title: Longitudinal assessment of hepatitis C fibrosis progression by collagen and smooth muscle actin morphometry in comparison to serum markers.
abstract: BACKGROUND
  Assessment of fibrosis progression in chronic liver disease relies upon non-invasive tools and changes in semi-quantitative histopathology scores that may not be reliable.
  
  
  OBJECTIVE
  To assess the diagnostic performance of the FibroSURE (FS) index and collagen/alpha smooth muscle actin (α-SMA) morphometry in relation to longitudinal changes in fibrosis on paired biopsies.
  
  
  METHODS
  The study cohort included 201 chronic hepatitis C (CHC) nonresponders enrolled in a prior phase II anti-fibrotic study. Serum FS and paired biopsies, with both collagen and α-SMA morphometry, were evaluated at baseline and week 52.
  
  
  RESULTS
  Study patients were mostly male (67%) and Caucasian (77%), with Ishak stages 2 (n = 79), 3 (n = 88) and 4 (n = 30), excluded (n = 4 stage 1 or 5). Mean biopsy length was 22.9 mm. For baseline Ishak 2/3 vs. 4, there were no significant differences in AUROCs for collagen (0.71), SMA (0.66) or FS (0.70). At week 52, 62% of patients had no change in Ishak stage, but collagen/α-SMA increased by 34-51% (P < 0.0001), and FS decreased by 5% (P = 0.008). Among the 33% of patients with +/-1 Ishak stage change, FS changes were not significant, but α-SMA increased 29-72%, and collagen increased by 12-38% (P = 0.01 for +1 only).
  
  
  CONCLUSIONS
  Longitudinal changes in collagen and α-SMA morphometry are apparent prior to change in histological stage or FibroSURE in CHC nonresponders with intermediate fibrosis. This likely reflects quantitative morphological differences that are not detected by routine histological staging or serum markers such as FibroSURE.
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.|Duke University Medical Center, Durham, NC, USA.|Liver Cell Biology, Centenary Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Patel
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.|Duke University Medical Center, Durham, NC, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Tillmann
authors.affiliation: Duke University Medical Center, Durham, NC, USA.
authors.forename: B
authors.initials: B
authors.lastname: Matta
authors.affiliation: Inova Research Center, Inova Fairfax Medical Campus, Falls Church, VA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Sheridan
authors.affiliation: Infectious Diseases Therapeutic Area Unit, GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Gardner
authors.affiliation: Liver Cell Biology, Centenary Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: N A
authors.initials: NA
authors.lastname: Shackel
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Hepatic Pathology Consultation and Research, Inova Fairfax Hospital, Falls Church, VA, USA.
authors.forename: Z D
authors.initials: ZD
authors.lastname: Goodman
mesh_terms: D000199:Actins / Q000096:biosynthesis*; D000367:Age Factors; D015415:Biomarkers; D001706:Biopsy; D015331:Cohort Studies; D003094:Collagen / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology* / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology; D012737:Sex Factors
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015415:Biomarkers; D003094:Collagen