Role of liver biopsy in nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the "gold standard" for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.

Keywords: Grading and staging; Histopathology; Liver biopsy; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis.

Figure 1

Histologic features, grading, and staging of nonalcoholic fatty liver disease. A: Mixed large and small droplet steatosis, single droplet, with nucleus pushed to one side, HE stain, 600 ×; B: Microvesicular steatosis, nuclei in the center with foamy cytoplasm, and megamitochondria HE stain, 600 ×; C: Ballooned hepatocytes with flocculent cytoplasm, HE stain, 600 ×; D: Loss of cytoplasmic expression of keratin 8/18 in ballooned hepatocytes, 600 ×; E: Mallory-Denk body, HE stain, 600 ×; F: Mallory-Denk body in blue-green color and dense perisinusoidal fibrosis, Trichrome stain, 600 ×; G: Portal lipogranuloma, HE stain, 400 ×; H: Mallory-Denk bodies and satellitosis HE stain, 600 ×; I: Delicate perisinusoidal fibrosis, Trichrome stain, 600 ×; J: Bridging fibrosis, Trichrome stain, 200 ×.

Figure 2

Pediatric nonalcoholic fatty liver disease. A: Periportal accentuation of steatosis with sparing of zone 3, pediatric nonalcoholic fatty liver disease (NAFLD), HE stain, 200 ×; B: Portal fibrosis without zone 3 perisinusoidal fibrosis, pediatric NAFLD, Trichrome stain, 100 ×.