title: Correlation of FIBROSpect II with histologic and morphometric evaluation of liver fibrosis in chronic hepatitis C.
abstract: OBJECTIVE
  Accurate disease staging in chronic hepatitis C (CHC) infection helps guide treatment and may provide prognostic information. Liver biopsies are invasive, costly, and associated with morbidity. We hypothesized that a noninvasive test of liver fibrosis can accurately stage liver fibrosis. We prospectively evaluated the FIBROSpect II (FSII) biomarker panel versus pathology assessment and a quantitative measure of fibrosis.
  
  
  METHODS
  Liver biopsy specimens and serum were obtained from 252 CHC patients, including 50 posttransplant, from 3 tertiary centers. Biopsy specimens were scored centrally and independently at each site, along with central quantification of fibrosis by digitized morphometry. Serum tests were performed blinded to clinical or histologic evaluation.
  
  
  RESULTS
  The mean biopsy specimen length was 1.95 +/- 0.87 cm; prevalence of stage F2 through F4 fibrosis was 77%. Agreement between central and site readings for individual stages was modest (k = 0.674), with concordant readings in 106 of 248 (43%) biopsy specimens. The area under the receiver operating characteristic curve for FSII and morphometry for stages F2 through F4 for concordant biopsy specimens were 0.823 and 0.728, respectively. Sensitivity and specificity for FSII were 83.5% and 66.7%, respectively, with an accuracy of 80.2%. The aspartate aminotransferase to platelet ratio index sensitivity and specificity for predicting F2 through F4 were 30.4% and 100%, respectively, the indeterminate rate was 40.4%, and the accuracy rate was 48.4%. The accuracy of FSII in concordant biopsy specimens in the posttransplant cohort was 73%.
  
  
  CONCLUSIONS
  Serum biomarkers can differentiate mild from moderate-to-severe fibrosis. This prospective study validates the performance characteristics of FSII in CHC patients and a posttransplant cohort. Assessing the diagnostic utility of biomarkers is limited by variability in methods to quantify fibrosis and poor interobserver agreement for histologic staging.
authors.affiliation: Division of Gastroenterology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina 27705, USA. Keyur.patel@duke.edu
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Don C
authors.initials: DC
authors.lastname: Rockey
authors.forename: Nezam H
authors.initials: NH
authors.lastname: Afdhal
authors.forename: Katie M
authors.initials: KM
authors.lastname: Smith
authors.forename: Esther
authors.initials: E
authors.lastname: Oh
authors.forename: Keith
authors.initials: K
authors.lastname: Hettinger
authors.forename: Marc
authors.initials: M
authors.lastname: Vallée
authors.forename: Anouk
authors.initials: A
authors.lastname: Dev
authors.forename: Margaret
authors.initials: M
authors.lastname: Smith-Riggs
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D000328:Adult; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers; D001706:Biopsy; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006651:Histocytochemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D008099:Liver / Q000473:pathology* / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000097:blood* / Q000145:classification / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D044967:Serum / Q000737:chemistry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D000511:alpha-Macroglobulins / Q000032:analysis
chemical_list: D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D000511:alpha-Macroglobulins; D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases