A number of areas within liver transplant continue to evolve as the field matures. The advent of increasingly effective therapy for HCV will dramatically reduce the burden of recurrent disease within the next few years. HCC has become a well established indication for transplant with an increasing emphasis on adjuvant therapies to reduce the risk of tumor recurrence and potentially expand the acceptable limits of tumor burden amenable to liver transplant. Renal dysfunction is a frequent complication of decompensated liver disease and an important predictor of diminished post-transplant survival. Newer approached to therapy including terlipressin will reduce the impact of renal dysfunction in liver transplant candidates and potentially reduce the need for combined liver/kidney transplant. Increasing attention is being paid to role of comorbidities such as diabetes and hypertension on long-term recipient outcomes. Retransplantation remains a challenge with a variety of models available to predict outcomes. Cardiac disease pretransplant is an area of active investigation with newer entities such as cirrhotic cardiomyopathy a growing concern. These are some of many evolving issues in liver transplant which will be addressed to update our readers and which in turn will enhance the care of patients with liver disease.
Front Cover 1
Liver Transplantation:Update of Conceptsand Practice 2
Copyright 3
Contributors 4
Contents 8
Clinics In Liver Disease 12
Preface 14
Evolving Trends in Liver Transplantation 16
Key points 16
Introduction 16
History 16
MELD 17
Advantages of the MELD score 18
Disadvantages of the MELD score 18
MELD exceptions 19
Evidence-based modifications to the MELD score 20
Can we improve the MELD allocation policy? 21
Future changes to liver allocations 22
Summary 22
References 23
Cardiac and Pulmonary Issues in LT Assessment Candidates 26
Key points 26
Introduction 26
Cardiac issues 27
Preexisting Coronary Artery Disease 27
Cirrhotic Cardiomyopathy 28
Alcohol-Related Cardiomyopathy 29
Posttransplant Metabolic Syndrome 30
Pulmonary issues 30
Hepatic Hydrothorax 31
Hepatopulmonary Syndrome 32
Portopulmonary Syndrome 33
Hemorrhagic Hereditary Telangiectasia 35
Concomitant Lung Conditions 37
References 37
Renal Dysfunction in End-Stage Liver Disease and Post–Liver Transplant 40
Key points 40
Introduction 40
Patients with cirrhosis and ESLD 41
Revised Definition of Renal Dysfunction in Patients with Liver Disease 41
Estimating Renal Function in Patients with Cirrhosis and ESLD 41
Types of renal dysfunction 42
Prerenal Azotemia 42
The HRS 42
Intrinsic Renal Disease 43
Role of RRT 47
Evaluation for CLKT 47
Kidney injury in the post–liver transplant period 47
Summary 52
References 52
Acute-On-Chronic Liver Failure 58
Key points 58
Introduction 58
ACLF is not decompensated cirrhosis 59
Physiology of ACLF 59
Renal 61
Brain 62
Circulatory 62
Pulmonary 63
Definitions of ACLF 64
APASL 64
EASL-CLIF 64
NACSELD 65
Regional Differences in Defining ACLF 65
Predictive models 66
ACLF in pretransplant patients 67
Medical therapy 67
Liver Assist Devices 67
ACLF and outcomes after LT 68
Unresolved questions 68
References 69
Hepatitis Viruses and Liver Transplantation 72
Key points 72
Antiviral management of hepatitis C virus in liver transplant recipients 73
The Diagnosis of HCV Recurrence 73
Antiviral Treatment to Prevent HCV Recurrence 75
Treatment on the liver transplant waitlist 75
Prophylactic and preemptive HCV treatment 77
Antiviral Therapy for the Treatment of Significant Recurrent HCV 77
Recent advances in the antiviral management of liver transplant recipients with hepatitis B 81
Antiviral Strategies to Prevent HBV Recurrence 82
HBV treatment on the transplant waitlist 82
HBV reinfection prevention strategies after liver transplantation and the evolving role of HBIG 82
De Novo Infection and the Use of Hepatitis B Core Antibody-Positive Donors 84
Treatment of Recurrent and De Novo HBV Infection After LT 84
Hepatitis E virus in liver transplant recipients: an emerging cause of graft dysfunction? 85
The Evolving Epidemiology of HEV 85
HEV in Liver Transplant Recipients 86
Donor-Derived HEV Infection 89
Summary and recommendations 90
References 90
Liver Transplant for Hepatocellular Cancer 100
Key points 100
Very small tumors 100
Very large tumors 102
Extended Criteria—Tumor Size and Number 102
Downstaging 103
Tumor Biology 103
Waiting time 105
Summary 107
References 107
The Adolescent Liver Transplant Patient 110
Key points 110
Introduction 110
Definition of adolescence 111
Specific issues in adolescence 111
Indications for transplantation 111
Chronic Liver Failure 111
Biliary Atresia 112
Inherited Metabolic Liver Disease 112
a1-Antitrypsin deficiency 112
Alagille syndrome 113
Progressive Familial Intrahepatic Cholestasis 113
Tyrosinemia Type I 113
Cystic Fibrosis 113
Wilson Disease 114
Autoimmune liver disease types I and II 114
Fibropolycystic Liver Disease 114
Primary Immunodeficiency 114
Timing of Transplantation for Adolescents with Chronic Liver Failure 114
Acute liver failure 115
Drug-Induced Liver Failure 115
Viral hepatitis 115
Management of adolescents with acute liver failure 115
Inborn errors of metabolism 116
Crigler–Najjar Type I 117
Primary Hyperoxaluria 117
Liver tumors 117
Pretransplant evaluation 117
Renal Function 117
Cardiac Assessment 117
Respiratory Assessment 117
Neuropsychological Assessment 118
Contraindications for transplantation 118
Preparation for transplantation 118
Immunization 118
Management of Hepatic Complications 118
Nutritional Support 118
Psychological Preparation 118
Liver Transplant Surgery 118
Post-Transplant Management 119
Survival and Quality of Life 119
Nutrition, growth, and endocrine development 119
Psychosocial development 119
Neurocognitive function 119
Quality of life 120
Risk Factors Affecting Survival 120
Late technical complications 120
Maintaining graft function 120
Immunosuppression 120
Acute and chronic rejection 120
Graft hepatitis 120
Recurrent disease 121
Adverse effects of immunosuppression 121
Renal function 121
Diabetes mellitus 121
Cardiovascular disease 121
Sexual health 121
Contraception and pregnancy 121
Sexually transmitted diseases 122
Risk-taking behaviors 122
Adherence 122
Transition to Adult Care 122
Summary 123
References 123
Expanded Criteria Donors 130
Key points 130
The spectrum of donor quality: ideal, standard, and expanded 130
Donor Risk Factors for Graft Dysfunction 130
Older donor age 130
Donation after cardiac death status 132
Steatosis 133
Cold ischemia time 135
Donor Risk Factors for Disease Transmission 135
Viral hepatitis B 135
Hepatitis B core antibody positive donors 135
HBsAg+ donors 136
Viral hepatitis C 136
Human immunodeficiency virus 137
Centers for Disease Control and Prevention classification of donors at increased risk for infection transmission 137
Cancer 138
References 140
Challenges in Living Donor Liver Transplantation 148
Key points 148
Introduction 148
LDLT for hepatocellular carcinoma 149
ABO-incompatible LDLT 151
Donor risk and complications 152
References 154
Multivisceral Transplantation 158
Key points 158
Introduction 158
Intestinal failure 159
Indications 159
Contraindications 161
Types of grafts 161
Isolated Intestinal Transplant 162
Combined Liver–Pancreas–Small Bowel Transplant 162
Multivisceral Transplantation 162
Surgical technique 164
Postoperative management 164
Immunosuppression 165
Nonsurgical Complications 165
Rejection 165
Graft-versus-host disease 167
Posttransplant lymph proliferative disorder 168
Cytomegalovirus 169
Outcomes 169
Summary 170
References 170
Recurrence of Nonviral Liver Diseases After Liver Transplantation 172
Key points 172
Introduction 172
AIH, PBC, and PSC 173
AIH 173
PBC 174
PSC 175
ALD 176
Nonalcoholic fatty liver disease 177
Other rare indications for LT 178
Summary 178
References 178
Immunosuppression 184
Key points 184
Part I: current immunosuppression practices 184
Part II: minimization as a goal for transplantation 188
Overview 188
Management of Immunosuppression with the Aim of Decreasing Adverse Effects 189
Immunosuppression-induced kidney injury 189
Metabolic syndrome 189
Malignancy and infections 190
HCV recurrence 190
Clinical Observation of Minimization of CNI Immunosuppression in Liver Transplantation 191
Long-term Management of Immunosuppression in Adult Transplant Recipients 191
Minimization in the Pediatric Liver Transplant Setting 193
Feasibility of Immunosuppression Minimization 194
Can IM Be Personalized? 194
Part III: tolerance 195
Conceptual Approach to the Induction of Donor-Specific Tolerance 195
Clinical and Experimental Approach to the Induction of Donor-Specific Tolerance 195
Molecular therapeutics 195
Cellular therapeutics 196
Experimental Models of Liver Transplant Tolerance in Animals 196
Liver transplant tolerance in humans 198
Lessons from Tolerance in Renal Transplantation and the Quest for Biomarkers 200
Current Clinical Tolerance Trials 202
Summary 203
References 204
Improving Long-Term Outcomes After Liver Transplantation 214
Key points 214
Introduction 214
Causes of death after LT 215
The impact of immunosuppression and rejection on outcomes 216
Impact of Acute Cellular Rejection on Overall Patient and Graft Survival Varies with Underlying Liver Disease 216
Immunosuppression in Patients with HCV Infection 218
Corticosteroids 218
Calcineurin inhibitors 218
Mycophenolate mofetil 218
T-cell–depleting therapies 218
Interleukin-2 receptor inhibition 219
Rejection and immunosuppression-related morbidity and mortality in other etiologies of liver disease 219
Posttransplant MS and long-term mortality and graft loss 220
Components of MS post-LT 220
Obesity 220
Posttransplant Pharmacotherapy of Obesity 221
Diabetes 221
Dyslipidemia 222
Hypertension 223
Cardiovascular Disease 223
Malignancy 223
References 225
Hepatic Retransplant 228
Key points 228
Why do liver transplants fail? 230
Should hepatitis C recurrence preclude retransplant? 232
Liver allocation for hepatic retransplant: the status quo 233
Can the timing of retransplant predict patient survival? 235
Which recipient characteristics are associated with worse prognosis? 236
Better donor grafts, better outcomes 237
Achieving optimal outcomes after retransplant: the utility of risk prediction models 237
Technical challenges of hepatic retransplant 240
Summary 242
References 243
Index 250
Evolving Trends in Liver Transplantation
Listing and Liver Donor Allocation
Russell H. Wiesner, MD rwiesner@mayo.edu, Mayo College of Medicine, Rochester, MN 55905, USA
The success of liver transplantation in the past three decades as a life-saving procedure for patients with end-stage liver disease has led to the ever-increasing disparity between the demands for liver transplantation and the supply of donor liver organs. Donor allocation and distribution remains a challenge and a moral issue as to how these organs can be equitably distributed. This article reviews the evolution of the liver allocation policy and discusses in detail the challenges clinicians face today in this area of medicine.
Keywords
Liver transplantation
MELD
Liver donor allocation
Chronic liver disease
Key points
• The MELD-based allocation policy is excellent at prioritizing patients with chronic liver disease on the waiting list based on survival.
• Exception criteria are needed because of such conditions as hepatocellular cancer, with tumor progression being used as a surrogate for patient survival.
• MELD can be tweaked by adding serum sodium and other variables; but overall the impact would be minimal and reprograming is expensive and cumbersome.
Introduction
The success of liver transplantation in the past three decades as a life-saving procedure for patients with end-stage liver disease has led to the ever-increasing disparity between the demands for liver transplantation and the supply of donor liver organs. This demand has been fueled by an increasing prevalence of cirrhosis and hepatocellular cancer (HCC) related to the hepatitis C epidemic, and to the increase in obesity-related liver disease.1 Today, nearly 1 in 10 patients waiting for a donor liver organ die on the waiting list.2 Therefore, donor allocation and distribution remains a challenge and a moral issue as to how these organs can be equitably distributed. This article reviews the evolution of the liver allocation policy and discusses in detail the challenges we face today.
History
Donor liver allocation dates back to the Transplantation Act of 1983 when there were only a few liver transplant centers in the United States. However, with the increasing success of liver transplantation and expanded indications, the number of patients seeking this life-saving procedure continued to grow. At the same time, the number of institutions offering liver transplantation also increased. By the mid-1990s, livers were allocated based on blood type; time on the liver transplant waiting list; and whether a patient was in the intensive care unit (ICU), hospital, or an outpatient. There was no criterion to define which patients should be in the ICU or which patients should be hospitalized. Indeed, many centers admitted patients to the ICU solely to facilitate their placement at the top of the liver waiting list. In retrospect, it was noted in the model for end-stage liver disease (MELD) era that the number of patients proceeding to liver transplantation from the ICU dropped dramatically from 24% in the pre-MELD era to 13% in the post-MELD era.3 There was also noted to be a strong relationship between the number of centers in an organ procurement unit, and the number of patients undergoing liver transplant directly from the ICU.
An attempt to rectify this problem was made in 1998 by implementation of a new system incorporating the Child-Turcotte-Pugh score (CTP) as an index for liver disease severity and prognosis. This scoring system was originally used to predict the outcome of portal-cava shunt surgery in patients with cirrhosis.4 Adoption of the CTP-based allocation system was intended primarily to reflect waiting list mortality and severity of liver disease. However, the use of the CTP score for the prioritization of liver transplant candidates had several major drawbacks. First, ascites and encephalopathy were subjectively assessed and were influenced by such therapies as diuretics, albumin administration, and lactulose therapy. In addition, a score of three points was allocated for any serum bilirubin value higher than 3.0 mg/dL and any serum albumin level value of 2.8 mg/dL or less. This “ceiling and floor affect” for bilirubin and albumin, respectively, meant that many patients ended up with the same overall CTP score, even though they may have had vastly different values of these two variables. Indeed, a patient with a serum bilirubin of 25 mg/dL received the same CTP score as the patient who had a serum bilirubin of 3 mg/dL. As a result, time spent on the waiting list became the major selection factor of liver candidates having identical CTP scores. Finally, there was no parameter in the CTP score that reflected renal function, a key prognostic marker in patients with end-stage cirrhosis. Two studies found time spent on the waiting list was not associated with risk of death on the waiting list.5,6 In the end, the revised allocation policy based on the CTP score ultimately proved unworkable and unfair to patients with the most severe liver disease. Because of considerable disagreement among transplant centers on how livers should be allocated, the United Network for Organ Sharing (UNOS) and the Department of Health and Human Services intervened in 1999 and challenged the transplant community with “The Final Rule.”7 Among the conditions of the Final Rule were that allocation policies should be based on objective and measurable medical criteria of patients or categories of patients who are medically suitable candidates for liver transplantation. In addition, it noted that patients should be rank-ordered according to severity of disease and predicted mortality on the liver waiting list. The Final Rule stipulated that waiting time should be deemphasized, that allocation should be designed to achieve equitable allocation of organs among patients, and that organs should be distributed over as broad a geographic area as feasible in order of decreasing medical urgency. Finally, the Final Rule noted that neither place of residence nor place of listing should be a major determinant of access to a liver transplant. This challenge was ultimately met by the adoption of the MELD score by UNOS in February 2002.
MELD
The MELD score was first used and published in 2000 by Malinchoc and colleagues8 to predict survival in patients undergoing elective transjugular intrahepatic portal-cava systemic shunts. In 2001, the Mayo Clinic group modified the score to predict mortality in a wide range of liver disease etiologies and severities.9 In the final model, cause of liver disease was eliminated from the model and three biochemical variables were used: (1) serum bilirubin, (2) international normalized ratio (INR), and (3) serum creatinine level. Retrospective studies demonstrated that the MELD score had a high degree of discriminative ability in prediction of 3-month survival in patients with cirrhosis, regardless of the cause of liver disease, and was independent of complications of liver disease, such as ascites, encephalopathy, variceal bleeding, and spontaneous bacterial peritonitis.9 The final assessment of the MELD score was made using 3437 patients on the UNOS liver transplant waiting list. In this study the MELD score was found to be superior to the CTP score for predicting 3-month survival.10 The C statistic for predicting 3-month survival on the waiting list was 0.83. This study led to the adoption of the MELD score for liver donor allocation in the United States in February 2002. Since that time, the MELD score has been validated around the world and is presently used in many countries today to allocate donor liver organs.11–13 Indeed, there are more than 1000 papers published in the last decade on the MELD score. The MELD score has been thoroughly scrutinized and a decade later remains the standard by which to predict mortality in patients with end-stage liver disease.
Advantages of the MELD score
Advantages of the MELD score are its statistical validation and the use of objective widely available laboratory tests (serum bilirubin, serum creatinine, and INR of prothrombin). Today several online calculators are available for calculating the MELD score. It initially was thought that the MELD score might prioritize sicker patients who were more likely to die following liver transplantation.
The impact of the MELD allocation policy resulted in a reduction in waiting list registration by 12%, a reduction in death on the waiting list by 5%, decreased median waiting times from 676 to 416 days, and patients transplanted within 30 days of listing increased from 23% in the pre-MELD era to 37% in the post-MELD era.14 In the MELD era although sicker patients were transplanted posttransplant survival actually slightly improved, thus dispelling concerns that many had about reducing death on the waiting list, but increasing death posttransplant.15,16 However, transplantation of sicker patients with higher MELD scores has led to an increase in the cost of liver transplantation and resource...
| Erscheint lt. Verlag | 9.10.2014 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizinische Fachgebiete ► Chirurgie ► Viszeralchirurgie |
| Medizinische Fachgebiete ► Innere Medizin ► Gastroenterologie | |
| ISBN-10 | 0-323-32035-X / 032332035X |
| ISBN-13 | 978-0-323-32035-1 / 9780323320351 |
| Haben Sie eine Frage zum Produkt? |
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