title: Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Tokiya
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Komiyama
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Tsuguru
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Konomi
authors.initials: K
authors.lastname: Kuwabara
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Takaura
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Nakakuki
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takada
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Tamaki
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Itakura
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hashiguchi
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015994:Incidence; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D003094:Collagen; D004549:Elastin