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Non-alcoholic fatty liver disease other diagnostic studies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2] Parth Vikram Singh, MBBS[3]

Overview

Liver biopsy may be helpful in the diagnosis of non-alcoholic fatty liver disease. Findings on biopsy include macrovesicular steatosis, inflammation, ballooning degeneration, zone 3 perivenular/periportal/perisinusoidal fibrosis and, finally, mallory bodies.

Other Diagnostic Studies

  • Liver biopsy is considered as a gold-standard for diagnosing, grading, and staging NAFLD, but it is invasive, costly, and associated with rare acute bleeding. Liver biopsy is not typically required to diagnose MASLD, but may be useful when the etiology of liver disease is uncertain, when noninvasive tests are inconclusive, or when MASLD coexists with other liver diseases such as autoimmune hepatitis or viral hepatitis.
  • Invasive test
  • Associated with significant bleeding risk in patients with clotting abnormalities due to hepatic disease.

Complications

Complications of liver biopsy are rare but include

Findings

Classically, biopsy reveals:[1][2]

Interpretation

Histo-pathological classification

Depending on degree of steatosis, necroinflammatory activity, and degree of fibrosis non-alcoholic liver disease can be classified as follows:

Grading

NAFLD activity score is employed for grading steatohepatitis of NASH. NAS represents the sum of scores for steatosis, lobular inflammation, and ballooning.[4]

Component Range Score
Steatosis <5% 0
5-33% 1
34-66% 2
>66% 3
Lobular Inflammation None 0
<2 focci 1
2-4 2
>4 3
Hepatocyte Balloning None 0
Few ballooned cells 1
Many ballooned cells 2
Interpretation 0-2 Non-diagnostic
3-4 Borderline
5-8 Diagnostic

Staging

Based on the degree of fibrosis on biospy NASH can be classified into 5 stages.[5]

Stage Histologic description
F0 Absence of fibrosis
F1 Perisinusoidal or portal fibrosis
F2 Perisinusoidal and portal or periportal fibrosis
F3 Septal and bridging fibrosis
F4 Cirrhosis

References

  1. Angula P. Nonalcoholic Fatty Liver Disease. NEJM. 2002 346(16):1221-31
  2. Brunt EM, Janney CG, Di Bisceglie AM et al. Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions. Am. J. Gastroenterol. 1999; 94(9):2467-2474
  3. Skelly et al. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001;35:195-9
  4. Vizuete J, Camero A, Malakouti M, Garapati K, Gutierrez J (2017). “Perspectives on Nonalcoholic Fatty Liver Disease: An Overview of Present and Future Therapies”. J Clin Transl Hepatol. 5 (1): 67–75. doi:10.14218/JCTH.2016.00061. PMC 5411359. PMID 28507929.
  5. Tilg H, Petta S, Stefan N, Targher G (January 2026). “Metabolic Dysfunction-Associated Steatotic Liver Disease in Adults: A Review”. JAMA. 335 (2): 163–174. doi:10.1001/jama.2025.19615. PMID 41212550 Check |pmid= value (help).

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