Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients

Liver Int. 2010 Apr;30(4):546-53. doi: 10.1111/j.1478-3231.2009.02192.x. Epub 2010 Jan 13.


Backgrounds: To optimize management and predict long-term clinical courses in patients with chronic hepatitis B (CHB), noninvasive tests to determine the degree of hepatic fibrosis have been developed.

Aims: This study aimed to validate a simple, noninvasive FIB-4 index, which was first derived from an HCV-HIV-co-infected population, in patients with CHB and to compare it with other noninvasive tests for predicting cirrhosis.

Methods: From 2006-2008, a total of 668 consecutive CHB patients who underwent liver biopsies were enrolled. The fibrosis stage was assessed according to the Batts and Ludwig system by a single pathologist blinded to patients' data.

Results: For prediction of significant (F > or = 2) and severe (F > or = 3) fibrosis, and cirrhosis (F = 4), the area under the receiver-operating characteristic curves were 0.865, 0.910 and 0.926 respectively. In predicting cirrhosis, it demonstrated diagnostic values comparable to the age-spleen platelet ratio index (0.937, P=0.414) and age-platelet index (0.928, P=0.888), and better outcomes than spleen-platelet ratio index (0.882, P=0.007), aspartate aminotransferase (AST)-platelet ratio index (0.731, P<0.001) and AST-alanine aminotransferase ratio index (0.730, P<0.001). FIB-4 cut-offs of 1.6 and 3.6 provided 93.2% negative predictive value and 90.8% positive predictive value for detection of cirrhosis respectively. Based on these results, liver biopsy could be avoided in 70.5% of the study population. These cut-offs were validated internally using bootstrap resampling methods, showing good agreement.

Conclusions: FIB-4 is a simple, accurate and inexpensive method of predicting cirrhosis, with outcomes comparable to other noninvasive tests and may reduce the need for liver biopsy in the majority of CHB patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood*
  • Biopsy, Needle
  • Cohort Studies
  • Diagnosis, Differential
  • Disease Progression
  • Female
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / pathology*
  • Humans
  • Immunohistochemistry
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / pathology*
  • Liver Cirrhosis / virology
  • Male
  • Platelet Count
  • Predictive Value of Tests
  • RNA, Viral / blood
  • ROC Curve
  • Reproducibility of Results
  • Severity of Illness Index
  • Viral Load


  • Biomarkers
  • RNA, Viral
  • Aspartate Aminotransferases
  • Alanine Transaminase