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The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT. A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n = 15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary-artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (deltaO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively. A significant correlation between deltaO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p < 0.05). PGI2 treatment induced a significant decrease in deltaO2 after 24 and 48 h after reperfusion (p < 0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418 +/- 99 vs. 638 +/- 156 U/L, p < 0.1). These results suggest that administration of PGI2 after OLT improves hepatic-splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.

The number of pregnancies following liver transplantation is increasing due to better patient and graft survival and quality of life. Out of 156 women of a reproductive age, there were 19 pregnancies in 16 women, 12 on CsA and seven on tacrolimus, which occurred between 7/92 and 1/97. The median age of the women was 27.9 yr, median time after transplantation 33 months. There were four spontaneous and two induced abortions in the first trimenon. Ten women delivered ten healthy babies; three newborns had problems (alcoholic embryopathy due to recurrent alcohol abuse of his mother, pneumonia, weight < 2000 g). In eight women mostly mild complications were observed, such as hypertension (n = 5), nonspecific elevation of liver enzymes (n = 2), infection (n = 3) and premature labor (n = 1). Mean gestational age was 39 wk and mean birth weight 2900 g. One case of prematurity and three cases of growth retardation occurred. Cesarean sections were performed in 7 patients (54%) for maternal hypertension (n = 2), presumed fetal hypoxia (n = 4) and breech position (n = 1). All children are normally developed, the oldest being 5 yr old. Although experience with tacrolimus is limited, pregnancies following liver transplantation carry an acceptable risk if carefully monitored by an experienced team of transplant surgeons and obstetricians.

The introduction of quadruple induction therapy after liver transplantation with the murine anti-interleukin-2 receptor (IL-2R) antibody (BT563) has decreased the incidence of serious side effects, such as tachycardia, hypertension, rash, fever and nausea since it does not lyse its target cell. To investigate the immunosuppressive efficacy of BT563, a placebo-controlled trial was performed and BT563 was added to the standard triple induction after liver transplantation. Forty consecutive recipients of primary orthotopic liver transplants (OLT) (median age 47 yr [range 18-65]) were randomized. All patients received triple immunosuppression with cyclosporine A (CyA), prednisolone (PRED) and azathioprine (AZA). In addition, 19 patients received BT563 (Biotest, Dreieich, Germany) at a dose of 10 mg/d from day 0 until day 12. The remaining 21 patients received a placebo infusion at the same days after transplantation. Minimal follow-up for all patients was 3 yr. Patient survival at 3 yr was 74% in the BT563 group and 90% in placebo group. Similar results were observed for graft survival. Two acute rejection episodes were detected in the BT563 group and 9 acute rejections (5 steroid-resistant) were observed in the placebo group (p < 0.034). The incidences of sepsis, pneumonia, cholangitis, urinary tract infections as well as cytomegalo-virus (CMV) infections were similar in both groups. Side effects of the BT563 therapy and/or post-transplant lymphoproliferative disease (PTLD) were not detected. Quadruple induction therapy with BT563 significantly reduces the incidence of rejection episodes after liver transplantation, while infectious complications and/or PTLD is not increased. Therefore, the anti-IL2 receptor antibody BT563 constitutes a safe and efficient addition to the immunosuppressive induction regimen following OLT.

Donor organ shortage calls for widening of criteria for organ transplantation. In exceptional cases, even livers with macroscopic alterations may be accepted for transplantation. The case of a patient who received a liver graft from a donor with previously unknown adult polycystic degeneration is reported. The liver showed only small bilobar cysts with less than 10% of hepatic replacement and was successfully used for orthotopic liver transplantation. Two years after transplantation the patient is in good clinical condition and has returned to work.

Many therapeutic measures have been employed to prevent or at least ameliorate postoperative renal impairment following liver transplantation. Recent clinical phase II studies have demonstrated that the new natriuretic peptide urodilatin has beneficial effects on renal function following heart and liver transplantation. The present study reports the first prospective randomized placebo-controlled trial of prophylactic urodilatin administration following liver transplantation. Seventy consecutive recipients of primary liver transplants were included in the study following randomization, and 33 patients continuously received urodilatin at a dose of 20 ng/kg/min for 7 d. The remaining 37 patients received a placebo infusion for the same time period. The course of serum creatinine and urea did not differ between the two groups nor did the daily urine production. However, the urodilatin group showed a higher preoperative median serum creatinine and a significant reduction on days 1 and 2, whereas this observation was not made in the placebo group. Furthermore, less furosemide was administered to the patients in the urodilatin group during the first 2 d. The incidence of postoperative hemodialysis and the number of treatments did not differ between the groups either (urodilatin group 4, vs. placebo group 6 and 22 for both groups, respectively). Side effects of the urodilatin therapy were not detected. The prophylactic low-dose urodilatin administration resulted in a trend towards amelioration of the renal function, but did not result in significant differences between the two experimental groups. Further studies, using higher doses, will be required to define the value of urodilatin for prevention of renal impairment after liver transplantation.

Liver transplantation (LTX) is an approved method to treat patients with end-stage liver cirrhosis and acute liver failure due to Wilson's disease. Initially, there was some consideration about the indication for LTX in the case of Wilson's disease with severe neurological impairment but normal liver function. From 1988 until 1995, 13 out of 700 LTX (1.9%) were performed for Wilson's disease. Indications for LTX were (I) intractable neurological impairment with normal liver function (n = 4; including one patient with Child A cirrhosis), (II) fulminant hepatic failure (n = 3), and (III) end-stage liver cirrhosis (n = 6) (Child B, n = 1; Child C, n = 5). There were 8 females and 5 males with a mean age of 27 yr (range 15-34 yr). All patients of group I required continuous nursing care before LTX, in spite of pretreatment with d-penicillamine and zinc. The most frequent symptoms in these patients were dysphagia (n = 4), dysarthria (n = 4), tremor (n = 4), sialorrhea (n = 3), ataxia (n = 3), dystonia (n = 3) and handwriting difficulties (n = 3). All patients of group II presented with hemolytic anemia. The survival rate was 100%, and all patients were doing well after a mean follow-up period of 32.8 months (range 8-68 months). The postoperative course was without severe infectious and other complications. All patients of group I revealed the first signs of improvement for all types of neurological symptoms 4-6 wk after LTX. One patient has been without any symptoms from 18 months until 5.5 yr after LTX. Two patients with short-term follow-up also had noticeable improvement of neurological impairment, but residual symptoms are still present. One patient showed only slight improvement. We conclude that Wilson's disease may be a good indication for LTX for both neurological manifestation with stable liver function and hepatic manifestation with cirrhosis or acute liver failure.

In a retrospective study the records of 302 adult patients (167 male, 135 female) after orthotopic liver transplantation (OLT) with a minimum follow-up of 6 months (median follow-up 18 months, maximum 5 yr) were reviewed with regard to cardiovascular risk factors. In 197 patients data concerning the occurrence of arterial hypertension, hyperglycemia, or hypercholesterolemia prior to OLT were available. We found a highly significant increase of cardiovascular risk factors following OLT. Obesity was found in 17.4% of male and 22.2% of female recipients after OLT. Hypercholesterolemia was evident in 66.2% of liver graft recipients. Hypertriglyceridemia occurred in 49.7% of all male patients. In females there was a significantly different prevalence of hypertriglyceridemia comparing patients with a follow-up period up to 2 yr and more than 2 yr (50% vs. 24.6%, p = 0.018). Nearly 45% of all patients met the criteria for arterial hypertension, with a slight increase in male patients beyond the second year of survival (p = 0.094). Hyperglycemia had a significantly higher frequency in male than in female patients (30.5% vs. 10.4%, p < 0.005). Furthermore we observed a clear trend towards reduction of occurrence of hyperglycemia more than 24 months after OLT, but not reaching statistical significance. No correlation was detected when serum levels of triglycerides, and cholesterol, body-mass-index, and arterial blood pressure were compared with applied dosages of immunosuppressive agents [cyclosporin A (CyA), tacrolimus, and prednisolone]. Only decreasing tacrolimus application was significantly correlated with decreasing glucosemia (p = 0.041). Patients receiving tacrolimus instead of CyA as primary immunosuppressant showed a significantly lower prevalence of hypercholesterolemia. Even hypertension, hyperglycemia, hypertriglyceridemia, and obesity had a lower occurrence in patients treated with tacrolimus although not reaching statistical significance.

The introduction of cyclosporine A (CsA) and FK506 significantly improved the outcome of liver transplantation. However, the postoperative course and outcome of liver transplant recipients in still compromised by rejection, over-immunosuppression-induced infection and immunosuppression-associated toxicity. In the present study, we evaluated the reason for conversion between immunosuppressive regimens in 121 patients, 60 treated with FK506 and 61 patients treated with CsA-based immunosuppression. Five patients treated primarily with CsA (8.3%) were converted to FK506 therapy because of refractory acute of chronic rejection within 12 months following liver transplantation (LTX). In 2 patients, conversion was performed after Re-LTX. In 4 of these 5 patients, rejection was successfully treated according to histological and laboratory investigations, while in the remaining patient, graft function improved with persisting histological evidence of chronic rejection. Moderate and severe neurologic symptoms during the early postoperative period, i.e. organic brain syndromes (OBS), seizures, hemiparesis, dysphasia, dysathria and cerebellar symptoms were observed in 21.3% of patients treated with FK506 and in 11.7% of patients treated with CsA (p = n.s.). Five patients treated primarily with FK506 were converted to CsA due to severe neurotoxicity. Early postoperative renal insufficiency was observed to a similar extent with 42.6% of FK506- and 36.7% of CsA-treated patients. 8.3% of FK506-treated patients and 11.7% of CsA-treated patients required hemodialysis (p = n.s.) There patients were converted from FK506 to CsA due to persisting renal insufficiency. Moderate and severe neurologic symptoms were observed more frequently under treatment with FK506 than CsA, and all conversions from FK506 to CsA (13.3%) were performed because of neuro- or nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Since we may soon be able to choose between primarily CsA- or FK506-based immunosuppression, it is important to establish the superior immunosuppressive agent for the individual patient. In the present study, 121 patients, 61 randomly assigned to FK506- and 60 assigned to CsA-based immunosuppression, were analyzed according to the primary diagnosis for liver transplantation. One-year patient survival was similar in all groups. However, the incidence and severity of acute rejection within the 1st year after transplantation was significantly higher in patients transplanted due to HCV disease who were receiving FK506 (58.8%) compared with those patients receiving CsA (27.8%; p < or = 0.05). Furthermore, the incidence of moderate and severe neurotoxicity was significantly higher during the 1st month after LTX in patients transplanted owing to HCV disease treated with FK506 (35.3%) compared with those patients receiving CsA (16.7%; p < or = 0.05). Irrespective of the immunosuppressive regimen, the incidence of early postoperative neurotoxicity was significantly lower in patients transplanted owing to HBV disease, alcoholic cirrhosis and various other liver diseases summarized than in patients transplanted due to HCV disease receiving FK506 therapy. During the 1st year, the incidence and severity of rejection in patients transplanted due to alcoholic cirrhosis and PBC was significantly lower in patients treated with FK506 (11.1% for both groups) compared with those patients receiving CsA (54.5% and 60.0%, respectively; p < or = 0.05. Furthermore, this was accompanied by a lower incidence of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)