Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma

PLoS One. 2016 Apr 29;11(4):e0154558. doi: 10.1371/journal.pone.0154558. eCollection 2016.

Abstract

Background & aims: The fibrosis stage, which is evaluated by the distribution pattern of collagen fibers, is a major predictor for the development of hepatocellular carcinoma (HCC) for patients with hepatitis C. Meanwhile, the role of elastin fibers has not yet been elucidated. The present study was conducted to determine the significance of quantifying both collagen and elastin fibers.

Methods: We enrolled 189 consecutive patients with hepatitis C and advanced fibrosis. Using Elastica van Gieson-stained whole-slide images of pretreatment liver biopsies, collagen and elastin fibers were evaluated pixel by pixel (0.46 μm/pixel) using an automated computational method. Consequently, fiber amount and cumulative incidences of HCC within 3 years were analyzed.

Results: There was a significant correlation between collagen and elastin fibers, whereas variation in elastin fiber was greater than in collagen fiber. Both collagen fiber (p = 0.008) and elastin fiber (p < 0.001) were significantly correlated with F stage. In total, 30 patients developed HCC during follow-up. Patients who have higher elastin fiber (p = 0.002) in addition to higher collagen fiber (p = 0.05) showed significantly higher incidences of HCC. With regard to elastin fiber, this difference remained significant in F3 patients. Furthermore, for patients with a higher collagen fiber amount, higher elastin was a significant predictor for HCC development (p = 0.02).

Conclusions: Computational analysis is a novel technique for quantification of fibers with the added value of conventional staging. Elastin fiber is a predictor for the development of HCC independently of collagen fiber and F stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / metabolism*
  • Collagen / metabolism
  • Elastin / metabolism*
  • Female
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / pathology
  • Humans
  • Incidence
  • Liver / metabolism*
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Risk Factors

Substances

  • Collagen
  • Elastin

Grants and funding

This study was supported by grants from The New Energy and Industrial Technology Development Organization (Project no. P10003) for the data collection and Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare, Japan for the study design.