Liver & intrahepatic bile ducts

Noninfectious hepatitis

Metabolic dysfunction associated steatotic liver disease (MASLD) / Metabolic dysfunction associated steatohepatitis (MASH)


Editorial Board Member: Kimberley J. Evason, M.D., Ph.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Yoshihiro Ikura, M.D.

Last author update: 21 April 2025
Last staff update: 21 April 2025

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PubMed Search: Metabolic dysfunction associated steatotic liver disease / Metabolic dysfunction associated steatohepatitis

Yoshihiro Ikura, M.D.
Page views in 2025 to date: 15,209
Cite this page: Ikura Y. Metabolic dysfunction associated steatotic liver disease (MASLD) / Metabolic dysfunction associated steatohepatitis (MASH). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverNASH.html. Accessed April 29th, 2025.
Definition / general
  • Metabolic dysfunction associated steatotic liver disease (MASLD) is hepatic steatosis generated in association with overweight / obesity, type 2 diabetes mellitus or other metabolic dysregulations (see Diagrams / tables) (Hepatology 2023;78:1966)
  • Metabolic dysfunction associated steatohepatitis (MASH) is an aggressive form of MASLD characterized by marked inflammatory damage and hepatocyte ballooning
Essential features
  • Macrovesicular hepatosteatosis accentuated on zone 3, potentially accompanying fibroinflammatory changes in metabolic patients
  • Morphologically, MASLD covers all forms of hepatic steatosis with or without inflammation / fibrosis
  • Histologic grade is assessed using a scoring system including steatosis, lobular inflammation and ballooning degeneration (Hepatology 2005;41:1313)
  • MASH is not the sole progressive form of MASLD (J Hepatol 2015;62:1148)
  • Patients are at risk for fibrosis, cirrhosis and hepatocellular carcinoma
  • Other liver diseases, such as autoimmune liver diseases, may be a complication (see Diagrams / tables) (Hepatology 2023;78:1966, World J Gastroenterol 2024;30:1949)
Terminology
  • As described above, metabolic dysfunction associated steatotic liver disease (MASLD) refers to any fatty liver disease caused by metabolic dysregulation and metabolic dysfunction associated steatohepatitis (MASH) refers to an aggressive form of the disease characterized by inflammation and ballooning in addition to steatosis (see Diagrams / tables)
  • Steatotic liver disease in moderate habitual drinkers with metabolic dysfunction is now classified as MASLD, while cases involving increased alcohol intake are referred to as metabolic dysfunction and alcohol related liver disease (MetALD) (see Diagrams / tables)
  • Nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction associated fatty liver disease (MAFLD) have been used as former nomenclatures of MASLD (J Hepatol 2020;73:202)
  • Cytoplasmic inclusions known as Mallory-Denk bodies (see Microscopic images) are also termed Mallory hyaline and intracytoplasmic hyaline
ICD coding
  • ICD-10: K76.0 - fatty (change of) liver, not elsewhere classified
Epidemiology
Pathophysiology
  • Hepatic manifestation of metabolic disorders
  • Oxidative stress and lipotoxicity are considered key factors in disease progression (Hepatology 2006;43:506, J Atheroscler Thromb 2009;16:893)
  • Genetic variants in patatin-like phospholipase domain containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), membrane bound O-acyltransferase domain containing 7 (MBOA7) and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) are known modifiers of MASLD (Clin Med (Lond) 2018;18:s54, J Hepatol 2018;68:268)
Etiology
Diagrams / tables

Images hosted on other servers:
Classification of steatotic liver disease

Classification of steatotic liver disease

MASLD and autoimmune liver diseases overlap

MASLD and autoimmune liver diseases overlap

Differential diagnosis of steatotic liver diseases

Differential diagnosis of steatotic liver diseases

Clinical features
Diagnosis
Radiology description
Radiology images

Images hosted on other servers:

Bright liver

Hypodensity on CT

Increased signal on T1 weighted MRI

MRI based fat content evaluation

Prognostic factors
Case reports
Treatment
  • Mainstay of therapy for MASLD is to treat the underlying metabolic abnormalities
  • While numerous clinical trials have been conducted, practical applications have been slow to emerge; however, in 2024, resmetirom received accelerated approval from the FDA for clinical use in MASLD (Drugs 2024;84:729)
Gross description
  • Swollen soft liver with yellowish-brown color
  • Surface of the affected liver becomes irregular with progression of fibrosis
  • Some cases show cirrhosis or hepatocellular carcinoma
Gross images

Contributed by Yoshihiro Ikura, M.D.
Diffuse fatty change of the liver

Diffuse fatty change of the liver

Frozen section description
  • Lipid stain methods (oil red O, Sudan black B, filipin, etc.) to detect liver fat can be performed on frozen sections
Frozen section images

Contributed by Yoshihiro Ikura, M.D.
Lipid droplets

Lipid droplets

Microscopic (histologic) description
  • Predominantly macrovesicular steatosis in ≥ 5% hepatocytes under low magnification (4x or lower) is a sole histologic requirement for diagnosis of MASLD
  • Disease severity is evaluated separately by grade of activity and stage of fibrosis
  • Activity grade is assessed according to nonalcoholic fatty liver disease activity score (NAS) using the sum of 3 components (total 0 - 8 points) (Hepatology 2005;41:1313)
    • Steatosis
      • 0: < 5%
      • 1: 5 - 33%
      • 2: 34 - 66%
      • 3: > 66%
    • Lobular inflammation
      • 0: none
      • 1: < 2 foci/20x field
      • 2: 2 - 4 foci/20x field
      • 3: > 4 foci/20x field
    • Ballooning degeneration
      • 0: none
      • 1: few
      • 2: many
  • Fibrosis stage is assessed into 5 levels (Hepatology 2005;41:1313)
    • Stage 0: none
    • Stage 1: perivenular (zone 3) fibrosis
    • Stage 2: perivenular + portal fibrosis
    • Stage 3: bridging fibrosis
    • Stage 4: cirrhosis
  • Other characteristic findings are Mallory-Denk bodies, glycogenated nuclei, giant mitochondria (megamitochondria) and lipogranuloma
  • Histologic changes of concomitant liver conditions may be seen (Hepatology 2023;78:1966, World J Gastroenterol 2024;30:1949)
  • In MASLD associated cirrhosis, steatotic hepatocytes may become depleted, resulting in a loss of visible steatosis; however, the term cryptogenic cirrhosis should not be used for this condition (J Hepatol 2020;73:202)
Microscopic (histologic) images

Contributed by Yoshihiro Ikura, M.D.
Zone 3 steatosis

Zone 3 steatosis

Lobular inflammation

Lobular inflammation

Hepatocellular ballooning and Mallory-Denk bodies

Hepatocellular ballooning and Mallory-Denk bodies

Mallory-Denk bodies (ubiquitin)

Mallory-Denk bodies (ubiquitin)


Hepatocellular ballooning (CK18)

Hepatocellular ballooning (CK18)

Perivenular fibrosis (trichrome)

Perivenular fibrosis (trichrome)

Glycogenated nuclei

Glycogenated nuclei

Giant mitochondria

Giant mitochondria


Lipogranuloma

Lipogranuloma

MASLD associated cirrhosis (trichrome)

MASLD associated cirrhosis (trichrome)

Positive stains
Negative stains
Sample pathology report
  • Liver, needle biopsy:
    • Moderate steatosis, consistent with metabolic dysfunction associated steatotic liver disease
    • NAS 6 points = steatosis 2 + inflammation 2 + ballooning 2
    • Stage 2 (perivenular + portal fibrosis), Kleiner-Brunt methodology
Differential diagnosis
Practice question #1

A 71 year old woman (nondrinker) presented with possible diagnosis of hepatocellular carcinoma and SLD with abdominal ultrasound. Percutaneous liver biopsy was performed for definitive diagnosis. The photomicrograph above shows nontumorous liver tissue (background). What information has the lowest priority for accurate pathologic diagnosis?

  1. Autoantibodies
  2. Genetic test results
  3. Medications
  4. Metabolic factors
  5. Virus markers
Practice answer #1
B. Genetic test results. Liver histology shows inflammatory damage associated with lymphoid follicle formation and steatosis. These morphological features are common findings in both autoimmune hepatitis and chronic hepatitis C. Indeed, this case was positive for hepatitis C virus genotype 3. ALD, MASLD and drug induced SLD should always be investigated as possible comorbid pathological mechanisms (Clin Pract 2024;14:2542). Some genetic disorders cause SLD but the incidence is very low. Answer A is incorrect because autoimmune diseases should be ruled out. Answer C is incorrect because steatosis is relatively common in drug induced liver injury. Answer E is incorrect because chronic hepatitis C is most likely in cases with such histology. Answer D is incorrect because MASLD is the most common type of SLD.

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Reference: Metabolic dysfunction associated steatotic liver disease (MASLD) / Metabolic dysfunction associated steatohepatitis (MASH)
Practice question #2

Which of the following is correct concerning the intracellular inclusion seen in the figure above (arrow)?

  1. Actin positive
  2. CK18 negative
  3. Related to viral infection
  4. Specific for alcoholic liver damage
  5. Ubiquitin positive
Practice answer #2
E. Ubiquitin positive. The inclusion shown is a Mallory-Denk body. It is a ubiquitinated aggregate of keratin filament that occurs in ballooned hepatocytes. Answer A is incorrect because the intracellular inclusion is negative for actin. Answer B is incorrect because the intracellular inclusion is positive for CK18. Answer C is incorrect because the intracellular inclusion is not related to viral infection. Answer D is incorrect because the intracellular inclusion is not restricted to alcohol related liver injury.

Comment Here

Reference: Metabolic dysfunction associated steatotic liver disease (MASLD) / Metabolic dysfunction associated steatohepatitis (MASH)
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