Hepatotoxicity: The adverse effects of drugs and other chemicals on the liver

Hepatotoxicity: The adverse effects of drugs and other chemicals on the liver

GASTROENTEROLOGY 2000;118:984–985 PRINT AND MEDIA REVIEWS Lawrence S. Friedman, M.D. Print and Media Review Editor Gastrointestinal Unit, Blake 456D ...

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GASTROENTEROLOGY 2000;118:984–985

PRINT AND MEDIA REVIEWS Lawrence S. Friedman, M.D. Print and Media Review Editor Gastrointestinal Unit, Blake 456D Massachusetts General Hospital Boston, Massachusetts 02114

Textbook of Gastroenterology. 3rd edition. Edited by Tadataka Yamada, David H. Alpers, Loren Laine, Chung Owyang, and Don W. Powell. 3504 pp. $269.00. Lippincott Williams & Wilkins, Philadelphia, Pennsylvania. 1999. ISBN 0-39758735-X. The breadth of knowledge and the scope of practice in gastroenterology have grown exponentially in the past 3 decades. Our understanding of basic mechanisms is constantly growing. This has been paralleled by an expansion of our approaches to therapy. The gastroenterologist at the dawn of the 21st century needs to be able to find a source of information to use as a starting point. The 2-volume third edition of Yamada’s Textbook of Gastroenterology in 143 chapters with 210 contributors substantially meets this need. Nearly 30% of the chapters have new authors, and all have been updated. The textbook is divided into 4 major parts. The first part includes chapters dealing with basic mechanisms of normal and abnormal gastrointestinal function. Physiology, biochemistry, motility, and nutrition are covered in 27 separate chapters. The second part is dedicated to approaches to common gastrointestinal problems. It includes discussions of the evaluation and management of the signs and symptoms of disease from dyspepsia to diarrhea, as well as psychosocial factors and genetic counseling. This part also includes chapters on advice to travelers and risks to health-care providers. Part 3 is the standard discussion of specific gastrointestinal disease states. It covers the gastrointestinal organ structures and abdominal cavity abnormalities and has a variety of chapters on gastrointestinal manifestations of other diseases. Hepatology is not included. Part 4 includes diagnostic and therapeutic modalities in gastroenterology. These chapters run the gamut from clinical decision making through endoscopic practice, pathology, and imaging. The chapters are well organized with an outline at the beginning of each chapter and a highlighted box at the end of the chapter that refers the reader to other chapters in which some of the same issues are discussed. Excellent tables, charts, and illustrations are plentiful. Although there are obvious differences in style, this is not a major drawback because of the large number of chapters. References are extensive and as up-to-date as can be expected (1997–1998) in such a large text. I have few criticisms of this textbook. There are a large number of photographs throughout. The only full-color photos are in 2 relatively small sections in the middle of each volume. These are referenced in the black-and-white photos in the chapters. This is obviously the publisher’s cost-saving decision but does detract from several of the chapters. Several authors have written more than one chapter. The use of more contribu-

tors would have broadened the viewpoint of this book. There is a chapter that discusses evidence-based medicine and how to assess studies in the literature. Additional chapters might have included an overview of current bench and clinical research techniques, ethics, cost-effective clinical practice, ‘‘office’’ gastroenterology, and the use of computers and the Internet in gastroenterology. This still remains the specialty textbook with the broadest approach to the study of gastroenterology. Gastroenterology requires a mastery of multiple disciplines. Chapters describing surgical techniques, imaging modalities, pathology, and pediatrics are all necessary in an up-to-date text. These volumes meet these requirements. In an age when many of us have personal computers on our desks and in our pockets, there is still a major role for the textbook and journal. We can hold and turn pages as we peruse through a variety of topics. This does come at a hefty price, but it is well worth the $269.00 and the 10 pound per volume weight. Bottom Line: This textbook is a must for gastroenterologists and others who are involved with diseases of the gastrointestinal tract. MARSHALL S. BEDINE, M.D. Johns Hopkins at Greenspring Station Lutherville, Maryland Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver. 2nd edition. By H. J. Zimmerman. 800 pp. $145.00. Lippincott Williams & Wilkins, Philadelphia, Pennsylvania. 1999. ISBN 0-7817-1952-6. Dr. Zimmerman was the foremost consultant regarding drug hepatotoxicity for many years. His considerable contributions to our understanding of hepatotoxic reactions from drugs are amply demonstrated in this book. The volume is well organized. Dr. Zimmerman wrote well, and the stories he recounts about evolution of knowledge in many areas, particularly about specific drug-induced injuries, are both interesting and informative. Dr. Zimmerman begins chapter 1 by stating that ‘‘Chemical injury to the liver is a many-faceted phenomenon’’ and then proceeds through 25 chapters to fill in the details. The first edition of this book, published in 1978, was a milestone in defining the important emerging field of drug- and chemicalinduced hepatotoxicity. The second edition offers a thorough, scholarly, and well-written update of more than 2 decades of remarkable progress. Between editions, great strides have been made in understanding mechanisms of drug metabolism with considerable attention directed toward the roles of the various enzymes in the cytochrome P-450 system that often lead to the production of highly reactive metabolites. Equally important

May 2000

have been advances in the understanding of the role of defense systems, including hepatoprotectants and pathways that are important in detoxifying reactive intermediate metabolites. The book is divided into 4 major sections beginning with thorough discussions of the pathogenesis of chemical- and drug-induced injury followed by descriptions of models of experimental hepatotoxicity and a compilation of information concerning environmental hepatotoxins. The last section is a book within a book describing the spectrum of drug-induced liver disorders, with chapters devoted to presentations of hepatotoxicity for major classes of therapeutic agents and the problems caused by individual drugs within these groups. There are many laudable sections. The roles of cytochrome P-450 enzymes in drug metabolism and their contribution to the pathogenesis of hepatotoxicity are fully developed. Risk factors affecting susceptibility to drug-induced hepatic injury, e.g., age, sex, patterns of use, and interactions with other agents, are presented in detail. Furthermore, there is emphasis on the limits of present knowledge on factors predisposing an individual to an adverse drug reaction. The section on histopathology created in conjunction with Dr. Kamal Ishak of the Armed Forces Institute of Pathology is excellent, and the photomicrographs are superb. The chapter on the hepatotoxic effects of alcohol is especially well done and amply demonstrates the many situations in which interactions between regular or excessive use of alcohol and therapeutic agents may co-promote hepatotoxicity. There have been reports of hepatic injury of some type from more than 900 therapeutic agents, and reports about more agents appear each month. The spectrum of types of reactions recognized as an adverse reaction to a therapeutic agent covers the gamut of known liver disorders. Hepatitis of all types (acute, chronic, and fulminant), cholestasis, granulomas, steatosis, vascular disorders, and a variety of tumors both benign and malignant are all within the spectrum. The vast majority of



drugs associated with hepatotoxicity have entered the market within the past half century. Dr. Zimmerman addresses the question as to how new drugs should be tested, comments on risk-benefit considerations, and serves as narrator and guide to the lessons learned thus far regarding agents in which recognition of the presence and extent of hepatotoxicity escaped detection during development and testing, only to become apparent after release into the broad marketplace. The second edition of Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver will undoubtedly be useful to clinicians and scientists from many disciplines. There is much for the hepatologist, gastroenterologist, pathologist, and pharmacologist. As stated at the beginning of the volume, drug-induced hepatotoxicity is multifaceted, and increased understanding will hopefully lead to more rationally developed and reasonably tested agents, and to a heightened awareness by clinicians of the possible roles of therapeutic drugs as causes of liver injury. Both the breadth and the limitations of present knowledge are fully examined. Future generations of books on hepatotoxicity will undoubtedly be replete with the use of genetic testing to determine whether an individual is likely to develop an adverse drug reaction. Keen observation, extensive testing, and careful postmarketing evaluation, coupled with knowledge on the metabolism of an individual agent and what resulted when similar agents were given to humans, continue to dominate our approaches. Bottom Line: This volume provides a full and exciting view of a field that is at the end of one era and the beginning of another. The book serves us well as a reliable guide to where we are. I recommend it without reservation. WILLIS C. MADDREY, M.D. University of Texas Southwestern Medical Center Dallas, Texas