- Email: [email protected]
Molecular biology and immunology in hepatology
February 2004
to contraindicate use of argon plasma coagulation, a concept that is not widely accepted in the United States. There are no books comparable to this one for teaching the fundamentals of gastrointestinal endoscopy. Training guidelines from the ASGE cover some of the areas presented, but not in as much detail or with the graphical illustrations provided on the CD. Videotapes available from the ASGE cover some of the therapeutic endoscopic procedures in more depth than this text, but do not cover the basics of endoscopy, as well as this text and its accompanying CDs. All beginning trainees in gastrointestinal endoscopy should be required to read Practical Gastrointestinal Endoscopy and study the accompanying CDs. They should do so at the beginning of their gastrointestinal fellowship and then return to the material frequently during training. Instructors of endoscopy should find the material helpful in their own teaching practices. I also encourage senior endoscopists to read this text as a good review of the basics and to pick up some pearls that will enhance their own endoscopic skills. I only hope the authors follow up this text with a similar book for teaching advanced endoscopy such as ERCP and endoscopic ultrasonography. Bottom Line: Required reading for all gastroenterology trainees and their instructors.
MICHAEL B. KIMMEY, M.D. University of Washington Seattle, Washington Bile Acids and Pregnancy–Falk Workshop. Edited by U. Leuschner, P.A. Berg, and J. Holtmeier. 80 pp. $56.00. Kluwer Academic Publishers, Boston, Massachusetts, 2002. ISBN 0-7923-8782-1. Web address for ordering: www.wkap.nl This little book contains summaries, some very brief, of a Falk Workshop held in June 2002 in Freiburg. The title is misleading, as the first portion of the book deals with the as of yet still unanswered question: why does the pregnant woman not reject her fetus? Of these 5 papers, 3 are abstracts only. The remaining 2 are fascinating. Dr. Vacchio, from the NIH, discusses the transient state of tolerance induced in the pregnant woman, a state that allows the foreign fetus to stay aboard until maturity. Pregnancy is “non-inflammatory”—not associated with trauma, which elicits a “danger” signal, and awakens the immune system. Instead, the steroids and cytokines of the placenta bias the mother’s immune system to Th-2 type responses, thus allowing the pregnancy to proceed. Later in the book Dr. Formby from the Rasmus Institute in Santa Barbara notes that 30% of human pregnancies are lost early in gestation and that the cause of the 60% or more of pregnancies that result in spontaneous abortion remains unknown, but may be due to immune mechanisms (“rejection” of the fetus). These investigators propose that one of the steroid modulators of the maternal immune response is progesterone. The latter two thirds of the book deals with more familiar territory– bile acids and pregnancy–with emphasis on the disorder known as intrahepatic cholestasis of pregnancy (ICP).
PRINT AND MEDIA REVIEWS
619
Three of these papers are from Professor Reyes’s unit in Santiago, Chile, where ICP is quite common. He reviews the clinical hallmarks of the condition, and the data on alterations in progesterone and bile acid metabolism in affected pregnancies. Ursodeoxycholic acid (Urso–marketed by Falk as Ursofalk) ameliorates the pruritus of ICP, and reverses the abnormalities in progesterone and bile acid metabolism. One of the most vexing problems about ICP is its association with an increase in prematurity and stillbirth. Dr. Palma reports data demonstrating a decrease in prematurity and an attendant increase in birth weight in patients with ICP treated with Urso. Is normal pregnancy a relatively cholestatic state? We know that there is a “physiologic cholestasis” of the newborn–reflecting immaturity of the mechanisms of the enterohepatic circulation of bile acids. Dr. Arrese et al. would have us believe so, and argue that women with ICP have either an inherited exaggeration if this normal physiology, or a polymorphism in the response to certain xenobiotics. Dr. Mazzella and the group from Bologna are quite persuasive that the appropriate dose of Urso for ICP is 20 –25 mg⫺1 䡠 kg⫺1 䡠 day, higher than the dose usually used in treating PBC. The final chapter, from Calmus and the group at Hopital Cochin in Paris, explores the immune modulatory effects of bile acids, and the beneficial effects of Urso. It’s too bad that the editor was unsuccessful in getting a real manuscript from several of his participants–the abstracts are tantalizing, and not all of us could go to the meeting. The chapter by Dr. Marin looks interesting, but was written in Faulknerian sentences that were virtually impenetrable. What did I learn? First of all, the data supporting the use of Urso in ICP is becoming more and more compelling, even for those of us living in the United States where the use of any medication in pregnancy is scrutinized. Its use is backed up by clinical and experimental studies showing improvement in laboratory results and outcome. Secondly, the field of the relative “immune privilege” of pregnancy is a fascinating one, particularly for those of us who struggle to understand the immune responses to hepatitis C, and to control the immune reactions to liver transplantation.
CAROLINE A. RIELY, M.D. Departmemts of Medicine and Pediatrics University of Tennessee Health Science Center Memphis, Tennessee Molecular Biology and Immunology in Hepatology. Edited by T. Tusji, T. Higashi, M. Zeniya, and K.-H. Meyer zum Bu¨ schenfelde. 362 pp. $145.00. Elsevier, 2002. ISBN 0-444-50653-5. Web address for ordering: www.elsevier.com Many key diseases of the liver involve viruses, the immune system, or both. Substantial progress in molecular virology and molecular immunology makes possible a synthesis of these diverse areas, and this has been attempted in a book, “Molecular Biology and Immunology in Hepatology: Advances in the
620
PRINT AND MEDIA REVIEWS
Treatment of Intractable Liver Disease.” The title is odd, because the strongest parts of the book are more about pathogenesis than about therapeutics. Nevertheless, the 25 chapters by a total of 50 contributors cover the major aspects of liver disease on which molecular biology and immunology may be brought to bear: viral hepatitis, autoimmune liver disease, and liver transplantation. In addition, there are chapters dealing with hepatocellular carcinoma, alcoholic liver disease, and fibrosis. The major strength of this book is the high level of scholarship displayed in the majority of the chapters. Among other excellent chapters, those dealing with the molecular biology of hepatitis B virus, the immunology of hepatitis C infection, and T cell recognition during autoimmune hepatitis, stand out in dealing with their subject matter succinctly and with great precision. Generally, the approach is scholarly and synthesizes models of liver pathogenesis from the primary literature, although several weaker chapters are more like textbook summaries of established background information. A couple of chapters don’t seem to belong with the rest. One example is the chapter dealing with living related donor liver transplantation, which contains no immunology and no molecular biology, and is a discussion of ethical and technical matters relating to the surgery. This appears linked to the main themes of the book only though the anatomical location of the subject matter. There ought to be emerging information about the immunology and molecular biology of the regenerating liver, but perhaps this is still in the pipeline, and the chapter reflects the state of the art. A chapter on treatment of hepatocellular carcinoma similarly reviews the clinical options, but contains little science. In contrast, a later chapter on adoptive immunotherapy using lymphocyte-activated killer (LAK) cells reviews the available scientific information in detail. Against a generally strong text, there are many distracting errors of grammar, incorrect uses of terminology, and a few factual errors. For instance, some chapters correctly define every abbreviation the first time we meet it; others simply do not define their abbreviations. In matters of information, a superantigen is not a peptide (p. 213), it’s a protein. The glycolipid ligand for the NK-T cell receptor is not abbreviated alpha-Gal-Ser (p. 233), which would presumably be alphaGalactosyl Serine, it is alpha-Gal-Cer, for alpha-Galactosyl Ceramide. In summary, this is a valuable book, which will serve 2 constituencies: basic researchers who need to integrate their understanding of biology with the clinical context, and clinicians who need insight into the biological background of current thinking and practice. While the book is very good, it could be better. It suffers from trying to be several different things: a scientific review of pathogenesis and science-based therapeutics, and–at the same time–a place to discuss matters related to patient care, such as donor selection for transplants. It could have been strengthened by the elimination of the chapters that deal only with clinical issues, and with a firm editorial hand in correcting errors of all kinds.
GASTROENTEROLOGY Vol. 126, No. 2
Bottom Line: A valuable work, with notable weaknesses.
IAN NICHOLAS CRISPE, M.B., B.S., PH.D. David H. Smith Center for Vaccine Biology and Immunology The University of Rochester Rochester, New York Current Diagnosis and Treatment in Gastroenterology, 2nd edition. Edited by Scott L. Friedman, Kenneth R. McQuaid, and James H. Grendell. 867 pp. $59.95. Lange Medical Books/McGrawHill, New York, New York, 2003. ISBN 0838515517. Web address for ordering: www.books.mcgraw-hill.com This is the second edition of Current Diagnosis and Treatment in Gastroenterology, a soft-cover reference that provides concise, cost-effective approaches to diagnosis and management of major gastrointestinal, biliary, pancreatic, and liver diseases. The intended audience is actually not gastroenterologists, but rather medical students, house staff, primary care providers, surgeons, and physician extenders needing a practical reference to aid in the care of their patients with gastrointestinal and liver diseases, both in the office and in the hospital. I feel this text meets its aims, and is written at a level appropriate for the intended audience. However, clinically focused gastroenterologists, especially gastrointestinal fellows, will appreciate the straightforward summaries and strategies provided. This book contains 54 chapters organized into the following 6 sections: general approach to gastrointestinal diseases (chapters 1–15), esophageal diseases (16 –19), diseases of the stomach and small intestine (20 –25), diseases of the colon and rectum (26 –29), diseases of the pancreas (30 –32), and diseases of the liver and biliary system (33–54). Thirteen of the chapters have been completely revised. The editors selected authors actively involved in patient care and teaching; the list of contributors contains many of the thought leaders in gastroenterology and hepatology. Despite a diverse authorship, the editors did an excellent job in arranging the flow of information in each chapter to present the material in a fairly uniform manner. For each topic, chapters follow the same basic format: general considerations which may include information on pathophysiology and epidemiology, clinical findings including signs and symptoms, labs, and imaging, differential diagnosis, complications, treatment, and prognosis. The book is liberally illustrated with tables and figures, including imaging studies, photomicrographs, artist renderings, and algorithms, all with focused, easy-to-follow legends. These superb visual presentations are one of the aspects of the book that I most enjoyed. Scattered throughout the chapters there are also sections entitled “Essentials of Diagnosis” which contain 2–5 bullets of information. These areas are highlighted by a logo of a microscope, which is easily spotted while quickly leafing through a chapter. The index is fairly extensive, with listings of tables and figures. One thing that is not uniform is the location of references. Some chapters have these scattered throughout the chapter, at the end of particular sections, whereas others have them listed
to contraindicate use of argon plasma coagulation, a concept that is not widely accepted in the United States. There are no books comparable to this one for teaching the fundamentals of gastrointestinal endoscopy. Training guidelines from the ASGE cover some of the areas presented, but not in as much detail or with the graphical illustrations provided on the CD. Videotapes available from the ASGE cover some of the therapeutic endoscopic procedures in more depth than this text, but do not cover the basics of endoscopy, as well as this text and its accompanying CDs. All beginning trainees in gastrointestinal endoscopy should be required to read Practical Gastrointestinal Endoscopy and study the accompanying CDs. They should do so at the beginning of their gastrointestinal fellowship and then return to the material frequently during training. Instructors of endoscopy should find the material helpful in their own teaching practices. I also encourage senior endoscopists to read this text as a good review of the basics and to pick up some pearls that will enhance their own endoscopic skills. I only hope the authors follow up this text with a similar book for teaching advanced endoscopy such as ERCP and endoscopic ultrasonography. Bottom Line: Required reading for all gastroenterology trainees and their instructors.
MICHAEL B. KIMMEY, M.D. University of Washington Seattle, Washington Bile Acids and Pregnancy–Falk Workshop. Edited by U. Leuschner, P.A. Berg, and J. Holtmeier. 80 pp. $56.00. Kluwer Academic Publishers, Boston, Massachusetts, 2002. ISBN 0-7923-8782-1. Web address for ordering: www.wkap.nl This little book contains summaries, some very brief, of a Falk Workshop held in June 2002 in Freiburg. The title is misleading, as the first portion of the book deals with the as of yet still unanswered question: why does the pregnant woman not reject her fetus? Of these 5 papers, 3 are abstracts only. The remaining 2 are fascinating. Dr. Vacchio, from the NIH, discusses the transient state of tolerance induced in the pregnant woman, a state that allows the foreign fetus to stay aboard until maturity. Pregnancy is “non-inflammatory”—not associated with trauma, which elicits a “danger” signal, and awakens the immune system. Instead, the steroids and cytokines of the placenta bias the mother’s immune system to Th-2 type responses, thus allowing the pregnancy to proceed. Later in the book Dr. Formby from the Rasmus Institute in Santa Barbara notes that 30% of human pregnancies are lost early in gestation and that the cause of the 60% or more of pregnancies that result in spontaneous abortion remains unknown, but may be due to immune mechanisms (“rejection” of the fetus). These investigators propose that one of the steroid modulators of the maternal immune response is progesterone. The latter two thirds of the book deals with more familiar territory– bile acids and pregnancy–with emphasis on the disorder known as intrahepatic cholestasis of pregnancy (ICP).
PRINT AND MEDIA REVIEWS
619
Three of these papers are from Professor Reyes’s unit in Santiago, Chile, where ICP is quite common. He reviews the clinical hallmarks of the condition, and the data on alterations in progesterone and bile acid metabolism in affected pregnancies. Ursodeoxycholic acid (Urso–marketed by Falk as Ursofalk) ameliorates the pruritus of ICP, and reverses the abnormalities in progesterone and bile acid metabolism. One of the most vexing problems about ICP is its association with an increase in prematurity and stillbirth. Dr. Palma reports data demonstrating a decrease in prematurity and an attendant increase in birth weight in patients with ICP treated with Urso. Is normal pregnancy a relatively cholestatic state? We know that there is a “physiologic cholestasis” of the newborn–reflecting immaturity of the mechanisms of the enterohepatic circulation of bile acids. Dr. Arrese et al. would have us believe so, and argue that women with ICP have either an inherited exaggeration if this normal physiology, or a polymorphism in the response to certain xenobiotics. Dr. Mazzella and the group from Bologna are quite persuasive that the appropriate dose of Urso for ICP is 20 –25 mg⫺1 䡠 kg⫺1 䡠 day, higher than the dose usually used in treating PBC. The final chapter, from Calmus and the group at Hopital Cochin in Paris, explores the immune modulatory effects of bile acids, and the beneficial effects of Urso. It’s too bad that the editor was unsuccessful in getting a real manuscript from several of his participants–the abstracts are tantalizing, and not all of us could go to the meeting. The chapter by Dr. Marin looks interesting, but was written in Faulknerian sentences that were virtually impenetrable. What did I learn? First of all, the data supporting the use of Urso in ICP is becoming more and more compelling, even for those of us living in the United States where the use of any medication in pregnancy is scrutinized. Its use is backed up by clinical and experimental studies showing improvement in laboratory results and outcome. Secondly, the field of the relative “immune privilege” of pregnancy is a fascinating one, particularly for those of us who struggle to understand the immune responses to hepatitis C, and to control the immune reactions to liver transplantation.
CAROLINE A. RIELY, M.D. Departmemts of Medicine and Pediatrics University of Tennessee Health Science Center Memphis, Tennessee Molecular Biology and Immunology in Hepatology. Edited by T. Tusji, T. Higashi, M. Zeniya, and K.-H. Meyer zum Bu¨ schenfelde. 362 pp. $145.00. Elsevier, 2002. ISBN 0-444-50653-5. Web address for ordering: www.elsevier.com Many key diseases of the liver involve viruses, the immune system, or both. Substantial progress in molecular virology and molecular immunology makes possible a synthesis of these diverse areas, and this has been attempted in a book, “Molecular Biology and Immunology in Hepatology: Advances in the
620
PRINT AND MEDIA REVIEWS
Treatment of Intractable Liver Disease.” The title is odd, because the strongest parts of the book are more about pathogenesis than about therapeutics. Nevertheless, the 25 chapters by a total of 50 contributors cover the major aspects of liver disease on which molecular biology and immunology may be brought to bear: viral hepatitis, autoimmune liver disease, and liver transplantation. In addition, there are chapters dealing with hepatocellular carcinoma, alcoholic liver disease, and fibrosis. The major strength of this book is the high level of scholarship displayed in the majority of the chapters. Among other excellent chapters, those dealing with the molecular biology of hepatitis B virus, the immunology of hepatitis C infection, and T cell recognition during autoimmune hepatitis, stand out in dealing with their subject matter succinctly and with great precision. Generally, the approach is scholarly and synthesizes models of liver pathogenesis from the primary literature, although several weaker chapters are more like textbook summaries of established background information. A couple of chapters don’t seem to belong with the rest. One example is the chapter dealing with living related donor liver transplantation, which contains no immunology and no molecular biology, and is a discussion of ethical and technical matters relating to the surgery. This appears linked to the main themes of the book only though the anatomical location of the subject matter. There ought to be emerging information about the immunology and molecular biology of the regenerating liver, but perhaps this is still in the pipeline, and the chapter reflects the state of the art. A chapter on treatment of hepatocellular carcinoma similarly reviews the clinical options, but contains little science. In contrast, a later chapter on adoptive immunotherapy using lymphocyte-activated killer (LAK) cells reviews the available scientific information in detail. Against a generally strong text, there are many distracting errors of grammar, incorrect uses of terminology, and a few factual errors. For instance, some chapters correctly define every abbreviation the first time we meet it; others simply do not define their abbreviations. In matters of information, a superantigen is not a peptide (p. 213), it’s a protein. The glycolipid ligand for the NK-T cell receptor is not abbreviated alpha-Gal-Ser (p. 233), which would presumably be alphaGalactosyl Serine, it is alpha-Gal-Cer, for alpha-Galactosyl Ceramide. In summary, this is a valuable book, which will serve 2 constituencies: basic researchers who need to integrate their understanding of biology with the clinical context, and clinicians who need insight into the biological background of current thinking and practice. While the book is very good, it could be better. It suffers from trying to be several different things: a scientific review of pathogenesis and science-based therapeutics, and–at the same time–a place to discuss matters related to patient care, such as donor selection for transplants. It could have been strengthened by the elimination of the chapters that deal only with clinical issues, and with a firm editorial hand in correcting errors of all kinds.
GASTROENTEROLOGY Vol. 126, No. 2
Bottom Line: A valuable work, with notable weaknesses.
IAN NICHOLAS CRISPE, M.B., B.S., PH.D. David H. Smith Center for Vaccine Biology and Immunology The University of Rochester Rochester, New York Current Diagnosis and Treatment in Gastroenterology, 2nd edition. Edited by Scott L. Friedman, Kenneth R. McQuaid, and James H. Grendell. 867 pp. $59.95. Lange Medical Books/McGrawHill, New York, New York, 2003. ISBN 0838515517. Web address for ordering: www.books.mcgraw-hill.com This is the second edition of Current Diagnosis and Treatment in Gastroenterology, a soft-cover reference that provides concise, cost-effective approaches to diagnosis and management of major gastrointestinal, biliary, pancreatic, and liver diseases. The intended audience is actually not gastroenterologists, but rather medical students, house staff, primary care providers, surgeons, and physician extenders needing a practical reference to aid in the care of their patients with gastrointestinal and liver diseases, both in the office and in the hospital. I feel this text meets its aims, and is written at a level appropriate for the intended audience. However, clinically focused gastroenterologists, especially gastrointestinal fellows, will appreciate the straightforward summaries and strategies provided. This book contains 54 chapters organized into the following 6 sections: general approach to gastrointestinal diseases (chapters 1–15), esophageal diseases (16 –19), diseases of the stomach and small intestine (20 –25), diseases of the colon and rectum (26 –29), diseases of the pancreas (30 –32), and diseases of the liver and biliary system (33–54). Thirteen of the chapters have been completely revised. The editors selected authors actively involved in patient care and teaching; the list of contributors contains many of the thought leaders in gastroenterology and hepatology. Despite a diverse authorship, the editors did an excellent job in arranging the flow of information in each chapter to present the material in a fairly uniform manner. For each topic, chapters follow the same basic format: general considerations which may include information on pathophysiology and epidemiology, clinical findings including signs and symptoms, labs, and imaging, differential diagnosis, complications, treatment, and prognosis. The book is liberally illustrated with tables and figures, including imaging studies, photomicrographs, artist renderings, and algorithms, all with focused, easy-to-follow legends. These superb visual presentations are one of the aspects of the book that I most enjoyed. Scattered throughout the chapters there are also sections entitled “Essentials of Diagnosis” which contain 2–5 bullets of information. These areas are highlighted by a logo of a microscope, which is easily spotted while quickly leafing through a chapter. The index is fairly extensive, with listings of tables and figures. One thing that is not uniform is the location of references. Some chapters have these scattered throughout the chapter, at the end of particular sections, whereas others have them listed