Metabolic Dysfunction-Associated Steatotic Liver Disease Signs and Symptoms

Cập nhật: 12 March 2025
Được đánh giá bởi

Giới thiệu

Steatotic Liver Disease (SLD)

  • Overall term used to cover the different etiologies of steatosis
  • Patient usually presents asymptomatic but may describe vague right upper quadrant pain, fatigue and malaise   
  • Fatty liver is usually an incidental finding on abdominal imaging that reveals hepatic steatosis and laboratory study results of elevated liver enzymes   
    • Assessment of potential SLD etiology and for presence of advanced fibrosis through non-invasive tests should be done in individuals with an incidental finding of steatosis as this could identify the risk of liver-related and/or cardiovascular outcomes and appropriate care
  • Patient with persistent abnormal liver enzymes, with insulin resistance and/or metabolic syndrome risk factors should be screened for metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD)   
    • MASLD better reflects the pathophysiology and cardiometabolic implications of the disease compared to the term NAFLD   
      • MASLD is the term preferred by multi-society experts from 56 countries including the American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL) and Asian Pacific Association for the Study of the Liver (APASL) during a consensus survey conducted using modified Delphi process
    • Diagnosis is based on specific set of positive criteria regardless of alcohol consumption and does not require exclusion of other causes of chronic liver disease 

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

  • Considered as a hepatic manifestation of metabolic syndrome (obesity, type 2 diabetes mellitus [T2DM], insulin resistance, dyslipidemia and hypertension)   
    • Obesity and T2DM strongly impact the natural history of MASLD including progression to MASLD/metabolic dysfunction-associated steatohepatitis (MASH)-related advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC)
  • MASLD can progress to liver fibrosis and progressive liver disease over time including cirrhosis and HCC
    • Cirrhosis occurs in approximately 12% of MASLD patients    
    • Increased risk of progressive fibrosis and development of cirrhosis and its complications (eg hepatic encephalopathy, esophageal varices, ascites) is noted in males >50 years old, postmenopausal women and those with multiple cardiometabolic risk factors
  • May coexist with other liver disease such as alcohol-related liver disease (ALD), chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, primary biliary cholangitis and primary hemochromatosis  
  • Relevant comorbidities of MASLD include obesity, T2DM, insulin resistance, dyslipidemia, cardiovascular disease (CVD), atherosclerosis, kidney disease, obstructive sleep apnea (OSA) and polycystic ovary syndrome (PCOS)

Dịch tễ học

  • MASLD is the most common chronic liver disorder   
  • Becoming a serious health issue in many Asian countries  
  • Leading cause of liver cirrhosis and HCC   
  • Major cause of mortality in patients with MASLD is CVD
  • Prevalence is two times higher in males than in females   
    • Prevalence is increasing because of increasing prevalence of obesity and obesity-related diseases 
  • Global prevalence of MASLD in patients with T2DM is 55.5%

Sinh lý bệnh

  • MASLD results from multifactorial and complex factors including genetic, epigenetic and environmental factors 
    • Insulin resistance, which is the key metabolic dysfunction in MASLD, promotes de novo lipogenesis of the liver affecting micro- and macrovascular homeostasis leading to atherosclerosis  
      • Chronic hyperglycemia causes damage to the vascular endothelial cells, stimulates smooth muscle cell proliferation, enhances platelet activity, and induces production of reactive oxygen species (ROS) leading to accelerated atherogenesis  
    • Imbalance between triglyceride production in the liver and catabolism of non-esterifed fats which is dependent on oxidation in the mitochondria and export of triglycerides to very low-density lipoproteins (VLDL)  
    • Excessive fat accumulation in the liver may be due to lipolysis from adipose tissue, de novo lipogenesis, and excessive intake of fat and sugar from diet 
      • Expression of acetyl-coenzyme-A carboxylase (ACC1), the first enzyme in de novo lipogenesis, is decreased in MASLD patients and ACC1 is converted to malonyl-CoA, the accumulation of which inhibits carnitine palmitoyl transferase (CPT)-1 which is responsible for transporting fatty acids within the mitochondria and decreasing β oxidation 
    • Non-parenchymatous hepatic cells become dysfunctional and endothelial dysfunction results to increased recruitment of systemic myeloid lineage cells which induce and enhance inflammation and cell damage and as MASLD progresses, endothelial dysfunction worsens resulting to the development of complications related to hepatic inflammation and fibrosis, from hepatic microcirculation dysfunction to portal hypertension  
    • Production of excessive ROS resulting in hepatic inflammation and fibrosis through the activation of hepatic stellate cells  
      • Excessive production of ROS also results in oxidation of low-density lipoprotein (LDL)-cholesterol promoting transformation of macrophages into foam cells and leading to formation of atherosclerotic lesions and progression of atherosclerosis as a result of endothelial dysfunction and vascular smooth muscle cell proliferation  
    • Low-grade inflammation aggravates endothelial dysfunction, changes vascular tone, and promotes vascular plaque formation  

Signs and Symptoms

  • Patient presents with elevated serum aminotransferase level detected during health screening or as part of the investigation for another illness   

Extrahepatic Manifestations 

  • Associated with subclinical atherosclerosis as shown by increased carotid intima media thickness, coronary artery calcification score, arterial stiffness, and endothelial dysfunction 
  • Increased risk of fatal and/or non-fatal CV events with higher risk in patients with severe liver disease  
    • Evaluation for CVD risk is recommended for patients with MASLD because CVD is the most common cause of mortality in MASLD patients   
  • Patients with MASLD also have a higher risk of chronic kidney disease (CKD), T2DM, diabetic peripheral polyneuropathy and OSA

Yếu tố nguy cơ

  • Major risk factors include: 
    • Arterial hypertension  
    • Central obesity  
    • Dietary factors (eg high-calorie diets high in saturated fats and cholesterol, soft drinks high in fructose, processed foods)  
    • Dyslipidemia   
    • Insulin resistance  
    • Metabolic syndrome   
    • Overweight or obesity 
      • Associated with hepatic steatosis, hepatocyte injury, and liver inflammation and fibrosis 
    • Sarcopenia 
    • Sedentary lifestyle or occupation or low level of physical activity 
    • T2DM  
  • Other risk factors include:  
    • Epigenetic factors: MicroRNAs (miR), DNA methylation, histone modification   
    • Genetic predisposition: Patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), glucokinase regulator (GCKR),  glycerol-3-phosphate acyltransferase mitochondrial (GPAM), membrane-bound O-acyltransferase domain containing 7 (MBOAT7), hydroxysteroid 17-beta dehydrogenase-13 (HSD17B13), apolipoprotein E (APOE), mitochondrial amidoxime reducing component 1 (MTARC1)
    • Gut microbiota   
    • Hyperuricemia   
    • Hypopituitarism   
    • Hypothyroidism   
    • Personal or family history of T2DM, premature vascular disease, atherogenic dyslipidemia and high blood pressure (BP), fatty liver   
    • Polycythemia   
    • PCOS
    • Sleep apnea syndrome  
    • Jejunoileal bypass surgery
    • Highest risk in 40-65 years old
    • Higher risk in Hispanics and Asians while lower risk in African-Americans