Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence?

1. Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence? Dr. FathAlla Sidkey Mohamed Prof. of Hepatology HPB Unit, Internal Medicine Department Alexandria University

2. NAFLD • Non-alcoholic fatty liver disease (NAFLD) defines the hepatic consequences of over-nutrition in individuals without secondary causes of hepatic steatosis. • Includes a spectrum of pathologic conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), with or without cirrhosis and hepatocellular carcinoma (HCC). Dig Liver Dis 2017;49:471–483

3. NAFLD • NAFLD is viewed as the hepatic event of the metabolic syndrome (MetS). • MetS and its individual components predict the development and progression of NAFLD;on the other hand, NAFLD is a precursor for the future development of MetS components. Dig Liver Dis 2017;49:471–483

4. Worldwide estimated prevalence of NAFLD

6. 65%

7. People with T2DM are at high risk of developing NAFLD, and a twofold to fourfold higher risk of developing serious liver-related complications (cirrhosis, liver failure and HCC).

8. On the other hand • NAFLD is associated with an approximate doubling in the risk of incident T2DM, independently of overweight/obesity and other common risk factors. This association is ameliorated with improvement or resolution of NAFLD over time. • Ballestri S, et al. J Gastroenterol Hepatol 2016;31:936–44.

9. EASL guidelines 2016 J Hepatol 2016;64:1388–1402.

10. Pathophysiology

11. Pathophysiology Williams KH, et al. Endocrine Reviews, 2013, 34(1):84–129.

12. IR in NAFLD Accumulation of DAG molecules

13. HTN & NAFLD • Up to 50% of hypertensive patients have NAFLD. QiaLY, et al. Medicine 2016;95:e4293.

14. NAFLD & HTN • Aprospective study of Chinese normotensive individuals showed that imaging-diagnosed NAFLD was also a determinant of faster progression of arterial stiffness,which is an early risk marker of HTN. Zheng X, et al. J Clin Hypertens 2015;17:582–91.

15. EASL guidelines 2016

16. Pathophysiology • Specific genetic polymorphisms encoding angiotensinogen are more common in patients with NAFLD than in control subjects, • Systemic IR and chronic inflammation in NAFLD may lead to the development of HTN. possibly via induction of nuclear factor (NF)-κB and activation of the sympathetic nervous system.

17. Pathophysiology • In IR states, insulin activates the mitogen-activated protein kinase pathway that induces vasoconstriction. • Altered adipokine profile (e.g. hypoadiponecti- naemia and hyperleptinaemia) in NAFLD may also lead to HTN development via chronic sympatho- activation and induction of chronic inflammation. • NAFLD, possibly via dyslipidaemia and hyper- uricaemiais also associated with endothelial dysfunction.

18. NASH and atherosclerosis are two aspects of a shared disease V. Bieghs et al. Atherosclerosis 220 (2012) 287–93

19. NAFLD/NASH & atherosclerosis: “Tale of 2 pathways” Lonardo A, et al. J hepatol, 2018 (68): 335–52

20. Conclusions • NAFLD is a multisystem disease, which plays an important role in the development of atherosclerosis/CVD& T2DM by disrupting the regulation of multiple metabolic and inflammatory pathways. • The link between NAFLD/ NASH and HTN, T2DM & atherosclerosis/CVD is more complex than previously believed.

21. Conclusions • T2DM and, to a lesser extent, HTN are among the strongest clinical risk factors for the progression of NAFLD. • Because of the strong link between NAFLD and the risk of HTN, T2DM and CVD events, more careful surveillance of patients with NAFLD is highly recommended.