Table Of ContentSpringer
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K. Okita (Ed.)
Liver Cirrhosis
With 41 Figures
Springer
KIWAMU OKITA, M.D., Ph.D.
Professor and Chairman
First Department of Internal Medicine
Yamaguchi University School of Medicine
1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
ISBN 978-4-431-68345-2 ISBN 978-4-431-68343-8 (eBook)
DOI 10.1007/978-4-431-68343-8
This symposium was supported by funds from the Viral Hepatitis Research Foundation of Japan.
Printed on acid -free paper
© Springer-Verlag Tokyo 2001
Softcover reprint of the hardcover 1st edition 2001
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SPIN: 10773972
Preface
Since 1998, the Japanese Society of Hepatology has campaigned to fight hepatocellu
lar carcinoma (HCC). Because the mortality rate for this disease has reached more
than 30 per 100,000 population, the organizing committee chose HCC as the main
topic of the 1999 Yamaguchi Symposium on Liver Diseases. Regarding hepatocar
cinogenesis, we know that HCC often develops secondary to liver cirrhosis; thus liver
cirrhosis must be recognized as a prevalent pathological condition leading to HCC.
If we can control liver fibrosis, we can reduce the risk for HCC among patients with
chronic hepatitis. To achieve this goal, we must know more about hepatic fibrosis.
Professor Michael J.P. Arthur is familiar as a leading scientist in this field. We were
fortunate that he accepted our invitation to speak. His lecture titled "Mechanisms of
the Progression and Regression of Liver Fibrosis" provided important advice for
developing antifibrotic agents. We also invited Professor Mark A. Zern, who has been
studying hepatic fibrosis for some time. In the symposium he talked about novel
approaches, including gene therapy, to treat acute and chronic hepatic diseases in the
21st century. In addition to the informative talks by those guests from abroad, the
lecture by Dr. J. Fujimoto was very impressive. He revealed that gene therapy using
hepatocyte growth factor (HGF) could inhibit progression to liver cirrhosis in rats
repeatedly injected with dimethylnitrosamine (DMN). Dr. Fujimoto has already pub
lished his finding that administration of HGF reduced hepatocarcinogenesis in rats.
We look forward to the progress of his study and its confirmation in human studies
as early as possible.
In view of the number of patients with chronic liver diseases caused by HBV and
HCV, however, we cannot simply wait for the development of elegant antifibrotic
drugs. For this reason, the presentation showing that interferon therapy in chronic
hepatitis C reduced the risk of HCC should be considered seriously. Two days of dis
cussions were beneficial for understanding the biology of hepatic bibrosis. Therefore,
this proceedings will be useful for physicians and hepatologists who are interested not
only in hepatic fibrogenesis but also in hepatocarcinogenesis.
The organizing committee expresses sincere thanks to all participants and to the
Viral Hepatitis Research Foundation of Japan, with special gratitude for their finan
cial support.
ORGANIZING COMMITTEE OF THE YAMAGUCHI SYMPOSIUM
ON LIVER DISEASE
Kiwamu Okita, M.D., Yamaguchi University, Ube
Kenichi Kobayashi, M.D., Kanazawa University, Kanazawa
Masamichi Kojiro, M.D., Kurume University, Kurume
Masao Ornata, M.D., University of Tokyo, Tokyo
Norio Hayashi, M.D., Osaka University, Osaka
v
Table of Contents
Preface. .. . . . . . . . . . .. . . . . . . . . .. . . . . . . . . . . . . .. . .... . . . . . . . . . . . . . V
List of Participants .............................................. IX
Mechanisms of Progression and Regression of Liver Fibrosis
M.J.P. ARTHUR ................................................. .
Analysis of Proteins and Genes Dominantly Expressed in Stellate Cells
of Activated Phenotype: the Molecular Approach to Liver Fibrosis
N. KAWADA .................................................... 10
Novel Therapeutic Modalities for Hepatic Diseases
H. WEGE, J. Wu, and M.A. ZERN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Gene Therapy for Liver Cirrhosis: Novel Treatment in the New Millennium
J. FUJIMOTO and T. UEKI ......................................... 30
Present Status and Future of Gene Therapy for Hepatic Fibrosis
T. UENO, T. NAKAMURA, H. UENO, K. TANIKAWA, and M. SATA . . . . . . . . . . . 36
Inhibitory Effects of the Herbal Medicine Sho-saiko-to on Liver Fibrosis
K. KAYANO, I. SAKAIDA, and K. OKITA ............................... 44
Resolution of Fibrosis in Hepatitis C Patients with Sustained Response to
Interferon: Long-Term Effects of Interferon Therapy on Histological
Improvement
Y. SHIRATORI, H. YOSHIDA, and M. OMATA ........................... 56
Factors Related to the Development of Hepatocellular Carcinoma
from Chronic Liver Diseases Type Band C
T. OKANOUE, Y. MURAKAMI, M. MINAMI, and Y. ITOH . . . . . . . . . . . . . . . . . . 65
Quasispecies of Hepatitis C Virus in Serum and in Three Different Parts
of the Liver of Patients with Chronic Hepatitis
M. HONDA, A. SAKAI, S. KANEKO, and K. KOBAYASHI ................... 73
Development of Hepatocellular Carcinoma in Liver Cirrhosis:
Pathomorphologic Viewpoint
M. KOJIRO ..................................................... 80
VII
VIII Table of Contents
HGF-Related Proteins in Hepatocellular Carcinoma (HCC)
S. HIRONO, K. NAGATA, A. MORIUCHI, M. ONAGA, H. FUJIWARA, T. HORI,
A. IDO, T. SHIM OMURA, K. HAYASHI, N. KITAMURA, and H. TSUBOUCHI 87
Significance of al-6 Fucosylation in Hepatocellular Carcinoma
E. MIYOSHI, K. NODA, N. TANIGUCHI, Y. SASAKI, and N. HAYASHI. . . . . . . . . 93
Energy Metabolism in Liver Cirrhosis: Its Characteristics, Clinical
Significance, and Possible Intervention
H. MORIWAKI, M. TAJIKA, Y. MIWA, and M. KATO . . . . . . . . . . . . . .. . . . . . . . 105
Effects of Abnormal Hormone Dynamics on Protein-Energy Malnutrition
in Cirrhotic Patients: Pathophysiological and Therapeutic Implications
A. WATANABE .................................................. 112
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
List of Participants
Arthur, Michael J.P. School of Medicine
University of Southampton
Southampton, Hampshire, UK
Fujimoto, Jiro First Department of Surgery
Hyogo College of Medicine
Hyogo, Japan
Hayashi, Norio Department of Molecular Therapeutics
Osaka University Graduate School of Medicine
Osaka, Japan
Hino, Keisuke First Department of Internal Medicine
Yamaguchi University School of Medicine
Yamaguchi, Japan
Hirakawa, Kazuhide First Department of Surgery
Hyogo College of Medicine
Hyogo, Japan
Hirono, Shuichi Second Department of Internal Medicine
Miyazaki Medical College
Miyazaki, Japan
Honda, Masao First Department of Internal Medicine
Kanazawa University, School of Medicine
Ishikawa, Japan
Ichida, Takafumi Third Department of Internal Medicine
Niigata University School of Medicine
Niigata, Japan
Kayano, Kozo First Department of Internal Medicine
Yamaguchi University, School of Medicine
Yamaguchi, Japan
Kawada, Norifumi Third Department of Internal Medicine
Osaka City University Medical School
Osaka, Japan
IX
X List of Participants
Kobayashi, Kenichi First Department of Internal Medicine
Kanazawa University, School of Medicine
Ishikawa, Japan
Kojiro, Masamichi Department of Pathology
Kurume University School of Medicine
Fukuoka, Japan
Kurokawa, Fumie First Department of Internal Medicine
Yamaguchi University School of Medicine
Yamaguchi, Japan
Miyoshi, Eiji Department of Molecular Therapeutics
Osaka University Graduate School of Medicine
Osaka, Japan
Moriwaki, Hisataka First Department of Internal Medicine
Gifu University School of Medicine
Gifu, Japan
Nakamura, Toru Second Department of Internal Medicine
Kurume University School of Medicine
Fukuoka, Japan
Nakanishi, Toshio First Department of Internal Medicine
Hiroshima University, School of Medicine
Hiroshima, Japan
Okanoue, Takeshi Third Department of Internal Medicine
Kyoto Prefectural University of Medicine
Kyoto, Japan
Okita, Kiwamu First Department of Internal Medicine
Yamaguchi University School of Medicine
Yamaguchi, Japan
Okuno, Masataka First Department of Internal Medicine
Gifu University School of Medicine
Gifu, Japan
Ornata, Masao Department of Gastroenterology
The University of Tokyo, Faculty of Medicine
Tokyo, Japan
Sakaida, Isao First Department of Internal Medicine
Yamaguchi University School of Medicine
Yamaguchi, Japan
Shiratori, Yasushi Department of Gastroenterology
The University of Tokyo, Faculty of Medicine
Tokyo, Japan
List of Participants XI
Suzuki, Chieko First Department of Internal Medicine
Yamaguchi University School of Medicine
Yamaguchi, Japan
Takahara, Terumi Third Department of Internal Medicine
Toyama Medical and Pharmaceutical University,
Faculty of Medicine
Toyama, Japan
Tanikawa, Kyuichi Director General, Japanese Society for Hepatology
Kurume University School of Medicine
Fukuoka, Japan
Ueki, Koji First Department of Surgery
Hyogo College of Medicine
Hyogo, Japan
Ueno, Takato Second Department of Internal Medicine
Kurume University School of Medicine
Fukuoka, Japan
Watanabe, Akiharu Third Department of Internal Medicine
Toyama Medical and Pharmaceutical University,
Faculty of Medicine
Toyama, Japan
Zern, Mark A. University of California
Davis Medical Center Transplant Research Program
Sacramento, CA, USA
