Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study

Lancet. 2001 Apr 7;357(9262):1069-75. doi: 10.1016/S0140-6736(00)04258-6.


Background: Liver biopsy is thought mandatory for management of patients with hepatitis C virus (HCV) infection, especially for staging fibrosis. We aimed, in our prospective study, to assess the predictive value of a combination of basic serum biochemical markers for diagnosis of clinically significant fibrosis (including early stages).

Methods: We assessed liver-biopsy patients with detectable HCV by PCR, for eligibility, and took a blood sample on the day of the procedure. The analysis was done in a first-year period for 205 patients and then tested in a second period on 134 patients. We devised a fibrosis index that included the most informative markers (combined with age and sex) for the first-year group. 11 serum markers were assessed as well as fibrosis stage: F0=no fibrosis and F1=portal fibrosis; and for clinically significant fibrosis, F2=few septa, F3=many septa, and F4=cirrhosis. Statistical analysis was by logistic regression, neural connection, and receiver-operating characteristic (ROC) curves.

Findings: First-year and second-year patient-group characteristics and biochemical markers did not differ. The overall frequency of clinically significant fibrosis was 40% (138 patients). The most informative markers were: alpha2 macroglobulin, alpha2 globulin (or haptoglobin), gamma globulin, apolipoprotein A1, gamma glutamyltranspeptidase, and total bilirubin. The areas (SD) under the ROC curves for the first-year (0.836 [0.430]) and second-year groups (0.870 [0.340]) did not differ (p=0.44). With the best index, a high negative predictive value (100% certainty of absence of F2, F3, or F4) was obtained for scores ranging from zero to 0.10 (12% [41] of all patients), and high positive predictive value (>90% certainty of presence of F2, F3, or F4) for scores ranging from 0.60 to 1.00 (34% [115] of all patients).

Interpretation: A combination of basic serum markers could be used to substantially reduce the number of liver biopsies done in patients with chronic HCV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein A-I / blood
  • Bilirubin / blood
  • Biomarkers / blood*
  • Biopsy
  • Female
  • Haptoglobins / analysis
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Liver / pathology
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / virology
  • Logistic Models
  • Male
  • Middle Aged
  • Neural Networks, Computer
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Sensitivity and Specificity
  • alpha-Macroglobulins / analysis
  • gamma-Globulins / analysis
  • gamma-Glutamyltransferase / blood


  • Apolipoprotein A-I
  • Biomarkers
  • Haptoglobins
  • alpha-Macroglobulins
  • gamma-Globulins
  • gamma-Glutamyltransferase
  • Bilirubin