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


RESULTS
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).


CONCLUSIONS
A combination of basic serum markers could be used to substantially reduce the number of liver biopsies done in patients with chronic HCV infection.
Imbert-Bismut
F
F
Department of Biochemistry, Hospitalier Pitié-Salpêtrière, Paris, France.
Ratziu
V
V
Pieroni
L
L
Charlotte
F
F
Benhamou
Y
Y
Poynard
T
T
D016632:Apolipoprotein A-I / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D005260:Female; D006242:Haptoglobins / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016571:Neural Networks, Computer; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D000511:alpha-Macroglobulins / Q000032:analysis; D005719:gamma-Globulins / Q000032:analysis; D005723:gamma-Glutamyltransferase / Q000097:blood
D016632:Apolipoprotein A-I; D015415:Biomarkers; D006242:Haptoglobins; D000511:alpha-Macroglobulins; D005719:gamma-Globulins; D005723:gamma-Glutamyltransferase; D001663:Bilirubin