Non-alcoholic fatty liver disease other diagnostic studies
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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
- Pain
- Hypotension
- Peritonitis
- Intraperitoneal hemorrhage
- Biliary injury
Findings
Classically, biopsy reveals:[1][2]
- Macrovesicular steatosis
- Inflammatory cells
- Ballooning degeneration
- Zone 3 perivenular/periportal/perisinusoidal fibrosis
- Mallory bodies
Interpretation
- Histologic changes in NAFLD are very similar to those in alcoholic hepatitis and may also mimic those seen in chronic HCV infection.
- The spectrum of abnormalities varies from simple bland steatosis to NASH, in which steatosis is associated with mixed inflammatory cell infiltration, mostly lobular, and liver injury.
- Cell injury is manifested by hepatocyte ballooning as well as by Mallory hyaline and acidophilic bodies.
- Fibrosis is classically perisinusoidal/perivenular and may lead to bridging fibrosis and cirrhosis.
- Although portal tracts are relatively spared in adult NAFLD, children with this condition may have a predominance of portal inflammation and fibrosis as opposed to lobular involvement.
- Compared with alcoholic hepatitis, NASH is associated with a higher prevalence of nuclear vacuoles and steatosis, while alcoholic hepatitis tends to produce periportal and pericellular fibrosis.
- Alcoholic hepatitis presents with identical histology but patient history and/or biochemistry will indicate prolonged, excessive alcohol intake.[3]
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
- ↑ Angula P. Nonalcoholic Fatty Liver Disease. NEJM. 2002 346(16):1221-31
- ↑ 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
- ↑ 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
- ↑ 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.
- ↑ 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
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