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Immunosuppressive Biologic Agents

Historical Perspective The development of potent immunosuppressive therapies transformed liver transplantation from the experimental procedure pioneered by Thomas Starzl and Sir Roy Calne into the preferred clinical treatment for end-stage liver disease. The greatest incremental improvements in clinical outcomes have tracked closely with the introduction of improved pharmacological agents and the subsequent development of guidelines for their proper use. Today the 1-year and 5-year survival following…

Novel Immunosuppressive Drugs

The introduction of more potent immunosuppressive agents in the 1990s resulted in a reduction of acute rejection and graft loss. However, the improved short-term success has translated into only modest gains in long-term renal allograft survival. The main cause of late graft loss was suspected to be secondary to the inexorable problem of nephrotoxicity associated with calcineurin inhibitor (CNI)–based immunosuppression. Recent studies using C4d staining of…

Novel Immunosuppression in Patients with Hepatic Malignancies

Orthotopic liver transplantation (OLT) for malignancy, specifically hepatocellular carcinoma (HCC), has dramatically increased in the last several decades. Unfortunately, cancer recurrence remains a formidable problem. At present, calcineurin-based immunosuppression (IS) regimens are employed by most transplant centers around the world. However, preclinical data suggest that calcineurin inhibitors (CNIs) may promote both primary tumor growth and distant metastasis. Several clinical series link CNI-based IS to reduced recurrence-free…

Treatment of Acute and Chronic Rejection

Advances in the treatment of rejection have mirrored the evolution of liver transplantation. In the earliest days of transplantation, clinical outcomes were marred by fatal complications related to ischemia, preservation injury, surgical technique, and infection. Grafts that would survive long enough to succumb to rejection were rare. Moreover, tackling rejection was not yet part of the transplant paradigm, and organs that did survive were eventually ruined…

Special Considerations for Immunosuppression in Children

The admonition that “children are not small adults” is well justified in the immunosuppressive management of children after liver transplantation. When compared with adults, several key differences are apparent when considering immunosuppression for children: Children are more immunoresponsive than adults. The incidence of rejection varies with age. Exposure to immunosuppression may span many decades in transplanted children. The risk for recurrent disease, as well as the…

Induction and Maintenance of Immunosuppression

Progress in liver transplantation in essence has been a story of the progress in developing immunosuppressant drugs. Although initial attempts at liver transplantation in Denver and Cambridge in the 1960s and 1970s using azathioprine, steroids, and antilymphocyte globulin had some success, it was not until the development of cyclosporine in 1978 that liver transplantation became a truly viable option with good chances of long-term success. From…

Graft-Versus-Host Disease

Graft-versus-host disease (GVHD) occurs when histoincompatible lymphocytes from an allogenic donor engraft in a transplant recipient. GVHD is frequent after bone marrow transplantation but relatively rare after liver transplantation. GVHD typically occurs 1 to 6 weeks after liver transplantation (LT) and presents with fever, rash, diarrhea, and/or pancytopenia. Unlike GVHD after BMT, in which the biliary epithelium is a major target, the transplanted liver is not…

ABO, Tissue Typing, and Crossmatch Incompatibility

The ABO blood group antigens and the human leukocyte antigens (HLA) encoded by the major histocompatibility gene complex represent substantial barriers to transplantation of tissues and organs between individuals. The antigens of these two systems are expressed on most cells in the body, and antibodies directed against either ABO or HLA antigens of the donor can cause severe damage to the graft. The allogeneic donor HLA…

Leukocyte Chimerism—Meaning and Consequences

Between 1953 and 1956, a strong association between donor leukocyte chimerism and acquired donor-specific tolerance was demonstrated in studies of mouse models. Bone marrow transplantation a dozen years later in immune-deficient and cytoablated human recipients was a logical extension. In contrast, when clinical organ transplantation was precociously accomplished between 1959 and 1962 in the presumed absence of leukocyte chimerism, it promptly became dogma that organ alloengraftment…

Rejection After Transplantation

Liver transplantation is recognized as optimal therapy for end-stage liver disease. Results today are excellent, with unadjusted 1-year and 5-year patient survival rates of 88.4% and 73.8%, according to the Scientific Registry of Transplant Recipients (SRTR). The incidence of acute rejection after transplantation commonly ranges from 25% to 46% within the first year after transplantation, with the highest incidence in the first 7 to 10 days…

Transplant-Related Malignancies

Over the last 20 years, liver transplantation has become an integral part of the treatment of patients with end-stage liver disease. Every year in the United States alone, more than 6000 such procedures are performed with ever-improving outcomes. Improvements in surgical technique and posttransplant medical care and the development of better immunosuppressants have resulted in 1-year posttransplant survival close to 90% and 5-year survival close to…

Pathology of NonNeoplastic Disease After Transplantation

Liver transplantation has enjoyed tremendous success, in part because of the unique immunological properties of the liver and in part because of the development of new pharmaceutical agents to treat rejection and infection. Fortunately, liver allografts are infrequently lost to rejection or opportunistic infection. Recurrent disease, however, remains a serious problem and is a frequent cause of graft dysfunction and loss. Recurrent Hepatitis C Hepatitis C,…

Histopathology of Liver Transplantation

Liver transplantation is used to treat a broad spectrum of end-stage liver diseases. Hepatitis C virus (HCV) and alcoholic and nonalcoholic fatty liver disease–induced cirrhosis are the leading indications in North America, Europe, and South America, whereas in Asia, hepatitis B virus (HBV)-induced cirrhosis still accounts for a large percentage of liver transplants. Original disease recurrence is common in adults, but less so in children, and…

Role of the Posttransplant Clinical Nurse Coordinator

The posttransplant clinical nurse coordinator (PTCNC) is an integral part of the patient care delivery team. The PTCNC is involved in the continuum of patient care that begins postoperatively in the hospital and continues to coordinate this care in the outpatient setting. Throughout this continuum many forces define the PTCNC’s responsibilities, knowledge requirements, and resource needs related to the coordination of patient care. This chapter briefly…

Neurological Complications

Liver transplants have become relatively frequent procedures throughout the world, with improving survival rates; this means that physicians, regardless of their specialty, are likely to participate in the care of these inherently complex cases. More than 5,500 people in the United States receive a liver transplant every year, whereas 15,357 patients were waiting for liver transplant in 2011, according to the Organ Procurement and Transplant Network…

Neuropsychiatric Complications

Neuropsychiatric complications after liver transplantation are common, with the incidence ranging from 10% to 70% and neuropathological findings common at autopsy. In one of the earliest papers discussing outcomes in liver transplantation, Starzl et al noted a high incidence of acute neuropsychiatric complications including altered mental status, seizure, and central pontine myelinolysis. Several risk factors for neuropsychiatric complications after liver transplantation have been identified, including advanced age…

Late Complications and Recurrence of Disease After Transplantation

As outcomes after liver transplantation improve from advances in surgical technique, intensive care, and immunosuppression, patients are living longer. As a result, graft and patient survival are largely now dependent on early recognition and treatment of primary disease recurrence and comorbid conditions. Unfortunately, many patients after liver transplant remain focused on their liver disease, when most should be concentrating on primary care issues such as cancer…

Recurrent Hepatitis C After Transplantation

Complications of chronic hepatitis C, including cirrhosis and hepatocellular carcinoma, remain the most common indication for liver transplantation, accounting for nearly half of all liver transplants in the United States. However, this large group of transplant recipients faces a lower chance of long-term posttransplant survival than those transplanted for other indications. Recurrent hepatitis C is the most common cause of graft loss, which results in death…

Infections After Transplantation

Despite the remarkable surgical advances in orthotopic liver transplantation (OLT) and the development of many effective prophylactic strategies, infection can still be a frequent cause of morbidity and mortality after transplantation. The spectrum and manifestations of these infections are broad and variable and often reflect the fact that a patient awaiting liver transplantation is a unique host who is usually in an impaired state of health…

Arterial Complications After Transplantation

Vascular complications continue to be a major source of morbidity and mortality after orthotopic liver transplantation (OLT). Arterial complications of OLT threaten outcomes for patients and allografts. Hepatic arterial thrombosis (HAT) interrupts the allograft's blood supply and produces early graft loss, long-term dysfunction, or patient death, making these surgical complications life threatening. Considering the ongoing scarcity of hepatic allografts, vascular complications can have a profound impact…