We are pleased to serve as editors of the third edition of Handbook of Liver Disease. The field of hepatology has continued to advance exponentially since publication of the second edition in 2004. We stand at the threshold of an exciting new era of therapy for chronic hepatitis C with the introduction of protease inhibitors and, in the near future, polymerase inhibitors to our armamentarium, which promises to expand rapidly in coming years. Treatment of chronic hepatitis B has also evolved with the introduction of entecavir and tenofovir, which have proved to be more potent and less likely to result in the development of resistance than older nucleoside and nucleotide analogs.
Pharmacogenetic testing has entered mainstream practice with the introduction of IL28B genotype testing for determination of responsiveness to pegylated interferon and the study of ITPA genotypes to predict the likelihood of anemia in patients treated with ribavirin. Genetic advances promise to inform other areas of hepatology, including prediction of hepatotoxicity from drugs as well as susceptibility to many metabolic liver diseases and gallstone formation. Our understanding of the pathogenic mechanisms involved in portal hypertension and associated complications has become more sophisticated, and approaches to enhance the reversibility of liver fibrosis, even when the underlying cause cannot be eliminated, loom on the horizon. Prognostication and determination of candidacy for liver transplantation have become more refined at the same time that surgical techniques have advanced. These are exciting times to study the liver and to care for patients with acute and chronic liver diseases.
The goal of this handbook remains the same as that for the first two editions—to provide a concise, accurate, up-to-date, and readily accessible reference for students of the liver and for busy practitioners. We continue to use an outline format, lists, tables, and figures in color to convey information efficiently, yet without losing the depth and richness of the field. State-of-the-art summaries are presented economically but without scrimping on necessary details of the scientific underpinnings needed for optimal decision-making in practice.
This edition has a new feature in the online version of the book, namely, board-review questions for each chapter prepared by the follows in the Division of Gastroenterology and Hepatology at Stanford University School of Medicine. We believe that these review questions will be of particular use to readers preparing for the certification and recertification examinations in gastroenterology and hepatology.We have been fortunate to retain many of the renowned authors from the previous editions, all of whom are authorities in their respective fields. In this edition, we welcome two new senior authors—Drs. Marina Berenguer and Christopher Bowlus—and a number of new co-authors who have enhanced the diversity and currency of the book. We continue to believe that this handbook will serve as a useful and valuable reference for busy practicing gastroenterologists and hepatologists, internists, family practitioners, other specialists, and trainees in gastroenterology and hepatology or internal medicine.
Lawrence S. Friedman and Emmet B. Keeffe
Foreword
In the 1970s, hepatology as a specialty was compared with neurology: both hepatologists and neurologists could name the “lesion,” but neither could do anything about it. Physicians had access to a few heroic options (e.g., portosystemic shunt surgery) and therapy for a limited spectrum of liver diseases (e.g., corticosteroid therapy for autoimmune hepatitis, phlebotomy for hemochromatosis), but for most liver disorders, all they could do was watch with concern and consternation as diseases progressed inexorably. In the past three decades—in little more than a single human generation—advances in hepatology have been staggering.
In the 1970s, no therapy was available for chronic viral hepatitis (the use of corticosteroids was misguided), nor did salvage therapy exist for acute liver failure or end-stage liver disease. For the diagnosis of cholecystitis and hepatic mass lesions, we relied on radioisotope scintigraphy, an imaging approach that is now largely forgotten; we debated the value, now disproven, of corticosteroids for acute fulminant hepatitis and drug-induced liver injury (DILI); we considered whether splenorenal shunting was better than portacaval shunting (yes in Atlanta, no in Boston); we pursued medical dissolution therapy and, later, lithotripsy for gallstones; we debated whether asymptomatic primary biliary cirrhosis (PBC) shortened life spans (no in New Haven, yes in Rochester); we chased down many false leads to explain what was then called “non-A, non-B” hepatitis; and nonalcoholic fatty liver disease was not even on our radar screens.
Since wandering in the dark prior to the 1970s with the misperception that only two types of viral hepatitis existed, we have arrived at our present day elucidation of five distinct and well-characterized types of viral hepatitis. Fewer than 20 years elapsed between the discovery of the envelope protein of hepatitis B and the development of a hepatitis B vaccine (with the 1976 Nobel Prize to Baruch Blumberg along the way). Early dabbling with interferon to the availability of the current generation of highly potent oral drugs took fewer than 30 years. Today, although we cannot cure hepatitis B, we can treat it and prevent its complications. Who in the 1970s would have imagined the impact of therapy on the natural history of chronic hepatitis B—slowing of fibrosis and even reversal of cirrhosis, rescue therapy for and prevention of hepatic decompensation, and a 30% reduction in listing for liver transplantation—in the half decade after the introduction of oral antiviral agents?Transfusion-associated hepatitis—most of which, in retrospect, was caused by hepatitis C—occurred in 30% of transfusion recipients prior to the 1970s; it declined to 10% in the early 1970s with the switch from commercial to volunteer blood donors, to under 5% when surrogate markers were introduced to screen blood, and to almost never (1 in 2.3 million transfusions) with sensitive nucleic acid amplification to test donor blood. Who could have predicted in the 1970s that hepatitis C was not primarily a transfusion-associated disease or that the annual incidence of acute hepatitis C would fall by almost 90% in the 1990s?Although a vaccine remains elusive, we should celebrate the progress that took place in as little as 23 years, from the ultimate discovery of hepatitis C virus (HCV) in 1988 to a nearly 80% cure rate with protease inhibitor-pegylated interferon-ribavirin antiviral therapy in 2011 (and the 2000 Lasker Award to Michael Houghton and Harvey Alter along the way). Now that two hepatitis C protease inhibitors have been approved in the United States, attention is turning to the two dozen plus new protease inhibitors, polymerase inhibitors, NS5A inhibitors, and other agents in development and to the promise, even a first glimpse, of cures with all-oral regimens.
Perhaps the largest impact on the transformation of hepatology into an “activist” specialty was liver transplantation, which began haltingly as an experimental, last-ditch measure in the 1970s to become routine in little more than a decade; improvements in outcome followed better timing and more rational organ allocation, novel immunosuppressive drugs and strategies, and refinements in surgical technique. Currently, we are much better at navigating between levels of immunosuppression that prevent rejection but that limit predisposition to infection, and the frequency of recurrence of primary disease has been reduced in some disorders (e.g., hepatitis B) but not others (e.g., hepatitis C). Still vexing is the shortage of donor livers, barely touched by recent excursions into accepting living-donor allografts, split-liver allografts, and marginal donor livers. To address the donor shortage, we may have to rely in the future on xenotransplantation, artificial livers, and stem cells, which, today, remain a remote dream.
From old debates about the value of colchicine and methotrexate for PBC, now mostly discarded, we have moved on to an elucidation of the target antigen of mitochondrial antibodies and of the genetic underpinning of PBC. Now well established is the value of ursodeoxycholic acid (UDCA) and its long-term impact on the natural history of the disease, at least in patient subgroups, as reflected by the reduction in the rate of liver transplantation for PBC that paralleled the broad adoption of UDCA therapy.
Fatty liver has been transformed from an unappreciated curiosity to what is recognized now as one of the most common liver disorders; attention has been focused on its association with insulin resistance and the metabolic syndrome as well as on its supporting role in progressive hepatic fibrosis and its contribution to “cryptogenic” cirrhosis. Fatty liver is now recognized as a comorbid factor in hepatitis C and a negative predictor of hepatitis C treatment response. Indeed, the link between fatty liver and hepatitis C is intimate; HCV and lipids rely on the same low-density lipoprotein (LDL) assembly/secretion pathway. By masquerading as a lipoprotein and, essentially, hijacking this lipid metabolic pathway, HCV reduces its visibility to the host adaptive immune response, thereby contributing to its success as a human pathogen. An explanation for the mechanism of hepatic injury in fatty liver remains elusive, although the nontriglyceride-lipotoxicity hypothesis is gaining traction. Similarly elusive have been attempts to identify treatments for fatty liver disease.
Today, we have laparoscopic cholecystectomy, previously unimagined diagnostic and therapeutic endoscopic interventions for biliary tract disorders, and sophisticated digital hepatobiliary imaging. For variceal bleeding, non selective beta blockade is the cornerstone of prophylaxis; the combination of endoscopic ligation and pharmacologic therapy is the accepted approach to an acute bleed; endoscopic surveillance and ligation as well as beta blockade have an established role in preventing rebleeding after an initial bleed; and the transjugular intrahepatic portosystemic shunt (TIPS) has supplanted portosystemic shunt surgery for refractory bleeding (often as a bridge to liver transplantation). A role for TIPS has also been demonstrated in refractory ascites and hydrothorax, hepatorenal syndrome (HRS), and hepatic vein occlusion. Pharmacologic interventions are available now to treat HRS type 1 (terlipressin plus albumin), prevent (norfloxacin or trimethoprim-sulfamethoxazole) and treat (third-generation cephalosporins and intravenous albumin) spontaneous bacterial peritonitis (SBP), and manage hepatic encephalopathy (antimicrobials such as rifaximin, besides lactulose). The importance of intravascular volume expansion is recognized now as a mainstay of the management of refractory ascites and SBP.
For the treatment of hepatocellular carcinoma (HCC), which has been increasing in incidence each decade (in parallel with an aging cohort of patients who have chronic hepatitis C), we have evolved from occasional resection a generation ago to a contemporary menu that includes chemotherapy (recently approved sorafenib, an oral multikinase inhibitor that targets serine/threonine and tyrosine receptor kinases), surgical resection, angiographic chemoembolization, and percutaneous ablation.
All these advances are covered in succinct, well-documented, and clear chapters in this edition of the Handbook of Liver Disease. In addition, the current edition reflects recent advances in our understanding of the genetic bases for bilirubin conjugation and excretion disorders, familial intrahepatic cholestatic disorders, Wilson disease, hemochromatosis, alpha-1 antitrypsin deficiency, alcohol-metabolizing enzymes, responsiveness to interferon-based therapy for hepatitis C and susceptibility to ribavirin-associated hemolysis, acute fatty liver of pregnancy, and the risk of DILI. In addition, the Handbook includes detailed chapters summarizing other important liver diseases, including DILI; acute liver failure; autoimmune hepatitis, autoimmune biliary disorders, and overlap syndromes; acute and chronic alcoholic liver disease; the multisystem manifestations of end-stage liver disease; liver disorders of pregnancy; granulomatous disorders; infections of the liver besides viral hepatitis; vascular disorders affecting the liver; hepatic manifestations of systemic disease; the risk of surgery in patients with liver disease and postoperative jaundice; and disorders of the gallbladder and bile ducts. Coverage of liver disease in the early 21st century would be incomplete without a review of the protean hepatic manifestations of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (including infiltrative opportunistic infections and malignancies, viral hepatitis, fatty liver, antiretroviral drug hepatotoxicity, and AIDS cholangiopathy), and this topic is well covered. The chapters are enhanced by instructive illustrations, useful tables, and suggested diagnostic and therapeutic algorithms. In addition, the anchoring of every topic to an understanding of pathophysiology as the foundation for diagnosis and management is one of the clear longitudinal themes threaded through all the chapters.
Whereas medical information in the 1970s was disseminated primarily through physical textbooks and journals, medical information today is available digitally from the vast reaches of cyberspace. At the touch of a button, physicians (and patients) can access a wealth of timely and updated information without ever touching a book. Why, then, publish a physical Handbook of Liver Disease in 2011? The answer is simple. Like a foundational lecture, the Handbook provides organizational perspective and a thoughtful overview of the field—thematically unified, scholarly, succinct, and evidence-based—an ideal starting point for the novice and the expert, for the generalist and the specialist. Some textbooks oversimplify, sacrificing accuracy and depth for easily digestible summaries. Others overwhelm readers with complexity and distracting detail. The Handbook, however, strikes an ideal balance between these extremes of depth and simplification. Of course, a physical text can be only as current as its publication date, and, given the accelerated pace of progress, both predictable and unpredicted advances will have occurred by the time the Handbook is published. If anything, this level of structural obsolescence is a metaphor for the rapidity of change and inspires us to imagine what hepatology will look like in another generation.
In the 1970s, no therapy was available for chronic viral hepatitis (the use of corticosteroids was misguided), nor did salvage therapy exist for acute liver failure or end-stage liver disease. For the diagnosis of cholecystitis and hepatic mass lesions, we relied on radioisotope scintigraphy, an imaging approach that is now largely forgotten; we debated the value, now disproven, of corticosteroids for acute fulminant hepatitis and drug-induced liver injury (DILI); we considered whether splenorenal shunting was better than portacaval shunting (yes in Atlanta, no in Boston); we pursued medical dissolution therapy and, later, lithotripsy for gallstones; we debated whether asymptomatic primary biliary cirrhosis (PBC) shortened life spans (no in New Haven, yes in Rochester); we chased down many false leads to explain what was then called “non-A, non-B” hepatitis; and nonalcoholic fatty liver disease was not even on our radar screens.
Since wandering in the dark prior to the 1970s with the misperception that only two types of viral hepatitis existed, we have arrived at our present day elucidation of five distinct and well-characterized types of viral hepatitis. Fewer than 20 years elapsed between the discovery of the envelope protein of hepatitis B and the development of a hepatitis B vaccine (with the 1976 Nobel Prize to Baruch Blumberg along the way). Early dabbling with interferon to the availability of the current generation of highly potent oral drugs took fewer than 30 years. Today, although we cannot cure hepatitis B, we can treat it and prevent its complications. Who in the 1970s would have imagined the impact of therapy on the natural history of chronic hepatitis B—slowing of fibrosis and even reversal of cirrhosis, rescue therapy for and prevention of hepatic decompensation, and a 30% reduction in listing for liver transplantation—in the half decade after the introduction of oral antiviral agents?Transfusion-associated hepatitis—most of which, in retrospect, was caused by hepatitis C—occurred in 30% of transfusion recipients prior to the 1970s; it declined to 10% in the early 1970s with the switch from commercial to volunteer blood donors, to under 5% when surrogate markers were introduced to screen blood, and to almost never (1 in 2.3 million transfusions) with sensitive nucleic acid amplification to test donor blood. Who could have predicted in the 1970s that hepatitis C was not primarily a transfusion-associated disease or that the annual incidence of acute hepatitis C would fall by almost 90% in the 1990s?Although a vaccine remains elusive, we should celebrate the progress that took place in as little as 23 years, from the ultimate discovery of hepatitis C virus (HCV) in 1988 to a nearly 80% cure rate with protease inhibitor-pegylated interferon-ribavirin antiviral therapy in 2011 (and the 2000 Lasker Award to Michael Houghton and Harvey Alter along the way). Now that two hepatitis C protease inhibitors have been approved in the United States, attention is turning to the two dozen plus new protease inhibitors, polymerase inhibitors, NS5A inhibitors, and other agents in development and to the promise, even a first glimpse, of cures with all-oral regimens.
Perhaps the largest impact on the transformation of hepatology into an “activist” specialty was liver transplantation, which began haltingly as an experimental, last-ditch measure in the 1970s to become routine in little more than a decade; improvements in outcome followed better timing and more rational organ allocation, novel immunosuppressive drugs and strategies, and refinements in surgical technique. Currently, we are much better at navigating between levels of immunosuppression that prevent rejection but that limit predisposition to infection, and the frequency of recurrence of primary disease has been reduced in some disorders (e.g., hepatitis B) but not others (e.g., hepatitis C). Still vexing is the shortage of donor livers, barely touched by recent excursions into accepting living-donor allografts, split-liver allografts, and marginal donor livers. To address the donor shortage, we may have to rely in the future on xenotransplantation, artificial livers, and stem cells, which, today, remain a remote dream.
From old debates about the value of colchicine and methotrexate for PBC, now mostly discarded, we have moved on to an elucidation of the target antigen of mitochondrial antibodies and of the genetic underpinning of PBC. Now well established is the value of ursodeoxycholic acid (UDCA) and its long-term impact on the natural history of the disease, at least in patient subgroups, as reflected by the reduction in the rate of liver transplantation for PBC that paralleled the broad adoption of UDCA therapy.
Fatty liver has been transformed from an unappreciated curiosity to what is recognized now as one of the most common liver disorders; attention has been focused on its association with insulin resistance and the metabolic syndrome as well as on its supporting role in progressive hepatic fibrosis and its contribution to “cryptogenic” cirrhosis. Fatty liver is now recognized as a comorbid factor in hepatitis C and a negative predictor of hepatitis C treatment response. Indeed, the link between fatty liver and hepatitis C is intimate; HCV and lipids rely on the same low-density lipoprotein (LDL) assembly/secretion pathway. By masquerading as a lipoprotein and, essentially, hijacking this lipid metabolic pathway, HCV reduces its visibility to the host adaptive immune response, thereby contributing to its success as a human pathogen. An explanation for the mechanism of hepatic injury in fatty liver remains elusive, although the nontriglyceride-lipotoxicity hypothesis is gaining traction. Similarly elusive have been attempts to identify treatments for fatty liver disease.
Today, we have laparoscopic cholecystectomy, previously unimagined diagnostic and therapeutic endoscopic interventions for biliary tract disorders, and sophisticated digital hepatobiliary imaging. For variceal bleeding, non selective beta blockade is the cornerstone of prophylaxis; the combination of endoscopic ligation and pharmacologic therapy is the accepted approach to an acute bleed; endoscopic surveillance and ligation as well as beta blockade have an established role in preventing rebleeding after an initial bleed; and the transjugular intrahepatic portosystemic shunt (TIPS) has supplanted portosystemic shunt surgery for refractory bleeding (often as a bridge to liver transplantation). A role for TIPS has also been demonstrated in refractory ascites and hydrothorax, hepatorenal syndrome (HRS), and hepatic vein occlusion. Pharmacologic interventions are available now to treat HRS type 1 (terlipressin plus albumin), prevent (norfloxacin or trimethoprim-sulfamethoxazole) and treat (third-generation cephalosporins and intravenous albumin) spontaneous bacterial peritonitis (SBP), and manage hepatic encephalopathy (antimicrobials such as rifaximin, besides lactulose). The importance of intravascular volume expansion is recognized now as a mainstay of the management of refractory ascites and SBP.
For the treatment of hepatocellular carcinoma (HCC), which has been increasing in incidence each decade (in parallel with an aging cohort of patients who have chronic hepatitis C), we have evolved from occasional resection a generation ago to a contemporary menu that includes chemotherapy (recently approved sorafenib, an oral multikinase inhibitor that targets serine/threonine and tyrosine receptor kinases), surgical resection, angiographic chemoembolization, and percutaneous ablation.
All these advances are covered in succinct, well-documented, and clear chapters in this edition of the Handbook of Liver Disease. In addition, the current edition reflects recent advances in our understanding of the genetic bases for bilirubin conjugation and excretion disorders, familial intrahepatic cholestatic disorders, Wilson disease, hemochromatosis, alpha-1 antitrypsin deficiency, alcohol-metabolizing enzymes, responsiveness to interferon-based therapy for hepatitis C and susceptibility to ribavirin-associated hemolysis, acute fatty liver of pregnancy, and the risk of DILI. In addition, the Handbook includes detailed chapters summarizing other important liver diseases, including DILI; acute liver failure; autoimmune hepatitis, autoimmune biliary disorders, and overlap syndromes; acute and chronic alcoholic liver disease; the multisystem manifestations of end-stage liver disease; liver disorders of pregnancy; granulomatous disorders; infections of the liver besides viral hepatitis; vascular disorders affecting the liver; hepatic manifestations of systemic disease; the risk of surgery in patients with liver disease and postoperative jaundice; and disorders of the gallbladder and bile ducts. Coverage of liver disease in the early 21st century would be incomplete without a review of the protean hepatic manifestations of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (including infiltrative opportunistic infections and malignancies, viral hepatitis, fatty liver, antiretroviral drug hepatotoxicity, and AIDS cholangiopathy), and this topic is well covered. The chapters are enhanced by instructive illustrations, useful tables, and suggested diagnostic and therapeutic algorithms. In addition, the anchoring of every topic to an understanding of pathophysiology as the foundation for diagnosis and management is one of the clear longitudinal themes threaded through all the chapters.
Whereas medical information in the 1970s was disseminated primarily through physical textbooks and journals, medical information today is available digitally from the vast reaches of cyberspace. At the touch of a button, physicians (and patients) can access a wealth of timely and updated information without ever touching a book. Why, then, publish a physical Handbook of Liver Disease in 2011? The answer is simple. Like a foundational lecture, the Handbook provides organizational perspective and a thoughtful overview of the field—thematically unified, scholarly, succinct, and evidence-based—an ideal starting point for the novice and the expert, for the generalist and the specialist. Some textbooks oversimplify, sacrificing accuracy and depth for easily digestible summaries. Others overwhelm readers with complexity and distracting detail. The Handbook, however, strikes an ideal balance between these extremes of depth and simplification. Of course, a physical text can be only as current as its publication date, and, given the accelerated pace of progress, both predictable and unpredicted advances will have occurred by the time the Handbook is published. If anything, this level of structural obsolescence is a metaphor for the rapidity of change and inspires us to imagine what hepatology will look like in another generation.
-- Jules L. Dienstag, MD
Key Features
- Expedite diagnostic and therapeutic decision making with a highly templated outline format that uses full-color illustrations, tables, algorithms and figures, key point boxes, and alert symbols to present information at a glance.
Website Features
- Consult the book from any computer at home, in your office, or at any practice location.
- Instantly locate the answers to your clinical questions via a simple search query.
- Quickly find out more about any bibliographical citation by linking to its MEDLINE abstract.
New to this edition
- Apply some of the latest treatments for liver disease including the role of pretreatment IL28B testing for patients with hepatitis B and C; radiofrequency ablation and sorafenib in cases of hepatocellular carcinoma; the use of the drug rifaximin to treat hepatic encephalopathy; and much more.
- Make optimal use of genetic testing to assess your patients' risk of metabolic liver disease and to personalize treatment regimens for chronic hepatitis C.
- Offer your liver transplantation patients the best prognosis and follow-up with the latest information on outcomes and the management of complications.
- Use blood test panels and noninvasive imaging techniques to evaluate the degree of liver fibrosis.
- Make informed treatment decisions with the latest clinical trial results for portal hypertension, autoimmune liver diseases, acute liver failure, and hepatic infections.
- Search the complete text online, download all the images, and test your knowledge with 200 board-style review questions at www.expertconsult.com.
Contents
- Chapter 1 - Assessment of liver function and diagnostic studies
- Chapter 2 - Acute liver failure
- Chapter 3 - Acute viral hepatitis
- Chapter 4 - Chronic viral hepatitis
- Chapter 5 - Autoimmune hepatitis
- Chapter 6 - Alcoholic liver disease
- Chapter 7 - Fatty liver and nonalcoholic steatohepatitis
- Chapter 8 - Drug-induced and toxic liver disease
- Chapter 9 - Cirrhosis and portal hypertension: an overview
- Chapter 10 - Portal hypertension and gastrointestinal bleeding
- Chapter 11 - Ascites and spontaneous bacterial peritonitis
- Chapter 12 - Hepatorenal syndrome
- Chapter 13 - Hepatic encephalopathy
- Chapter 14 - Primary biliary cirrhosis
- Chapter 15 - Primary sclerosing cholangitis
- Chapter 16 - Hemochromatosis
- Chapter 17 - Wilson disease and related disorders
- Chapter 18 - Alpha-1 antitrypsin deficiency and other metabolic liver diseases
- Chapter 19 - Budd–Chiari syndrome and other vascular disorders
- Chapter 20 - The liver in heart failure
- Chapter 21 - The liver in pregnancy
- Chapter 22 - The liver in systemic disease
- Chapter 23 - Pediatric liver disease
- Chapter 24 - Liver disease in the elderly
- Chapter 25 - Hepatobiliary complications of HIV
- Chapter 26 - Granulomatous liver disease
- Chapter 27 - Hepatic tumors
- Chapter 28 - Hepatic abscesses and cysts
- Chapter 29 - Other infections involving the liver
- Chapter 30 - Surgery in the patient with liver disease and postoperative jaundice
- Chapter 31 - Liver transplantation
- Chapter 32 - Cholelithiasis and cholecystitis
- Chapter 33 - Diseases of the bile ducts
- Chapter 34 - Tumors of the biliary tract
Product Details
- Paperback: 536 pages
- Publisher: Saunders; 3 edition (August 26, 2011)
- Language: English
- ISBN-10: 143771725X
- ISBN-13: 978-1437717259
List Price: $99.95