Role of Extracellular Vesicles in the Pathophysiology, Diagnosis and Tracking of Non-Alcoholic Fatty Liver Disease

Abstract

<jats:p>Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting approximately one-third of the global population. Most affected individuals experience only simple steatosis—an accumulation of fat in the liver—but a proportion of these patients will progress to the more severe form of the disease, non-alcoholic steatohepatitis (NASH), which enhances the risk of cirrhosis and hepatocellular carcinoma. Diagnostic approaches to NAFLD are currently limited in accuracy and efficiency; and liver biopsy remains the only reliable way to confirm NASH. This technique, however, is highly invasive and poses risks to patients. Hence, there is an increasing demand for improved minimally invasive diagnostic tools for screening at-risk individuals and identifying patients with more severe disease as well as those likely to progress to such stages. Recently, extracellular vesicles (EVs)—small membrane-bound particles released by virtually all cell types into circulation—have emerged as a rich potential source of biomarkers that can reflect liver function and pathological processes in NAFLD. Of particular interest to the diagnosis and tracking of NAFLD is the potential to extract microRNAs miR-122 and miR-192 from EVs circulating in blood, particularly when using an isolation technique that selectively captures hepatocyte-derived EVs.</jats:p>

A look to the future in non‐alcoholic fatty liver disease: Are glucagon‐like peptide‐1 analogues or sodium‐glucose co‐transporter‐2 inhibitors the answer?

“…8 There are several non-invasive methods to identify individuals with NAFLD (eg, NAFLD score, FIB-4 score, alanine transaminase [ALT]: aspartate transaminase [AST] ratio, AST:platelet ratio). There are problems, however, with these scores as they are largely based on blood test results, which have a poor predictive value, 9 and liver function tests, which poorly reflect liver damage. 10 Abdominal imaging and transient elastography can aid the diagnosis of steatosis and fibrosis.…”

“…10 Abdominal imaging and transient elastography can aid the diagnosis of steatosis and fibrosis. 9 Biomarkers such as cytokeratin-18, a protein released during hepatocyte death which correlates with liver dysfunction, have been studied in NAFLD. 9,10 However, the cytokeratin-18 level is raised in any form of liver damage and is therefore not specific to NAFLD.…”

“…9 Biomarkers such as cytokeratin-18, a protein released during hepatocyte death which correlates with liver dysfunction, have been studied in NAFLD. 9,10 However, the cytokeratin-18 level is raised in any form of liver damage and is therefore not specific to NAFLD. Adiponectin, which has a role in lipid and glucose metabolism by influencing insulin receptors, has also been suggested as a biomarker in NAFLD.…”

“…15,16 Although multifaceted, the key steps in the development and progression of NAFLD are the development of IR, 3,4 a high fat diet and obesity. 9 Obesity contributes to the pathophysiology by causing adipocyte hypertrophy and hypoxia, leading to macrophage influx and proinflammatory state. 16 Obesity, however, is not the sole, or indeed key contributory factor to the development and progression of NAFLD as it can also be seen in lean individuals.…”

“…17 These processes ultimately lead to a pro-inflammatory state and hepatocyte injury. 9 As a result of their shared aetiology, NAFLD is intrinsically linked with metabolic syndrome and type 2 diabetes (T2D 23 Interestingly, GLP-1 analogues reduce glucagon secretion and hepatic fat accumulation by blocking the endoplasmic reticulum stress response. 24 Indeed, the GLP-1 analogue liraglutide reduced postprandial triglyceride and apolipoprotein B48 elevations in people with T2D after a fat-rich meal.…”