Epidemiology

The frequency of alcohol–related end stage organ disease is surprisingly low given the prevalence of alcoholism (nearly 9% of US adults) (Grant 1994) and the toxic effects of ethanol on the liver and heart. There is not a direct concordance between alcohol use, alcohol abuse or dependence and either the development of alcoholic cirrhosis (Simko 1983; Arria, Tarter, and Van Thiel 1991) or alcoholic cardiomyopathy (Hosenspud 1994). Evidence from the natural history of alcoholic liver disease suggests that the risk of alcoholic liver disease increases with habitual alcohol intake of 20 g ethanol/day for women and 80g ethanol/day for men (Diehl 1997) (there are approximately 10g of ethanol per standard drink). But, despite the amount of heavy drinking, the lifetime incidence of alcoholic cirrhosis only approaches 50% of people who drink excessively (i.e., consumption of 227g pure ethanol or nearly one–fifth of a gallon of hard liquor per day) for over two decades (Lelbach 1975). Inconsistencies in the risk of cirrhosis by level of alcohol consumption may be due to lack of controlling for body size, gender, and alcohol consumption patterns (frequency and temporal patterns) (Parrish, Higuchi, and Dufour 1991). Nevertheless, alcohol related end stage liver disease results typically from 10 to 20 years of heavy drinking. Though a diagnosis of alcohol-induced liver disease can be supported by medical data (liver biopsy and liver enzyme profiles) in conjunction with a history of heavy alcohol consumption, a patient may not meet the criterion for alcohol abuse or dependence in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).

Introduction

Organ transplant candidates and recipients pose special pharmacologic problems because of organ–system insufficiency or failure, often multisystem, and the medical need for polypharmacy. The use of immunosuppressant agents post–transplantation complicates psychiatric assessment because of associated neuropsychiatric side effects. Because patients are also at risk for unusual infections that require aggressive treatment, neuropsychiatric syndromes resulting both from the medications and the infections further complicate psychiatric differential diagnosis (Trzepacz et al. 1991). The potential for drug–drug interactions is high, and can result in drug toxicity and delirium.

The psychologic stresses of undergoing organ transplantation are also high. Clinically significant depression or anxiety may be difficult to distinguish from secondary psychiatric symptoms, e.g., due to medications (e.g., ganciclovir, cyclosporine, prednisone) or to medical disorders (e.g., hypoxia, cytomegalovirus infection). Identification and treatment of primary psychiatric disorders in organ transplant patients is covered in detail elsewhere (Trzepacz et al. 1991; Trzepacz, DiMartini, and Tringali 1993b).

General issues in organ insufficiency

Some of the organs that are transplanted also play important roles in drug metabolism and clearance (for a review, see DiMartini and Trzepacz 1999). The liver is the most involved in detoxification and metabolism, with the kidneys responsible for excretion of some drugs (e.g., digoxin, lithium, gabapentin) and many metabolites of hepatically altered drugs. The heart is responsible for movement of blood that transports drugs and oxygen to all tissues. Third spacing of drugs into peritoneum (ascites) or interstitial tissues (edema) in the context of hepatic, cardiac, or renal failure may lower effective levels in the bloodstream, requiring adjustment of doses.

The transplant patient faces extraordinary challenges in their emotional and social lives as they undergo the physical transformations associated with the transplantation process. The need for an organ transplant may occur acutely or as a consequence of chronic organ insufficiency, each with its own set of biopsychosocial consequences. The interrelationships between physiology and psychological health are important for bodily health. Even immunological functions show links between brain and other body areas that may bridge emotional and physical states in complex and heretofore poorly understood ways. Pharmacological interventions often cross the bloodbrain barrier, causing psychiatric side effects – for example, during uremia or hypocholesterolemia combined with cyclosporine treatment.

Our book opens with a chapter, “The mystique of transplantation: biologic and psychiatric considerations”, by Thomas Starzl, the distinguished pioneer of liver transplantation from the laboratory to the human situation. Starzl traces the history of immunological barriers that were overcome in order to allow orthotopic organ transplantation, including engraftments of kidney, liver, lung, heart, pancreas, intestine and multiple abdominal viscera. He describes bidirectional immunologic confrontation between graft and host and the important discovery of donor leukocyte chimerism in solid organ transplantation, contrasting it with bone marrow transplantation, where host cells are deliberately cytoablated.

The closing chapter, by Maureen Martin, “Current trends and new developments in transplantation”, addresses new approaches to clinical immunosuppression, based on the concept of chimerism, which use bone marrow and stem cell-derived factors combined with solid organ transplantation.