Non-Alcoholic Fatty Liver Disease: A Treatment Review
Non-alcoholic fatty liver (NAFLD) is the most common chronic liver disease worldwide.1 It represents “the hepatic manifestation of the metabolic syndrome (MetS)” and “may progress from simple steatosis (ie, fat accumulation in ≥5% of hepatocytes) to necroinflammation and fibrosis, leading to non-alcoholic steatohepatitis (NASH) and, in some cases, to cirrhosis and even hepatocellular carcinoma.”2 NAFLD is associated with several cardiovascular (CV) risk factors, such as obesity, dyslipidemia, hyperglycemia, hypertension, and smoking, and is characterized by several forms of dyslipidemia, including atherogenic dyslipidemia, postprandial lipemia, and high-density lipoprotein (HDL) dysfunction.2 A recent article by Katsiki and colleagues2 reviews the associations between NAFLD, dyslipidemia, and vascular disease, particularly focusing on the role of treatment with lipid-lowering drugs.
Pathogenesis of NAFLD
The histological changes associated with NAFLD occur independently of alcohol abuse or other forms of chronic hepatic disease.3 Lipid droplets, consisting of excess fat, accumulate in the hepatocytes. The accumulation is caused by lipid abnormalities—eg, increased whole body lipolysis, liver free fatty acid (FFA) uptake, very low density lipoprotein (VLDL) synthesis and reduced FFA and triglyceride (TG) export. These abnormalities, in turn, lead to an induction of inflammatory and oxidative stress and abnormal adipokine production. An inflammatory cascade occurs. Hepatic phospholipid and bile acid homeostasis and gut microbiota are disrupted.2
Obesity and insulin resistance may contribute to the pathophysiologic process through insulin signaling inhibition, decreased glycogen synthesis, and induced gluconeogenesis. Additionally, NAFLD has been associated with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Additional CV risk factors include hypertension and cigarette smoking.2
Additional mechanisms connecting NAFLD with dyslipidemia are listed in Table 1. Conditions associated with cardiovascular and non-cardiac vascular disease risk in patients with NAFLD are listed in Table 2.
The American Association for the Study of Liver Diseases, the American College of Gastroenterology, and the American Gastroenterological Association published practice recommendations for the diagnosis and management of NAFLD, beginning with lifestyle interventions.4 Nutritional approaches recommended by the authors include a Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH). The authors also encourage aerobic and anaerobic exercise as well as nutritional therapy (eg, vitamins E and D, polyphenols, minerals, and long-chain n-3 polyunsaturated fatty acids).2 Additionally, weight reduction is recommended as the first-line therapeutic intervention for NAFLD.2