Noninvasive Evaluation of Nonalcoholic Fatty Liver Disease

Semin Liver Dis. 2015 Aug;35(3):291-303. doi: 10.1055/s-0035-1562948. Epub 2015 Sep 17.


Key issues in patients with nonalcoholic fatty liver disease (NAFLD) are the differentiation of nonalcoholic steatohepatitis (NASH) from simple steatosis and staging of liver fibrosis, as patients with NASH/advanced fibrosis are at greatest risk of developing complications of end-stage liver disease. The controlled attenuation parameter is the most promising noninvasive technique for detecting and quantifying hepatic steatosis, but needs to be implemented with the XL probe and compared with ultrasound that, despite its limitations, remains the most widely used method. Cytokeratin-18 is currently the most extensively validated serum marker of NASH as a stand-alone test or as part of prediction models. However, it is not widely available and thus has not been introduced yet into practice. Transient elastography, as well as FIB-4 and NAFLD fibrosis scores are the best methods to rule out severe fibrosis and cirrhosis. However, the high rate of unreliable results with transient elastography remains a challenge, which is not completely addressed by the use of the XL probe. Given the high prevalence of NAFLD in the general population, these noninvasive methods could be used in clinical practice as first-line tools to screen patients with NAFLD to help determine those who may still require a liver biopsy.

Publication types

  • Review

MeSH terms

  • Biomarkers / blood
  • Biopsy
  • Elasticity Imaging Techniques*
  • Humans
  • Keratin-18 / blood*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / etiology
  • Liver* / diagnostic imaging
  • Liver* / metabolism
  • Liver* / pathology
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Predictive Value of Tests
  • Prognosis
  • Reproducibility of Results
  • Severity of Illness Index


  • Biomarkers
  • KRT18 protein, human
  • Keratin-18