title: Fibrogenesis and Carcinogenesis in Nonalcoholic Steatohepatitis (NASH): Involvement of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinase (TIMPs).
abstract: Nonalcoholic steatohepatitis (NASH) is emerging worldwide because life-styles have changed to include much over-eating and less physical activity. The clinical and pathophysiological features of NASH are very different from those of HBV- and HCV-chronic liver diseases. The prognosis of NASH is worse among those with nonalcoholic fatty liver diseases (NAFLD), and some NASH patients show HCC with or without cirrhosis. In the present review we discuss fibrogenesis and the relationship between fibrosis and HCC occurrence in NASH to clarify the role of MMPs and TIMPs in both mechanisms. Previously we proposed MMP and TIMP expression in the multi-step occurrence of HCC from the literature based on viral-derived HCC. We introduce again these expressions during hepatocarcinogenesis and compare them to those in NASH-derived HCC, although the relationship with hepatic stem/progenitor cells (HPCs) invasion remains unknown. Signal transduction of MMPs and TIMPs is also discussed because it is valuable for the prevention and treatment of NASH and NASH-derived HCC.
authors: Department of Internal Medicine, Sanno Hospital, International University of Health and Welfare, Tokyo 107-0052, Japan. iokazaki@iuhw.ac.jp.
authors: Isao
authors: I
authors: Okazaki
authors: Department of Surgery, International University of Health and Welfare Hospital, Tochigi 329-2763, Japan. norotaku@gmail.com.
authors: Takuji
authors: T
authors: Noro
authors: Department of Surgery, International University of Health and Welfare Hospital, Tochigi 329-2763, Japan. t-nobuhiro@iuhw.ac.jp.
authors: Nobuhiro
authors: N
authors: Tsutsui
authors: Department of Radiology, International University of Health and Welfare Hospital, Tochigi 329-2763, Japan. yamanouchi@iuhw.ac.jp.
authors: Eigoro
authors: E
authors: Yamanouchi
authors: Department of Pathology, International University of Health and Welfare Hospital, Tochigi 329-2763, Japan. hajimek@iuhw.ac.jp.
authors: Hajime
authors: H
authors: Kuroda
authors: Department of Pathology, Ofuna Chuo Hospital, Kanagawa 247-0056, Japan. masayuki-nakano@ofunachuohp.net.
authors: Masayuki
authors: M
authors: Nakano
authors: Department of Internal Medicine, Kitasato University Medical Center, Saitama 364-8501, Japan. yokomori@insti.kitasato-u.ac.jp.
authors: Hiroaki
authors: H
authors: Yokomori
authors: Department of Regenerative Medicine, Tokai University School of Medicine and Institute of Medical Sciences, Isehara 259-1193, Japan. yutakai@is.icc.u-tokai.ac.jp.
authors: Yutaka
authors: Y
authors: Inagaki