Metabolic-associated fatty liver disease: a selective review of pathogenesis, diagnostic approaches, and therapeutic strategies

Abstract

Background: Metabolic associated fatty liver disease (MAFLD) is a novel terminology introduced in 2020 to provide a more accurate description of fatty liver disease associated with metabolic dysfunction. It replaces the outdated term nonalcoholic fatty liver disease (NAFLD) and aims to improve diagnostic criteria and tailored treatment strategies for the disease. NAFLD, the most prevalent liver disease in western industrialized nations, has been steadily increasing in prevalence and is associated with serious complications such as cirrhosis and hepatocellular carcinoma. It is also linked to insulin resistance syndrome and cardiovascular diseases. However, current studies on NAFLD have limitations in meeting necessary histological endpoints.

Objective: This literature review aims to consolidate recent knowledge and discoveries concerning MAFLD, integrating the diverse aspects of the disease. Specifically, it focuses on analyzing the diagnostic criteria for MAFLD, differentiating it from NAFLD and alcoholic fatty liver disease (AFLD), and exploring the epidemiology, clinical manifestations, pathogenesis, and management approaches associated with MAFLD. The review also explores the associations between MAFLD and other conditions. It discusses the heightened mortality risk associated with MAFLD and its link to chronic kidney disease (CKD), showing that MAFLD exhibits enhanced diagnostic accuracy for identifying patients with CKD compared to NAFLD. The association between MAFLD and incident/prevalent CKD is supported by cohort studies and meta-analyses.

Conclusion: This literature review highlights the importance of MAFLD as a distinct terminology for fatty liver disease associated with metabolic dysfunction. The review provides insights into the diagnostic criteria, associations with CKD, and management approaches for MAFLD. Further research is needed to develop more accurate diagnostic tools for advanced fibrosis in MAFLD and to explore the underlying mechanisms linking MAFLD with other conditions. This review serves as a valuable resource for researchers and healthcare professionals seeking a comprehensive understanding of MAFLD.

Keywords: clinical manifestations; diagnostic criteria; epidemiology; hepatic steatosis; metabolic associated fatty liver disease (MAFLD); non-alcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH); pathogenesis.

Figure 1

Overview of glucose metabolism in MAFLD. ER, Endoplasmic reticulum; DNL, De novo lipogenesis; AMP, Adenosine monophosphate.

Figure 2

Overview of fat metabolism in MAFLD: Green arrow = Increase expression in MAFLD, Red arrow = Decrease expression in MAFLD. 1. Excessive lipid uptake: Due to increase expression of FABP1, FATP2, FATP5, and CD36 resulting hepatic steatosis. 2. De novo lipogenesis: Overexpression of SREBP1c and down regulation of ChREBP result in upregulation of key enzymes in de novo lipogenesis resulting in hepatic lipid accumulation. 3. β-Oxidation of fatty acids: Reactive oxygen species produced due to increased ω-oxidation due to fatty acid oxidation inhibits the protective effects of PPARα leading to marked steatosis and inflammation. 4. Export of hepatic lipids: Due to excessive lipid intake, endoplasmic reticulum stress develops leading to decrease in ApoB100 and increase in steatosis. FABP1, Fatty acid binding protein 1; FATP2/5, fatty acid transport proteins 2/5; CD36, cluster of differentiation 36; ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase; SCD1, stearoyl-CoA desaturase-1; SREBP1c, sterol regulatory element-binding protein 1c; ChREBP, carbohydrate regulatory element-binding protein; MTTP, microsomal triglyceride transfer protein, ApoB100.