The following are key points to remember from this review on nonalcoholic fatty liver disease and the heart:

1. This review provides new data demonstrating the relationship between cardiometabolic risk factors, coronary heart and other cardiovascular diseases, and nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease (NAFLD) encompasses a continuum of liver disease progressing from steatosis defined as >5% of fatty infiltration of hepatocytes to nonalcoholic steatohepatitis (NASH) (fatty infiltration plus necroinflammation), to fibrosis, and then finally to cirrhosis.
2. NALFD is important worldwide with an estimated prevalence of 25% and US prevalence based the National Health and Nutrition Examination Survey (NHANES) of about 30%. NASH is now second to hepatitis C virus as the most common etiology of liver disease among those awaiting liver transplant. The diagnosis requires the exclusion of significant alcohol consumption and other etiologies of hepatic steatosis, and other coexisting causes of chronic liver disease. Routine hepatic ultrasound screening is not recommended but should be considered in obesity, features of the metabolic syndrome, and diabetes with elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST).
3. Liver biopsy is necessary to accurately assess the degree of inflammation, cell injury, and degree of fibrosis or fibrosis stage. However, imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging are safer and less expensive without significantly sacrificing sensitivity and specificity.
4. Each of the components of the metabolic syndrome are risk factors for coronary heart disease (CHD) and other arterial sites and NAFLD. Conversely, NAFLD is associated with insulin resistance and type 2 diabetes mellitus (T2DM) and the atherogenic lipid phenotype with high triglycerides, increase in very low-density lipoprotein (VLDL) remnant particles and small LDL particles, each of which is highly atherogenic. Because of the shared cardiometabolic plasma analytes, the degree to which NAFLD and NASH contribute to atherosclerotic cardiovascular disease (ASCVD) is not clear, not surprising considering that the prevalence of NAFLD in T2DM is >70%. However, NAFLD is associated with increase in carotid intima-media thickness and coronary artery calcification independent of the CV risk factors.
5. Nearly all the pathobiologic processes in the development of CVD are found in NAFLD prior to the development of CHD and diabetes. This includes increase in asymmetric dimethylarginine (ADMA), the inhibitor of nitric oxide synthase, resulting in endothelial dysfunction, increase in homocysteine and prothrombotic factors, platelet activation, and increase in the markers of inflammation associated with plaque formation and instability. The increase in plasma and hepatic free fatty acids with hepatic insulin resistance and increase in glucose production leads to systemic insulin resistance, oxidative stress, altered lipid metabolism, and worsening systemic inflammation with interleukin (IL)-6, high-sensitivity C-reactive protein, tumor necrosis factor α, IL1β, and vascular growth factors.
6. In addition to CHD, NAFLD is associated with an increase in aortic valve sclerosis, mitral annular calcification, atrial fibrillation, ventricular arrhythmias, and abnormal early diastolic relaxation and increase in left ventricular filling pressures. These findings are independent of and additive to prevalence in diabetics. NAFLD is also associated with an increase in epicardial fat, which is associated with an increase in coronary artery calcification.
7. Treatment and prevention of NAFLD is similar to that of diabetes, the metabolic syndrome, and risk factors for ASCVD. Initial approach is lifestyle modification with target of regular exercise with weight loss to optimal weight by diet rich in fruits, vegetables, fiber, and a low glycemic index and limited saturated fats. Weight loss of 7-10% is associated with a significant reduction in NASH parameters. Even a small amount of alcohol may be harmful.
8. Patients in whom NAFLD is diagnosed should be assessed for the metabolic syndrome. Those who are obese should be referred to weight loss programs and considered for bariatric surgery. The marked weight loss associated with bariatric surgery can lead to significant improvement in both histology and hepatic transaminases. Diabetes should be treated with metformin for glycemic control, insulin resistance, and weight loss, although it does not affect NAFLD/NASH biopsy findings. Consideration for the second agent should be given to a glucagon-like peptide analogue (GLP-1 agonist) or pioglitazone in the absence of congestive heart failure. Each has been shown to reduce hepatic steatosis.
9. The dyslipidemia should be treated with a statin and hypertension with an angiotensin-receptor blocker, which has been shown to decrease liver enzymes. In the absence of the metabolic syndrome, there is evidence of benefit in NAFLD/NASH for statins and vitamin E. Statins reduced CV events in a clinical trial in NAFLD and reduced NAFLD and fibrosis score with marked improvement in biopsies. Oxidative stress, one of the mechanisms of liver disease progression, may be reduced with vitamin E, which in trials showed improvement in steatosis but not fibrosis.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Echocardiography/Ultrasound, Magnetic Resonance Imaging, Diet, Hypertension

Keywords: Angiotensin Receptor Antagonists, Atherosclerosis, Bariatric Surgery, Carotid Intima-Media Thickness, Coronary Disease, Diabetes Mellitus, Type 2, Diet, Dyslipidemias, Glucagon-Like Peptide 1, Hepatocytes, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Fatty Liver, Inflammation, Lipids, Liver Cirrhosis, Liver Transplantation, Magnetic Resonance Imaging, Metabolic Syndrome, Obesity, Primary Prevention, Risk Factors, Tomography, Triglycerides, Ultrasonography, Vitamin E, Weight Loss, Weight Reduction Programs

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