title: Intermediate fibrosis staging in hepatitis C: a problem not overcome by optimal samples or pathologists' expertise.
abstract: OBJECTIVE
  The prediction of intermediate stage of fibrosis in chronic hepatitis C represents a prognostic factor for disease progression. Studies evaluating biopsy performance in intermediate stage considering current patterns of liver samples and pathologists' variability are scarce. We aimed to evaluate the effect of optimal liver specimens (≥ 20 mm and/or ≥ 11 portal tracts) and pathologists' expertise on agreement for intermediate stage of fibrosis in chronic hepatitis C.
  
  
  METHODS
  Guided biopsies with large TruCut needle were initially scored by four pathologists with different expertise in liver disease and posteriorly reviewed by a reference hepatopathologist to evaluate fibrosis agreement.
  
  
  RESULTS
  Of the 255 biopsies initially selected, 240 met the criteria of an optimal fragment (mean length 24 ± 5 mm; 16 ± 6 portal tracts) and were considered for analysis. The overall agreement among all fibrosis stages was 77% (κ = 0.66); intraobserver and interobserver agreement was, respectively, 97% (k = 0.96) and 73% (κ = 0.60). Excluded samples (< 20 mm and < 11 portal tracts) presented a lower agreement (40%; κ = 0.24). Stratifying fibrosis stages, an interobserver agreement of 42% was found in intermediate stage (F2), ranging from 0 to 56% according to pathologists' expertise, compared to 97% in mild (F0-F1) and 72% in advanced fibrosis (≥ F3) (p < 0.001). Of the 23% misclassified cases, fibrosis understaging occurred in 82% of specimens, predominantly in F2, even when evaluated by a hepatopathologist.
  
  
  CONCLUSIONS
  Liver biopsy presents intrinsic limitations to assess intermediate stage of fibrosis not overcome by optimal samples and experienced pathologists' analysis, and should not be considered the gold standard method to evaluate intermediate fibrosis in chronic hepatitis C.
authors.affiliation: Department of Internal Medicine Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Chindamo
authors.affiliation: Department of Pathology Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Nunes-Pannain
authors.affiliation: Department of Internal Medicine Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: João M
authors.initials: JM
authors.lastname: Araújo-Neto
authors.affiliation: Department of Internal Medicine Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Henrique S
authors.initials: HS
authors.lastname: Moraes-Coelho
authors.affiliation: Institute of Public Health Studies. Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ronir R
authors.initials: RR
authors.lastname: Luiz
authors.affiliation: Department of Internal Medicine Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Cristiane A
authors.initials: CA
authors.lastname: Villela-Nogueira
authors.affiliation: Department of Internal Medicine Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Perez
mesh_terms: D001707:Biopsy, Needle; D002983:Clinical Competence; D003430:Cross-Sectional Studies; D003951:Diagnostic Errors / Q000517:prevention & control; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000821:virology; D008103:Liver Cirrhosis / Q000473:pathology* / Q000821:virology; D015588:Observer Variation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012720:Severity of Illness Index