Nonalcoholic fatty liver disease (NAFLD) has become the leading chronic liver disease worldwide, with a global prevalence of 20–25%. The early stage of NAFLD is simple hepatic steatosis, which is often benign and reversible but may progress to nonalcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis, and liver cancer. The economic toll of this expanding disease prevalence will increase along with the number of individuals who have cirrhosis or end-stage liver disease that requires liver transplantation. In addition, patients diagnosed with NAFLD have a considerably higher risk of developing cardiovascular disease, diabetes, and other metabolic illnesses.
The major cause of death in those with NAFLD is cardiovascular disease. The development of NAFLD has been linked to obesity, insulin resistance, nutrition, genetic predisposition, the microbiome, and metabolic status; nevertheless, the key mechanisms that cause NAFLD are still a mystery. Genetic studies have revealed at least five genes linked to NAFLD risk, including patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), glucokinase regulator (GCKR), membrane bound O-acyltransferase domain-containing 7 (MBOAT7) and hydroxysteroid 17β- dehydrogenase (HSD17B13). All these genes were mainly involved in lipid metabolism, indicating the critical role of lipids in the pathology of NAFLD.
Studies have revealed that disorders of cholesterol, triglyceride and phospholipid metabolism contribute to the development of NAFLD. Inhibition of lipid synthesis by inactivation of diacylglycerol acyltransferase enzymes 2 (DGAT2) or monoacylglycerol acyltransferase 2 (MGAT2) is a promising therapeutic opportunity. However, no drugs currently have clear clinical benefits. Therefore, more research on the pathophysiology and treatment of NAFLD is helpful for the discovery and development of new pharmaceuticals. NAFLD patients might benefit from early identification and treatment before the development of effective medications. Liver biopsies are the gold standard for the diagnosis of NAFLD; ultrasound or magnetic resonance imaging (MRI) are also widely used to evaluate hepatic lipid contents; however, there is no effective method to screen whether individuals have NAFLD or are at high risk. There is an urgent need for noninvasive methods for early NAFLD diagnosis. We encourage submissions on all aspects of this timely and dynamic issue on this topic, from original research to reviews and discussions.
Keywords:
NAFLD, NASH, Lipid metabolism, Noninvasive methods, Cardiovascular disease, Early diagnosis, Therapeutic strategy
Topics:
• Early detection of NAFLD
• Current therapy for NAFLD
• New targets for treating NAFLD
• Treatment to reduce cardiovascular risks associated with NAFLD
• Translational implications and challenges of lipid metabolism in NAFLD
Questions to be answered:
• Which type of lipid accumulation is the key driver for the development of NAFLD?
• Are there any new methods for the early detection of NAFLD?
• What is the mechanistic link between NAFLD and cardiovascular disease?
• What are the challenges in NAFLD drug development?
• What are the dynamic changes in the lipid profile in the development of NAFLD?
