Open AccessElastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma
Author(s) -
Yutaka Yasui,
Tokiya Abe,
Masayuki Kurosaki,
Masakazu Higuchi,
Yasuyuki Komiyama,
Teruo Yoshida,
Tsuguru Hayashi,
Konomi Kuwabara,
Kenta Takaura,
Natsuko Nakakuki,
Hitomi Takada,
Nobuharu Tamaki,
Shinichi Suzuki,
Hiroyuki Nakanishi,
Kaoru Tsuchiya,
Jun Itakura,
Yuka Takahashi,
Akinori Hashiguchi,
Michiie Sakamoto,
Namiki Izumi
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0154558
Subject(s) - elastin , collagen fiber , van gieson's stain , hepatocellular carcinoma , elastic fiber , fiber , pathology , fibrosis , lysyl oxidase , medicine , chemistry , immunohistochemistry , anatomy , biochemistry , extracellular matrix , h&e stain , organic chemistry
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.