Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease--the role of transient elastography and plasma cytokeratin-18 fragments

Aliment Pharmacol Ther. 2014 Feb;39(3):254-69. doi: 10.1111/apt.12569. Epub 2013 Dec 5.


Background: Non-alcoholic fatty liver disease (NAFLD) affects 15-40% of the general population. Some patients have non-alcoholic steatohepatitis (NASH) and progressive fibrosis, and would be candidates for monitoring and treatment.

Aim: To review current literature on the use of non-invasive tests to assess the severity of NAFLD.

Methods: Systematic literature searching identified studies evaluating non-invasive tests of NASH and fibrosis using liver biopsy as the reference standard. Meta-analysis was performed for areas with adequate number of publications.

Results: Serum tests and physical measurements like transient elastography (TE) have high negative predictive value (NPV) in excluding advanced fibrosis in NAFLD patients. The NAFLD fibrosis score comprises of six routine clinical parameters and has been endorsed by current American guidelines as a screening test to exclude low-risk individuals. The pooled sensitivities and specificities for TE to diagnose F ≥ 2, F ≥ 3 and F4 disease were 79% and 75%, 85% and 85%, and 92% and 92% respectively. Liver stiffness measurement often fails in obese patients, but the success rate can be improved with the use of the XL probe. A number of biomarkers have been developed for the diagnosis of NASH, but few were independently validated. Serum/plasma cytokeratin-18 fragments have been most extensively evaluated and have a pooled sensitivity of 66% and specificity of 82% in diagnosing NASH.

Conclusions: Current non-invasive tests are accurate in excluding advanced fibrosis in NAFLD patients, and may be used for initial assessment. Further development and evaluation of NASH biomarkers are needed.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers / metabolism
  • Biopsy
  • Elasticity Imaging Techniques / methods*
  • Fatty Liver / diagnosis*
  • Fatty Liver / pathology
  • Humans
  • Keratin-18 / blood*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / pathology
  • Non-alcoholic Fatty Liver Disease
  • Obesity / complications
  • Sensitivity and Specificity


  • Biomarkers
  • Keratin-18