Support of the Acutely Failing Liver

162 Pages·2000·0.2 MB·English

by  Achilles A. Demetriou

TISSUE ENGINEERING INTELLIGENCE UNIT 4
Achilles A. Demetriou and Frederick D. Watanabe
Support of the
Acutely Failing Liver
Second Edition
T
ISSUE
E
NGINEERING
I
NTELLIGENCE
U 4
NIT
Support of the Acutely
Failing Liver
Second Edition
Achilles A. Demetriou, M.D., Ph.D.
Frederick D. Watanabe, M.D.
Cedars-Sinai Medical Center
Los Angeles, California, U.S.A.
LANDES BIOSCIENCE EUREKAH.COM
GEORGETOWN, TEXAS AUSTIN, TEXAS
U.S.A. U.S.A.
S A F L
UPPORT OF THE CUTELY AILING IVER
SECOND EDITION
Tissue Engineering Intelligence Unit
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Landes Bioscience
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CONTENTS
1. The Liver: A Brief Historical Perspective ...............................................1
Elaine Kahaku
2. Acute Liver Failure: Definitions and Etiology.........................................5
Donna E. Goldman, Graham M. Woolf
Definitions: Types of Hepatic Failure....................................................5
Severe Acute Liver Failure (SALF).........................................................8
Etiology.................................................................................................8
Viral Causes of Liver Failure..................................................................8
Drug-Induced Hepatotoxicity.............................................................12
Toxins.................................................................................................13
Miscellaneous Causes of Hepatic Failure.............................................13
Hepatic Failure in Infants and Children..............................................15
3. Acute Hepatic Encephalopathy: Pathophysiology and Diagnosis .........21
Steven D. Colquhoun, Caroline A. Connelly
Pathophysiology..................................................................................21
Cerebral Edema and Related Effects....................................................23
Other Mechanisms..............................................................................27
Diagnosis ............................................................................................29
Summary.............................................................................................31
4. Acute Hepatic Encephalopathy: Treatment..........................................35
Olivier Detry, Jody E. Margulies, Nicholas Arkadopoulos,
Achilles A. Demetriou
Standard Treatment ............................................................................35
Experimental Treatments....................................................................37
Summary.............................................................................................42
5. Medical Management of Acute Liver Failure........................................45
Frederick D. Watanabe, Elaine Kahaku, Achilles A. Demetriou
Patient Environment and Monitoring.................................................45
Fluids, Electrolytes and Nutrition .......................................................46
Hepatic Encephalopathy and Cerebral Edema.....................................48
Renal Impairment...............................................................................50
Pulmonary Disease..............................................................................51
Infection..............................................................................................51
Coagulation and Hemorrhage.............................................................52
6. Surgical Management of Acute Liver Failure........................................55
Walid S. Arnaout, David Reybould
Definitions and Patient Selection ........................................................55
Transplant Evaluation.........................................................................59
Anesthetic Considerations...................................................................61
Surgical Technique..............................................................................62
Results.................................................................................................66
Summary.............................................................................................68
7. Liver Support System Development.....................................................73
Jacek Rozga, Kyung.S. Suh, Helene Lilja, Walid S. Arnaout,
Achilles A. Demetriou
Historical Perspective..........................................................................73
The Challenge.....................................................................................74
Past Accomplishments: Laboratory Studies..........................................74
Past Accomplishments: Clinical Studies...............................................78
Current Status of Liver Support ..........................................................79
8. Clinical Experience with a Bioartificial Liver........................................97
Frederick D. Watanabe, Elaine Kahaku, Theodore Khalili, Paul Ting,
Anthony Navarro, Achilles A. Demetriou
Methods..............................................................................................97
Results...............................................................................................100
Discussion.........................................................................................104
9. Clinical Use of a Bioartificial Liver
to Treat Acetaminophen-Induced Fulminant Hepatic Failure............107
Olivier Detry, Nikolaos Arkadopoulos, Elaine Kahaku,
Frederick D. Watanabe, Jacek Rozga, Achilles A. Demetriou
Methods............................................................................................107
Results...............................................................................................109
Discussion.........................................................................................110
10. Development of a Strategy for Management of Severe Acute
Liver Failure: The Liver Support Unit................................................113
Achilles A. Demetriou, Frederick D. Watanabe
Defining the Clinical Need ...............................................................113
Liver Support Unit Logistics..............................................................113
Critical Clinical Care Issues...............................................................114
11. Other Experimental Therapeutic Strategies: Liver Gene Therapy ......117
Jacek Rozga, Helen Lilja, Walid Arnaout, Achilles A. Demetriou
Transplantation of Genetically-Altered Cells.....................................117
Direct Gene Delivery ........................................................................120
12. Other Experimental Therapeutic Strategies:
Hepatocyte Transplantation...............................................................129
Helene Lilja, Nikolaos Arkadopoulos, Susumu Eguchi,
Raoul J. Rosenthal, David A. Moscioni, Achilles A. Demetriou,
Jacek Rozga
Correction of Specific Genetic Defects..............................................130
Treatment of Acute Liver Insufficiency..............................................130
Other Considerations........................................................................131
Modulation of Transplanted Cell Antigenicity..................................136
Human Hepatocyte Studies...............................................................136
Optimal Technique...........................................................................137
Other Cell Transplantation...............................................................148
Index..................................................................................................151

EDITORS
Achilles A. Demetriou, M.D., Ph.D.
Department of Surgery
Liver Support Unit
Esther and Mark Schulman Chair
in Surgery and Transplantation Medicine
Cedars-Sinai Medical Center
Los Angeles, California, U.S.A.
Chapters 5, 7-12
Frederick D. Watanabe, M.D.
Liver Transplant
Liver Support Unit
Cedars-Sinai Medical Center
Los Angeles, California, U.S.A.
Chapters 5, 8-10
CONTRIBUTORS
Nikolaos Arkadopoulos Caroline A. Connelly
Liver Support Research Laboratory Center for Liver Diseases
Cedars-Sinai Medical Center and Transplantation
Los Angeles, California, U.S.A. Cedars-Sinai Medical Center
Chapters 4, 9, 12 Los Angeles, California, U.S.A.
Chapter 3
Walid S. Arnaout
Liver Transplantation Olivier Detry
Center for Liver Diseases Liver Support Research Laboratory
and Transplantation Cedars-Sinai Medical Center
Cedars-Sinai Medical Center Los Angeles, California, U.S.A.
Los Angeles, California, U.S.A. Chapter 4
Chapters 6, 7, 11
Susumu Eguchi
Steven D. Colquhoun Liver Support Research Laboratory
Liver Transplantation Cedars-Sinai Medical Center
Center for Liver Diseases Los Angeles, California, U.S.A.
and Transplantation Chapter 12
Cedars-Sinai Medical Center
Los Angeles, California, U.S.A.
Chapter 3
Donna E. Goldman Anthony Navarro
Center for Liver Diseases Liver Support Research Laboratory
and Transplantation Cedars-Sinai Medical Center
Cedars-Sinai Medical Center Los Angeles, California, U.S.A.
Los Angeles, California, U.S.A. Chapter 8
Chapter 2
David Reybould
Elaine A. Kahaku Cedars-Sinai Medical Center
Liver Support Research Laboratory Los Angeles, California, U.S.A.
Cedars-Sinai Medical Center Chapter 6
Los Angeles, California, U.S.A.
Chapters 1, 5, 8, 9 Raoul J. Rosenthal
Liver Support Research Laboratory
Theodore Khalili Cedars-Sinai Medical Center
Liver Support Research Laboratory Los Angeles, California, U.S.A.
Cedars-Sinai Medical Center Chapter 12
Los Angeles, California, U.S.A.
Chapter 8 Jack Rozga
Surgical Research, CSMC
Helene Lilja Cedars-Sinai Medical Center
Liver Support Research Laboratory Los Angeles, California, U.S.A.
Cedars-Sinai Medical Center Chapters 7, 9, 11, 12
Los Angeles, California, U.S.A.
Chapters 7, 11, 12 Kyung S. Suh
Liver Support Research Laboratory
Jody E. Margulies Cedars-Sinai Medical Center
Liver Support Research Laboratory Los Angeles, California, U.S.A.
Cedars-Sinai Medical Center Chapter 7
Los Angeles, California, U.S.A.
Chapter 4 Paul Ting
Liver Support Research Laboratory
David A. Moscioni Cedars-Sinai Medical Center
Liver Support Research Laboratory Los Angeles, California, U.S.A.
Cedars-Sinai Medical Center Chapter 8
Los Angeles, California, U.S.A.
Chapter 12 Graham M. Woolf
Cedars-Sinai Medical Center
Los Angeles, California, U.S.A.
Chapter2
PREFACE
S
evere liver dysfunction results in massive physiologic derangement and high
mortality. A concerted multidisciplinary effort is needed to support patients
with severe acute liver failure (SALF) and treat them appropriately. This
requires mobilization of significant resources. There is a need to put in place clinical
teams to provide comprehensive diagnostic and therapeutic plans and to critically
assess emerging technologic advances. In addition to clinical expertise, there is a
need for an appropriate scholarly, scientific environment that can allow meaningful
experimental studies to be carried out to advance knowledge in the field. Five
years ago, at Cedars-Sinai Medical Center, we established the Liver Support Unit
(LSU) to meet these needs.
In this monograph, members of the LSU present the most current
understanding of the pathophysiology of liver failure and how its various forms
and manifestations are classified, and summarize the state of the art in the diagnosis
and management of the disease. In addition, basic laboratory as well as clinical
experimental work carried out in the LSU is presented, with particular
emphasis on the use of liver support systems in an attempt to “bridge” patients
with severe forms of liver failure to either transplantation or liver repair and
regeneration.
This work is dedicated to the clinical and research fellows trained at the LSU
in recognition of their dedication, creativity and hard work, both at the bedside
and in the laboratory; to the Critical Care and General Clinical Research Center
nurses; and to the Perfusion Team members at our institution for their support
and commitment to achieving the best possible clinical care.
Achilles A. Demetriou
Frederick D. Watanabe
Los Angeles, California, U.S.A.