Longitudinal assessment of hepatitis C fibrosis progression by collagen and smooth muscle actin morphometry in comparison to serum markers

Aliment Pharmacol Ther. 2016 Feb;43(3):356-63. doi: 10.1111/apt.13471. Epub 2015 Nov 11.


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.

Aim: 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Actins / biosynthesis*
  • Age Factors
  • Biomarkers
  • Biopsy
  • Cohort Studies
  • Collagen / metabolism*
  • Disease Progression
  • Female
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / complications*
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / physiopathology*
  • Liver Function Tests
  • Male
  • Middle Aged
  • Muscle, Smooth / pathology
  • Sex Factors


  • ACTA2 protein, human
  • Actins
  • Biomarkers
  • Collagen