Volume 62 - 1999 - Fasc.3 - Symposium
1000 Liver Transplants at Cliniques Saint-Luc, An Update Symposium (Brussels, 30-10-98) - Introduction
The pediatric liver transplant program at the Université Catholique de Louvain, Cliniques Saint-Luc, Brussels : Overall results in 444 children (1984-1997)
Between 1984 and 1997, a total of 444 children (< 15 years) received an orthotopic liver transplant (OLT) at Saint-Luc University Clinics. Bihary atresia constituted the indication for OLT in 304 cases (68%). Median age (range) at OLT was 2.1 years (0.3-14.5). 177 children (40%) received a whole liver graft, 184 (41%) a reducedsize graft, 26 (6%) a split liver graft, whereas a living-related donor graft was used in 57 children (13%). Most grafts were ABO-identical or -compatible, in 395 cases (89%) and 40 (9%), respectively. Overall actuarial patient survivals at one and five years were 85% and 81%. The overall rltransplaintation rate was 19%. The results of @- and multivariate statistical analyses showed a significant impact of year of transplantation (learning curve effect), with a 15% improvement of patient survival between the 1984-7 and the 1995-7 periods (p < 0.002). Results differed according to the indications for OLT, the best survivals being recorded for familial cbolestasis, the worst for liver tumor (p = 0.004). Five year patient survival was significantly better after elective OLT (82%), when compared to highly urgent OLT (63%) (p < 0.001). Patient survivals were comparable in the children receiving primary cyclosporin-A niicroemulsion or tacro@us immunosuppression, which were significantly higher than in the historical group treated with cyclosporin-A. No impact of the age at OLT, type of graft and iscbemic time could be reported. In conclusion, this series illustrates the progressive improvements introduced in our pediatric liver transplant program between 1984 and 1997, including the technical variants allowing pediatric OLT using adult donors as well as the introduction of new immunosuppressive strategies. (Acta gasttoenterol. belg., 1"9, 62, 285-289).
Paediatric orthotopic liver transplantation : lessons from a 532 transplant single centre experience with 532 transplants in 446 children
Cholestatic childhood liver diseases
Liver transplantation in metabolic disorders
Liver transplantation in pediatric patients represents about 10% of a total of 23.000 transplantations registred in the European Liver Transplantation Register (ELTR)since 1968. The pediatric patients show a specific spectrum of indications with cholestatic liver disorders ranking first, followed by hepatic based metabolic disorders. There has been a significant improvement of survival in transplantation since the early 80ies. The overall survival standard is nowadays in the range of 80%. There is a trend towards even better results in metabolic disorders. The clinical presentation of liver disease caused by metabolic disorders shows a wide range from acute liver, cerebral, cardiac and renal failure to chronic end stage liver, kidney and heart disease potentially complicated by hepatocellular carcinoma. In many cases, the diagnosis of a underlying metabolic disorder is very difficult and time consuming so the decision to do a liver transplantation may be necessary before a final diagnosis is established. Having these problems in mind, the consideration of absolute and relative contraindications for liver transplantation in metabolic disorders is even more difficult than it is already in cholestatic or inflammatory liver disorders. The individual evaluation of a patient suffering from a hepatic metabolic disorder must consider in addition the often dramatic restriction of quality of life due to rigorous dietary restrictions or other therapies. This makes clear that suitable methods to measure quality of life must be developed and applied in order to fulfill this goal. The extension of indications for liver transplantation even to disorders with only partial defects in otherwise healthy livers was possible by using innovative surgical techniques such as partial, living related, split, in situ split and auxiliary orthotopic transplantation. These techniques allowed to reduce the mortality on pediatric waiting lists significantly without restricting the general donor pool. However, living related liver transplantation is handicaped by the heterozygous status of the parent donor. This plays a role especially in patients with progressive familial intrabepatic cholestasis (PFIC) and Wilson's disease.
Adult liver transplantation : UCL experience
Objective : to evaluate the impact of standardized operative and peri-operative care on the outcome of liver transplantation in a single center series of 395 adult patients. Method and material: between February 1984 and December 31, 1998, 451 orthotopic liver transplantations were performed in 395 adult patients (>- 15 years) at the University Hospitals St-Luc in Brussels. Morbidity and mortality of the periods 1984-1990 (Gr I 174 pat.) and 1991-1998 were compared (Gr 11 - 221 pat.). During the second period anti-infectious chemotherapy and perioperative care were standardized and surgical technique changed from classical orthotopic liver transplantation with recipients' vena cava resection (and use of veno-venous bypass) towards liver implantation with preservation of the vena cava (without use of bypass). Immunosuppression was cyclosporine based from 1984 up to 1996 and tacrolimus based during the years 1997 and 1998. Immunosuppression was alleviated during the second period due to change from quadruple to triple and even double therapy and due to the introduction of low steroid dosing and of steroid withdrawal, once stable graft function was obtained. Indications for liver grafting were chronic liver disease (284 pat 71,9%), hepatobiliary tumor (52 pat - 13,2%), acute liver failure (40 pat - 10,1%) and metabolic disease (19 pat - 4,8%). Regirafting was necessary because of graft dysfunction (21 pat), technical failure (12 pat), immunological failure (18 pat) and recurrent viral allograft disease (5 pat) ; three of these patients were regrafted at another institution. Follow-up was complete for all patients with a minimum of 9 months. Results. actuarial 1, 5 and 10 years survival rates for the whole group were 77,9%, 65,7% and 58,3%. These survival rates were respectively 77,3%, 69,711/O. 62,5% and 73,2%, 59,6% 51,4% for benign chronic liver disease and acute liver failure ; those for malignant liver disease were 80,6%, 44,3% and 36,7%. Early (< 3 months) and late (> 3 months) posttransplant mortalities were 14,4% (57 pat) and 21.2% (84 pat). Early mortality lowered from 20% in Gr I to 9,4% in Gr 11 (p < 0.02) ; this was due to a significant reduction during the second period of bacteria] (99/174 pat. - 56.9% vs 82/221 pat. 37.1%), fungal (14 pat. - 8% vs 7 pat. - 3.2%) and viral (87 pat. 50% vs 49 pat. - 22.2%) infections (p < 0.05) as well as of perioperative bleeding (92 pat. - 52.9% vs 39 pat. - 17.6% - p < 0.001). Late mortality remained almost identical throughout the two periods as lethal outcome was, mainly caused by recurrent allograft diseases, cardiovascular and tumor problems. Morbidity in these series was important considering that almost, half of the patients had a technical complication, mostly related to bleeding (131 pat - 33,2%) and binary problems (66 pat - 16.7%). Retransplantation index was 1.1 (54 pat. 14%). Early retransplantation mortality was 24% ; it lowered, although not yet significantly, during the second period (8/25 pat. 32% vs. 5/29 pat. - 17.2%). Conclusion: Despite a marked improvement of results, liver transplantation remains a major medical and surgical undertaking. Standardization of operative and perioperative care, less haemoffaghic surgery and less agressive immunosuppression are the keys for further improvement.
Acute liver failure and transplantation. Adult UCL experience
Liver transplantation and autoimmunity
Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent good indications for orthotopic liver transplantation (OLT). While there is effective treatment for AIH (steroids with or without azathioprine) and PBC (ursodeoxycholic acid) no such treatment is currently established for PSC. The need of transplantation can be delayed for AIH and PBC with appropriate therapies, while treatment options for PSC are still controversially discussed. Although the time point for liver transplantation can be roughly estimated for AIH by failure of immunosuppressive therapy and for PBC by prognostic models, the prediction of survival in patients with PSC is more difrlcult, and further complicated by the risk of developing cholangiocellular carcinoma. Long term (5-year) outcome after liver transplantation approaches 80 to 90% for autoimmune liver diseases unless cholangiocellul@r carcinoma complicates PSC at the time of OLT. The risk of disease recurrence has been recognised for each of these entities although its clinical relevance is controversial and not exactly determined today. As survival after liver transplantation is steadily increasing, recurrent autoimmune liver disease may become a clinical problem in the future. Recently de novo autoimmune hepatitis after liver transplantation has been reported from several transplant centres, although its importance still needs to be established.
Hepatocellular carcinoma : from ethanol injection to liver transplantation
Liver transplantation in viral hepatitis. New insights
Liver transplantation is the only therapeutic option for end- stage liver disease. When disease is due to hepatitis B, C or D viruses, transplantation is aggravated by important morbidity related to the recurrence of viral infections. The risk of reinfection has led to the identification of prognostic criteria and measures for preventing or diminishing the reinfection hazard. HBV recurrences can be diminished with the use after transplantation of immunoglobulins against the HBsAg (HBIg). With this prophylaxis the risk of reinfection is proportional to the viremic load before transplantation; it is high (> 90%) in patients with elevated viremia, low in non-viretnic HBsAg carriers (such as those with fulniinant hepatitis or HDV coinfection), intermediate in the remaining cases. The recent availability of potent antivirals against the HBV has provided a tool to further reduce the reinfection risk. Antiviral therapy or immunoprophylaxis, however, may lead to the emergence of resistant mutants; combination therapies appear in order to prevent this event. There is at present no valid prognostic indicator to identify HCV transplants at risk of recurrent disease or prophylactic measure to prevent reinfection. Reinfection is virtually universal and the course of infection is apparently benign over the short term in the majority of cases; the disease is rapidly progressive with cholestatic features miniicking chronic rejection in 10-20% of HCV reinfected transplants. Neither the HCV genotype nor coinfection with HGV appear to influence the clinical outcome. The long-term prognosis appears at present less favourable than previously perceived ; several studies indicate a progressive reduction of the survival curve due to insidious HCV cirrhosis developing over 5 to 7 years. Interferon or Ribavirin monotherapy are not effective for prevention or therapy of recurrences while their combined use yields promising results.
Follow-up of the adult patient after transplantation
Experience with living related liver transplantation in 63 children
Cost containment and managed care in liver transplantation