Pathology of nonalcoholic fatty liver disease
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a significant complication of obesity and is recognized as the hepatic manifestation of the metabolic syndrome. The process occurs in adults and children and is characterized by the presence of increased amounts of fat in the liver (steatosis). With inflammation, cell death and scarring (fibrosis), the process may result in end-stage liver disease, or be a precursor for hepatocellular carcinoma. Excess hepatic fat is now recognized as an independent marker for increased cardiovascular risk. Even though imaging studies and laboratory-based tests are accurate at detecting significant steatosis and/or advanced fibrosis, respectively, the diagnosis and characterization of NAFLD ultimately depend on histopathologic evaluation, as the parenchymal alterations that comprise the spectrum of injury in NAFLD include patterns as well as specific lesions. Histologic findings in children may differ from those in adults. In this Review, the histologic features that are diagnostic and discriminatory between steatosis and steatohepatitis, the significance of the distinction between steatosis and steatohepatitis, the types and locations of fibrosis, and the histologic variances between adult and pediatric NAFLD are discussed. Clinical advantages as well as potential drawbacks of liver biopsy are presented. Current pathophysiologic concepts relevant to histologic findings are discussed.
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Steatosis in adults with NAFLD usually begins in pericentral hepatocytes and then extends into other lobular zones during disease progression.
“Steatosis in adults with non-alcoholic fatty liver disease (NAFLD) usually begins in pericentral hepatocytes and then extends into other lobular zones during disease progression.154”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [154]
Cites
Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.
MATTEONI, C., YOUNOSSI, Z., GRAMLICH, T., BOPARAI, N., LIU, Y., & MCCULLOUGH, A. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70506-8 · Cited by 3,345 · see citing works
Obesity and Diabetes in the Developing World — A Growing Challenge
Hossain, P., Kawar, B., & El Nahas, M. (2007) · New England Journal of Medicine · doi:10.1056/nejmp068177 · Cited by 2,200 · see citing works
Sampling Variability of Liver Biopsy in Nonalcoholic Fatty Liver Disease
Ratziu, V., Charlotte, F., Heurtier, A., Gombert, S., Giral, P., Bruckert, E., Grimaldi, A., Capron, F., & Poynard, T. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.03.084 · Cited by 2,106 · see citing works
Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Fabbrini, E., Magkos, F., Mohammed, B. S., Pietka, T., Abumrad, N. A., Patterson, B. W., Okunade, A., & Klein, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904944106 · Cited by 972 · see citing works
Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss
Gregor, M. F., Yang, L., Fabbrini, E., Mohammed, B. S., Eagon, J. C., Hotamisligil, G. S., & Klein, S. (2009) · Diabetes · doi:10.2337/db08-1220 · Cited by 488 · see citing works
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Cited by
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Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110025 · Cited by 2,575 · see citing works
Bile acid signaling in metabolic disease and drug therapy
Li, T., & Chiang, J. Y. L. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008201 · Cited by 935 · see citing works
Intestinal microbiota in patients with nonalcoholic fatty liver disease
Mouzaki, M., Comelli, E. M., Arendt, B. M., Bonengel, J., Fung, S. K., Fischer, S. E., McGilvray, I. D., & Allard, J. P. (2013) · Hepatology · doi:10.1002/hep.26319 · Cited by 749 · see citing works
Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives
Arab, J. P., Karpen, S. J., Dawson, P. A., Arrese, M., & Trauner, M. (2017) · Hepatology · doi:10.1002/hep.28709 · Cited by 634 · see citing works
Recent insights into the pathogenesis of nonalcoholic fatty liver disease
Arab, J. P., Arrese, M., & Trauner, M. (2018) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043617 · Cited by 573 · see citing works
Trevaskis, J. L., Griffin, P. S., Wittmer, C., Neuschwander-Tetri, B. A., Brunt, E. M., Dolman, C. S., Erickson, M. R., Napora, J., Parkes, D. G., & Roth, J. D. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00476.2011 · Cited by 277 · see citing works
Self-citationAdaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH
Sutti, S., Jindal, A., Locatelli, I., Vacchiano, M., Gigliotti, L., Bozzola, C., & Albano, E. (2014) · Hepatology · doi:10.1002/hep.26749 · Cited by 270 · see citing works
Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis
Zhu, C., Kim, K., Wang, X., Bartolome, A., Salomao, M., Dongiovanni, P., Meroni, M., Graham, M. J., Yates, K. P., Diehl, A. M., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat0344 · Cited by 250 · see citing works
Itoh, M., Kato, H., Suganami, T., Konuma, K., Marumoto, Y., Terai, S., Sakugawa, H., Kanai, S., Hamaguchi, M., Fukaishi, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082163 · Cited by 211 · see citing works
Goetzman, E. S., & Prochownik, E. V. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00129 · Cited by 199 · see citing works
Haas, J. T., Vonghia, L., Mogilenko, D. A., Verrijken, A., Molendi-Coste, O., Fleury, S., Deprince, A., Nikitin, A., Woitrain, E., Ducrocq-Geoffroy, L., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0076-1 · Cited by 155 · see citing works
Bruzzì, S., Sutti, S., Giudici, G., Burlone, M. E., Ramavath, N. N., Toscani, A., Bozzola, C., Schneider, P., Morello, E., Parola, M., et al. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.06.015 · Cited by 139 · see citing works
Wang, Y., Parlevliet, E. T., Geerling, J. J., van der Tuin, S. J. L., Zhang, H., Bieghs, V, Jawad, A. H. M., Shiri‐Sverdlov, R., Bot, I., de Jager, S. C. A., et al. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12490 · Cited by 126 · see citing works
Retained NK cell phenotype and functionality in non-alcoholic fatty liver disease
Stiglund, N., Strand, K., Cornillet, M., Stål, P., Thorell, A., Zimmer, C. L., Näslund, E., Karlgren, S., Nilsson, H., Mellgren, G., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01255 · Cited by 72 · see citing works
Pizarro, M., Solís, N., Quintero, P., Barrera, F., Cabrera, D., Rojas‐de Santiago, P., Arab, J. P., Padilla, O., Roa, J. C., Moshage, H., et al. (2015) · Liver International · doi:10.1111/liv.12794 · Cited by 66 · see citing works
Greig, J. A., Limberis, M. P., Bell, P., Chen, S.-J., Calcedo, R., Rader, D. J., & Wilson, J. M. (2017) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.014 · Cited by 56 · see citing works
Chen, X., Sun, X., Shen, T., Chen, Q., Chen, S., Pang, J., Mi, J., Tang, Y., You, Y., Xu, H., et al. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.08.005 · Cited by 30 · see citing works
Distinct hepatocyte identities in liver homeostasis and regeneration
Chen, F., Schönberger, K., & Tchorz, J. S. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100779 · Cited by 30 · see citing works
- Authors
- Brunt, E. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Brunt, Elizabeth M.
- ORCID
- Brunt, Elizabeth M.
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2010-03-02
- Volume
- 7
- Issue
- 4
- Pages
- 195-203
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- OpenAlex
- W2090739153
- Cited by
- 484
- References
- 5
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 25 · 2023: 25 · 2022: 24 · 2021: 27 · 2020: 35 · 2019: 29 · 2018: 37 · 2017: 30 · 2016: 31 · 2015: 33 · 2014: 42 · 2013: 37 · 2012: 34
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- non-alcoholic fatty liver disease, histopathology, steatosis, steatohepatitis, liver biopsy, liver fibrosis, pediatric NAFLD, metabolic syndrome, obesity, hepatocellular carcinoma, cardiovascular risk, liver imaging
- MeSH terms
- Adult, Biopsy, Child, Diagnosis, Differential, Fatty Liver, Fibrosis, Humans, Immunohistochemistry, Inflammation, Obesity, Severity of Illness Index, Prevalence, Metabolic Syndrome
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