Liver transplantation in patients over 60 years of age.

Liver transplantation was previously only offered to patients under 60 years of age. We have analyzed the outcome after acceptance on the waiting list and after liver transplantation of patients over 60 years old. A total of 150 patients over 60 years old were listed for a first liver transplantation during 1990-1998. The annual number increased throughout the period. Primary biliary cirrhosis, primary sclerosing cholangitis, and acute hepatic failure were the most frequent diagnoses. A total of 119 patients received a first liver allograft. The patient 1-year survival was 75% and 3-year survival 62%, which was not significantly lower (P = 0.21) than that of the younger patients. When correcting for year of transplantation, the survival was, however, moderately but significantly lower than among the younger patients. Survival among those > 65 years (n = 38) did not differ from that of patients 60-65 years of age (n = 81). We conclude that an increasing number of patients over 60 years old can be listed for liver transplantation and receive a liver allograft with highly satisfying results.

Liver transplantation in the Nordic countries, 1982-1998: changes of indications and improving results.

BACKGROUND: Liver transplantation has become an established therapeutic option for patients with life-threatening liver disease. The aim of the present study was to analyse the results of and developments in liver transplantation in the Nordic countries during a 15-year period. METHODS: Data on all patients receiving a liver allograft in the Nordic countries during 1982-98 and waiting list data for all patients listed for a liver transplantation after 1989 were obtained from the Nordic Liver Transplantation Registry. RESULTS: A total of 1485 first liver transplantations were performed during 1982-98. The annual number of first liver transplantations increased steadily up to 1993, thereafter remaining around 150-170 per year. There are major differences between countries both in the number of transplants adjusted to populations performed per year, with more than twice as many performed in Sweden as in Norway, and in the relative distribution of patients in accordance with diagnosis. The number of patients more than 60 years old increased and comprised 13%-14% of the total patient population during 1996-98. Primary biliary cirrhosis, primary sclerosing cholangitis, acute hepatic failure, malignant liver disease, and alcoholic cirrhosis are the five most frequent diagnoses. The over-all 1-year patient survival probability has increased from 66% among patients receiving a transplant in 1982-89 to 83% in 1995-1998. The waiting time remains stable, with a median waiting time of 35 days during 1990-98. The mortality of patients while on the waiting list is 7.4% and is not increasing. CONCLUSION: Results of liver transplantation in the Nordic countries are very similar to those obtained in other countries. Waiting time and mortality remain low. There are, however, major differences between the countries both as to the number of transplantations performed and as to distribution of diagnoses.

Reconstitution of the actin-scavenger system after orthotopic liver transplantation for end-stage liver disease: a prospective and longitudinal study.

Serum levels of the actin scavenger Gc-globulin (group-specific component, vitamin D-binding protein), a member of the albumin multigene family, are decreased in severe liver disease but have not been evaluated in relation to liver transplantation. We measured Gc-globulin and Gc-globulin-actin complex ratio daily for 2 weeks after transplantation in 17 patients with end-stage liver disease. Before transplantation, Gc-globulin levels were significantly less in the patients than in healthy controls (235 +/- 106 v 340 +/- 35 mg/L, respectively; P<.001), whereas complex ratio level was in the normal range. Five patients (group N) had pretransplantation Gc-globulin values within the normal range (mean +/- 2 SD), and 12 patients had subnormal values (group S). In group N, mean Gc-globulin levels posttransplantation remained stable at a lower level than before transplantation but still within normal range. In this group, cold ischemia time correlated inversely with Gc-globulin levels on day 2 (r = -0.88; P <.05). In group S, normal mean levels were reached at a mean of 11 days after transplantation. However, almost half these patients had subnormal Gc-globulin levels at day 14. Complex ratio levels remained normal in the study period in both groups. Prothrombin index levels (plasma coagulation factors II, VII, and X) were identical in both groups and returned to normal 7 days posttransplantation, whereas plasma albumin levels were less than normal in both groups and further decreased after transplantation. In conclusion, the maintenance (group N) or reestablishment (group S) of serum Gc-globulin to normal levels occurred in the early posttransplantation course in the same time frame as the prothrombin index. Gc-globulin synthesis seems unrelated to albumin synthesis. A prolonged cold ischemia time may cause reduced Gc-globulin levels early after transplantation.

The Nordic multicenter double-blind randomized controlled trial of prophylactic ursodeoxycholic acid in liver transplant patients.

BACKGROUND: Prophylactic treatment with ursodeoxycholic acid (UDCA) has been reported to reduce the incidence of acute rejection after liver transplantation compared with historical controls. We investigated this in a prospective, randomized, placebo-controlled multicenter study. METHODS: Fifty-four liver transplant patients were allocated to the UDCA treatment group (15 mg/kg/day), and 48 patients were allocated to the placebo group. Trial medicine was started on the first postoperative day and was given for 3 months. Follow-up was for 12 months. Treatment was stratified for adults with chronic liver disease (n=77), adults with acute liver failure (n=10), and children (n=15). RESULTS: The frequency of patients with acute rejection was 65% in the UDCA treatment group and 68% in the placebo group. The frequency of steroid-resistant rejection was similar in both groups. The probability of acute rejection, analyzed according to the intention-to-treat policy with Kaplan-Meier analysis, was similar in both treatment groups. No significant differences were found in patient survival and graft survival probabilities. For the biochemical markers of cholestasis, only gamma-glutamyltransferase was significantly improved after 2 months of UDCA treatment. CONCLUSIONS: The initial optimistic report of a beneficial effect of prophylactic treatment with UDCA on acute rejection after liver transplantation was not confirmed in this controlled study.

Liver function, cerebral blood flow autoregulation, and hepatic encephalopathy in fulminant hepatic failure.

In acute liver failure, massive hepatic necrosis may result in impaired regulation of cerebral blood flow (CBF), development of encephalopathy, and cerebral edema. In 10 consecutive patients with fulminant hepatic failure (FHF), CBF autoregulation was found to be absent, as transcranial Doppler mean flow velocity (Vmean) in the middle cerebral artery increased from 49 (27-59) to 69 (49-92) cm/s (P < .05) during a 30- (28-34) mm Hg rise in mean arterial pressure (MAP). In 7 patients, restoration of CBF autoregulation was shown within 48 (24-120) hours after spontaneous hepatic recovery or liver transplantation, before complete alleviation of hepatic encephalopathy (HE). The extraordinarily rapid restoration of CBF autoregulation in patients with FHF following re-establishment of liver function is unique compared with other conditions affecting the CBF autoregulation, indicating a close connection between liver function and regulation of cerebral circulation. Because CBF autoregulation was restored after initial alleviation of HE, it does not appear to be of major pathophysiological importance in the mediation of HE.

Intraoperative measurement of graft blood flow--a necessity in liver transplantation.

Portal venous and hepatic arterial flow was measured intraoperatively in the 70 most recent patients undergoing liver transplantation in our institution. Impaired graft flow due to vascular abnormalities was detected in six patients. One patient suffered from arterial steal due to stenosis of the recipient celiac trunk with blood shunting from the hepatic to the splenic artery. Ligation of the recipient hepatic artery restored the arterial graft flow. In two patients we found reduced portal venous flow due to large portosystemic collaterals. The collaterals accountable for the impaired portal flow were identified and ligated, which restored portal venous graft flow. Excessive sensitivity of the portal venous flow to the position of the graft was found in a 6-month-old boy. Portal venous flow varied considerably, depending upon the position of the graft, and intraoperative flow measurement allowed the best position of the graft to be identified. Two patients developed arterial thrombosis in the early postoperative course. Immediate laparatomy with thrombectomy resulted in good, palpable pulsation in the graft artery in both patients. Intraoperative flow measurement demonstrated satisfactory arterial flow in one patient, whereas there was no net flow in the other patient's graft artery. Pulsation in this patient was caused by blood oscillating in and out of the liver. In conclusion, we find that causes of primary graft dysfunction due to technically flawed reperfusion of the graft can be identified and alleviated by intraoperative measurement of the flow in the graft vessels.

Induction of immunosuppression by microemulsion cyclosporine in liver transplantation.

Twenty-five liver transplant patients were administered liquid microemulsion cyclosporine (Neoral, 5 mg/kg b.i.d.) via a nasogastric tube until they could take oral medication. The first dose was given within 6 hr after surgery. Adequate trough levels of cyclosporine were obtained from the first postoperative day. The total exposure to the drug was low on the first postoperative day, but a significantly improved pharmacokinetic profile with a high maximal concentration and a low time to maximal concentration was found from the second postoperative day. The absorption from Neoral increased during the first week. After 1 week, a low within-patient variation coefficient for dose-adjusted cyclosporine trough levels was found (17%). The between-patient variation coefficient was low during the whole postoperative period (31%). We conclude that in liver transplant patients adequate immunosuppressant blood levels of cyclosporine can be obtained in the immediate postoperative period using Neoral without the need to go to the intravenous form of the drug.

[Fulminant liver failure before and after introduction of liver transplantation at Rikshospitalet]. / Fulminant leversvigt før og efter indførelse af levertransplantation på Rigshospitalet.

The impact of liver transplantation on the survival in fulminant hepatic failure was evaluated in a retrospective study including 87 patients admitted to Rigshospitalet over a three and a half year period before and a three and a half year period after the Danish liver transplantation programme was started. The number of admissions increased by 178% in the second period. Fifty-two percent of the patients had acetaminophen induced liver failure, which over the last seven years has become the most common cause of severe acute liver disease in Denmark. In about half of the patients high volume plasmapheresis was used as liver-assist either alone or in combination with liver transplantation. Three patients in grade 4 hepatic coma (one with Hepatitis B, two with acetaminophen intoxication) were withdrawn from the waiting list for emergency liver transplantation after high volume plasmapheresis due to recovery. In patients with an estimated survival chance of less than 5-10% liver transplantation was performed with a survival rate of 60%. The survival rate for the non-liver transplanted patients was 49% in the same period compared to 30% in the three and a half year period before liver transplantation started.

Postoperative electrolyte and mineral balance after restorative proctocolectomy with ileoanal reservoir.

Postoperative electrolyte and mineral balance was studied in nine patients with ulcerative colitis who underwent restorative proctocolectomy with ileoanal reservoir (J-pouch). The study was carried out during the first seven days of bowel function after construction of the reservoir and temporary ileostomy, and again after the ileostomy was closed and bowel continuity re-established. Stool volume and intestinal sodium excretion were reduced by respectively 40 and 45% after ileostomy was closed (p < 0.05), but potassium excretion was unchanged. The concentration of sodium was higher in ileostomy effluents, whereas the concentration of potassium was higher in stools after the ileostomy was closed (p < 0.05). Significant changes in blood and urinary electrolytes or minerals were not recorded. It is concluded that a major reduction in stool volume and intestinal excretion of sodium is already present in the early postoperative period after bowel continuity has been re-established.

Cerebral blood flow velocity during high volume plasmapheresis in fulminant hepatic failure.

High volume plasmapheresis has previously been found to improve neurological statuses in patients with fulminant hepatic failure. We investigated the relationship between the neurological status and cerebral blood flow velocity (Vmean) during high volume plasmapheresis in 18 consecutive patients (ten females and eight males) with fulminant hepatic failure, with a mean age of 43 (range 9 to 57) years. The mean arterial pressure (MAP) and intracranial pressure (ICP) were also recorded. A total of 16% of body weight was exchanged with fresh frozen plasma per day. Thirty-six plasma exchanges wer performed with a median of 2 (range 1 to 8) per patient. Eleven of the patients survived (61%), nine after liver transplantation. Following the first high volume plasmapheresis, the coma score improved from 6 (1-8) to 2 (0-8) (p < 0.05), Vmean increased from 40 (14-152) to 62 (16-186) cm s-1 (p < 0.05), and MAP from 72 (35-118) to 94 (47-138) mmHg (p < 0.05). The intracranial pressure (ICP) was monitored and remained unchanged in nine patients whereas the cerebral perfusion pressure (MAP minus ICP) increased in the surviving group from 55 (40-74) to 80 (50-91) mmHg (p = 0.07) in contrast to no changes in the non survival group. In conclusion this study suggests that the neurological status, may improve during high volume plasmapheresis as MAP and Vmean increase the cerebral oxygen delivery.

[Radiological findings in patients with a J-shaped ileal reservoir]. / Billeddiagnostiske fund hos patienter med J-formet ileumreservoir.

This study comprised 116 patients with either ulcerative colitis or familial adenomatous polyposis, who were treated from 1983 to 1990. The patients were subjected to total colectomy followed by formation of an ileoanal reservoir (J-pouch). In a retrospective study the radiological findings of the J-pouch and the reservoir related complications are presented and a description of the applied technique for pouchography is given. A total of 513 radiological investigations were performed--median two per patient (range: 1-44). All 116 patients were subjected to pouchography while 59 patients additionally underwent conventional X-ray investigations, 42 patients were referred to ultrasound and ten patients to CT. Fourty-five percent of the patients presented no radiological complications at all. Patients with a normal primary pouchogram showed a significantly lower risk of long term complications related to the pouch. Pouchography was a useful method for excluding pouch pathology before restoring intestinal continuity as well as showing fistulas or cavities. In cases of leakage and especially stenosis and pouchitis pouchography was, however, less reliable. Ultrasound examination combined with CT-scan was beneficial in diagnosing abscesses.

[Liver transplantation in Denmark. First-year experiences]. / Levertransplantation i Danmark. Det første års erfaringer.

During the first 12 months of the Danish Liver Transplantation program, which began in October 1990, 21 transplantations were performed in 11 women, six men and three children. One patient required a retransplant. Fourteen operations were performed electively and six patients were transplanted for acute and subacute fulminant liver failure and coma, two patients had reduced size livers because of large donor liver. There were no peroperative deaths. One of the elective patients died after three weeks from multiorgan failure and sepsis. Two of the emergency patients died after 20 and 22 days. One from graft dysfunction due to stenosis of the celiac trunk and the other of exudative pericarditis. One patient died from chronic rejection and CMV-infection after seven months. Complications were relatively few and acute rejection occurred in 40% of the patients. Fifteen patients are discharged with normal liver function and 11 of these were back at work, school or previous functions in the home. It is concluded that these results are comparable to the best results from other centres but that 21 transplants in 12 months must be a minimum activity.