G. Gubernatis

Transplantation einer Spenderleber auf zwei Empfänger (Splitting-Transplantation) - Eine neue Methode in der Weiterentwicklung der Lebersegmenttransplantation

Tumor surgery in this field is no longer such a high risk as previously. Prolonged survival can be achieved by resection of hepatocellular carcinomas in non-cirrhotic livers (3-year survival 58%, n = 54 patients) and for colorectal liver metastases (3-year survival 44%, n = 124 patients). But surgery is rarely successful for the most frequent type of liver malignancy, the hepatocellular carcinoma in cirrhosis. Central bile duct carcinomas are now resected more frequently than in the past. Liver grafting seems indicated in special cases of liver and bile duct tumors. The future developments of operating on the in situ-perfused liver was discussed and the first operation on an ex situ-liver was demonstrated.SummaryA donor liver was divided in such a way that the left part (segment 11 and III without caval vein) could be transplanted into a child, the right part (segment I, IV, V to VIII) into an adult successfully. Common bile duct and common hepatic artery remained with the left part of the liver, portal vein with the right one. In the recipient of the left part of the liver the own caval vein was preserved and anastomosed with the left hepatic vein; the other anastomoses were carried out in the typical way. In the recipient of the right part of the liver the right hepatic artery of the graft was anastomosed with the recipients common hepatic artery using a saphenous interponate. Two separate intrahepatic bile ducts were anastomosed with a Roux-en-Y loop of the jejunum. The other anastomoses were carried out in the typical way. Thus the possibility of using one donor liver for two recipients (splitting transplantation) has been demonstrated.ZusammenfassungEin Spenderleberorgan wurde so getrennt, daß der linke Teil (Segment II und III ohne Vena cava) auf ein Kind, der rechte Teil (Segment 1, IV, V bis VIII) auf einen Erwachsenen erfolgreich transplantiert werden konnte. Choledochus und Arteria hepatica communis bzw. propria blieben beim linken Leberteil, Vena portae beim rechten. Beim Empfänger der linken Seite blieb die eigene Vena cava erhalten; in sie wurde die linke Vena hepatica anastomosiert; die übrigen Anastomosen wurden in üblicher Weise durchgeführt. Beim Empfänger des rechten Leberteiles wurde die spenderseitige Arteria hepatica dextra mit einem Saphenainterponat verlängert und mit der Arteria hepatica communis des Empfängers anastomosiert; zwei getrennte Hepaticusäste wurden mit einer Jejunumschlinge anastomosiert. Die übrigen Anastomosen wurden in typischer Weise ausgeführt. Die Möglichkeit der Verwendung einer Spenderleber für zwei Empfänger (Splitting-Transplantation) ist damit gezeigt.

Liver transplantation in HBs antigen (HBsAg) carriers. Prevention of hepatitis B virus (HBV) recurrence by passive immunization.

Liver transplantation in HBs-antigen (HBsAg) positive allograft recipients is associated with a high risk of HBV recurrence some time after surgery. So far, results of measures to prevent recurrent HBV-infection by means of treatment with interferon, hepatitis B vaccination and short-term passive immunization with hepatitis B immunoglobulin (HBIg) or monoclonal antibody to HBsAg (anti-HBs) have been disappointing. In the present study the results of long-term, anti-HBs monitored passive immunization with HBIg is reported. In 23 HBsAg-positive liver transplant recipients an anti-HBs level of greater than or equal to 100 IU/l was maintained for 6 or 12 months, respectively. The rate of recurrent infection was found to be less than 20% under HBIg substitution, whereas 11 graft recipients with no or only short-term HBIg prophylaxis were reinfected by month 15 after transplantation. HBV recurrence was associated with chronic liver disease and recurrent cirrhosis in the allograft.

LIGNOCAINE METABOLITE FORMATION AS A MEASURE OF PRE-TRANSPLANT LIVER FUNCTION

A method for rapid assessment of hepatic function in liver donors based on the formation of the lignocaine metabolite monoethylglycinexylidide (MEGX), was used in a prospective study of 69 donor-recipient pairs. The probability of graft survival over 120 days was significantly higher for livers from donors with MEGX test values above 90 micrograms/l than for those from donors with MEGX values of 90 micrograms/l or below. Other liver function tests (bilirubin, prothrombin time, activity of aminotransferases, glutamate dehydrogenase, and cholinesterase, indocyanine green clearance, and galactose elimination capacity) were inefficient at predicting early outcome of transplantation. For a 20-day graft survival, the MEGX test showed prognostic sensitivity of 73% and specificity of 78%. These findings suggest that the MEGX formation test could be valuable for selection of donor organs.

HTK-solution (Bretschneider) for human liver transplantation. First clinical experiences.

ZusammenfassungDie kardioplegische Lösung HTK nach Bretschneider ist bisher noch nicht im Bereich der klinischen Lebertransplantation verwendet worden. Hier werden die ersten Ergebnisse von 14 Patienten vorgestellt, denen eine mit HTK-Lösung protektionierte Leber transplantiert wurde. Die Eignung der HTK-Lösung konnte gezeigt werden. Alle Transplantate zeigten eine Primärfunktion mit Ausnahme eines Transplantates, bei dem die initiale Nichtfunktion zweifelsfrei spenderbedingt war. Die höchsten friihpostoperativen Werte der Transaminasen, die als Zeichen des Ischämieschadens herangezogen wurden, waren durchschnittlich und vergleichbar mit den Transaminasenausschüttungen nach anderen Lösungen. Unter Verwendung der HTK-Lösung konnte eine Primarfunktion selbst bei solchen Transplantaten erzielt werden, die prospektiv als solche von problematischer oder geringer Qualität eingeschätzt worden waren, and Lebern mit schlechten Funktionstesten (MegX) funktionierten von Beginn an. Deshalb scheint die HTK-L6sung die Ausweitung der Akzeptanzkriterien für Spenderlebern zu ermöglichen. Es war nicht das Ziel dieser Studie, die kalte Ischämiezeit zu verlängern, aber drei Transplantate mit 11 h and 12 h 25 min nahmen unmittelbar nach Reperfusion ihre Funktion auf. Wie weft die kalte Ischämiezeit ausgedehnt werden kann, ist noch eine offene Frage. Alle Spenderlebern wurden aufgrund der geringen Viskosität der HTK-Lösung schlagartig gekühlt und homogen perfundiert. Alle Lebern hatten eine weiche Konsistenz nach der Perfusion, was kein oder nur ein geringes Zellödem bedeutet. Aus diesen Gründen ist HTK eine effektive Lösung für die Leberkonservierung.SummaryThe cardioplegic HTK-solution (Bretschneider) has not been used in human liver transplantation as yet. Herein the first results obtained from 14 patients with HTK-preserved liver grafts are presented. The suitability of HTK-solution could be shown. All grafts functioned primarily except one, where initial non-function was obviously due to donor reasons. The early postoperative peak values of transaminases as a sign of ischemic damage were average and similar to the values of other flushout solutions. Using HTK primary function could be achieved even in livers prospectively assessed as only of fair quality, and livers with poor donor function tests (MegX) functioned from the beginning. HTK-solution therefore seems to allow widening of the acceptance criteria for donor livers. It was not the aim of this trial to extend cold ischemic time, but 3 livers with 11 h and 12 h 25 showed immediate function. How far cold ischemic time can be extended is a still open question. All livers were rapidly cooled and homogeneously flushed out due to the low viscosity of HTK-solution. All livers had a soft consistency after perfusion indicating a low degree of cell edema. HTK therefore is an effective solution for liver preservation.

Arterial ketone body ratio as a predictor of donor liver viability in human liver transplantation

The viability of the donor liver was assessed with regard to early postoperative survival in human liver transplantations from 40 brain-dead donors at Hannover Medical College and 13 living donors at Kyoto University by measuring the arterial ketone body ratio (AKBR). Of 40 grafts harvested from brain-dead patients in Hannover, 35 survived the first week after operation, but 5 developed initial nonfunction of the transplanted graft within the first week. The mean AKBR values were 1.11±0.11 for grafts that survived and 0.44±0.10 for grafts that failed (P<0.01). The AKBR values of the 5 initially nonfunctioning cases were all below 0.7. Of 13 grafts harvested from the living donors in Kyoto, all survived the first week. The AKBR values of the donors were all above 1.0, with a mean value of 1.87±0.23. Among all 53 cases, the survival rate of the grafts with AKBR above 0.7 was significantly higher than that of the grafts with AKBR below 0.7 (100% vs. 62%, P<0.01). NO other donor parameters, including age, dose of dopamine administered, and clinical laboratory findings, were significantly related to differences in graft survival rates. AKBR is a useful index for the evaluation of donor liver viability. Grafts used from donors with AKBR of less than 0.7 have a significantly increased risk of early nonfunction. Grafts from donors with AKBR of greater than 1.0 have, in our experience, always been viable after transplantation.

Evaluation of the liver graft before procurement : Significance of arterial ketone body ratio in brain-dead patients

Hepatic energy metabolism was assessed by measuring the blood ketone body ratio (KBR), that is, the ratio of acetoacetate to β-hydroxybutyrate in the arterial blood, in 31 brain-dead patients in an intensive care unit (ICU) in Japan and in 25 donors just before procurement of the liver for transplantation in Germany. In the study in Japan, 7 of the 12 brain-dead patients treated with highdose catecholamine showed significantly decreased KBRs, revealing the detrimental effect of catecholamine on livermmetabolism. In contrast, 8 of the 9 untreated patients with blood pressure below 80 mm Hg showed almost normal KBRs. In the 25 donors in Germany, KBR was maintained within the normal range. Based upon conventional criteria, 21 livers were selected for use and the other 4 were discarded. Nineteen of the grafts were able to normalize KBR within 24 h after reperfusion, while 2 failed to function and required a second transplantation. It was suggested that a KBR in the normal range in donors is a prerequisite to immediate recovery of metabolic function of the liver graft after transplantation, and that hypotensive donors as a potential source of liver grafts may warrant further study.

Liver Transplantation in Pigs: A Model for Studying Reperfusion Injury

A model of orthotopic liver transplantation in pigs was developed to investigate reperfusion injury of the liver. To have direct access to the liver for organ monitoring a relaparotomy was performed 6 h after revascularization. The details of modification in anesthesia and surgical technique are given. Salient features of the technique include (1) the use of an extremely short cuff of the donor suprahepatic caval vein, (2) the use of a central venous catheter fixed in a hepatic vein, and (3) the use of an aortic graft for standardized arterial reconstruction. Twenty-nine transplantations were performed. The total anesthetic time was 13.28 +/- 1.45 h and the operative time was 10.06 +/- 0.77 h. The animals withstood this long procedure remarkably well.

HLA compatibility and different features of liver allograft rejection

The influence of human leukocyte antigen (HLA) on acute liver allograft rejection was investigated in 48 adult patients. The diagnosis of rejection was always based on the full triad of histological findings, clinical signs, and the required antirejection treatment. Sixty-two percent of the patients closely observed for 6 months postoperatively revealed acute rejection within the first 3 weeks, mostly on days 7–11. HLA compatibility was not observed to have any significant influence on the incidence of acute rejection. However, different histological and clinical features were revealed in conjunction with DR compatibility. Patients without DR compatibility showed a type of rejection with fever and increase of bilirubin, frequently associated with cholestasis and cholangitis, which sometimes persisted for weeks. Patients with 1 DR compatibility showed a predominant increase of transaminases, which was never associated with cholangitis. The conjunction of different DR compatibilities and various clinical signs may indicate possible pathways from immunological assault to the clinical appearance of acute rejection. A knowledge of a patients individual compatibility and an expectation of certain rejection patterns may lead to earlier and more reliable diagnosis and treatment.

Fat emulsions in parenteral nutrition after liver transplantation: The recovery of the allografts RES function and histological observations.

Following liver transplantation, the effect of post-operative parenteral nutrition with MCT LCT (Medium Chain Triglycerides/Long Chain Triglycerides) fat emulsions on the recovery of allografts RES function was investigated in a randomised prospective study of three groups of patients (group I, n = 14: 50g MCT LCT fats twice weekly, group II, n = 15: 0.7 g/kg body weight per day MCT LCT fats, group III, n = 17: 1.5 g/kg body weight per day MCT LCT fats). RES function was assessed using the (99m)Tc-HSA-MM-Clearance ((99m)Technitium-Human serum albumen-Millimicrosphere-Clearance). There were no statistically significant differences in the recovery of RES function between the groups. A negative effect on RES function as a result of the administration of MCT LCT fat emulsions up to 1.5 g/kg b.w. per day can therefore be excluded. The evaluation of liver biopsies before the administration of fats and at the end of TPN (Total Parenteral Nutrition) showed no evidence, in the 20 patients investigated, of any fatty changes in the liver caused by the infusion of fat.

Combination harvesting procedure for liver and whole pancreas

Combination harvesting procedures for the liver and whole pancreas can be carried out successfully in most instances, but this requires agreement between the liver and pancreas teams concerning the vascular supply for the grafts. If one donor team is in charge of both organs, the procedure has considerable economical advantages. Even if one organ is not suitable, partial success is sufficient to compensate for the effort and costs.