Abstract

Background: The association between the severity of coronary atherosclerosis and histopathologic findings in patients with non-alcoholic fatty liver disease (NAFLD) is not entirely understood. Considering the gold standard method, this study evaluates the histopathologic association between the severity of NAFLD and the grades of coronary atherosclerosis.
Methods: In this descriptive-analytical study, data from 205 cadavers who were referred to an Iranian (Tabriz) forensic medicine organization between 2015 and 2017 and underwent simultaneous liver and coronary artery biopsies were examined. Finally, 168 cases were entered based on the inclusion criteria. First, pathological slides of these cadavers were extracted from the forensic medicine archive and re-examined. Then, the selected cases’ blocks were extracted from the tissue block bank, and again, after preparing a new slide, they were stained with trichrome for accurate estimation of liver fibrosis.
Results: The assessment of NAFLD histological status in the studied cases revealed that 75.6% of the cases were classified as severity I, 18.4% as severity II, and 6% as severity III. Most cases with coronary atherosclerosis were classified as American Heart Association staging (AHA), type V (19.6%), and normal (19.6%). There was no statistically significant relationship between the severity of simple steatosis, steatohepatitis, and NAFLD, with coronary atherosclerosis. In subjects with higher severity of coronary atherosclerosis, the liver fibrosis rate is also higher, but no statistically significant difference was observed.
Conclusion: The present study revealed no significant histopathological association between NAFLD and coronary artery atherosclerosis grade.

Keywords: Non-alcoholic fatty liver disease NAFLD Coronary atherosclerosis Histology Cardiovascular diseases References

1. Younossi, Z., et al., Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology, 2019. 69(6): p. 2672-2682.
2. Brouwers, M.C., et al., Non-alcoholic fatty liver disease and cardiovascular disease: assessing the evidence for causality. Diabetologia, 2020. 63(2): p. 253-260.
3. Wolf, D. and K. Ley, Immunity and inflammation in atherosclerosis. Circulation research, 2019. 124(2): p. 315-327.
4. De Gaetano, M., et al., M1-and M2-type macrophage responses are predictive of adverse outcomes in human atherosclerosis. Frontiers in immunology, 2016. 7: p. 275.
5. G Athyros, V., et al., Treating heart failure with preserved ejection fraction related to arterial stiffness. Can we kill two birds with one stone? Current Vascular Pharmacology, 2015. 13(3): p. 368-380.
6. Francque, S.M., D. Van Der Graaff, and W.J. Kwanten, Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications. Journal of hepatology, 2016. 65(2): p. 425-443.
7. Kinner, S., S.B. Reeder, and T. Yokoo, Quantitative imaging biomarkers of NAFLD. Digestive diseases and sciences, 2016. 61(5): p. 1337-1347.
8. Vanni, E., et al., From the metabolic syndrome to NAFLD or vice versa? Digestive and liver Disease, 2010. 42(5): p. 320-330.
9. Mendler, M.H., G. Kanel, and S. Govindarajan, Proposal for a histological scoring and grading system for non‐alcoholic fatty liver disease. Liver International, 2005. 25(2): p. 294-304.
10. Majdouline, Y., et al., Endovascular shear strain elastography for the detection and characterization of the severity of atherosclerotic plaques: In vitro validation and in vivo evaluation. Ultrasound in medicine & biology, 2014. 40(5): p. 890-903.
11. Loria, P., A. Lonardo, and G. Targher, Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis. Clinical science, 2008. 115(1): p. 1-12.
12. Jaruvongvanich, V., et al., Nonalcoholic fatty liver disease is associated with coronary artery calcification: a systematic review and meta-analysis. Digestive and Liver Disease, 2016. 48(12): p. 1410-1417.
13. Kim, D., et al., Nonalcoholic fatty liver disease is associated with coronary artery calcification. Hepatology, 2012. 56(2): p. 605-613.
14. Sinn, D.H., et al., Non-alcoholic fatty liver disease and progression of coronary artery calcium score: a retrospective cohort study. Gut, 2017. 66(2): p. 323-329.
15. Younossi, Z.M., et al., Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver‐related mortality. Hepatology, 2011. 53(6): p. 1874-1882.
16. Younossi, Z.M., et al., The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology, 2016. 64(5): p. 1577-1586.
17. Lozano, R., et al., Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. The lancet, 2012. 380(9859): p. 2095-2128.
18. Bonci, E., et al., Association of nonalcoholic fatty liver disease with subclinical cardiovascular changes: a systematic review and meta-analysis. BioMed research international, 2015. 2015.
19. Alkhouri, N., et al., The inflamed liver and atherosclerosis: a link between histologic severity of nonalcoholic fatty liver disease and increased cardiovascular risk. Digestive diseases and sciences, 2010. 55(9): p. 2644-2650.
20. Kim, M.K., et al., Association between nonalcoholic fatty liver disease and coronary artery calcification in postmenopausal women. Menopause (New York, NY), 2015. 22(12): p. 1323.
21. Chen, C.-H., et al., Association between nonalcoholic fatty liver disease and coronary artery calcification. Digestive diseases and sciences, 2010. 55(6): p. 1752-1760.
22. Biddinger, S.B., et al., Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell metabolism, 2008. 7(2): p. 125-134.
23. Guillén, N., et al., Squalene in a sex-dependent manner modulates atherosclerotic lesion which correlates with hepatic fat content in apoE-knockout male mice. Atherosclerosis, 2008. 197(1): p. 72-83.
24. Arbonés-Mainar, J.M., et al., Accelerated atherosclerosis in apolipoprotein E-deficient mice fed Western diets containing palm oil compared with extra virgin olive oils: a role for small, dense high-density lipoproteins. Atherosclerosis, 2007. 194(2): p. 372-382.
25. Dai, W., Z. Zhang, and S. Zhao, The risk of type 2 diabetes and coronary artery disease in non-obese patients with non-alcoholic fatty liver disease: a cohort study. Frontiers in Cardiovascular Medicine, 2021. 8.
26. Kirby, R.S. and D. Halegoua‐DeMarzio, Coronary artery disease and non‐alcoholic fatty liver disease: Clinical correlation using computed tomography coronary calcium scans. JGH Open, 2021. 5(3): p. 390-395.
27. Doumas, M., et al., The role of statins in the management of nonalcoholic fatty liver disease. Current pharmaceutical design, 2018. 24(38): p. 4587-4592.