Evolution of Liver Transplantation at the University of Heidelberg: Interventions Influencing Patient Referral

Abstract

In Heidelberg, liver transplantation was first performed in 1987. In this article, we report our experience with an interdisciplinary approach (intervention) to improve the internal and external acceptance of the liver transplantation program. Formation of a transplant team and interdisciplinary standard setting of pre-, peri-, and postoperative protocols significantly stimulated this process. Involvement of the referring doctors in patient’s treatment by transferring competencies enhanced patients referral to our center and increased the numbers of patients on the waiting list, an indispensable factor for organ allocation by Eurotransplant and transplantation. Involvement of patient organizations increased patient acceptance in the program.

Liver transplantation in humans became a reality in 1963 when the first case was attempted at the University of Colorado (Denver) by Thomas E. Starzl (¹). The first patients did not survive surgery. Subsequent similar failures in Boston and Paris led to a temporary worldwide moratorium on liver transplantation. In Europe, the first successful program began in 1967 at Cambridge under the lead of Roy Calne. After the discovery of cyclosporin, transplantation ultimately moved from the realm of curiosity into routine therapy (²). It was tested in humans for the first time in 1978 (³). The results were startling: rejection was effectively inhibited in five of the seven patients receiving kidneys from mismatched deceased donors.

In Heidelberg, the first successful liver transplantation was performed in June of 1987. In 2001 the transplant center celebrated its 15th anniversary. At this time, liver transplantation had already become a major focus of the Department of Surgery. Since 2001 we registered a substantial increase in the number of transplanted patients resulting in 83 liver transplantations in 2004. The reasons for the increase in liver transplantation are multifactorial and required adaptations in the pre-, peri-, and postoperative management with a special emphasis on a multidisciplinary team approach. Heidelberg became the largest center for liver transplantation in southern Germany with a total of more than 700 liver transplants performed. Together with its successful program for kidney and combined pancreas and kidney transplantation, it is one of the largest transplant centers for visceral organs in Germany. In this article, we report some important nonsurgical factors that led to the successful evolution in liver transplantation in Heidelberg over almost two decades.

Patient Data

The data from all patients with liver transplantation between 1987 and 1996 were collected in a retrospective fashion. Those between 1997 and 2004 were collected in a prospective manner using the electronic database of the hospital. A total of 680 liver transplantations were recorded. Data concerning the patient’s assignment structure were extracted from our hospital database. The numbers of the patients on the waiting list of Eurotransplant and the numbers of patients transplanted were extracted from the annual reports of Eurotransplant, the ’Deutsche Stiftung für Organ Transplantation’ (DSO), and our own database.

Interdisciplinary Organization of the Transplantation Program

Due to the stagnating numbers of liver transplantations (Fig. 1) and a subsequent decrease in patient assignments for transplantation in our center (Fig. 2A), we took advantage of political decisions and structural difficulties in some other transplant centers in Southern Germany, and initiated in the year 2001 a task force to revitalize our transplantation program with the following objectives: to assemble an interdisciplinary transplant team consisting of transplant specialists from different departments and transplant specialists (Fig. 3) working closely together to use the individual expertise and to improve existing connections tapping the full potential of a University hospital; to establish standards to achieve high quality in the care of transplant patients; to strengthen the position of the University of Heidelberg as a liver transplantation center; and we assured high performance by introducing a quality management. The transplant task force regularly met to establish standards in preoperative evaluation of transplant patients, to set standards in surgical- and anaesthesiological treatment and to adjust postoperative in- and outpatient care. It also established a section of liver transplantation in the department of gastroenterology. The standard immunosuppressant regimen was re-evaluated and adapted to the individual needs of the transplant patients. All protocols were standardized and written down in a manual, the ’Heidelberg Manual of Liver Transplantation’ (⁴). The manual also serves as a guideline for careful medical evaluation of patients to be listed on the waiting list of Eurotransplant. The decision to list a patient is made interdisciplinary by a transplant surgeon and hepatologist, transplant nurses, the transplant coordinator and, if necessary, specialists from other disciplines. Interdisciplinary routine rounds on the ward with transplant surgeons, hepatologists and anaesthesiologists were established, including colleagues from the department of nephrology and infectiology, and in selected cases from other departments.

FIGURE 1.: Annual numbers of liver transplantations performed in Heidelberg from 1987-2004.

FIGURE 2.: (A) Development of the numbers of patient’s admitted to be listed on the waiting list of Eurotransplant at the University of Heidelberg. After an initial increase between 1987 and 1990, the numbers stagnated started to decrease in 1999. Beginning in 2001, numbers could be increased again following the new standards in our transplantation center. (B) Numbers of patients effectively listed on the waiting list of Eurotransplant between December 2001 and December 2004.

FIGURE 3.: Departments involved in the successful formation of the transplant team. Transplant specialists of each section or department helped in developing standardized protocols that were summarized in the ‘Heidelberg Manual for Liver Transplantation.’

Further interest of the task force was the definition of a new concept in patient’s treatment after successful liver transplantation in particular in the transfer of essential competences to the hands of doctors not assigned to the University Hospital resulting in a policy of early postoperative patient transfer for further treatment from the surgical department to the department of gastroenterology or to the referral center. Responsibility for outpatient treatment was placed on the hands of the referring doctors in close collaboration with the transplant center. Great efforts were also made to integrate the patient’s organizations for liver transplantation in Germany.

Respecting these maxims, the involvement of the different parties in the decision making process and the coordinated action in defining the goals in liver transplantation resulted in an increased mutual trust among doctors not only within the transplant center but also between referring doctors and the transplantation team.

Patient Referral Structure and Outpatient Activities

To increase the cooperation with the referring doctors, representatives of the transplant team visited them and introduced the novel concept in liver transplantation and distributed the ‘Heidelberg Manual of Liver Transplantation.’ The transplant team further organized meetings and symposia for patients and referring doctors. These efforts and the active involvement of the referring hospitals and gastroenterologists in the care of transplant patients resulted in increasing number of patient’s referred to our transplant program. Between 2001 and 2004 the number of referring doctors increased about 71% with an increase of more than 550% in referred patients to be evaluated for liver transplantation compared to the year 2000 (Fig. 2A, B). The transplanted patients were referred by a total of 13 University hospitals, 97 County hospitals and 120 doctors in private practice (Fig. 4). About 70% of the patients were referred by University or County hospitals and 30% by doctors in private practice. Of these, 83% referred only one patient per year, 12% referred two to four, 3% five to nine, and 2% more than nine patients per year. University hospitals did assign most of the patients, followed by County hospitals and doctors in private practice. The doctors in private practice were 53% internists, 42% generalists, 4% pediatricians, and only 1% surgeons.

FIGURE 4.: Demographic allocation of liver transplantation patients in the State of Baden-Württemberg, Germany in 2001 (A, n=33) and 2004 (B, n=180). Each phone represents one patient.

The increase of patients referred to our center for evaluation for liver transplantation strongly correlated with the numbers of patients on the waiting list resulting in a more than fourfold increase of patients listed (Fig. 2B) in the last 3 years.

The increase in patient referral positively affected the outpatient activities. In 2002 1,066 patients were seen in outpatient clinics. In 2003 we registered an increase of 24%, in 2004 another 20% resulting in 1,582 consultations. In all, 38% of the patients were listed on the waiting list of Eurotransplant and came for periodic controls, 32% were in control after transplantation, 19% were assigned for a first evaluation for liver transplantation, 9% were patients which were evaluated for liver transplantation but not listed due to the steady state of their disease, and 2% were patients in control because of complications after liver transplantation.

Major Surgical and Anaesthesiological Changes

Major changes were made in surgical strategies. First, routine cavo-caval side to side anastomosis according to Belghiti (⁵) was implemented. It significantly facilitated the procedure and decreased the operation time by avoiding the use of the biomechanic pump. Additionally, we consequently used vascular staplers to dissect in the donor the liver veins from the cava, and the argon beamer for bleeding control. The anaesthesiologists standardized their intra- and perioperative protocol by maintaining the central venous pressure during hepatectomy below 5 mmHg, and by accepting haemoglobin levels between 6 and 8 mg/dl during and after surgery without blood substitution (^6,7). If necessary, retransfusions, except in patients with hepatocellular carcinoma, were primarily performed by using the cell saver. These factors led to a significant decrease of the blood units used during surgery. The results of our adaptations in the surgical and anaesthesiological treatment are summarized by Mehrabi et al. (⁸).

Liver Transplant Activities

All the activities described above resulted in a substantial increase of successfully performed liver transplantations from 18 in the year 2000 to 30 in 2001, 38 in 2002, and 76 in 2003 to 83 in 2004 (Fig. 1).

DISCUSSION

A successful liver transplantation center is defined by its quality of surgery, patient management and its case load (⁹). Due to its allocation system the case load in the Eurotransplant area is mainly linked to the quantity of patients actively listed on the waiting list. Factors positively influencing the waiting list and the transplantation rate are among other things, the increase in the numbers of indications for liver transplantation (¹⁰), adaptations of the surgical procedure (⁵), expansion of the donor pool (^11–13), acceptance of older and in selected cases marginal organs (^14,15), optimization of the allocation criteria for the recipients (¹⁶), and finally living-related transplantations (¹⁷).

To reach and maintain a high case load sophisticated logistics are indispensable. In this article, we report the evolution of liver transplantation in the transplant center in Heidelberg with special attention on its organization and patient referral structure. The complexity of liver transplantation calls for an interdisciplinary approach and a dedicated team of competent specialists (^18,19). Self-interest has to be subordinated to a team approach and standardization of pre-, intra-, and postoperative procedures substantially simplifies the patient’s management. One of the key factors was the implementation of a section of liver transplantation in the department of gastroenterology, consisting of dedicated hepatologists fully concentrating on liver transplantation and being involved in decision making in the treatment of patients pre-, peri-, and postoperatively. In our experience, the formation of a transplant team and verbalization of standardized protocols resulting in the ’Heidelberg Manual of Liver Transplantation’ significantly improved the mutual trust among the transplant specialists involvement in patients treatment. This standard setting and the improved communication gave positive signals to the referring partners. Offering regular further training, the organization of meetings and symposia stimulated the collaboration between the transplant center, patients and the referring doctors and enhanced the internal and external acceptance of our transplant program. Involvement of patient organizations turned out to be of crucial importance for liver transplant patients. The transfer of competences and responsibilities to the treating doctors outside the transplant center proved to be a key factor in the patient’s referral to us. An intern analysis of the patient’s satisfaction with the transplant program in Heidelberg showed very satisfied patients in 51%, 46% were satisfied, and only 3% were not satisfied.

ACKNOWLEDGMENTS

We respectfully thank Mrs. S. Gragert for her excellent work and the meticulous management of the database of liver transplantation patients.