Liver transplantation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:


Overview

Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and the donor organ is placed in the same anatomic location as the original liver. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure.

Liver Transplantation

History

  • In the 1960s, Thomas Starzl used dogs as the first animals for research on liver transplantation in Boston and Chicago.
  • In 1963, the first liver transplant in humans was attempted by a surgical team led by Dr. Thomas Starzl[1] of Denver, Colorado, United States.
  • Dr. Starzl performed several additional transplants over the next few years before the first short-term success was achieved in 1967 with the first one-year survival post-transplantation.
  • In 1970, the regimen for immunosuppressive therapy following transplant was introduced, but azathioprine and steroids did not improve survival rates of patients.
  • In the 1980s, with the introduction of cyclosporine by Sir Roy Calne, there was an improvement in rejection rates.
  • In 1983, liver transplantation was no longer an experimental modality, but a clinically acceptable form of therapy for both adult and pediatric patients with appropriate indications.
  • In 1986, the introduction of monoclonal antibodies such as muromonab-CD3 [OKT3] further contributed to improvement of quality of immunosuppressive therapy used in patients, with significant decline in rejection rates.
  • In 1988, University of Wisconsin (UW) solution was developed, which ensured a smooth surgery and longer preservation period.
  • In 1992, the concept of xenotransplantation and cloning techniques were introduced by Starzl.
  • In 1999, approximately 5000 procedures were carried out, in contrast to 100 which had been performed a decade earlier.
  • Recently, the introduction of newer immunosuppressive agents such as IL-2 receptor blockers and tacrolimus, have drastically increased patient survival rates to 1 and 5-year rates of approximately 85 and 70 percent respectively.[2]
  • Liver transplantation is now performed at over one hundred centers in the USA, as well as numerous centers in Europe and elsewhere. One year patient survival is 85-90%, and outcomes continue to improve, although liver transplantation remains a formidable procedure with frequent complications.
  • Unfortunately, the supply of liver allografts from non-living donors is far short of the number of potential recipients, a reality that has spurred the development of living donor liver transplantation.

Indications

Contraindications

Absolute contraindications: [3]

Relative contraindications:[3][4][5][6][7][8][9][10][11][12][13]

Pretransplant evaluation

Techniques

  • Before transplantation liver support therapy might be indicated (bridging-to-transplantation).
  • Artificial liver support like liver dialysis or bioartificial liver support concepts are currently under preclinical and clinical evaluation.
  • Virtually all liver transplants are done in an orthotopic fashion, that is the native liver is removed and the new liver is placed in the same anatomic location.
  • The transplant operation can be conceptualized as consisting of the hepatectomy (liver removal) phase, the anhepatic (no liver) phase, and the postimplantation phase.
  • The operation is done through a large incision in the upper abdomen.
  • The hepatectomy involves division of all ligamentous attachments to the liver, as well as the common bile duct, hepatic artery, and portal vein.
  • Usually, the retrohepatic portion of the inferior vena cava is removed along with the liver, although an alternative technique preserves the recipient's vena cava ("piggyback" technique).
  • The donor's blood in the liver will be replaced by an ice-cold organ storage solution, such as UW (Viaspan) or HTK until the allograft liver is implanted.
  • Implantation involves anastomoses (connections) of the inferior vena cava, portal vein, and hepatic artery.
  • After blood flow is restored to the new liver, the biliary (bile duct) anastomosis is constructed, either to the recipient's own bile duct or to the small intestine.
  • The surgery usually takes between five and six hours, but may be longer or shorter due to the difficulty of the operation and the experience of the surgeon.
  • The large majority of liver transplants use the entire liver from a non-living donor for the transplant, particularly for adult recipients.
  • A major advance in paediatric liver transplantation was the development of reduced size liver transplantation, in which a portion of an adult liver is used for an infant or small child.
  • Further developments in this area included split liver transplantation, in which one liver is used for transplants for two recipients, and living donor liver transplantation, in which a portion of healthy person's liver is removed and used as the allograft.
  • Living donor liver transplantation for pediatric recipients involves removal of approximately 20% of the liver (Couinaud segments 2 and 3).

Immunosuppressive management

  • Like all other allografts, a liver transplant will be rejected by the recipient unless immunosuppressive drugs are used.
  • The immunosuppressive regimens for all solid organ transplants are fairly similar, and a variety of agents are now available.
  • Most liver transplant recipients receive corticosteroids plus either tacrolimus or Cyclosporin or Mycophenolate Mofetil.
  • Liver transplantation is unique in that the risk of chronic rejection also decreases over time,although recipients need to take immunosuppresive medication for the rest of their lives.
  • It is theorized that the liver may play a yet-unknown role in the maturation of certain cells pertaining to the immune system.
  • There is at least one study by Dr. Starzl's team at the University of Pittsburgh which consisted of bone marrow biopsies taken from such patients which demonstrate genotypic chimerism in the bone marrow of liver transplant recipients.

Postimplant immunosuppression: ensures survival of the patient and allograft Immunosuppressive agents used in patients receiving a liver transplant include the following: Cyclosporine Tacrolimus Sirolimus Azathioprine Everolimus Mycophenolate Corticosteroids

Agents used for induction include: High-dose corticosteroids Antithymocyte globulin Monoclonal antibody Azathioprine Cyclosporine/Tacrolimus (calcineurin inhibitor) Antiproliferative agent

Agents for long-term immunosuppression: Cyclosporine Tacrolimus Azathioprine Prednisone

Results

  • Prognosis is quite good. 1-year survival (in Finland) is 83%, 5-year survival is 76% and 10-year survival is 66%. Majority of deaths happen during the first three months after transplantation.

Living donor transplantation

  • Living donor liver transplantation (LDLT) has emerged in recent decades as a critical surgical option for patients with end stage liver disease, such as cirrhosis and/or hepatocellular carcinoma often attributable to one or more of the following: long-term alcohol abuse, long-term untreated Hepatitis C infection, long-term untreated Hepatitis B infection.
  • The concept of LDLT is based on (1) the remarkable regenerative capacities of the human liver and (2) the widespread shortage of cadaveric livers for patients awaiting transplant. In LDLT, a piece of healthy liver is surgically removed from a living person and transplanted into a recipient, immediately after the recipient’s diseased liver has been entirely removed.
  • Historically, LDLT began as a means for parents of children with severe liver disease to donate a portion of their healthy liver to replace their child's entire damaged liver.
  • The first report of successful LDLT was by Dr. Silvano Raia at the Universidade de São Paulo (USP) Medical School in 1986.
  • Surgeons eventually realized that adult-to-adult LDLT was also possible, and now the practice is common in a few reputable medical institutes.
  • It is considered more technically demanding than even standard, cadaveric donor liver transplantation, and also poses the ethical problems underlying the indication of a major surgical operation (hepatectomy) on a healthy human being.

Complications of Liver Transplantation

  • To monitor the patient for complications, the following investigations are used:

Laboratory investigations

Imaging studies

External Links


References

  1. STARZL T, MARCHIORO T, VONKAULLA K, HERMANN G, BRITTAIN R, WADDELL W. "HOMOTRANSPLANTATION OF THE LIVER IN HUMANS". Surg Gynecol Obstet. 117: 659–76. PMID 14100514. 
  2. Kanwal F, Dulai GS, Spiegel BM, Yee HF, Gralnek IM (2005). "A comparison of liver transplantation outcomes in the pre- vs. post-MELD eras". Aliment. Pharmacol. Ther. 21 (2): 169–77. PMID 15679767. doi:10.1111/j.1365-2036.2005.02321.x. 
  3. 3.0 3.1 Martin P, DiMartini A, Feng S, Brown R, Fallon M (2014). "Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation". Hepatology. 59 (3): 1144–65. PMID 24716201. 
  4. Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, Duhamel A, Pageaux GP, Leroy V, Dharancy S, Louvet A, Boleslawski E, Lucidi V, Gustot T, Francoz C, Letoublon C, Castaing D, Belghiti J, Donckier V, Pruvot FR, Duclos-Vallée JC (2011). "Early liver transplantation for severe alcoholic hepatitis". N. Engl. J. Med. 365 (19): 1790–800. PMID 22070476. doi:10.1056/NEJMoa1105703. 
  5. Cooper C, Kanters S, Klein M, Chaudhury P, Marotta P, Wong P, Kneteman N, Mills EJ (2011). "Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with synthetic cohort". AIDS. 25 (6): 777–86. PMID 21412058. doi:10.1097/QAD.0b013e328344febb. 
  6. Mindikoglu AL, Regev A, Magder LS (2008). "Impact of human immunodeficiency virus on survival after liver transplantation: analysis of United Network for Organ Sharing database". Transplantation. 85 (3): 359–68. PMID 18301332. doi:10.1097/TP.0b013e3181605fda. 
  7. Terrault NA, Roland ME, Schiano T, Dove L, Wong MT, Poordad F, Ragni MV, Barin B, Simon D, Olthoff KM, Johnson L, Stosor V, Jayaweera D, Fung J, Sherman KE, Subramanian A, Millis JM, Slakey D, Berg CL, Carlson L, Ferrell L, Stablein DM, Odim J, Fox L, Stock PG (2012). "Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection". Liver Transpl. 18 (6): 716–26. PMC 3358510Freely accessible. PMID 22328294. doi:10.1002/lt.23411. 
  8. Cross TJ, Antoniades CG, Muiesan P, Al-Chalabi T, Aluvihare V, Agarwal K, Portmann BC, Rela M, Heaton ND, O'Grady JG, Heneghan MA (2007). "Liver transplantation in patients over 60 and 65 years: an evaluation of long-term outcomes and survival". Liver Transpl. 13 (10): 1382–8. PMID 17902123. doi:10.1002/lt.21181. 
  9. Prachalias AA, Pozniak A, Taylor C, Srinivasan P, Muiesan P, Wendon J, Cramp M, Williams R, O'Grady J, Rela M, Heaton ND (2001). "Liver transplantation in adults coinfected with HIV". Transplantation. 72 (10): 1684–8. PMID 11726833. 
  10. Wreghitt T (2001). "Liver Transplantation in Adults Coinfected With HIV. Transplantation 2001; 72: 1684". Transplantation. 72 (10): 1594–5. PMID 11726816. 
  11. Stock P, Roland M, Carlson L, Freise C, Hirose R, Terrault N, Frassetto L, Coates T, Roberts J, Ascher N (2001). "Solid organ transplantation in HIV-positive patients". Transplant. Proc. 33 (7-8): 3646–8. PMID 11750549. 
  12. Stock PG, Roland ME, Carlson L, Freise CE, Roberts JP, Hirose R, Terrault NA, Frassetto LA, Palefsky JM, Tomlanovich SJ, Ascher NL (2003). "Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study". Transplantation. 76 (2): 370–5. PMID 12883195. doi:10.1097/01.TP.0000075973.73064.A6. 
  13. Neff GW, Bonham A, Tzakis AG, Ragni M, Jayaweera D, Schiff ER, Shakil O, Fung JJ (2003). "Orthotopic liver transplantation in patients with human immunodeficiency virus and end-stage liver disease". Liver Transpl. 9 (3): 239–47. PMID 12619020. doi:10.1053/jlts.2003.50054. 
  • Eghtesad B, Kadry Z, Fung J (2005). "Technical considerations in liver transplantation: what a hepatologist needs to know (and every surgeon should practice)". Liver Transpl. 11 (8): 861–71. PMID 16035067. 
  • Adam R, McMaster P, O'Grady JG, Castaing D, Klempnauer JL, Jamieson N, Neuhaus P, Lerut J, Salizzoni M, Pollard S, Muhlbacher F, Rogiers X, Garcia Valdecasas JC, Berenguer J, Jaeck D, Moreno Gonzalez E (2003). "Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry". Liver Transpl. 9 (12): 1231–43. PMID 14625822. 
  • Reddy S, Zilvetti M, Brockmann J, McLaren A, Friend P (2004). "Liver transplantation from non-heart-beating donors: current status and future prospects". Liver Transpl. 10 (10): 1223–32. PMID 15376341. 
  • Tuttle-Newhall JE, Collins BH, Desai DM, Kuo PC, Heneghan MA (2005). "The current status of living donor liver transplantation". Curr Probl Surg. 42 (3): 144–83. PMID 15859440. 
  • Martinez OM, Rosen HR (2005). "Basic concepts in transplant immunology". Liver Transpl. 11 (4): 370–81. PMID 15776458. 
  • Krahn LE, DiMartini A (2005). "Psychiatric and psychosocial aspects of liver transplantation". Liver Transpl. 11 (10): 1157–68. PMID 16184540. 
  • Nadalin S, Malagò M, et al. Current trends in live liver donation. Transpl. Int. 2007;20:312-30.
  • Vohra V. Liver transplantation in India. Int Anesthesiol Clin. 2006;44:137-49.
  • Strong RW. Living-donor liver transplantation: an overview. J Hepatobiliary Pancreat Surg. 2006;13:370-7.
  • Fan ST. Live donor liver transplantation in adults. Transplantation. 2006;82:723-32.


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de:Lebertransplantationit:Trapianto di fegato he:השתלת כבד nl:Levertransplantatiefi:Maksansiirto



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