Liver transplantation overview

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

Liver trasnsplantation Microchapters
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Patient Information
Overview
Historical Perspective
Indications
Pre-surgical management
Choice of donor
Epidemiology and Demographics
Techniques
Complications
Acute rejection
Immune therapy
Post-surgical infection
Prognosis

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.

Acute rejection

Early acute cellular rejection mostly occurs within 90 days. Risk factors for acute rejection include elevated transplant recipient prothrombin time or bilirubin, donors older than 50 years, donor pre-surgical acidosis, cytomegalovirus infection especially genotype gB1, fewer human leukocyte antigen (HLA)-DR matches, and cold ischemia time greater than 15 hours. Clinical picture include fever, malaise, abdominal pain, and hepatosplenomegaly. elevated serum aminotransferases, alkaline phosphatase, gamma-glutamyl transpeptidase, and bilirubin level.

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.