Liver transplantation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]


Overview

When a healthy liver allograft is used in place of damaged liver tissue, it is termed as liver transplantation. Thomas Starzl used dogs as the first animals for research on liver transplantation in the 1960s. In 1963, the first liver transplant in humans was attempted by Dr. Thomas Starzl of Colorado, United States. The most common indications for liver transplantation in the United States are hepatitis C virus, alcoholic liver disease, autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, hepatitis B virus, liver disease due to inborn errors of metabolism, cancer, biliary atresia and acute liver failure. On the other hand, absolute contraindications to liver transplantation include hepatocellular carcinoma with metastasis, acute liver failure with persistently elevated intracranial pressure ICP >50mmHg, hemangiosarcoma, hilar cholangiocarcinoma, sepsis, and active alcohol or drug abuse. Pretransplant measures such as cardiopulmonary evaluation, screening for occult cancer, infection, and psychosocial evaluation must be performed prior to surgery. The most commonly used technique employed in patients is orthotopic transplantation. This involves removal of the native liver and placement of the donor organ in the same anatomic location as the original liver. Immunosuppressive agents used after transplantation include cyclosporine, everolimus, mycophenolate, corticosteroids, azathioprine, and tacrolimus in different combinations. The most common causes of death in liver transplant patients are infection, malignancy, and rejection. It is necessary to monitor patients for signs of complications and treat them effectively.

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 of Denver, Colorado, United States.[1]
  • Dr. Starzl performed many additional transplants until he was successful 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]
  • 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.

Indications

Liver transplantation is applicable to any acute or chronic condition resulting in irreversible liver dysfunction, provided that the recipient does not have other conditions that will preclude a successful transplant. Most liver transplants are performed for chronic liver diseases that lead to irreversible scarring of the liver, or cirrhosis.

Contraindications

Absolute contraindications for liver transplantation include:[3]

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

Patient evaluation prior to transplantation

Pre-transplant patient evaluation has the following objectives:

Pre-transplant evaluation is particularly aggressive in patients prior to transplantation to minimize post operative morbidity and mortality due to effects of surgery and immunosuppressive therapy.The following evaluations are required:

Laboratory investigations

Laboratory investigations essential for patient evaluation prior to liver transplantation are as follows:

General investigations

Cause specific investigations

Cardiopulmonary evaluation

Cardiopulmonary evaluation helps in the evaluation of the patient for pathologies that need to be ruled out prior to transplantation:[3][14]

Cancer screening

Prior to transplantation, screening for the following carcinomas is recommended:

Upper GI endoscopy

Bone densitometry

Vaccinations and evaluation for infection

Psychosocial evaluation and education

Techniques

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Orthotopic Liver Transplantation

Immunosuppressive management

Results

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:[29][42][43]
  • 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 diseased liver of the recipient 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[44]

Complications of Liver Transplantation

    • Laboratory investigations

Imaging studies

Acute and chronic graft rejection

Acute graft rejection:[45]

Chronic graft rejection:

Infection

Infections may be classified based on the duration post transplantation.

  • 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


References

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