Springer
Tokyo Berlin Heidelberg New York Hong Kong London Milan Paris
K. Okita (Ed.)
NASH and
Nutritional Therapy
With 35 Figures, Including 5 in Color
1 3
Kiwamu Okita, M.D., Ph.D.
Professor and Chairman
Department of Gastroenterology and Hepatology Yamaguchi University School of Medicine
1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan
ISBN 4-431-21388-0 Springer-Verlag Tokyo Berlin Heidelberg New York
Library of Congress Control Number: 2004113088
This symposium was supported by funds from the Viral Hepatitis Research Foundation of Japan.
Printed on acid-free paper
© Springer-Verlag Tokyo 2005 Printed in Japan
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broad- casting, reproduction on microfilms or in other ways, and storage in data banks.
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
Product liability: The publisher can give no guarantee for information about drug dosage and appli- cation thereof contained in this book. In every individual case the respective user must check its accu- racy by consulting other pharmaceutical literature.
Springer is a part of Springer Science+Business Media springeronline.com
Typesetting: SNP Best-set Typesetter Ltd., Hong Kong Printing and binding: Shinano Inc., Japan
Preface
Fatty liver disease including nonalcoholic steatohepatitis (NASH) involves the accu- mulation of triglycerides in hepatocytes with necrosis, inflammation, and often fibro- sis with progression to cirrhosis. The two-hit model summarizes the important early metabolic events leading to hepatocellular necrosis in NASH. In these proceedings, we present various new findings and a review of NASH. The liver has an important role in nutritional homeostasis, and liver diseases lead to abnormalities in nutrient metabolism and to subsequent malnutrition, especially in patients with liver cirrho- sis. Protein-energy malnutrition (PEM) is a common finding in cirrhotic patients; it may be present in 20% of patients with well-compensated disease and in more than 60% of patients with severe liver insufficiency. Therefore, special attention is required in the management of those patients; proper nutritional assessment and support for cirrhotic patients is essential. This volume also includes new findings on the nutri- tional aspects of the treatment of liver cirrhosis, which we hope will contribute to a better understanding of NASH and nutritional treatment.
We thank Otsuka Pharmaceutical Co. Ltd. for their continuing support.
Organizing Committee of the Yamaguchi Symposium on Liver Disease Kiwamu Okita, M.D., Yamaguchi University, Ube
Masamichi Kojiro, M.D., Kurume University, Kurume Masao Omata, M.D., The University of Tokyo, Tokyo Norio Hayashi, M.D., Osaka University, Osaka
Takeshi Okanoue, M.D., Kyoto Prefectural University of Medicine, Kyoto Secretary General
Isao Sakaida, M.D., Yamaguchi University, Ube
V
Table of Contents
Preface . . . . V List of Participants . . . . IX Nonalcoholic Fatty Liver (NAFL): Overview
S.H. Caldwell, A. Al-Osaimi, C. Chang, C. Davis, E.E. Hespenheide, L. Krugner-Higby, A.I. Hylton, J.C. Iezzoni, T.H. Le, R.K. Nakamoto,
J. Redick, and T. Peterson . . . . 1 Role of Leptin in Pathogenesis of NASH
K. Ikejima, T. Lang, S. Yamashina, N. Enomoto, Y. Takei, and
N. Sato . . . . 44 Zone 3 Predominance of Histopathological Features in
Nonalcoholic Steatohepatitis
H. Enzan, M. Toi, Y. Hayashi, T. Hamauzu, N. Kuroda, and M. Hiroi . . . 50 Genetic Background of Japanese Patients with Nonalcoholic Steatohepatitis (NASH)
T. Saibara, C. Namikawa, Z. Shu-Ping, M. Rui-Hong, Y. Nozaki, Y. Nemoto, M. Ono, N. Akisawa, S. Iwasaki, M. Hiroi, H. Enzan, and
S. Onishi . . . . 58 Predictors of Nonalcoholic Steatohepatitis in Japanese Patients:
Thioredoxin and NASH
T. Okanoue, N. Yamauchi, M. Furutani, A. Hirohama, Y. Sumida, and
T. Nakashima . . . . 64 Clinical Features of Patients with Nonalcoholic Fatty Liver Disease
E. Hashimoto, H. Kaneda, Y. Yoshioka, M. Taniai, K. Tokushige, and
K. Shiratori . . . . 73 Pathogenesis and Significance of Restricted Diet and Exercise Therapy in
Nonalcoholic Steatohepatitis (NASH)
T. Ueno, T. Nakamura, N. Sasaki, Y. Morita, E. Nagata, and M. Sata . . . 84
VII
VIII Table of Contents
Mammalian Target of Rapamycin (mTOR)
K. Yonezawa . . . . 92 Effect of Oral Supplementation with Branched-Chain Amino Acids on
Albumin Concentration in the Early Stage of Cirrhosis
S. Nishiguchi, D. Habu, and S. Shiomi . . . . 100 Nutritional Therapy in Patients with Liver Cirrhosis
M. Tsuchiya, I. Sakaida, M. Okamoto, and K. Okita . . . . 108
Subject Index . . . . 115
List of Participants
Caldwell, Stephen H. Division of Gastroenterology and Hepatology University of Virginia Health System
Virginia, USA
Enzan, Hideaki First Department of Pathology, Kochi Medical School Kochi, Japan
Hashimoto, Etsuko Institute of Gastroenterology
Tokyo Women’s Medical University, Tokyo, Japan Hayashi, Norio Department of Molecular Therapeutics
Osaka University Graduate School of Medicine Osaka, Japan
Hino, Keisuke Department of Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University School of Medicine Yamaguchi, Japan
Ichida, Takafumi Third Department of Internal Medicine, Niigata University Niigata, Japan
Ikejima, Kenichi Department of Gastroenterology
Juntendo University School of Medicine, Tokyo, Japan Kodama, Takahiro Department of Internal Medicine/Gastroenterology
Yamaguchi Central Hospital, Yamaguchi, Japan Kojiro, Masamichi First Department of Pathology
Kurume University School of Medicine, Fukuoka, Japan Nakanishi, Toshio Department of Radiology, School of Medicine
Hiroshima University, Hiroshima, Japan
Nishiguchi, Shuhei Department of Hepatology, Graduate School of Medicine Osaka City University, Osaka, Japan
Okanoue, Takeshi Third Department of Internal Medicine
Kyoto Prefectural University of Medicine, Kyoto, Japan
IX
Okita, Kiwamu Department of Gastroenterology and Hepatology Yamaguchi University School of Medicine Yamaguchi, Japan
Omata, Masao Department of Gastroenterology
Graduate School of Medicine, The University of Tokyo Tokyo, Japan
Onishi, Saburo Department of Internal Medicine, Kochi Medical School Kochi, Japan
Saibara, Toshiji Department of Internal Medicine, Kochi Medical School Kochi, Japan
Sakaida, Isao Department of Gastroenterology and Hepatology Yamaguchi University School of Medicine Yamaguchi, Japan
Sata, Michio Second Department of Medicine
Kurume University School of Medicine, Kurume, Japan Tanikawa, Kyuichi International Institute for Liver Research, Fukuoka, Japan Terai, Shuji Department of Gastroenterology and Hepatology
Yamaguchi University School of Medicine Yamaguchi, Japan
Tokushige, Katsutoshi Institute of Gastroenterology
Tokyo Women’s Medical University, Tokyo, Japan Tsuchiya, Masako Department of Gastroenterology and Hepatology
Yamaguchi University School of Medicine Yamaguchi, Japan
Ueno, Takato Research Center for Innovative Cancer Therapy Kurume University School of Medicine, Kurume, Japan Yonezawa, Kazuyoshi Biosignal Research Center, Kobe University, Kobe, Japan X List of Participants
