Trasplante
Hepático		 Documentación

12. BIBLIOGRAFIA

  1. Rimola A. Trasplante hepático. Med Clin (Barc) 1991; 97:388-394.
  2. Cuervas-Mons V. Trasplante hepático. Barcelona, Sandoz Pharma SAE 1993.
  3. Matesanz R. Presente y futuro de los trasplantes en España. Rev Clín Esp 1995:203-205
  4. Organización Nacional de Trasplantes. Memoria-ONT 1994. Rev Esp Trasp 1995; 4(2): 65_75.
  5. Benhamou Jp. Indications for liver transplantation in primary biliary cirrhosis. Hepatology 1994; 20:11S-13S
  6. Wiesner RH, Porayko MK, Dickson ER, Gores GJ, LaRusso NF, Hay JE, Wahlstrom HE, et al. Selection and timing of liver transplantation in primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology 1992; 16: 1290-1299
  7. Neuberger JM, Gunson BK, Buckels JAC, Elias E, Mc Master P. Referral of patients with primary biliary cirrhosis for liver trasplantation. Gut 1990; 31:1069-1072
  8. Rosen CB, Nagorney DM, Wisner RH, Coffey RJ jr, LaRusso NF, Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg 1991; 213: 21-25.
  9. Wiesner RH, Grambsch PM, Dickson ER, Ludwig J, McCarty RL, Hunter EB, Fleming TR, et al. Primary sclerosing cholangitis: natural history, prognostic factors, and survival analysis. Hepatology 1989; 10:430-436.
  10. Farrant JM, Hayllar KM, Wilkinson M, Kavani J, Portmann B, Westaby D, Williams R. Natural History and prognostic variables in primary sclerosing cholangitis. Gastroenterology 1991; 100: 1710-1717.
  11. Pugh RNG, Murray-Lyon IM, Dawson SL. Et al. Transection of oesophagus for bleeding oesophageal varices. Br J Surg 1973;60: 646-9
  12. Llach J, Gines P. Arroyo V et al. Prognostic value of arterial pressure, endogenous vasoactive systems, and renal function in cirrhotic patients admitted to the hospital for the treatment of ascites. Gastroenterology 1988; 94: 482-7
  13. Tito L, Rimola A,Llach J, et al. Recurrence of spontaneous bacterial peritonitis in cirrhosis: frecuency and predictive factors. Hepatology 1988; 8: 27-31
  14. Samuel D, Bismuth A, Mathieu D, et al. Passive immuprophylaxis after liver trasplantation in HbsAg positive patients. Lancet 1991; 337:813-5
  15. Davis SE, Portman BC, O’Grady JG, et al. Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis. Hepatology 1991; 113: 150-7
  16. Lauchart W, Muller R, Pichlmayr R. Immunoprophylaxis of hepatitis B virus reinfection in recipients of human liver allogratf. Transplant Proc 1987; 19: 2387-9
  17. Lauchart W, Muller R, Pichlmayr R. Long tern immunoprophylaxis of hepatitis B virus reinfection in recipients of human liver allograft. Transplant Proc 1987; 19:4051-3
  18. Samuel D, Muller R, Alexander G, et al. Liver transplantation in Europe patients with the hepatitis B surface antigen. N Engl J Med 1993; 329: 1842-7
  19. Rakela J. Hepatitis C viral infection in liver transplant patients: how bad is it relly?. Gastroenterology 1992; 103, 1:338-339
  20. McCaughan GW, O’Brien E, Sheil AGR. A follow up of 53 patients alive beyond 2 years following liver transplantation. Journal of gastroenterology and Hepatology 1993; 8: 569-573.
  21. Müller H. Otto G, Goeser T, Arnold J, Pfaff E, Theilmann L. Recurrence of hepatitis C virus after liver transplantation. Transplantation 1992; 54,4: 743-745
  22. Ferrell L, Wright T, Roberts J, Ascher N, Lake J. Hepatitis C viral infection in liver transplant recipients. Hepatology 1992; 16,4:865-876
  23. Samuel D, Feray C, Bismuth H. Liver transplantation for chronic viral hepatitis. In: Arroyo V, Bosch J, Rodes J. Treatments in hepatology (eds) Masson. Barcelona 1995, pp. 195-202
  24. Lidofsky SD. Liver transplantation for fulminant hepatic failure. Gastroenterol Clin North Am 1993; 22: 257-269
  25. Webberley M, Neuberger J. Changing indications in liver trasplantation. Baillieres Clin Gastroenterol 1994; 8: 495-515
  26. O’Grady JG, Alexander GJM, Hayllar KM et al. Early indicators of prognosis in fulminate hepatic failure. Gastroenterolgy 1989; 97: 439-443
  27. Vickers C, Neuberger J, Buckers J et al. Transplantation of the liver in adults and children with fulminant hepatic failure. J Hepatol 1988; 7: 143-148
  28. Lake JR. Changing indications for liver transplantation. Gastroenterol Clin North Am 1993; 22: 213-229
  29. Okuda K, Ohnishi K. Neoplasms of the liver. Tokio: Springer-Verlag, 3, 1987
  30. Escorsell A, Bruix J, Bru J, et al. Incidencia de carcinoma hepatocelular en pacientes con cirrosis hepática. Rentabilidad de la detección precoz. Gastroenterol Hepatol 1992; 15: 271-2
  31. Bismuth H, Houssin D, Ornowsky J, Merrigi F. Liver resections in cirrhotic patients: A western experience. World Surg 1986; 10: 311-317
  32. Pichlmayr R, Ringe B, Wittekind C et al. Liver grafting for malignant liver tumors. Transpl Proc 1989; 21: 2403-2405
  33. Fuster J, García-Valdecasas JC, Grande L, Tabet J, Bruix J, Anglada MT, et al. Hepatocellular carcinoma and cirrhosis. Results of surgical treatmen in an European series. Ann Surg. (Aceptado para publicación).
  34. Belghiti J, Panis Y, Farges O, Benhamou JP, Fekete F. Intrahepatic recurrence after resection of hepatocelular carinoma complicating cirrhosis. Ann Surg 1991; 214: 114-117
  35. Iwatsuki S, Starzl TE, Sheahan D et al. Hepatic resection versus transplantation for hepatocellular carcinoma. Ann Surg 1991; 214: 221-229
  36. Bismuth H, Chiche L, Adam R et al. Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg 1993; 218: 145-153
  37. Ringe B, WittekindC, Bechstein WO, Bunzendahl H, Pichlmayr R. The role of liver transplantation in hepatobiliary malignancy. A retrospective analysis of 95 patients with particular regard to tumor stage and recurrence. Ann Surg 1989; 88-98
  38. Valls C, Pamies JJ, Sancho C, et al. Computed tomography after lipiodol chemoembolization. Eur Radiol 1994; 4: 238-242
  39. Jaurrieta E, Fabregat J, Figueras J, et al. Liver transplantation in hepatocellular carcinom. Transpl Int 1992; 5(S1): S196-S197
  40. Iwatsuki S, Gordon RD, Shaw BWjr, Starzl TE. Role of liver transplantation in hepatocellular carcinoma. Transpl Int 1992; 5(S1): S196-S197
  41. Goldstein RM, Stone M, Tillery GW, et al. Is liver transplantation indicated for cholangiocarcinoma?. Am J Surg 1993; 166: 768-772
  42. Miros M, Kerlin P, Walker N, harper J, Lynch S, Strong R. Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis before liver transplantation. Gut 1991; 32: 1369-1379
  43. Jara P, Díaz MC, Hierro L, Camarena C, De la Vega A, Gasco C et al. Indications for selection for liver trasplantation in children. Transplantation Proceedings 1989, 21: 2450-2451
  44. Devictor D, Desplanques L, Debray D, Ozier Y, Dubousset AM, Valayer J, Houssin D, Bernard O, Huault G. Emergency liver trasplantation for fulminant liver failure in infants and children. Hepatology 1992; 16:1156-1162
  45. Laurent J, Gauthier F, Bernard O, Hadchouel M, Odievre M, Valayer J, Alagille D. Long term outcome after surgery for biliary atresia. Study of 40 patients surviving more than 10 years. Gastroenterology 1990; 99; 1793-1797
  46. Whittington PF, Balistreri WF. Liver Transplantation in pediatrics: indications, contraindications and pretransplant management- J Pediatr 1991; 118: 169-177
  47. Brant de Carvalho F, Reding R, Falchetti D, de Ville de Goyet J, de Hemptinne B, Sokal E, Otte JB, analysis of liver graft loss in infants and children below 4 years. Transplant Proc 1991; 23: 1454-1455
  48. De Ville de Goyet J, Hausleithner V, Reding R, Lerut J, Janssen M, Otte JB. Impact of innovative techiques on the waiting list and results in pediatric liver transplantation. Transplantation 1993; 56: 1130-1136
  49. Ringe B, Neuhay P, Lauchart W, et al. Experience with hepatic retransplantation. Transplant Proc 1986; 38: 366-94
  50. Shaw BWJr, Gordon RD, Iwatsuki S, et al. Hepatic retrasplantation. Transplat Proc 1985; 17 (1): 264-71

 

13. SUMMARY AND CONCLUSIONS

13.1 SUMMARY

  1. Orthotopic Liver Tansplantation (OLT), consist to remove the diseased liver of a person and replace it by a healthy one recovered from a donor. For some irreversible and progressive hepatopathies is the only way to cure (particularly in children and alcoholic cirrhosis). Otherwise is a debated treatment procedure (positive replication viral hepatitis, and tumors).
  2. OLT presents a mortality risk not to be despised, although from 1988-1989 changes in the indications, in the surgical procedures and inmunosupresors agents, conduced to improve the surviving rates as much as 78% in the first post-trasplant year.
  3. In Spain from 1.984, 2.708 OLT have been made, 85% from 1989. Among them, actually live 1.980 hepatic receptors. Last year 8.000 persons with alcoholic cirrhosis died. Compared with these data, in the last year 712 hepatic donors ere obtained. Although not all cirrhotic patients had indications for OLT, it is obvious that exists more candidates for transplantation than donors. So, during 1.994, 60 patients died while were included in the OLT waiting list.
  4. The Spanish data for organ donation, and liver transplantation means the highest rates per million persons in the world. However it is difficult to increase the number of donors. First, because the rates are already very high and second, because the common causes of cerebral death are dropping.
  5. There is not an Official Transplantation Registry in Spain. To compare or process data of indications or survival, data from European Liver Transplant Registry (ELTR), some published Spanish series and those ones from a coordination centre, Organización Nacional de Trasplantes (ONT), are used.
  6. Spanish National Transplant Organization (ONT) data shows good surviving rates. Between 1.989-1994 that rate reached 70% al the fifth post-transplant year in adults, and 80% in children. Emergency versus programmed OLT presents a surviving rate of 50-60%, during the first year.
  7. The main indication for OLT in adults was cirrhosis (75% of cases), and far behind retransplantation, fulminant liver failure, and tumors. In children pointed out biliar atresia (30%), retransplantation, fulminant liver failure, metabolic disorders and others.
  8. Concerning to the surviving rates different types of pathologies it is known the following data:
  1. Finally OLT surviving rate depends of a suitable indication, proper patient selection, contraindication absence, graft compatibility’s, programmed versus emergency surgical procedures, right use of inmunosupresor therapy agents, and quick graft failure sign detection with retransplantation procedure.
  2. In Spain exists a lesser retransplantation rate (10%), than in Europe or US (12-16%), and a better surviving rate at the first year (62% versus 50%). These differences could be related with the last period of time (1.989-1994) in which were made most part of the Spanish OLT and with the high survival rate that all the Spanish OLT team have got from 1.988.
  3. In the Spanish National Health System (SNS), the economic cost of each OLT surgical procedure and first post-transplant month is around 55.000$ (47.000-67.000) Lessen when the team does 40 or more OLT PER YEAR. After the first post-transplantation year the OLT cost is similar to renal transplantation. The maintenance treatment cost of a terminal cirrhotic patient could be similar to the surgical procedure.
  4. Eight of the seventeen Spanish Autonomic Communities (CCAA) have liver transplantation teams, with a total of 17 teams, Between CCAA exists significative differences in indication and number of OLT performed, per inhabitant.
  5. These differences suggest that it is necessary to advance in the way for proper selection criteria of the hepatopathies susceptibles to transplantation, with the aim to assure the equity of access to an OLT, if necessary. It needs also to advance to determine priorities of the candidates to this kind of therapy, with the aim to improve the graft management and the survival of the receptors.
  6. OLT is indicated if a person has irreversible and progressive hepatobiliar disease, whether other therapeutic approaches has a lack of results and its hope of survival in the next 12 months is lesser than that obtained with OLT. Those diseases are chronic cholestasis, non biliary cirrhosis cirrhosis cirrhosis cirrhosis cirrhosis, fulminant liver failure and acute hepatic insufficience, congenital disorders and some cases of liver tumors.
  7. Absolute OLT contraindications are active alcoholism or drug addiction, human inmunodefficiency viral disease, serious body tissue insufficience without possible cure, non controled extrahepatic infection, and malignant primary extrahepatic tumor. Nevertheless, other factors could difficult the transplant.
  8. These OLT indications and contraindications could change depending of the individual clinical status, diagnosis, systemic extension and proper time to obtain the donor liver. These factors have a different wight in the OLT indication and are reviewed in this Technical Report. The limitations in the obtaining organ process has obliged to establish priority criteria, also reviewed in this Technical Report.

13.2 CONCLUSIONS

  1. There is more candidates for Orthotopic Liver Transplantation (OLT) than donors of a healthy liver. Donors will not reach more than the actual amount (700 per year), while the number of OLT needs in the next years could be around 600-800 annual cases. Therefore some patients could die while included in the OLT waiting list. That issue makes it necessary to establish stringent criteria selection.
  2. The global survival of the Spanish OLT patients is good (70% at the fifth year in adults, 80% in children) if comparation is established with European or US data. Because the surviving rate is better in programmed versus emergency OLT, efforts should be made to detect in a precocious state the hepatic insufficiency and then to indicate the transplantation. Likewise it is necessary to detect quickly the primary fail of the graft, as a sign of transplant reject and the need of indicating or not the retransplantation.
  3. The high amount of resources should be used in OLT with best prognosis, like in alcoholic cirrhosis (if withdrawal is confirmed), cholestasic diseases and all indications in children. Other OLT with acceptable outcomes are fulminant liver failure, non-replication hepatitis B virus related diseases, and hepatitis C virus related diseases.
  4. The disposable resources should be restricted in OLT with the worst prognosis, as in the positive replication hepatitis B virus related diseases, and tumors (except cases within the indication criteria). OLT in tumors presents middle or even unacceptable outcomes because relapses. Because it will produce false expectations both to the patient and to the family, is not justified to indicate an OLT in those patients with absolute contraindications.
  5. In colangiocarcinoma and other tumor metastasis in liver, the transplantation is contraindicated. Therefore OLT is contraindicated in endocrinological metastasis except in a very few defined situations.
  6. In and out patient practitioners should know the therapeutical approach to OLT and the prognosis in its different indications. Its last aim is to lessen the OLT rate differences between Autonomic Communities and to increase the equity in organ distribution.
  7. The patient priorization system is based in two main criteria:
    1. Immediate death risk if there is not a quick access to an OLT.
    2. Successful outcome possibilities, in terms of years of life obtained.
  8. Geographical priorization is included in those main criteria. It tries to approach donors and transplantation to reduce the graft cold ischaemic period in order to obtain better outcomes, to lessen the health officers travels, and to promote the act of donation because the physical approaching of the donation-transplantation process. The first criteria means a priority for fulminant failure and the second one means the same to paediatric receptors.
  9. To advance in the second criteria priorization development is absolutely necessary to know better the medium and large term outcomes for each one of the patients subgroups.
  10. Lesser rate of retransplantation and highest survival per year in Spain versus Europe and US could be related with the lesser time the liver transplant is actually working in Spain. So, we could wait an increase in retransplantation rate in next years in our country.
  11. OLT economic cost range is between 47.000-67.000 $ in 1.994. This cost is similar to the treatment of patients with descompensated liver cirrhosis. After first year the cost will reduce to figures close to the kidney transplant.
  12. An Spanish official Liver Transplant Registry is absolutely due in order to unify coding, to know medium and large term outcomes and to analyse the needed and the used resources.

14. ABSTRACT

Indications and contraindications of the liver transplantation and retransplantation. (Indicaciones y contraindicaciones del trasplante y del retrasplante hepático) (Dec 1995). Author(s): Sáenz A, Navarro A, Conde J, Matesanz R. Agency: AETS (Agencia de Evaluación de Tecnologías Sanitarias). Madrid. Contact: Sáenz A. # pages # references: 50 pgs / 45 refs. Price: Free. Language: Spanish. English summary: Yes. Technology: Liver Transplantation / Liver retransplantation (LR)/Orthotopic liver transplantation (OLT). MeSH keywords: Chronic Liver disease /Orthotopic Liver Transplantation / Cirrhosis / Biliary atresia / retransplantation. Purpose of assessment: This report is a joint initiative of the Spanish National Transplant Organisation (Organización Nacional de Trasplantes, ONT) and the Agency for Health Technology Assessment (Agencia de Evaluación de Tecnologías Sanitarias, AETS). The aim of this report is the answering to the needs of the different liver transplantation teams, to develop a basic text that contents the Spanish’s today state of the liver transplantation and retransplantation, with its indications and contraindications and the priority criteria to access at these technological and surgical procedures.

Clinical review: Bibliographic review, Inhouse production, experts comments and external revision by all of the spanish liver transplantation teams.

Cost / economic analysis: Cost analysis for OLT.

Primary data collection: Articles published since 1989 to 1994.

Data sources: Medline. Information synthesis. Contributions from different health care professionals from the OLT medical and surgical teams. External review.

Content of report /main findings: For some irreversible and progressive hepatopathies OLT is the only way to cure (particularly in children and alcoholic cirrhosis). Otherwise is a debated treatment procedure (positive replication viral hepatitis, and tumors). OLT presents a non negligible mortality risk, although from 1988-1989 changes conduced to improve the five year survival rate as much as 78%. The spanish data for organ donation, and liver transplantation means the highest rates per million persons in the world. The main indication for OLT in adults was cirrhosis (75% of cases), and far behind retransplantation, fulminant liver failure, and tumors. In children pointed out biliar atresia (30%), retransplantation, fulminant liver failure, metabolic disorders and others. Spanish data shows good survival rates. That rate reached 70% at the fifth post-transplant year in adults, and 80% in children. Urgent versus programmed OLT presents a survival rate of 50-60%, during the first year. Unlike the OLT European Registry, the survival of the OLT in hepatocelular carcinoma in some spanish series is higher. It could be due to a better selection and to a previous tumor chemoembolization. In the Spanish National Health System (SNS), the economic cost of each OLT surgical procedure included the first post-transplant month is around 55.000 $ (47.000-67.000).

Recommendation / Conclusion: The higher amount of resources should be used in OLT with the best prognosis, like in alcoholic cirrhosis (if alcohol withdrawal is confirmed), cholestasic diseases and all indications in children. Other OLT with acceptable outcomes are fulminant liver failure, non replication hepatitis B virus related diseases, and hepatitis C virus related diseases. A spanish comprehensive Liver Transplant Registry is now a fundamental need in order to unify coding, to know medium and large term outcomes and to analyse the need and the use of resources.

 

Figura 10

*Existen argumentos a favor de las dos opciones.

 

 

Figura 11

* Ver tabla de contraindicaciones
** Ver tabla de indicaciones

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