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Fatty Liver Disease; NASH and Related Disorders

2005; Elsevier BV; Volume: 129; Issue: 5 Linguagem: Inglês

10.1053/j.gastro.2005.09.050

1528-0012

Michael Charlton,

Endoplasmic Reticulum Stress and Disease

NAFLD is the Rodney Dangerfield of liver diseases. It simply doesn’t get the respect it deserves. Even the acronyms NAFLD and NASH are, in essence, diagnoses of exclusion defined by lack of a causitory role of alcohol. Until quite recently, the United Network for Organ Sharing did not even list non-alcoholic fatty liver disease as a cause of liver failure leading to liver transplantation. Clinical trials in NAFLD have generally been of the size and quality associated with cereal box toys. Certainly, National Institutes of Health spending on basic research into NAFLD is unlikely to exceed even the smallest pork barrel appendage to the 2005 US Federal Budget. Perhaps most disrespectful of all, there were no textbooks devoted specifically to NAFLD, the most common cause of liver disease in the West. Until now.Fatty Liver Disease, NASH, and Related Disorders is a very timely and potentially important work that brings together many of the leading medical scientists involved in the study of fatty liver diseases. The editors are to be congratulated for putting together this path-finding tome. I was particularly interested to review this book, as I had already purchased a copy shortly after its publication. The book follows a logical format with 24 chapters covering the expected material ranging from an overview, reviews of known features of the pathophysiology, clinical findings, clinical management, and finishing with recent advances and future directions into NAFLD research. Critiquing a medical textbook is a hard, almost cruel task. Given the work:reward ratio, we are lucky anyone writes them. So I will get the quibbles out of the way first. If 24 chapters seems like a lot, given our current state of knowledge concerning NAFLD and NASH, perusal of this textbook largely confirms the impression. Overall, the textbook has something of the feel of a symposium syllabus to it. There is substantial repetition and overlap between the chapters describing the epidemiology, and metabolic changes associated with fatty liver disease. The same is true to a lesser extent for the chapters concerning the pathogenesis of fatty liver disease. I lost count of the number of references to obesity, insulin resistance, and the metabolic syndrome. As important as insulin resistance undoubtedly is in NAFLD, the role of other metabolic perturbations needs to be expanded.Fatty Liver Disease; NASH and Related Disorders has plenty of highlights. The chapter on mitochondrial injury and NASH is particularly well written and includes an excellent review and summary of the potential link between insulin resistance, hyperinsulinemia, oxidative stress, and mitochondrial injury. As this seems likely to be at the very core of the pathogenesis of NASH, it would have been desirable to increase this portion of the textbook. I found the chapter describing perspectives on NAFLD and NASH from the East to be very informative, given the superficial impression that North Americans have of the low prevalence of obesity in the East. The descriptions of the explosion of obesity in the East and differences in body fat distribution and cut-offs for body mass index categories for overweight and obesity are enlightening. Similarly, the review of NAFLD and NASH in children was welcome given the relative scarcity of reports in this increasingly important population of patients affected by fatty liver disease. As a researcher into the pathophysiology of NASH myself, I found the chapter on animal models of steatohepatitis to be of tremendous practical value. I have not read a better review of the available animal models of fatty liver disease including detailed descriptions of their genotypic and phenotypic characteristics. The only thing missing from this chapter is a more critical review of the relative pros and cons of the burgeoning number of animal models for fatty liver disease. For example, the methionine and choline-deficient dietary model is characterized by loss of weight and a failure to store fat in subcutaneous adipose tissues. The relevance of this model to obese, overfed, and sedentary humans with fatty liver disease is likely to be limited. This is a minor critique, however. The book is well illustrated with a collection of 13 color plates illustrating the histopathology of fatty liver disease. Some electron microscopy would have been desirable here. Color plates of some of the human phenotypes, such as lipodystrophy and acanthosis, might also have been welcome. In general, the textbook is very well referenced with well over 1000 references provided in total.In summary, this is a very welcome and enlightening textbook representing the collective knowledge regarding fatty liver disease. While readers will find themselves well versed in what is known about the metabolic associations with this condition, there is less clarity regarding the molecular biology and treatment of fatty liver diseases. This simply reflects our current state of knowledge and is not a shortcoming of the textbook itself.Bottom Line: Fatty Liver Disease, NASH, and Related Disorders is a comprehensive review including some welcome speculation about the pathogenesis of fatty liver disease. It is likely to appeal to hepatologists and researchers in the field. General gastroenterologists may also find the clinical management aspects of the book useful. I am already looking forward to the next edition. NAFLD is the Rodney Dangerfield of liver diseases. It simply doesn’t get the respect it deserves. Even the acronyms NAFLD and NASH are, in essence, diagnoses of exclusion defined by lack of a causitory role of alcohol. Until quite recently, the United Network for Organ Sharing did not even list non-alcoholic fatty liver disease as a cause of liver failure leading to liver transplantation. Clinical trials in NAFLD have generally been of the size and quality associated with cereal box toys. Certainly, National Institutes of Health spending on basic research into NAFLD is unlikely to exceed even the smallest pork barrel appendage to the 2005 US Federal Budget. Perhaps most disrespectful of all, there were no textbooks devoted specifically to NAFLD, the most common cause of liver disease in the West. Until now. Fatty Liver Disease, NASH, and Related Disorders is a very timely and potentially important work that brings together many of the leading medical scientists involved in the study of fatty liver diseases. The editors are to be congratulated for putting together this path-finding tome. I was particularly interested to review this book, as I had already purchased a copy shortly after its publication. The book follows a logical format with 24 chapters covering the expected material ranging from an overview, reviews of known features of the pathophysiology, clinical findings, clinical management, and finishing with recent advances and future directions into NAFLD research. Critiquing a medical textbook is a hard, almost cruel task. Given the work:reward ratio, we are lucky anyone writes them. So I will get the quibbles out of the way first. If 24 chapters seems like a lot, given our current state of knowledge concerning NAFLD and NASH, perusal of this textbook largely confirms the impression. Overall, the textbook has something of the feel of a symposium syllabus to it. There is substantial repetition and overlap between the chapters describing the epidemiology, and metabolic changes associated with fatty liver disease. The same is true to a lesser extent for the chapters concerning the pathogenesis of fatty liver disease. I lost count of the number of references to obesity, insulin resistance, and the metabolic syndrome. As important as insulin resistance undoubtedly is in NAFLD, the role of other metabolic perturbations needs to be expanded. Fatty Liver Disease; NASH and Related Disorders has plenty of highlights. The chapter on mitochondrial injury and NASH is particularly well written and includes an excellent review and summary of the potential link between insulin resistance, hyperinsulinemia, oxidative stress, and mitochondrial injury. As this seems likely to be at the very core of the pathogenesis of NASH, it would have been desirable to increase this portion of the textbook. I found the chapter describing perspectives on NAFLD and NASH from the East to be very informative, given the superficial impression that North Americans have of the low prevalence of obesity in the East. The descriptions of the explosion of obesity in the East and differences in body fat distribution and cut-offs for body mass index categories for overweight and obesity are enlightening. Similarly, the review of NAFLD and NASH in children was welcome given the relative scarcity of reports in this increasingly important population of patients affected by fatty liver disease. As a researcher into the pathophysiology of NASH myself, I found the chapter on animal models of steatohepatitis to be of tremendous practical value. I have not read a better review of the available animal models of fatty liver disease including detailed descriptions of their genotypic and phenotypic characteristics. The only thing missing from this chapter is a more critical review of the relative pros and cons of the burgeoning number of animal models for fatty liver disease. For example, the methionine and choline-deficient dietary model is characterized by loss of weight and a failure to store fat in subcutaneous adipose tissues. The relevance of this model to obese, overfed, and sedentary humans with fatty liver disease is likely to be limited. This is a minor critique, however. The book is well illustrated with a collection of 13 color plates illustrating the histopathology of fatty liver disease. Some electron microscopy would have been desirable here. Color plates of some of the human phenotypes, such as lipodystrophy and acanthosis, might also have been welcome. In general, the textbook is very well referenced with well over 1000 references provided in total. In summary, this is a very welcome and enlightening textbook representing the collective knowledge regarding fatty liver disease. While readers will find themselves well versed in what is known about the metabolic associations with this condition, there is less clarity regarding the molecular biology and treatment of fatty liver diseases. This simply reflects our current state of knowledge and is not a shortcoming of the textbook itself. Bottom Line: Fatty Liver Disease, NASH, and Related Disorders is a comprehensive review including some welcome speculation about the pathogenesis of fatty liver disease. It is likely to appeal to hepatologists and researchers in the field. General gastroenterologists may also find the clinical management aspects of the book useful. I am already looking forward to the next edition.