Comparison of three algorithms of non-invasive markers of fibrosis in chronic hepatitis C

Aliment Pharmacol Ther. 2012 Jan;35(1):92-104. doi: 10.1111/j.1365-2036.2011.04897.x. Epub 2011 Oct 28.


Background: Preliminary data suggest that performance of non-invasive markers for liver fibrosis in hepatitis C may improve when combined. Three algorithms based on the combination of Fibrotest, Forns' index and AST-to-platelet ratio (APRI) have been proposed: Sequential Algorithm for Fibrosis Evaluation (SAFE biopsy); Fibropaca algorithm; Leroy algorithm.

Aim: To compare three algorithms to diagnose significant fibrosis (≥ F2 by METAVIR) and cirrhosis (F4).

Methods: A total of 1013 HCV monoinfected cases undergoing liver biopsy were consecutively enrolled in seven centres. Fibrotest, APRI and Forns' index were measured at the time of liver biopsy, considered the reference standard.

Results: Overall, performance of combination algorithms was significantly higher than the single non-invasive methods (P < 0.0001). SAFE biopsy and Fibropaca algorithm saved a significantly higher number of liver biopsies than the single methods (P < 0.0001). For ≥ F2, Fibropaca algorithm saved more biopsies than SAFE biopsy (51.7% vs. 43.8%, P = 0.0003), but with lower accuracy (87.6% vs. 90.3%, P = 0.05). Regarding F4, the number of saved liver biopsies did not differ between SAFE biopsy and Fibropaca algorithm (79.1% vs. 76.2%, P = 0.12). However, SAFE biopsy showed a lower accuracy when compared with Fibropaca algorithm (91.2% vs. 94%, P = 0.02). As to Leroy algorithm, although it showed a good performance for ≥ F2 (93.5% accuracy), it saved less liver biopsies than SAFE biopsy and Fibropaca algorithm (29.2% vs. 43.8% and 51.7% respectively, P < 0.0001).

Conclusions: SAFE biopsy and the Fibropaca algorithm have excellent performance for liver fibrosis in hepatitis C, allowing a significant reduction in the need for liver biopsies. They can be useful in clinical practice and for large-scale screening.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Algorithms*
  • Apolipoprotein A-I / blood
  • Aspartate Aminotransferases / blood
  • Bilirubin / blood
  • Biomarkers / blood*
  • Biopsy
  • Cholesterol / blood
  • Female
  • Haptoglobins / metabolism
  • Hepatitis C / genetics
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / diagnosis*
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis*
  • Male
  • Middle Aged
  • Platelet Count
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • RNA, Viral / blood
  • Retrospective Studies
  • Sensitivity and Specificity
  • alpha-Macroglobulins / metabolism
  • gamma-Glutamyltransferase / blood


  • Apolipoprotein A-I
  • Biomarkers
  • Haptoglobins
  • RNA, Viral
  • alpha-Macroglobulins
  • Cholesterol
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Bilirubin