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Liver transplantation in adults
GASTROENTEROLOGY
CLINICAL
TRENDS
AND
1986;90:211-6
TOPICS
Liver Transplantation
in Adults
An Analysis of Costs and Benefits at the University of Pittsburgh DAVID H. VAN THIEL, RALPH TARTER, JUDITH S. GAVALER, WILLIAM M. POTANKO, and ROBERT R. SCHADE Departments of Medicine and Psychiatry, University of Pittsburgh Presbyterian-University Hospital, Pittsburgh, Pennsylvania
Orthotopic liver transplantation in humans has come of age. After 20 yr of experimental effort in animals and human beings, this procedure has reached such a level of success that it has been reviewed by a National Institutes of Health consensus development conference (June 20-23, 1983) where the following conclusion was reached: “liver transplantation is a therapeutic modality for end stage liver disease that deserves broader application.” Moreover, the conference made the statement that the procedure should be applied both to children and adults who have “irreversible liver injury” and “who have exhausted alternative medical and surgical treatments and are approaching the terminal phase of their illness” (1). The specific indications for the procedure in adults have been identified previously (l-4). Although fulminant hepatic failure due to toxin or drug exposure may warrant liver transplantation, the rapid progression of the disease and the multisystem organ failure that is associated with the condition frequently precludes application of the procedure for this indication. Specifically, the logistic and technical problems of donor procurement and life support required in such cases, until transplantation is possible, make this condition an unlikely frequent cause for the procedure. The following is a cost-benefit analysis of liver transplantation as applied to a single institution, the
Received December 18, 1984. Accepted June 12, 1985. Address requests for reprints to: David H. Van Thiel, M.D., University of Pittsburgh, 10007 Scaife Hall, Pittsburgh, Pennsylvania 15261. This work was supported in part by grants #5ROl AA04425 and #ROl AM32556 from the National Institute for Alcohol Abuse and Alcoholism and by the Gastroenterology Medical Research Foundation of Southwestern Pennsylvania. 0 1986 by the American Gastroenterological Association 0016-5085/86/$3.50
School
of Medicine,
and
University of Pittsburgh, and then only in adults. The data presented represent the investment made by the personnel and institutions involved since its onset in March 1981 until the end of December 1984. It is the purpose of this analysis to inform the medical-surgical community of both the initial and long-term costs and benefits of liver transplantation so that those interested in its application can make a rational decision concerning possible referrals to an institution performing or planning to perform the procedure. Because dollar costs are difficult to compare between institutions, the costs wherever possible will be reported in terms of number of personnel, days, or some other standard unit of service, such that conversions to actual local dollar costs at a particular institution can be made if one knows the dollar cost for each unit at that institution,
Costs and Benefits to the Transplantation Center Many of the costs of a liver transplantation program at a given center are indirect and are actually borne by some other program in the same institution. Examples are the cost of having a surgical program, a hepatology program, an intensive care unit (ICU), operating rooms, and a clinical pathology department. These costs will be ignored in this discussion except as they apply specifically to the liver transplant program. To this end, only the additional costs, above those already being expended before the initiation of the liver transplant program, will be recognized as costs of the liver transplantation program. The personnel costs ascribed solely to the liver transplant program at the University of Pittsburgh are shown in Table 1. The additional hospital facilities required by Presbyterian-univers-
212
Table
GASTROENTEROLOGY Vol. 90. No. 1
VAN THIEL ET AL.
1. institutional Personnel Costs Assumed by the University of Pittsburgh and PresbyterianUniversity Hospital as Part of Having a Liver Transolantation Program
Surgical personnel 1 Senior surgeon 3 Full-time associate
surgeons
2 Surgical fellows 3 Surgical house staff 1 Nurse coordinator 3 Secretaries
Gastroenterology-hepatology 1.5 Senior hepatologists
enhanced as a consequence of the uniqueness of the program and the opportunities it offers for research, data collection and management, and clinical health care delivery. Similarly, as a result of the national and international visibility of the institution and its staff, referrals not only for liver transplantation but also for other types of complex hepatobiliary diseases requiring advanced and unusual medical or surgical skills occur.
personnel
1 Hepatology fellow 1 Nurse coordinator
1 Secretary Anesthesia 2 Anesthesiologists Operating room personnel 2 Nurses 2 Circulators Psychiatry 9.5 Psychiatrist Clinical chemistry 2 Technicians, full-time Social services 2 Social workers, full-time Blood bank 1 Technician 1 Secretary 1 Runner Donor procurement agency personnel 1 full-time person
ity Hospital in order to have the liver transplantation program are shown in Table 2. These rather enormous expenditures have to be balanced by the benefit accrued by the institution from having a liver transplantation program. Certainly, programs anticipating a lesser volume of activity than that experienced in Pittsburgh might be able to function with less manpower and facilities. The reductions in manpower required, however, would appear to be limited solely to the surgical and hepatology personnel identified in Table 1 and a fractional reduction in the number of hospital beds consistent with the relative size of the program anticipated. The benefits to the institution are less easily identified and quantified. Nonetheless they certainly include the following: national and international recognition, local publicity, enhanced public relations, the sense of a common goal, and the excitement of being in the forefront of some aspect of the application of medical-surgical technology. In addition, the ability of an institution to attract, recruit, and maintain faculty and other personnel is
Costs and Benefits to the Patient The actuarial 4-yr survival rate for orthotopic hepatic transplantation performed in adults at the University of Pittsburgh from 1981 through April 1984 is shown in Figure 1.There are three important observations to be made from this figure. First, 80% of the deaths occurring after liver transplantation occur early during the first 3 mo. Second, after the first 3 mo there is a slight but steady decline in survival during the first year. Third, the survival curves after the first year are relatively flat. These long-term data are very encouraging. The total in-hospital time experienced by these patients from the time of surgery to their discharge is shown in Figure 2. The total time spent in the recovery room or the ICU, or both, by these same patients as a group and for each disease-specific indication is shown also. As can be seen from the figure, the total time spent in the hospital and the number of days spent in an KU after transplantation vary considerably, depending upon the indication for the procedure. Thus patients with hepatoma as the indication for transplantation spend the least amount of time in the hospital and also in an ICU, whereas patients with postnecrotic cirrhosis and primary biliary cirrhosis spend the most time in each. The volume of blood and blood products consumed by a given liver transplant patient is considTable
2. Hospital Facilities Required and Committed by Presbyterian-University Hospital for the Liver Transplantation Program at the University of Pittsbureh
In-hospital Surgical beds-60 Medical beds-6 Surgical ICU beds-4 Medical ICU beds-2 Recovery room beds-2 Operating rooms-l Out of hospital Follow-up clinics, medicine and surgery-6 daysiwk Outpatient lodging for family members and patients-38 rooms (family house)
January
1986
LlVER TRANSPLANTATION:
erable indeed. Table 3 demonstrates the volume of blood consumed by 37 adult liver transplant recipients who underwent a total of 46 transplant procedures during 1982.Figure 3 demonstrates the number of patients who received a given number of red blood cell units. In most cases, the volume of red blood cells used per patient was matched by the volume of plasma. Of particular interest is the fact that almost half of the total blood consumption by these patients occurred intraoperatively. Importantly, most patients require 530 U of blood and the survival rate for those requiring >30 U is considerably less than that of those who require less. It should be noted that the actual intraoperative consumption of blood products by these patients is not spaced evenly over the 8-18 h of the operation but tends to occur in bursts. In order to put this volume of blood consumption into perspective, Table 4 compares the use of similar blood products by the total 17,706 adult admissions to the PresbyterianUniversity Hospital in 1982 with that of the 37 adult patients who received a total of 46 liver transplants during the same period. It is readily apparent from these two tables that a disproportionate use of such products is consumed by the transplant population. Moreover, it immediately becomes obvious that the blood bank must be capable of providing these blood products with little advance notice while still maintaining the availability of these same products for other patients and programs within the hospital. Not only are the patients at the Presbyterian-University Hospital affected by the blood product consumption of the liver transplant program at the University of
i
50-
s
40-
= 2
30-
COSTS
AND BENEFITS
213
20 IO -
i
b 9 Ii
3
2
YEARS
MONTHS
Figure
, 4
survival course for adults receiving a liver 1. Actuarial transplant in Pittsburgh during the period March 1981 to December 1984.
Pittsburgh but so are all the other patients and hospitals (n = 34) served by the Central Blood Bank of Pittsburgh. The cost of a liver transplant to an individual patient includes the cost of all of the numerous laboratory tests utilized by the physicians caring for the patient both preoperatively and postoperatively. The cost of the preoperative work-up varies somewhat from institution to institution and according to the disease condition and thoroughness of the evaluation obtained before referral to the transplantation center. At the University of Pittsburgh, the preoperative evaluation consists of a variety of laboratory tests necessary to document specifically the diagnosis and the severity of the disease condition neces-
NON ICU 70
60
PBC (35)
Figure
2. Intensive Pittsburgh. sclerosing
PSC (18)
PNC (48)
HEP (7)
MISC (16)
PBC
PSC
PNC
(351
(181
(461
HEP (7)
MISC (16)
care (RX) and nonintensive care unit (NON ICU) hospital days utilized by adults receiving a liver transplant in The bars represent mean values and the brackets represent SEM. PBC, primary biliary cirrhosis; PSC, primary cholangitis: PNC, postnecrotic cirrhosis; HEP, hepatoma; MISC, miscellaneous diseases.
214
VAN THIEL ET AL.
Table
GASTROENTEROLOGY Vol. 90, No. 1
3. Blood Product Usage by 37 Liver Transplant Patients During 46 Transplant Operations at the Presbyterian-University Hospital During the Calendar Year 1982 Intraoperative use
Product RBCs (L’) FFP (U) Platelets (packs) Cryoprecipitate (packs]
Product
5087 4868 2747 338
Patients RBCs (LJ) FFP (U) Platelets lnacksl
sitating consideration for liver transplantation and averages $5705.00. The postoperative hospital costs are even more substantial and dwarf those of the preoperative period. These costs include measurement of the numerous liver enzymes [serum glutamic oxaloacetic transaminase (aspartate transaminase), serum glutamic pyruvic transaminase (alanine transaminase), alkaline phosphatase, and y-glutamyl transpeptidase] and bilirubin levels, the standard measures of renal function (creatinineblood urea nitrogen) and hematologic (complete blood cell count with platelet count) and electrolyte determinations obtained on these patients, as well as the daily monitoring of cyclosporine levels desired by the surgeons performing the transplant. The total cost of these tests is substantial and averages $46,585.00, being 85% of the total preoperative and postoperative laboratory charges. It is to be hoped that with increasing experience, the number and
14 g 12 0
SURVIVED
??DECEASED
8
“06 44
2 0
RED
BLOOD
CELL
Total patients 17,706 21,701 13,032 11.977
Transplant patients 37" 5087 (23.4%)" 4868 (37.4"h) 2747 (22.9%)
FFP, fresh frozen plasma; RBCs, red blood cells. ‘Forty-six transplant operations. b Percentage of total hospital consumption.
FFP, fresh frozen plasma; RBCs, red blood cells
%
4. Use of Blood Products by AJJ Patients Hospitalized at Presbyterian-University Hospital and the 37 Liver Transplant Patients During 1982
Total use
1903 1608 726 268
$10 i=
Table
UNITS
Figure 3. Red blood cell (RBC) consumption by adult patients undergoing orthotopic liver transplantation at the Presbyterian-university Hospital. On the ordinate is shown the number of patients who received a given number of RBC units. The abscissa indicates the number of RBC units. Note that the survival rate for patients receiving <30 U is 70%, whereas that for patients receiving >30 U is markedly less.
frequency of these tests can be reduced. Such a reduction in testing would reduce markedly the cost of the procedure borne by the patient, the insurance carrier, and/or, the government agency responsible. In addition to these hospital costs, the patient will be faced with physician and surgeon costs which, for our institution, have been defined previously (5). Several additional costs borne by the patient after successful liver transplantation are lifelong and need to be considered as well. These include the cost of lifelong medical-surgical follow-up; cyclosporine, prednisone, and other medications necessitated by the use of cyclosporine and steroids [e.g., antihypertensive agents); the risk of acquiring an opportunistic infection and the unknown risks of disease recurrence or the acquisition of a new disease such as non-A, non-B hepatitis as a consequence of the considerable use of blood products described above; and chronic rejection and other drug- or transplantrelated problems that are either ill defined or not yet recognized. The offsetting benefits to the individual incurred as a consequence of hepatic transplantation must be substantial indeed in order to balance these considerable costs. They include a new life consisting of an existence outside the hospital, a chance to return to gainful employment or to return to school, and the opportunity to have a family. As might be expected, these benefits are difficult to quantify, but some progress toward this end has been accomplished. At present 85% of the adults who receive a liver transplant and leave the hospital return to full-time gainful employment or some other useful activity such as school or homemaking. Four women who have had liver transplants have become pregnant after successful transplantation (one of them twice). All of their children have been normal despite continued use of maintenance immunosuppression therapy during the pregnancy. To assess “quality of life” after transplantation, a battery of tests measuring cognitive capacity, psychiatric status, and social functioning was administered to a cohort of 10 subjects (6). All of the subjects had
January 1986
undergone successful transplantations at least 1 yr previously. The mean interval between the time of transplantation surgery and psychological testing was 43.4 mo. The scores for these subjects on the cognitive battery of tests did not reveal the presence of any neuropsychological impairment when compared with those of patients with Crohn’s disease and against normative values. Thus, although not tested preoperatively in this small sample, it can be concluded that at least postsurgically, encephalopathy is not present. Psychiatric status was assessed in these same subjects using the Minnesota Multiphasic Personality Inventory. On none of the scales did the subjects score in the pathognomonic (T > 70) ranges. Trends for a psychiatric disturbance (T > 60) were depression (D), social withdrawal (ST), disrupted personality integration (SC), and social conformity (Pd). Although these deviations from normative values are indicative of a certain degree of posttransplantation psychiatric maladjustment, they do not differ from those found in the Crohn’s disease control subjects. Hence, the psychiatric status of patients after successful transplantation is comparable to that observed in patients with chronic illness and is therefore somewhat disturbed relative to values observed in a normal population. To assess measures of social functioning, the Sickness Impact Profile was administered to each of these same 10 subjects. This multidimensional test assesses the impact of the subject’s illness on routine everyday activities and social interactions. The scores obtained reflect the percentage of impairment observed on the various scales comprising the test battery. At a mean of 43 mo (minimum 1 yr) after successful transplantation these 10 patients had scores that did not differ from those obtained in patients with stable Crohn’s disease. When compared with normative values, however, the transplant subjects manifested problems in certain aspects of daily functioning. Self-rating of sleep and rest comprised the largest area of impairment (38%). Between 20% and 30% impairment was observed for work, recreation, pasttimes, and alertness. A lesser disruption was noted on social interaction, eating, home management, mobility, and emotional behavior. Psychosocial dysfunction was rated as slightly more impaired than physical dysfunction (18% vs. 13%).
Overall, the findings on this relatively small cohort of posttransplantation patients indicate that cognitive capacity is normal, whereas psychiatric and social functioning are somewhat disrupted. The magnitude of the disruption, though not different from that found in a chronic illness control group (Crohn’s disease), is nonetheless significant. Based
LIVERTRANSPLANTATION: COSTSANDBENEFITS
215
on these preliminary results, it does not appear that transplantation alone is sufficient to return the person to normality. Moreover, they suggest a need for psychosocial rehabilitation intervention in such patients after successful transplantation (6).Nonetheless, more than 80% of surviving adult recipients of an orthotopic liver transplant return to full-time gainful employment, would appear to be fully integrated into the normal working population, and are not functionally impaired. The benefits of liver transplantation to society are less difficult to identify and include the conversion of a health care consumer into a health care premium payer, and a reduction in the total cost of health care for the unique population to which hepatic transplantation is applied. The cost of care of patients with advanced liver disease who are either not considered candidates for transplantation or who were refused transplantation because of some complicating factor, such as portal vein thrombosis or extensive prior abdominal surgery, is substantial. Moreover, it should be remembered that even successful treatment in such cases leads only to the survival of a critically ill patient who will most certainly be admitted again to the hospital for yet another complication or a reoccurrence of the same problem, or to die. The cost of these multiple accrued hospitalizations and continued and possibly intensified care must be subtracted from that of the cost of the transplant procedure and the care of the patient for an equivalent time period, should transplantation be applied to realistically define the true cost of liver transplantation. The long-term or delayed consequences of having a transplantation program include the advancement of our present understanding of hepatic disease in general and those hepatic diseases that are only occasionally or rarely seen by the average health care practitioner in particular. Obviously, the funneling of such patients to regional centers of hepatic disease excellence can only improve the care provided them and that of generations to come. Equally benefited, however, are the broad fields of surgery, radiology, immunology, and infectious disease. The creation of a liver transplant center serves as an immediate focus for the refinement of training and education in these service areas, which frequently are called upon to contribute importantly to the overall success of the transplant program. Indeed, liver transplantation has established itself as a clinical entity (7). Its future is bright but it is also full of challenges (1).New and cheaper methods of monitoring and recognizing rejection need to be developed; safer and less costly immunosuppressive agents need to be identified; better surgical techniques that result in fewer postoperative problems
216
GASTROENTEROLOGY Vol. 90, No. 1
VAN THIEL ET AL.
need to be developed; and obviously more uniform and disease-specific indications for its application need to be developed. As knowledge and experience with its application increase, however, the costs associated with its performance are likely to decline while the success associated with its application is more likely to increase.
References 1. National Institutes of Health Concensus ment Statement. Liver transplantation. Hepatology 1984;4:13-45.
Conference DevelopJune 29-23, 1983.
2. Scharschmidt BF. Human liver transplantation: analysis of data on 540 patients from four cities. Hepatology 1984; 4:953-1015. 3. Grendell JH. Hepatic transplantation apd resection. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver diseases. Philadelphia: WB Saunders, 1982:1274-84. 4. MacDougall BR, Williams R. The indications for orthotopic liver transplantation. Transplant Proc 1979;11:247. 5. Van Thiel DH, Schade RR, Starzl TE, et al. Liver transplantation in adults. Hepatology 1982;2:637-40. 6. Tarter RE, Van Thiel DH, Hegedus AM, et al. Neuropsychiatric status of the liver transplantation. J Lab Clin Med 1984; 103:776-62. 7. Starzl TE, Iwatsuki S, Van Thiel DH, et al. Evolution of liver transplantation. Hepatology 1982;2:614-36.
CLINICAL
TRENDS
AND
1986;90:211-6
TOPICS
Liver Transplantation
in Adults
An Analysis of Costs and Benefits at the University of Pittsburgh DAVID H. VAN THIEL, RALPH TARTER, JUDITH S. GAVALER, WILLIAM M. POTANKO, and ROBERT R. SCHADE Departments of Medicine and Psychiatry, University of Pittsburgh Presbyterian-University Hospital, Pittsburgh, Pennsylvania
Orthotopic liver transplantation in humans has come of age. After 20 yr of experimental effort in animals and human beings, this procedure has reached such a level of success that it has been reviewed by a National Institutes of Health consensus development conference (June 20-23, 1983) where the following conclusion was reached: “liver transplantation is a therapeutic modality for end stage liver disease that deserves broader application.” Moreover, the conference made the statement that the procedure should be applied both to children and adults who have “irreversible liver injury” and “who have exhausted alternative medical and surgical treatments and are approaching the terminal phase of their illness” (1). The specific indications for the procedure in adults have been identified previously (l-4). Although fulminant hepatic failure due to toxin or drug exposure may warrant liver transplantation, the rapid progression of the disease and the multisystem organ failure that is associated with the condition frequently precludes application of the procedure for this indication. Specifically, the logistic and technical problems of donor procurement and life support required in such cases, until transplantation is possible, make this condition an unlikely frequent cause for the procedure. The following is a cost-benefit analysis of liver transplantation as applied to a single institution, the
Received December 18, 1984. Accepted June 12, 1985. Address requests for reprints to: David H. Van Thiel, M.D., University of Pittsburgh, 10007 Scaife Hall, Pittsburgh, Pennsylvania 15261. This work was supported in part by grants #5ROl AA04425 and #ROl AM32556 from the National Institute for Alcohol Abuse and Alcoholism and by the Gastroenterology Medical Research Foundation of Southwestern Pennsylvania. 0 1986 by the American Gastroenterological Association 0016-5085/86/$3.50
School
of Medicine,
and
University of Pittsburgh, and then only in adults. The data presented represent the investment made by the personnel and institutions involved since its onset in March 1981 until the end of December 1984. It is the purpose of this analysis to inform the medical-surgical community of both the initial and long-term costs and benefits of liver transplantation so that those interested in its application can make a rational decision concerning possible referrals to an institution performing or planning to perform the procedure. Because dollar costs are difficult to compare between institutions, the costs wherever possible will be reported in terms of number of personnel, days, or some other standard unit of service, such that conversions to actual local dollar costs at a particular institution can be made if one knows the dollar cost for each unit at that institution,
Costs and Benefits to the Transplantation Center Many of the costs of a liver transplantation program at a given center are indirect and are actually borne by some other program in the same institution. Examples are the cost of having a surgical program, a hepatology program, an intensive care unit (ICU), operating rooms, and a clinical pathology department. These costs will be ignored in this discussion except as they apply specifically to the liver transplant program. To this end, only the additional costs, above those already being expended before the initiation of the liver transplant program, will be recognized as costs of the liver transplantation program. The personnel costs ascribed solely to the liver transplant program at the University of Pittsburgh are shown in Table 1. The additional hospital facilities required by Presbyterian-univers-
212
Table
GASTROENTEROLOGY Vol. 90. No. 1
VAN THIEL ET AL.
1. institutional Personnel Costs Assumed by the University of Pittsburgh and PresbyterianUniversity Hospital as Part of Having a Liver Transolantation Program
Surgical personnel 1 Senior surgeon 3 Full-time associate
surgeons
2 Surgical fellows 3 Surgical house staff 1 Nurse coordinator 3 Secretaries
Gastroenterology-hepatology 1.5 Senior hepatologists
enhanced as a consequence of the uniqueness of the program and the opportunities it offers for research, data collection and management, and clinical health care delivery. Similarly, as a result of the national and international visibility of the institution and its staff, referrals not only for liver transplantation but also for other types of complex hepatobiliary diseases requiring advanced and unusual medical or surgical skills occur.
personnel
1 Hepatology fellow 1 Nurse coordinator
1 Secretary Anesthesia 2 Anesthesiologists Operating room personnel 2 Nurses 2 Circulators Psychiatry 9.5 Psychiatrist Clinical chemistry 2 Technicians, full-time Social services 2 Social workers, full-time Blood bank 1 Technician 1 Secretary 1 Runner Donor procurement agency personnel 1 full-time person
ity Hospital in order to have the liver transplantation program are shown in Table 2. These rather enormous expenditures have to be balanced by the benefit accrued by the institution from having a liver transplantation program. Certainly, programs anticipating a lesser volume of activity than that experienced in Pittsburgh might be able to function with less manpower and facilities. The reductions in manpower required, however, would appear to be limited solely to the surgical and hepatology personnel identified in Table 1 and a fractional reduction in the number of hospital beds consistent with the relative size of the program anticipated. The benefits to the institution are less easily identified and quantified. Nonetheless they certainly include the following: national and international recognition, local publicity, enhanced public relations, the sense of a common goal, and the excitement of being in the forefront of some aspect of the application of medical-surgical technology. In addition, the ability of an institution to attract, recruit, and maintain faculty and other personnel is
Costs and Benefits to the Patient The actuarial 4-yr survival rate for orthotopic hepatic transplantation performed in adults at the University of Pittsburgh from 1981 through April 1984 is shown in Figure 1.There are three important observations to be made from this figure. First, 80% of the deaths occurring after liver transplantation occur early during the first 3 mo. Second, after the first 3 mo there is a slight but steady decline in survival during the first year. Third, the survival curves after the first year are relatively flat. These long-term data are very encouraging. The total in-hospital time experienced by these patients from the time of surgery to their discharge is shown in Figure 2. The total time spent in the recovery room or the ICU, or both, by these same patients as a group and for each disease-specific indication is shown also. As can be seen from the figure, the total time spent in the hospital and the number of days spent in an KU after transplantation vary considerably, depending upon the indication for the procedure. Thus patients with hepatoma as the indication for transplantation spend the least amount of time in the hospital and also in an ICU, whereas patients with postnecrotic cirrhosis and primary biliary cirrhosis spend the most time in each. The volume of blood and blood products consumed by a given liver transplant patient is considTable
2. Hospital Facilities Required and Committed by Presbyterian-University Hospital for the Liver Transplantation Program at the University of Pittsbureh
In-hospital Surgical beds-60 Medical beds-6 Surgical ICU beds-4 Medical ICU beds-2 Recovery room beds-2 Operating rooms-l Out of hospital Follow-up clinics, medicine and surgery-6 daysiwk Outpatient lodging for family members and patients-38 rooms (family house)
January
1986
LlVER TRANSPLANTATION:
erable indeed. Table 3 demonstrates the volume of blood consumed by 37 adult liver transplant recipients who underwent a total of 46 transplant procedures during 1982.Figure 3 demonstrates the number of patients who received a given number of red blood cell units. In most cases, the volume of red blood cells used per patient was matched by the volume of plasma. Of particular interest is the fact that almost half of the total blood consumption by these patients occurred intraoperatively. Importantly, most patients require 530 U of blood and the survival rate for those requiring >30 U is considerably less than that of those who require less. It should be noted that the actual intraoperative consumption of blood products by these patients is not spaced evenly over the 8-18 h of the operation but tends to occur in bursts. In order to put this volume of blood consumption into perspective, Table 4 compares the use of similar blood products by the total 17,706 adult admissions to the PresbyterianUniversity Hospital in 1982 with that of the 37 adult patients who received a total of 46 liver transplants during the same period. It is readily apparent from these two tables that a disproportionate use of such products is consumed by the transplant population. Moreover, it immediately becomes obvious that the blood bank must be capable of providing these blood products with little advance notice while still maintaining the availability of these same products for other patients and programs within the hospital. Not only are the patients at the Presbyterian-University Hospital affected by the blood product consumption of the liver transplant program at the University of
i
50-
s
40-
= 2
30-
COSTS
AND BENEFITS
213
20 IO -
i
b 9 Ii
3
2
YEARS
MONTHS
Figure
, 4
survival course for adults receiving a liver 1. Actuarial transplant in Pittsburgh during the period March 1981 to December 1984.
Pittsburgh but so are all the other patients and hospitals (n = 34) served by the Central Blood Bank of Pittsburgh. The cost of a liver transplant to an individual patient includes the cost of all of the numerous laboratory tests utilized by the physicians caring for the patient both preoperatively and postoperatively. The cost of the preoperative work-up varies somewhat from institution to institution and according to the disease condition and thoroughness of the evaluation obtained before referral to the transplantation center. At the University of Pittsburgh, the preoperative evaluation consists of a variety of laboratory tests necessary to document specifically the diagnosis and the severity of the disease condition neces-
NON ICU 70
60
PBC (35)
Figure
2. Intensive Pittsburgh. sclerosing
PSC (18)
PNC (48)
HEP (7)
MISC (16)
PBC
PSC
PNC
(351
(181
(461
HEP (7)
MISC (16)
care (RX) and nonintensive care unit (NON ICU) hospital days utilized by adults receiving a liver transplant in The bars represent mean values and the brackets represent SEM. PBC, primary biliary cirrhosis; PSC, primary cholangitis: PNC, postnecrotic cirrhosis; HEP, hepatoma; MISC, miscellaneous diseases.
214
VAN THIEL ET AL.
Table
GASTROENTEROLOGY Vol. 90, No. 1
3. Blood Product Usage by 37 Liver Transplant Patients During 46 Transplant Operations at the Presbyterian-University Hospital During the Calendar Year 1982 Intraoperative use
Product RBCs (L’) FFP (U) Platelets (packs) Cryoprecipitate (packs]
Product
5087 4868 2747 338
Patients RBCs (LJ) FFP (U) Platelets lnacksl
sitating consideration for liver transplantation and averages $5705.00. The postoperative hospital costs are even more substantial and dwarf those of the preoperative period. These costs include measurement of the numerous liver enzymes [serum glutamic oxaloacetic transaminase (aspartate transaminase), serum glutamic pyruvic transaminase (alanine transaminase), alkaline phosphatase, and y-glutamyl transpeptidase] and bilirubin levels, the standard measures of renal function (creatinineblood urea nitrogen) and hematologic (complete blood cell count with platelet count) and electrolyte determinations obtained on these patients, as well as the daily monitoring of cyclosporine levels desired by the surgeons performing the transplant. The total cost of these tests is substantial and averages $46,585.00, being 85% of the total preoperative and postoperative laboratory charges. It is to be hoped that with increasing experience, the number and
14 g 12 0
SURVIVED
??DECEASED
8
“06 44
2 0
RED
BLOOD
CELL
Total patients 17,706 21,701 13,032 11.977
Transplant patients 37" 5087 (23.4%)" 4868 (37.4"h) 2747 (22.9%)
FFP, fresh frozen plasma; RBCs, red blood cells. ‘Forty-six transplant operations. b Percentage of total hospital consumption.
FFP, fresh frozen plasma; RBCs, red blood cells
%
4. Use of Blood Products by AJJ Patients Hospitalized at Presbyterian-University Hospital and the 37 Liver Transplant Patients During 1982
Total use
1903 1608 726 268
$10 i=
Table
UNITS
Figure 3. Red blood cell (RBC) consumption by adult patients undergoing orthotopic liver transplantation at the Presbyterian-university Hospital. On the ordinate is shown the number of patients who received a given number of RBC units. The abscissa indicates the number of RBC units. Note that the survival rate for patients receiving <30 U is 70%, whereas that for patients receiving >30 U is markedly less.
frequency of these tests can be reduced. Such a reduction in testing would reduce markedly the cost of the procedure borne by the patient, the insurance carrier, and/or, the government agency responsible. In addition to these hospital costs, the patient will be faced with physician and surgeon costs which, for our institution, have been defined previously (5). Several additional costs borne by the patient after successful liver transplantation are lifelong and need to be considered as well. These include the cost of lifelong medical-surgical follow-up; cyclosporine, prednisone, and other medications necessitated by the use of cyclosporine and steroids [e.g., antihypertensive agents); the risk of acquiring an opportunistic infection and the unknown risks of disease recurrence or the acquisition of a new disease such as non-A, non-B hepatitis as a consequence of the considerable use of blood products described above; and chronic rejection and other drug- or transplantrelated problems that are either ill defined or not yet recognized. The offsetting benefits to the individual incurred as a consequence of hepatic transplantation must be substantial indeed in order to balance these considerable costs. They include a new life consisting of an existence outside the hospital, a chance to return to gainful employment or to return to school, and the opportunity to have a family. As might be expected, these benefits are difficult to quantify, but some progress toward this end has been accomplished. At present 85% of the adults who receive a liver transplant and leave the hospital return to full-time gainful employment or some other useful activity such as school or homemaking. Four women who have had liver transplants have become pregnant after successful transplantation (one of them twice). All of their children have been normal despite continued use of maintenance immunosuppression therapy during the pregnancy. To assess “quality of life” after transplantation, a battery of tests measuring cognitive capacity, psychiatric status, and social functioning was administered to a cohort of 10 subjects (6). All of the subjects had
January 1986
undergone successful transplantations at least 1 yr previously. The mean interval between the time of transplantation surgery and psychological testing was 43.4 mo. The scores for these subjects on the cognitive battery of tests did not reveal the presence of any neuropsychological impairment when compared with those of patients with Crohn’s disease and against normative values. Thus, although not tested preoperatively in this small sample, it can be concluded that at least postsurgically, encephalopathy is not present. Psychiatric status was assessed in these same subjects using the Minnesota Multiphasic Personality Inventory. On none of the scales did the subjects score in the pathognomonic (T > 70) ranges. Trends for a psychiatric disturbance (T > 60) were depression (D), social withdrawal (ST), disrupted personality integration (SC), and social conformity (Pd). Although these deviations from normative values are indicative of a certain degree of posttransplantation psychiatric maladjustment, they do not differ from those found in the Crohn’s disease control subjects. Hence, the psychiatric status of patients after successful transplantation is comparable to that observed in patients with chronic illness and is therefore somewhat disturbed relative to values observed in a normal population. To assess measures of social functioning, the Sickness Impact Profile was administered to each of these same 10 subjects. This multidimensional test assesses the impact of the subject’s illness on routine everyday activities and social interactions. The scores obtained reflect the percentage of impairment observed on the various scales comprising the test battery. At a mean of 43 mo (minimum 1 yr) after successful transplantation these 10 patients had scores that did not differ from those obtained in patients with stable Crohn’s disease. When compared with normative values, however, the transplant subjects manifested problems in certain aspects of daily functioning. Self-rating of sleep and rest comprised the largest area of impairment (38%). Between 20% and 30% impairment was observed for work, recreation, pasttimes, and alertness. A lesser disruption was noted on social interaction, eating, home management, mobility, and emotional behavior. Psychosocial dysfunction was rated as slightly more impaired than physical dysfunction (18% vs. 13%).
Overall, the findings on this relatively small cohort of posttransplantation patients indicate that cognitive capacity is normal, whereas psychiatric and social functioning are somewhat disrupted. The magnitude of the disruption, though not different from that found in a chronic illness control group (Crohn’s disease), is nonetheless significant. Based
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on these preliminary results, it does not appear that transplantation alone is sufficient to return the person to normality. Moreover, they suggest a need for psychosocial rehabilitation intervention in such patients after successful transplantation (6).Nonetheless, more than 80% of surviving adult recipients of an orthotopic liver transplant return to full-time gainful employment, would appear to be fully integrated into the normal working population, and are not functionally impaired. The benefits of liver transplantation to society are less difficult to identify and include the conversion of a health care consumer into a health care premium payer, and a reduction in the total cost of health care for the unique population to which hepatic transplantation is applied. The cost of care of patients with advanced liver disease who are either not considered candidates for transplantation or who were refused transplantation because of some complicating factor, such as portal vein thrombosis or extensive prior abdominal surgery, is substantial. Moreover, it should be remembered that even successful treatment in such cases leads only to the survival of a critically ill patient who will most certainly be admitted again to the hospital for yet another complication or a reoccurrence of the same problem, or to die. The cost of these multiple accrued hospitalizations and continued and possibly intensified care must be subtracted from that of the cost of the transplant procedure and the care of the patient for an equivalent time period, should transplantation be applied to realistically define the true cost of liver transplantation. The long-term or delayed consequences of having a transplantation program include the advancement of our present understanding of hepatic disease in general and those hepatic diseases that are only occasionally or rarely seen by the average health care practitioner in particular. Obviously, the funneling of such patients to regional centers of hepatic disease excellence can only improve the care provided them and that of generations to come. Equally benefited, however, are the broad fields of surgery, radiology, immunology, and infectious disease. The creation of a liver transplant center serves as an immediate focus for the refinement of training and education in these service areas, which frequently are called upon to contribute importantly to the overall success of the transplant program. Indeed, liver transplantation has established itself as a clinical entity (7). Its future is bright but it is also full of challenges (1).New and cheaper methods of monitoring and recognizing rejection need to be developed; safer and less costly immunosuppressive agents need to be identified; better surgical techniques that result in fewer postoperative problems
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need to be developed; and obviously more uniform and disease-specific indications for its application need to be developed. As knowledge and experience with its application increase, however, the costs associated with its performance are likely to decline while the success associated with its application is more likely to increase.
References 1. National Institutes of Health Concensus ment Statement. Liver transplantation. Hepatology 1984;4:13-45.
Conference DevelopJune 29-23, 1983.
2. Scharschmidt BF. Human liver transplantation: analysis of data on 540 patients from four cities. Hepatology 1984; 4:953-1015. 3. Grendell JH. Hepatic transplantation apd resection. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver diseases. Philadelphia: WB Saunders, 1982:1274-84. 4. MacDougall BR, Williams R. The indications for orthotopic liver transplantation. Transplant Proc 1979;11:247. 5. Van Thiel DH, Schade RR, Starzl TE, et al. Liver transplantation in adults. Hepatology 1982;2:637-40. 6. Tarter RE, Van Thiel DH, Hegedus AM, et al. Neuropsychiatric status of the liver transplantation. J Lab Clin Med 1984; 103:776-62. 7. Starzl TE, Iwatsuki S, Van Thiel DH, et al. Evolution of liver transplantation. Hepatology 1982;2:614-36.