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: FO=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: α2 macroglobulin, α2 globulin (or haptoglobin), γ globulin, apolipoprotein A1, γ 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.