Metabolic dysfunction-associated steatotic liver disease

Last updated: November 13, 2023

Summarytoggle arrow icon

Metabolic dysfunction-associated steatotic liver disease (MASLD), is the accumulation of excess fat in hepatocytes in individuals with at least one cardiometabolic risk factor (e.g., hypertension, impaired glucose tolerance) in the absence of an alternative cause (e.g., heavy alcohol use, drug-induced liver injury). MASLD was previously known as nonalcoholic fatty liver disease. It is highly prevalent in patients with type 2 diabetes mellitus (T2DM), obesity, and/or metabolic syndrome. MASLD is usually asymptomatic and is a diagnosis of exclusion. Diagnostic findings may include hepatic steatosis on imaging and elevated transaminases. Patients with MASLD should be assessed for advanced liver fibrosis using a combination of laboratory-based noninvasive testing, such as the FIB-4, and vibration-controlled transient elastography. Metabolic dysfunction-associated steatohepatitis (MASH) is a subtype of MASLD characterized by chronic hepatocyte inflammation and damage due to lipid accumulation and is associated with a higher risk of progression to liver fibrosis and cirrhosis. MASH was previously known as nonalcoholic steatohepatitis (NASH). Biopsy may be indicated if there is diagnostic uncertainty. Management focuses on the prevention and treatment of associated metabolic conditions.

Definitiontoggle arrow icon

The nomenclature for steatotic liver disease was updated by international liver disease societies in June 2023. [1]

Epidemiologytoggle arrow icon

  • Global prevalence in the general adult population
    • MASLD: 25–30% [2][3]
    • MASH: 12–14% [2]
  • Prevalence in US patients with T2DM
    • MASLD: ∼ 70% [2]
    • MASH: 30–40% [2]

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

MASLD is a multifactorial disease with metabolic and genetic components. [2]

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

Diagnosticstoggle arrow icon

Approach [2][3][4]

It is only possible to distinguish MASLD from alcohol-associated fatty liver disease using patient history.

Initial studies

Laboratory studies [4]

There is often more ALT than AST (AST/ALT ratio < 1) when Lipids infiltrate the Liver.

Abdominal ultrasound [5]

Transaminase levels and abdominal ultrasound findings can be normal even in patients with advanced MASH and/or liver fibrosis and therefore should not be used to exclude advanced liver disease. [2]

Evaluation for advanced liver fibrosis [2][4]

All patients with suspected or confirmed MASLD should be evaluated for liver fibrosis.

Liver biopsy [3][4]

  • Indication: diagnostic uncertainty after noninvasive testing and imaging
  • Supportive findings for MASLD: hepatocellular lipid accumulation, mostly macrovesicular
  • Additional findings in MASH

Managementtoggle arrow icon

General principles

  • Currently, there are no curative treatments for MASLD.
  • Management is focused on the prevention and treatment of associated metabolic conditions.
  • Provide multidisciplinary care (e.g., involve the primary care physician, endocrinologist, hepatologist, and dietitian).
  • Refer to hepatology for:

Nonpharmacological management [2][3][4]

Pharmacological management [2][3]

Consider the following medications in consultation with a specialist (e.g., hepatologist) to reduce hepatic steatosis and/or steatohepatitis:

There are currently no FDA-approved medications for the treatment of MASLD.

Monitoring for liver fibrosis [2][3][4]

Reevaluate all patients with MASLD or cardiometabolic risk factors for MASLD for advanced liver fibrosis using noninvasive testing, e.g., the FIB-4 score.

Differential diagnosestoggle arrow icon

Complicationstoggle arrow icon

We list the most important complications. The selection is not exhaustive.

Prognosistoggle arrow icon

Referencestoggle arrow icon

  1. Rinella ME, Lazarus JV, Ratziu V, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023; Publish Ahead of Print.doi: 10.1097/hep.0000000000000520 . | Open in Read by QxMD
  2. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023; 77 (5): p.1797-1835.doi: 10.1097/hep.0000000000000323 . | Open in Read by QxMD
  3. Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings. Endocr Pract. 2022; 28 (5): p.528-562.doi: 10.1016/j.eprac.2022.03.010 . | Open in Read by QxMD
  4. Kanwal F, Shubrook JH, Adams LA, et al. Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2021; 161 (5): p.1657-1669.doi: 10.1053/j.gastro.2021.07.049 . | Open in Read by QxMD
  5. Hamer OW, Aguirre DA, Casola G, Lavine JE, Woenckhaus M, Sirlin CB. Fatty Liver: Imaging Patterns and Pitfalls. RadioGraphics. 2006; 26 (6): p.1637-1653.doi: 10.1148/rg.266065004 . | Open in Read by QxMD
  6. Latva-Rasku A, Honka MJ, Kullberg J, et al. The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients. Diabetes Care. 2019; 42 (5): p.931-937.doi: 10.2337/dc18-1569 . | Open in Read by QxMD
  7. Kuchay MS, Krishan S, Mishra SK, et al. Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial). Diabetes Care. 2018; 41 (8): p.1801-1808.doi: 10.2337/dc18-0165 . | Open in Read by QxMD
  8. Gastaldelli A, Cusi K, Fernández Landó L, Bray R, Brouwers B, Rodríguez Á. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. The Lancet Diabetes Endocrinol. 2022; 10 (6): p.393-406.doi: 10.1016/s2213-8587(22)00070-5 . | Open in Read by QxMD

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