Liver transplantation

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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

PRETRANSPLANTATION EVALUATION — Pretranplant evaluation has the following objectives: Assesment of ability of the patient to withstand surgery Assesment of ability of the patient to withstand immunosuppression Assesment of demands of post-transplantation care The following evaluations are required: Cardiopulmonary Screening for occult infection Screening for occult cancer Psychosocial evaluation

Laboratory testing — Laboratory essential for patient evaluation prior to liver transplantation are as follows: ●ABO-Rh blood typing ●Liver function tests: alanine aminotransferase aspartate aminotransferase alkaline phosphatase bilirubin international normalized ratio [INR]). ●Complete blood count with differential. ●Creatinine clearance. ●Serum sodium. ●Serum alpha-fetoprotein. ●Calcium and vitamin D levels. ●Serologies for: cytomegalovirus, Epstein-Barr virus, varicella, human immunodeficiency virus, hepatitis A, hepatitis B, hepatitis C, rapid plasma reagin. ●Urinalysis. ●Urine drug screen. Cardiopulmonary evaluation — The cardiopulmonary evaluation is designed to evaluate for: significant coronary artery disease, valvular heart disease, cardiomyopathy obstructive or restrictive lung disease hepatopulmonary syndrome, and pulmonary hypertension noninvasive cardiac testing for all patients over 40 years of age and for those younger than forty if there are multiple risk factors for coronary artery disease. pulse oximetry arterial blood gas pulmonary function testing chest imaging Electrocardiogram — We obtain an electrocardiogram to look for signs of cardiac arrhythmias, conduction defects, signs of prior cardiac ischemia, or chamber enlargement/hypertrophy. Cardiac stress testing — To screen for coronary artery disease, we obtain noninvasive cardiac testing for all patients over 40 years of age and for those younger than 40 years if there are multiple risk factors for coronary artery disease. However, the ideal evaluation of coronary artery disease prior to liver transplantation is unclear: submaximal cardiopulmonary exercise testing. If initial noninvasive testing is abnormal, cardiac catheterization is indicated. If clinically significant coronary artery stenoses are present, patients should be evaluated for revascularization prior to transplantation Echocardiography — We obtain transthoracic contrast-enhanced echocardiography to look for evidence of valvular heart disease or portopulmonary hypertension. Contrast-enhanced echocardiography is also part of the evaluation of patients with suspected hepatopulmonary syndrome. Portopulmonary hypertension refers to pulmonary arterial hypertension that is associated with portal hypertension. Symptoms and signs of pulmonary hypertension (PH) may be difficult to recognize because they are nonspecific. Initially, patients present with fatigue, exertional dyspnea and a loud pulmonic component of the second heart sound. If the echocardiography suggests PH, additional testing is required to confirm the diagnosis and to rule out other causes of PH. Pulse oximetry — Patients should undergo pulse oximetry to screen for hepatopulmonary syndrome. Hepatopulmonary syndrome is considered present when the following triad exists: ●Liver disease ●Impaired oxygenation ●Intrapulmonary vascular abnormalities, referred to as intrapulmonary vascular dilatations The presence of hepatopulmonary syndrome worsens the prognosis of patients with cirrhosis. As a result, patients with hepatopulmonary syndrome receive standard Model for End-stage Liver Disease (MELD) exception points. If the oxygen saturation on pulse oximetry is low (<96 percent [38]), patients should have a blood gas obtained while breathing room air and undergo transthoracic contrast-enhanced echocardiography. Testing should also be obtained to rule out alternative causes for a low oxygen saturation. Testing to rule out other causes includes a chest radiograph, pulmonary function tests, and chest computed tomography (CT). We also perform an arterial blood gas in patients with normal pulse oximetry to calculate their age-adjusted alveolar-arterial gradient. Additional testing for pulmonary disease — We obtain pulmonary function testing with diffusing capacity of the lungs for carbon monoxide to look for evidence of restrictive or obstructive lung disease in patients who are able to undergo testing. We also obtain a chest radiograph and chest CT scan to look for signs of pulmonary disease. Cancer screening — Cancer screening should include abdominal CT scanning or magnetic resonance imaging (MRI) to look for hepatocellular carcinoma (HCC) and a skin examination to look for evidence of skin cancer. Patients over the age of 50 years (younger if there is a history of colon cancer in a first-degree relative) or who have primary sclerosing cholangitis should undergo colonoscopy. Screening for cervical cancer, breast cancer, and prostate cancer should be obtained when indicated based on the patient's sex and age. Infectious disease evaluation and vaccinations — In addition to obtaining serologies for several viral infections, the infectious disease evaluation should include skin testing or interferon-gamma release assay for tuberculosis. If positive, treatment may be initiated prior to transplantation or deferred until after transplantation, depending on the clinical assessment of the patient (eg, treatment should be initiated prior to transplantation if the patient has any signs or symptoms of tuberculosis). Similarly, any required dental extractions should be carried out prior to transplantation. Patients from endemic areas should be screened for coccidiomycosis or strongyloides Several vaccinations are recommended prior to liver transplantation including hepatitis A, hepatitis B, pneumococcus, influenza, diphtheria, pertussis, and tetanus. Immunizations in solid organ transplantation candidates are discussed in detail elsewhere. Hepatic imaging and HCC staging — Hepatic imaging should be obtained to assess the vasculature (to ensure there are no anatomic barriers to transplantation) and, in the case of HCC, for tumor staging. This is typically done with multiphase contrast-enhanced CT scanning or contrast-enhanced MRI. If cross-sectional imaging cannot be obtained, the hepatic vasculature can be assessed with transabdominal ultrasonography with Doppler imaging or contrast-enhanced ultrasonography (where available).

Upper endoscopy — Upper endoscopy should be performed in patients with cirrhosis or portal hypertension to evaluate for varices

Bone density testing — Patients should be screened for osteoporosis with bone density testing. If osteoporosis is present, treatment should be initiated prior to transplantation. Oral bisphosphonates should be used with caution in patients with esophageal varices, and patients should be aware of the importance of taking the drugs as instructed (eg, sitting upright for at least 30 minutes after taking the drug). Patients who are osteopenic should receive calcium and vitamin D supplementation.

Psychosocial evaluation and education — In addition to a standard medical evaluation, initial assessment should include an educational session discussing the risks and benefits of transplantation, including the potential for poor outcomes. A psychological evaluation and assessment of the patient's social supports is another key part of the evaluation. The purpose of this assessment is to identify issues that may impair a successful outcome after transplantation. These potential problems include a lack of insight into the nature of the transplantation procedure, post-transplantation care, and substance use disorders. The assessment includes education of the family and/or the patient's support network. The ability to comply with complex medical and behavioral regimens is crucial after any organ transplantation procedure. Recipients must be able to incorporate complicated medication regimens, follow-up appointments, and frequent laboratory visits into their lives. Making spouses, friends, and family aware of these requirements encourages patient compliance and may improve long-term success In patients with a history of a substance use disorder (drugs or alcohol), treatment should be provided prior to transplantation in an effort to increase the likelihood of success after transplantation. The treatment requirements vary among different transplantation centers but often include participation in a structured rehabilitation and abstinence program, adequate social support to help maintain sobriety, and a minimum period of sobriety prior to listing for transplantation (eg, six months).


Orthotopic Liver Transplantation

Immunosuppressive management


  • Prognosis is quite good:
    • 1-year survival is 83%
    • 5-year survival is 76%
    • 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:[27][19][28]
  • The concept of LDLT is based on:
    • Remarkable regenerative capacities of the human liver
    • 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 was used as a means for parents of children with severe liver disease to donate a portion of their healthy liver to replace the damaged liver of their children.
  • In 1986, the first successful LDLT was performed at the Universidade de São Paulo (USP) Medical School, by Dr. Silvano Raia.
  • More technically demanding than standard, cadaveric donor liver transplantation
  • Has faced several ethical problems[29]

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:[30][30]

Chronic graft rejection:


  • After the first 6 months, risk of infection in transplant patients is equal to that of the population.

Cytomegalovirus (CMV)

  • Most common viral infection (affects 25-85% patients)
  • Occurrence: Between posttransplant months 1 and 3
  • Infection may be:
    • Primary
    • Reactivated

Pneumocystis carinii pneumonia (PCP)

Other less common organisms causing infection include:

External Links


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bg:Чернодробна трансплантация de:Lebertransplantation it:Trapianto di fegato he:השתלת כבד nl:Levertransplantatie fi:Maksansiirto