A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease

Tohru Utsunomiya, Masahiro Okamoto, Shigeki Wakiyama, Masaji Hashimoto, Kengo Fukuzawa, Takahiro Ezaki, Shinichi Aishima, Yasuji Yoshikawa, Taizo Hanai, Hiroshi Inoue, Graham F. Barnard, Masaki Mori

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8 Citations (Scopus)

Abstract

Aim: To study a more accurate quantification of hepatic fibrosis which would provide clinically useful information for monitoring the progression of chronic liver disease. Methods: Using a cDNA microarray containing over 22000 clones, we analyzed the gene-expression profiles of non-cancerous liver in 74 patients who underwent hepatic resection. We calculated the ratio of azanstained: total area, and determined the morphologic fibrosis index (MFI), as a mean of 9 section-images. We used the MFI as a reference standard to evaluate our method for assessing liver fibrosis. Results: We identified 39 genes that collectively showed a good correlation (r > 0.50) between gene-expression and the severity of liver fibrosis. Many of the identified genes were involved in immune responses and cell signaling. To quantify the extent of liver fibrosis, we developed a new genetic fibrosis index (GFI) based on gene-expression profiling of 4 clones using a linear support vector regression analysis. This technique, based on a supervised learning analysis, correctly quantified the various degrees of fibrosis in both 74 training samples (r = 0.76, 2.2% vs 2.8%, P < 0.0001) and 12 independent additional test samples (r = 0.75, 9.8% vs 8.6%, P < 0.005). It was far better in assessing liver fibrosis than blood markers such as prothrombin time (r = -0.53), type IV collagen 7s (r = 0.48), hyaluronic acid (r = 0.41), and aspartate aminotransferase to platelets ratio index (APRI) (r = 0.38). Conclusion: Our cDNA microarray-based strategy may help clinicians to precisely and objectively monitor the severity of liver fibrosis.

Original languageEnglish
Pages (from-to)383-390
Number of pages8
JournalWorld Journal of Gastroenterology
Volume13
Issue number3
DOIs
Publication statusPublished - Jan 21 2007

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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    Utsunomiya, T., Okamoto, M., Wakiyama, S., Hashimoto, M., Fukuzawa, K., Ezaki, T., Aishima, S., Yoshikawa, Y., Hanai, T., Inoue, H., Barnard, G. F., & Mori, M. (2007). A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease. World Journal of Gastroenterology, 13(3), 383-390. https://doi.org/10.3748/wjg.v13.i3.383