Liver transplantation overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
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Liver trasnsplantation Microchapters |
Overview
Historical perspectives
In 1952, Vittorio Staudacher was the first to perform a liver transplantation (LT) in a canine species. In 1968, Roy Calne and Roger Williams reported 5 cases of liver transplant, discussing the technical problems by details. In 1984, Bismuth reported the first left-lobe LT in a child. Now, there are hundreds of liver transplant centres in over 80 countries.
Liver transplantation indications
Indications for liver transplantation include acute liver failure, cirrhosis, Liver neoplasms, and metabolic disorders such as Familial amyloid polyneuropathy, Primary hyperoxaluria, Cystic fibrosis, alpha-1 antitrypsin deficiency, glycogen storage disease, tyrosinemia, hemochromatosis, Wilson disease, and Acute intermittent porphyria.
Pre-surgical management
Pre-surgical management for liver transplantation includes laboratory testings such as ABO-Rh blood typing, Liver biochemical and function tests (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, international normalized ratio, complete blood count, creatinine clearance,serum sodium, serum alpha-fetoprotein, and calcium and vitamin D levels. Cardiological testings include electrocardiogram, cardiac stress testing, echocardiography , pulse oximetry and ABG.
Immune therapy
Acute rejection after liver transplantation depends on antigen recognition by antigen-presenting cell. This stimulates T-cell receptors CD28, CD154, CD2, CD11a, and CD54. This causes maturation of T-cells. Blockage of this pathway by drugs can stop rejection reaction. Glucocorticoids upregulate interleukin-10 expression (inhibitory), and downregulate IL-2, IL-6, and interferon-gamma (stimulatory) synthesis by T cells. Glucocorticoids are the first line of initial therapy and treatment of acute rejection. Cyclosporine inhibits T-cell activation by binding intracellular cyclophilin and reducing calcineurinactivation. That leads to diminish interleukin-2 production markedly and decreased T-cell response. Tacrolimus inhibits IL-2 and interferon-gamma production. Tacrolimus is 100 times more potent than cyclosporine. Sirolimus binds to FK-binding protein but does not inhibit calcineurin. Sirolimus blocks the transduction signal from the IL-2 receptor, thus inhibiting T-cell and B-cell proliferation. Sirolimusdoesn't cause nephrotoxicity and neurotoxicity. Everolimus is the hydroxyethyl derivative of sirolimus. The mechanism of action of everolimus is similar to sirolimus by inhibition of mammalian target of rapamycin (mTOR). Muromonab is a monoclonal antibody directed against the CD3-antigen complex on mature T cells. Basiliximab and daclizumab are monoclonal antibodies against the IL-2 receptor. Blockade of the IL-2 receptor prevents T-cell proliferation. Azathioprine is a prodrug of 6-mercaptopurine. Azathioprine inhibits the de novo synthesis of purines and interferes with RNA and DNA synthesis, azathioprine inhibits the replication of T cells and B cells.
Prognosis
Prognosis is good. One-year survival rates are 83%, 5-year survival is 76% and 10-year survival is 66%. Mortality rates in donors are 0.2% in the USA and vary from 0.1 to 1.0% worldwide. The risk associated with left-lobe donation may be lower than that with right-lobe donation. Recurrence varies according to the cause; hepatitis B virus is the commonest cause of recurrence followed by hepatitis C virus. Recurrence of HBV after liver transplantation can be prevented by administering hepatitis B immune globulin at the time of transplantation. There is no established role for prophylactic or therapy following transplantation in HCV. Combination therapy for HCV may be peginterferon or standard interferon and ribavirin, monotherapy may be peginterferon, standard interferon, or ribavirin, and anti-HCV immune globulin.