Difference between revisions of "Liver transplantation"

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* Before transplantation liver support therapy might be indicated (bridging-to-transplantation).   
* Before [[Organ transplant|transplantation]] [[liver]] support therapy might be indicated (bridging-to-[[Organ transplant|transplantation]]).   
* Artificial liver support like [[liver dialysis]] or bioartificial liver support concepts are currently under preclinical and clinical evaluation.   
* 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.   
* 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 [[Organ transplant|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 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.   
* 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).   
* Usually, the retrohepatic portion of the [[inferior vena cava]] is removed along with the [[liver]], although an alternative technique preserves the recipient's [[Vena cavae|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  [[Histidine-tryptophan-ketoglutarate|HTK]] until the allograft liver is implanted.   
* The donor's [[blood]] in the [[liver]] will be replaced by an ice-cold organ storage solution, such as UW ([[Viaspan]]) or  [[Histidine-tryptophan-ketoglutarate|HTK]] until the [[allograft]] [[liver]] is implanted.   
* Implantation involves anastomoses (connections) of the inferior vena cava, portal vein, and hepatic artery.   
* Implantation involves [[Anastomosis|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.   
* After [[blood]] flow is restored to the new [[liver]], the [[Bile duct|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 [[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.   
* The large majority of liver transplants use the entire liver from a non-living donor for the [[Organ transplant|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.   
* A major advance in [[Pediatrics|pediatric]] 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.   
* 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).
* Living [[Blood donation|donor]] liver transplantation for [[Pediatrics|pediatric]] recipients involves removal of approximately 20% of the [[liver]] ([[Couinaud]] segments 2 and 3).
===Orthotopic Liver Transplantation===
===Orthotopic Liver Transplantation===

Revision as of 13:34, 15 January 2018

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


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


  • 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.
  • In December 2016, 147,128 liver transplants were performed in the US as compared to 7217 in 1998 based on data from the United Organ Sharing (UNOS) network.



Absolute contraindications: [3]

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

Pretransplant evaluation


Orthotopic Liver Transplantation

Immunosuppressive management


  • 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

  • Immediate postoperative complications of liver transplantation include:
  • The most common causes of death in liver transplant patients are as follows:
  • To monitor the patient for complications, the following investigations are used:

Laboratory investigations

Imaging studies

Acute and chronic graft rejection

Acute graft rejection:[19]

  • Occurrence: roughly 20-70 percent patients
  • Timing: 1-2 weeks post- transplantation
  • Outcome: Graft dysfunction
  • Clinical presentation:
    • Jaundice
    • Fever
    • Liver tenderness
    • Eosinophilia
  • Laboratory evidence:
    • Abnormal liver function tests
    • Elevated Bilirubin
    • Elevated alkaline phosphatase levels
    • Elevation of hepatocellular enzymes:
      • Alanine aminotransferase (ALT)
      • Aspartate aminotransferase (AST)
  • Treatment of acute rejection:
    • High-dose steroids:
      • Prednisolone 200 mg
      • Methylprednisolone 1 g for 3 days)
      • High-dose steroid bolus followed by a rapid taper over 1 week
  • Alternative therapies include:
    • Antibody treatments:
      • Monoclonal therapy (OKT3 )
      • Antithymocyte globulin

Chronic graft rejection:

  • Occurence: 5% of patients
  • Main cause of late stage graft failure
  • Features of chronic graft rejection include:
    • Gradual obliteration of small bile ducts
    • Microvascular changes
  • Symptoms:
    • Jaundice
    • Pruritu
  • Laboratory investigations:
    • Elevated serum alkaline phosphatase
    • Elevated bilirubin levels
  • Gold standard diagnostic modality: Liver biopsy


  • <1 month : Common conditions developing in patients in the early posttransplant period include intra-abdominal infections such as:
    • Cholangitis
    • Liver abcess
    • Abdominal abcess
  • 1-6 months: Infections commonly occur due to:
    • Viruses
    • Opportunistic organisms
  • After the first 6 months, risk of infection in transplant patients is equal to that of the population.
  • Infection is primarily nosocomial. Common organisms responsible for causing infection post-transplant are as follows:
    • Bacterial (most common):
      • Enterococci
      • Staphylococci
      • Gram-negative aerobes
      • Anaerobes
    • Fungal: Candida (75% of fungal infections)
    • Presenting symptoms:
      • Fever
      • Abdominal pain
      • Jaundice
  • Laboratory investigations:
    • Complete blood count (CBC)
    • Serum chemistries
    • Liver function tests
    • Coagulation panel
    • Urinalysis
    • Urine culture
    • Blood culture
  • Imaging:
    • Abdominal radiographs
    • Chest radiographs
    • Computed tomography (CT)
    • Abdominal ultrasonography
    • T-tube cholangiography
    • Endoscopic retrogrande cholangiopancreatography (ERCP) Liver biopsy
  • Treatment of infection:
    • Antimicrobials prescribed for nonimmunosuppressed patients

Cytomegalovirus (CMV)

  • Most common viral infection (affects 25-85% patients)
  • Occurrence: Between posttransplant months 1 and 3
  • Infection may be:
    • Primary
    • Reactivated
  • Clinical presentation:
    • Fevers
    • Malaise
    • Arthralgias
  • Laboratory investigations:
    • Atypical lymphocytes
    • Thrombocytopenia
    • Mildly elevated transaminase levels
  • Imaging findings:
    • CXR: CMV pneumonitis patients may have bilateral infiltrates on CXR
  • Serology:Indirect immunofluorescence testing method
  • Treatment: Ganciclovir intravenously for 2-4 weeks

Pneumocystis carinii pneumonia (PCP)

  • May occur along with CMV infection or alone
  • Diagnosis:Bronchoalveolar biopsy
  • Treatment: Trimethoprim-sulfamethoxazole

Other less common organisms causing infection include:

  • Fungi (especially Candida species)
  • Herpes simplex
  • Herpes zoster
  • Toxoplasma
  • Hepatitis C virus (HCV)
  • Hepatitis B infection
  • Malignancy:
    • In transplant patients, malignancy is the second leading cause of late mortality.
    • Common malignancies occuring patients after transplantation include:
      • Lymphomas
      • Squamous cell carcinoma : SCC of skin is the most common malignancy that occurs pos-tranplantation
      • Posttransplant lymphoproliferative disorder

External Links


  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. doi:10.1111/j.1365-2036.2005.02321.x. PMID 15679767.
  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. doi:10.1056/NEJMoa1105703. PMID 22070476.
  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. doi:10.1097/QAD.0b013e328344febb. PMID 21412058.
  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. doi:10.1097/TP.0b013e3181605fda. PMID 18301332.
  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. doi:10.1002/lt.23411. PMC 3358510. PMID 22328294.
  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. doi:10.1002/lt.21181. PMID 17902123.
  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.
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  17. Perry I, Neuberger J (2005). "Immunosuppression: towards a logical approach in liver transplantation". Clin. Exp. Immunol. 139 (1): 2–10. doi:10.1111/j.1365-2249.2005.02662.x. PMC 1809260. PMID 15606606.
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bg:Чернодробна трансплантация de:Lebertransplantation it:Trapianto di fegato he:השתלת כבד nl:Levertransplantatie fi:Maksansiirto