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Biochemical
markers of liver fibrosis in patients with hepatitis C virus
infection: a prospective study
Françoise Imbert-Bismut,
Vlad Ratziu, Laurence Pieroni, Frederic Charlotte, Yves Benhamou,
Thierry Poynard, for the MULTIVIRC group
Lancet Volume 357, Number 9262
07 April 2001
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Departments of Biochemistry (F Imbert-Bismut PhD, L Pieroni
PhD), Hepatogastroenterology (V Ratziu MD, Y Benhamou
MD, T Poynard MD), and Pathology, Hospitalier Pitié-Salpêtrière,
(F Charlotte MD); and Laboratoire d'Immunologie des
Tumeurs, Faculté des Sciences Pharmaceutiques et Biologiques
de Paris Université René Descartes, Paris, France
(V Ratziu, T Poynard)
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Correspondence to: Prof Thierry Poynard, Service d'Hépato-Gastroentèrologie,
Groupe Hospitalier Pitié-Salpêtrière, 75651
Paris, Cedex 13, France (e-mail:tpoynard@teaser.fr)
Summary
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: 2 macroglobulin, 2 globulin (or
haptoglobin), globulin, apolipoprotein A1, 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.
Lancet 2001; 357: 1069-75
