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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.

Key Points

  • The prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be higher than that of other forms of liver disease, largely because it correlates with the ongoing worldwide obesity epidemic

  • Clinical tests, serologic studies, imaging and ultrasound methods for detecting steatosis and liver 'stiffness' are best at screening for extremes of disease, but have yet to replace liver biopsy

  • Evaluation of liver biopsy samples can be hampered by sampling differences and technical considerations, such as needle size and placement; pathologist expertise also has a role

  • The microscopic findings of NAFLD include not only the lesions of steatosis, lobular and portal inflammation and hepatocyte ballooning, but also the pattern or patterns of injury

  • In adults, the processes are most concentrated in the perivenular region; in children, the process may mimic that of adults, or may be concentrated in the periportal regions

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Figure 1: The central findings of nonalcoholic steatohepatitis in an adult patient.
Figure 2: An immunohistochemical stain for the liver cell keratins K8 and K18 in a patient with steatohepatitis.

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Brunt, E. Pathology of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 7, 195–203 (2010). https://doi.org/10.1038/nrgastro.2010.21

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