Received on February 2, 2004
Accepted on April 9, 2004

Proteomics and Protein Markers

Prospective Analysis of Discordant Results between Biochemical Markers and Biopsy in Patients with Chronic Hepatitis C

¹ Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Université Paris VI, Paris, France
² Laboratoire de Biochimie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
³ Service d'Anatomie Pathologique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
⁴ Laboratoire de Virologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

^* To whom correspondence should be addressed. E-mail: tpoynard{at}teaser.fr.

Background: The FibroTest and ActiTest are noninvasive biochemical markers of liver injury that are intended for use as alternatives to liver biopsy in patients with chronic hepatitis C. The aims of this study were to assess the quality of biopsy and the prevalence of discordances between biopsy and markers, to identify factors associated with discordances, and to attribute these discordances to either markers or biopsy failure.

Methods: Fibrosis stage and activity grade were prospectively assessed on the same day by a liver biopsy and by markers. On the basis of risk factors for failure and independent endpoints, discordance was classified as being attributable to biopsy or to markers.

Results: Only 74 of 537 patients (14%) had a biopsy size 25 mm. Discordance was observed in 154 of 537 patients (29%), including 16% for fibrosis staging and 17% for activity grading. Steatosis, an inflammatory profile, and biopsy size were associated with discordance. Discordance was attributable to failure of markers in 13 patients (2.4%) and to biopsy failure in 97 (18%; P <0.001 vs Fibrotest and Actitest), and was nonattributable in 44 patients (8.2%). The most frequent failure attributable to markers was false negatives (1.3%) attributable to inflammation. The most frequent failure attributable to biopsy was false negatives of activity grading (10.1%) and of fibrosis staging (4.5%), both associated with smaller biopsy size and steatosis. False positives of fibrosis staging (3.5%) were associated with fragmented biopsies.

Conclusion: In this series, the size of liver biopsy is adequate in only a minor proportion (14%) of patients with chronic hepatitis C. When biopsy and marker results are discordant, a reason can be identified in more than two-thirds of cases and, in those cases, biopsy failure is >7 times more common than diagnostic failure of markers.