Reinhard Lange

Comparison of histidine-tryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution for organ preservation in human liver transplantation

Over a 30-month period, 60 patients (30 in each group) suffering from end-stage liver disease or primary hepatic malignancy and scheduled for liver transplantation were enrolled in a prospective, randomized study to compare two methods of liver preservation: histidinetryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution. Entry criteria for both groups were: age (18–65 years), elective surgery (transplantable or urgent category of the recipients), first transplantations and harvesting procedure performed by the same team. The parameters under investigation were the clinical and laboratory data preand post-transplantation, as well as follow-up data such as complications and survival. There were no significant differences in the two groups as far as the evaluation criteria were concerned, even when cold ischemia time was more than 15h (n=7). A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group. Hepatocellular injury (SGOT, SGPT, GLDH, lactate) appeared to be more marked in the HTK group. These results suggest that both HTK and UW solutions are appropriate for clinical use in liver transplantation, even if cold ischemia time is more than 15h.

Comparison of histidine-tryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution for organ preservation in human liver transplantation. A prospective, randomized study.

Abstract Over a 30‐month period, 60 patients (30 in each group) suffering from end‐stage liver disease or primary hepatic malignancy and scheduled for liver transplantation were enrolled in a prospective, randomized study to compare two methods of liver preservation: histidine‐tryptophan‐ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution. Entry criteria for both groups were: age (18–65 years), elective surgery (transplantable or urgent category of the recipients), first transplantations and harvesting procedure performed by the same team. The parameters under investigation were the clinical and laboratory data pre‐and post‐transplantation, as well as follow‐up data such as complications and survival. There were no significant differences in the two groups as far as the evaluation criteria were concerned, even when cold ischemia time was more than 15 h (n= 7). A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group. Hepatocellular injury (SGOT, SGPT, GLDH, lactate) appeared to be more marked in the HTK group. These results suggest that both HTK and UW solutions are appropriate for clinical use in liver transplantation, even if cold ischemia time is more than 15 h.

Acute liver necrosis in the HELLP syndrome: successful outcome after orthotopic liver transplantation: a case report

We discuss the case of a 30-year-old primipara woman who developed a liver rupture as a complication of the HELLP syndrome. A liver necrosis and bleeding made a hepatectomy necessary. A portocaval shunt was able to maintain the patient until she underwent urgent liver transplantation. In an excellent state of recovery, the woman and her baby were discharged from the hospital 66 days after having been admitted.

Heterotopic auxiliary liver transplantation in a 3-year-old boy with acute liver failure and aplastic anemia

BACKGROUND Auxiliary liver transplantation offers an alternative method to conventional transplantation in acute liver failure. It is especially challenging for children because lifelong immunosuppression may be avoided. However, experience with this procedure is rare and there is controversy about whether to place the graft orthotopically or heterotopically. METHODS We present the case of a 3-year-old boy with acute liver failure due to non-ABC hepatitis complicated by aplastic anemia who underwent auxiliary liver transplantation. Segments 2 and 3 of the graft were implanted heterotopically in the right lower abdomen. RESULTS Good liver function was immediately restored. Aplastic anemia resolved 3 weeks after transplantation. Immunosuppressive therapy was discontinued after 14 months, and the graft was left to atrophy. Thirty-nine months after transplantation the boy is alive and well with normal liver function tests and normal blood cell counts. CONCLUSIONS Heterotopic auxiliary liver transplantation allowed recovery of the native liver in a child with acute liver failure and aplastic anemia due to non-ABC hepatitis.

Monitoring of soluble HLA class I size variants after liver transplantation.

To monitor soluble HLA class I (sHLA-I) and their size variants after liver transplantation (LTX) plasma samples from 22 LTX patients were studied by sHLA-I ELISA, SDS-PAGE, and densitometry. Samples collected were classified into three groups: Group 1 comprised samples taken during episodes without complications, group 2 during episodes of cholangitis/cholestasis (CC), and group 3 during episodes of acute rejection (AR). Compared to group 1 (0.27 +/- 0.03 SEM microg/ml) mean sHLA-I increments in groups 2 and 3 were with 0.53 +/- 0.05 SEM microg/ml and 0.47 +/- 0.04 SEM microg/ml increased (p < 0.001). The same samples were studied by SDS-PAGE and the 43, 39, and 35 kD sHLA-I variants were quantified densitometrically. In samples of group 1 ratios of 43 vs. 39 kD bands revealed a mean of 2.1 +/- 0.3, whereas in group 2 and 3 these were only 0.8 +/- 0.1 SEM and 0.9 +/- 0.1 SEM, respectively, (p < 0.001). For the relation between 43 and 35 kD variants a reduced ratio of 1.1 +/- 0.2 SEM was confined to group 3 samples (p < 0.001), as groups 1 and 2 had ratios of 13.4 +/- 2.3 SEM and 8.4 +/- 2.9 SEM, respectively. This indicates that elevated sHLA-I levels during CC or AR are mainly caused by increases of 39 and/or 35 kD sized molecules. Therefore, our study demonstrates, that after LTX the contribution of sHLA-I size variants to total sHLA-I amounts changes drastically during immune activation pointing to different mechanisms of sHLA-I release.

Auxiliary liver transplantation in acute liver failure in the rat – an illustrated description of a new surgical approach

Introduction: To investigate auxiliary liver transplantation successfully in rats suffering from acute liver failure, we developed a new surgical approach. Methods: A 70% hepatectomized liver graft was implanted into the right upper quadrant of the abdomen. The donor portal vein was anastomosed with the recipients right renal artery using the splint technique. The donor infrahepatic vena cava was attached onto the recipient vena cava end to side. The bile duct was implanted into the duodenum.

Outcome and management of blunt liver injuries in multiple trauma patients.

Abstract Background: In Germany, abdominal trauma in multiple- trauma patients can be observed in about 25–35% of all cases. Due to major bleeding complications, the initial treatment of blunt abdominal trauma in multiple-trauma patients has high priority. The aim of this study was to discuss management, treatment and outcome of blunt liver injury in multiple-trauma patients treated in our department. Methods: The clinical records of 1192 multiple-trauma patients [injury severity score (ISS) 3–18] treated at the Surgical Department of the University Clinic of Essen from January 1975 to February 1998 were reviewed. Seventy-five patients with an ISS above 18 operated on due to a blunt liver injury could be included. The mean age was 29.82±1.80 years (60 males and 15 females). The degree of injury in this group was high (ISS 37.12±1.06). Results: Twenty-three of the 75 (30.6%) patients died during their hospital stay. Deceased patients were older (27±2 years versus 37±4 years; P<0.01) and had a higher ISS (ISS=34.5±1 versus 43.2±2; P<0.01). In nine cases, death was strongly related to liver injury. Operational blood loss was higher in the group of multiply injured patients with liver injury and in those patients who did not survive (P<0.05). An increased mortality could be seen in this selected patient group when compared with our large collective of multiply injured patients. The age of the patients, the ISS and operative blood loss were the significant factors that influenced the operative mortality after blunt hepatic injuries in our study.

Tierexperimentelle Untersuchungen zur Arterialisierung der Pfortader bei der Lebertransplantation am Göttinger Miniaturschwein

The aim of the present experimental investigation was to assess the circulatory, biochemical and histopathological consequences of complete portal vein arterialization of the transplanted liver in ‘Göttinger’ miniature pigs. Orthotopic liver transplantations using a passive portojugular shunt were performed in six male ‘Göttinger’ miniature pigs. Using an iliac artery segment interposition of the animal donor, the hepatic artery (HA) of the transplant liver was anastomized end-to-end and the portal vein (PA) also united with the internal iliac artery stump end-to-end. The central anastomosis was performed onto the suprarenal aorta. Portal vein blood was drained into the infrahepatic caval vein via an end-to-side shunt (PCS). During the course, the following parameters were determined: arterial blood pressure, venous pressure, cardiac output, electromagnetic blood flow measurements across the HA, PA, and PCS, PA mean pressure, transaminases, partial thromboplastin time and fibrinogen. Liver biopsies and autopsy specimens were investigated. One of six animals died a few hours postoperatively, two of six died after 48 and 72 h, respectively, whereas three pigs survived the scheduled 7 days. The cardiac output fell intraoperatively initially by an average of 20 % but had approximately the starting volume of 2.2 l/min at the end of the operation. Although the diameter of the anastomosis was reduced to 4 mm, the flow in the arterialized PA on average was 340 ml/min when the vessel clamp was opened. At the end of operation the mean was 380 ml/min, the interval of measurement being 75 min. The flow across the PCS and the HA were constant during the course. As mechanism for this phenomenon, autoregulation of the liver blood flow on a sinusidal level has been suggested. The biochemical results and the histopathological findings showed no change compared to previous findings in a control group of animals in which liver transplantion was performed by our team. Complete arterialization of the PA is well tolerated in liver transplantation in ‘Göttinger’ miniature pigs with regard to circulation and liver function in a short-term trial of a maximum of 7 days. Long-term results are still to come.ZusammenfassungZiel der hier vorgelegten tierexperimentellen Untersuchungen war es, die zirkulatorischen, laborchemischen und histopathologischen Konsequenzen einer vollständigen Arterialisierung der Pfortader der Transplantatleber am Göttinger Miniaturschwein zu beurteilen. An 6 männlichen Göttinger Miniaturschweinen wurden orthotope Lebertransplantationen unter Verwendung eines passiven porto-jugulären Shunts durchgeführt. Mittels eines Iliakalarteriensegmentinterponats des Spendertiers wurde die A. hepatica (AH) der Transplantatleber End-zu-End anastomosiert; die Pfortader (PA) wurde mit dem Stumpf der internen Iliakalarterie ebenfalls End-zu-End verbunden. Die zentrale Anastomose erfolgte auf die suprarenale Aorta. Das Pfortaderblut wurde über einen End-zu-Seit-Shunt (PCS) in die infrahepatische V. cava drainiert. Es wurden folgende Parameter im Verlauf bestimmt: arterieller Blutdruck, Venendruck, Herzzeitvolumen, elektromagnetische Blutflußmessung über AH, PA, PCS, PA-Mitteldruck, Transaminasen, TPZ, Fibrinogen, Leberbiopsien und Sektionspräparate wurden histologisch untersucht. 1/6 Tieren starb wenige Stunden postoperativ. 2/6 Tieren starben nach 48 bzw. 72 h, 3 Tiere überlebten die vorgesehenen 7 Tage. Das HZV fiel intraoperativ initial um im Mittel 20% ab und lag zum Ende der Operation wieder im Bereich der Ausgangswerte von 2,2 l/min. Der Fluß in der arterialisierten PA lag trotz des reduzierten Durchmessers der Anastomose von 4 mm bei Öffnung der Gefäßklemme im Mittel bei 340 ml/min, zum Ende der Operation (Intervall der Messung 75 min) bei im Mittel 380 ml/min. Der Fluß über dem PCS und der AH blieb im Verlauf konstant. Als Mechanismus für dieses Phänomen wird eine Autoregulation der Leberdurchblutung auf sinusoidaler Ebene diskutiert. Von seiten der Laborparameter ebenso wie bei den histopathologischen Untersuchungen ergaben sich keine Veränderungen gegenüber einem historischen Kontrollkollektiv lebertransplantierter Tiere aus unserer Arbeitsgruppe. Die komplette Arterialisierung der PA wird bei der Lebertransplantation am Göttinger Miniaturschwein sowohl zirkulatorisch als auch leberfunktionell im Kurzzeitversuch über maximal 7 Tage gut toleriert. Langzeitergebnisse stehen noch aus.

Temporary heterotopic auxiliary liver transplantation with arterialization of the portal vein as treatment of acute liver failure

A 46-year-old female patient with fulminant hepatitis B was auxiliary transplanted with a left liver lobe (segment 2–4). The anastomosis of the hepatic vein was performed end-to-side onto the right common iliac vein. The portal vein and the hepatic artery were anastomosed via a joint interposition (iliac bifurcation of the donor) with the right external iliac artery. The portal vein received its blood via the internal branch and the liver artery via the external branch of the interposition. The bile duct was stented and drained into a Goretex prothesis percutaneously (Fig. 1). Neurologically, the patient improved within 24 h. Liver enzymes, synthesis parameters and bilirubin normalized steadily. Bile secretion was 120–180 ml/day. A radioisotope scan of the hepatobiliary elimination of Tc-99 m-labelled iminodiacetate on day 6 showed that the graft provided the entire hepatic function (Fig. 2). The further clinical course was determined by a fungal septicaemia, caused by a focus present but unrecognized at the time of transplantation, in spite of antimycotic therapy. In order to overcome septicaemia, immunosuppression was stopped completely on the 9th postoperative day. On the 14th postoperative day, a dramatic increase in serum liver enzyme activities occurred. Bile production ceased. The patient died on the 15th postoperative day. The autopsy confirmed the generalized mycotic septicaemia. There was no thrombosis of the graft vessels. In histological tissue sections of the graft, differentiation between acute rejection and septic autolysis was impossible. A high risk for thrombotic complications, due to the low pressure gradient between the portal vein and the inferior caval vein, has previously been identified as a major disadvantage of heterotopic auxiliary liver transplantation [1,2]. This problem was eliminated here by arterialization of the portal vein. Permanent arterialization of the portal vein in liver transplantation has so far only been used as makeshift in cases of portal vein thrombosis [3]. These experiences showed that a liver graft with arterialized portal flow can function well; only

Injury to hepatocytes and non-parenchymal cells during the preservation of human livers with UW or HTK solution: a determination of hepatocellular enzymes in the effluent perfusate for preoperative evaluation of the transplant quality

Abstract  In 50 livers harvested for transplantation, injury was assessed by determination of the enzymes in the effluent perfusate after cold ischemia. The results were compared to the histology and the clinical course after transplantation. Whereas the release of the markers of endothelial cell injury did neither correlate with the history of the graft nor with the postoperative course, the release of hepatocellular enzymes in the perfusate did indicate preexisting damage of the liver even when the biopsy showed normal liver tissue. Of 12 livers with high activity of hepatocellular enzymes in the effluent (activity of more than twice the median), 7 showed delayed onset of function or a primary non‐function. In the other 38 livers with an enzyme activity below this borderline no delayed function or primary non‐function was observed. Because of additional influences a prognosis of the function after transplantation was not possible, but the determination of the enzymes in the effluent of marginal livers probably allows the preoperative recognition of organs which will do well.