between hepatotoxic and hepatoprotective substances was 0.5959 ± 0.03899 (95% Cl 0.5194 to 0.6723 p=0.01542). FIB-4 index of the naïve/sham/ vehicle control treated animals was less than that of the hepatotoxicant treated animals. Hepatoprotective chemicals exhibit FIB-4 index approximately to or less than that of the naive/vehicle /sham treated animals. The ratio of FIB-4 index of toxicant treated to FIB-4 of the naïve/sham/ vehicle control treated animals was greater than 1. Hepatotoxicity also correlated with decreased platelet count.

Conclusion: FIB-4 index is a simple, sensitive, objective tool that can be used in preclinical hepatic toxicological/ safety pharmacology studies as an auxiliary and complimentary tool to aid in detection of hepatoactive substances.

Keywords

Hepatotoxicity, Hepatoprotective, Animal models, Liver damage, Carbon tetrachloride, Paracetamol

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