Hypertension diabetes atherosclerosis and NASH Cause or consequence

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

NAFLD • Non-alcoholic fatty liver disease (NAFLD) defines the hepatic consequences of overnutrition 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

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

Worldwide estimated prevalence of NAFLD

65%

• People with T 2 DM 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).

On the other hand • NAFLD is associated with an approximate doubling in the risk of incident T 2 DM, 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.

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

Pathophysiology

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

IR in NAFLD Accumulation of DAG molecules

HTN & NAFLD • Up to 50% of hypertensive patients have NAFLD. Qia LY, et al. Medicine 2016; 95: e 4293.

NAFLD & HTN • A prospective 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 .

EASL guidelines 2016

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.

Pathophysiology • In IR states, insulin activates the mitogenactivated protein kinase pathway that induces vasoconstriction. • Altered adipokine profile (e. g. hypoadiponectinaemia and hyperleptinaemia) in NAFLD may also lead to HTN development via chronic sympathoactivation and induction of chronic inflammation. • NAFLD, possibly via dyslipidaemia and hyperuricaemia is also associated with endothelial dysfunction.

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

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

Conclusions • NAFLD is a multisystem disease, which plays an important role in the development of atherosclerosis/CVD & T 2 DM by disrupting the regulation of multiple metabolic and inflammatory pathways. • The link between NAFLD/ NASH and HTN, T 2 DM & atherosclerosis/CVD is more complex than previously believed.

Conclusions • T 2 DM 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, T 2 DM and CVD events, more careful surveillance of patients with NAFLD is highly recommended.