Systematic review with meta-analysis: direct comparisons of biomarkers for the diagnosis of fibrosis in chronic hepatitis C and B

Aliment Pharmacol Ther. 2016 Jan;43(1):16-29. doi: 10.1111/apt.13446. Epub 2015 Oct 30.


Background: Blood tests and transient elastography (TE), proposed as alternatives to biopsy for identifying advanced fibrosis (METAVIR-stage-F2 or greater) or cirrhosis, have never been compared using an intention to diagnose approach, with direct comparisons only, and Bayesian approach.

Aim: To permit more appropriate comparisons.

Methods: From an overview of articles (2002-2014), we selected studies that directly compared the diagnostic accuracy of FibroTest, aspartate aminotransferase-platelet ratio index (APRI), FIB4 or TE, with biopsy as a reference, in patients with chronic hepatitis C (CHC) or B (CHB). Investigators abstracted and checked study details and quality by using pre-defined criteria. Bayesian method in intention to diagnose was the primary outcome.

Results: Of 1321 articles identified, 71 studies including 77 groups according to aetiology (All-CB) were eligible: 37 Only-C, 28 Only-B and 12 Mixed-C-B. There were 185 direct comparisons between the area under the ROC curves (AUROCs), 99 for the diagnosis of advanced fibrosis and 86 for cirrhosis. In All-CB, Bayesian analyses revealed significant AUROCs differences in identifying advanced fibrosis in favour of FibroTest vs. TE [credibility interval: 0.06(0.02-0.09)], FibroTest vs. APRI [0.05 (0.03-0.07)] and for identifying cirrhosis TE vs. APRI [0.07 (0.02-0.13)] and FIB4 vs. APRI [0.04(0.02-0.05)]. No differences were observed between TE and FibroTest, for identifying cirrhosis in All-CB, and in sub-groups (Only-C, Only-B, Mixed-CB) for both cirrhosis and fibrosis.

Conclusions: In CHC and CHB, APRI had lower performances than FIB-4, TE and FibroTest. TE had lower performance than FibroTest for identifying advanced fibrosis in All-CB, without significant difference for identifying cirrhosis in all groups.

Publication types

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

MeSH terms

  • Area Under Curve
  • Aspartate Aminotransferases / blood
  • Bayes Theorem
  • Biomarkers
  • Biopsy
  • Elasticity Imaging Techniques
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / diagnostic imaging
  • Hepatitis B, Chronic / pathology*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / diagnostic imaging
  • Hepatitis C, Chronic / pathology*
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnostic imaging
  • Liver Cirrhosis / pathology*


  • Biomarkers
  • Aspartate Aminotransferases