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LIVER TRANSPLANTATION

Patient Selection.

The success of liver transplantation is closely related to the rational selection of patients most likely to benefit from the procedure. Patients should be without additional end-organ failure (other than that clearly related to hepatic insufficiency) and should be candidates for a major operative intervention. In general, dependence on alcohol or other harmful substances should be resolved for at least 6 months. Extrahepatic malignancy, sepsis, and diffuse mesenteric venous thrombosis represent absolute contraindications. Isolated portal vein thrombosis is a relative contraindication. The patient's liver function should be such that complications of dysfunction are emerging, with the predicted life span of the patient managed medically less than 2 years. With the improvements in survival after allotransplantation realized in the past decade, it is also appropriate to consider patients with metabolic diseases or moderately advanced liver disease with significant alterations in quality of life such as extreme fatigue, refractory pruritus, or liver transplantation.

SELECTION OF DONORS

Immediate function of a transplanted liver is imperative. Unlike kidney, pancreas, or, to some extent, heart transplantation, no artificial means is readily available to support an anhepatic patient in the event of graft failure. Without a rapid restoration of synthetic function, death from bleeding or cerebral edema generally ensues within 72 hours. The single most important factor determining the early function of a liver allograft is the viability of the donor liver. Although this seems obvious, determining the state of the

Several factors have been investigated to aid in the prediction of PNF. The most widely noted is the estimated parenchymal fat content. Donor liver biopsy specimens that show a 40% or greater parenchymal replacement by fat have a higher chance of PNF, and in some settings this is a

OPERATION ON THE DONOR

Harvest of the donor organ should be performed by an experienced surgeon, with particular care taken to optimize the preharvest resuscitation of the heart-beating cadaver. Because immediate hepatic

IMMEDIATE PREOPERATIVE MANAGEMENT

Patients awaiting liver transplantation are prioritized on a national waiting list based on severity of disease as defined by the UNOS. Status 4 patients are at home and 

OPERATION ON THE RECIPIENT

Few surgical procedures require the fastidious attention to technical detail required in liver transplantation. Technical errors are translated directly into infectious complications or marginal biliary function. Thus, transplantation should be performed only by surgeons proficient in the procedure. In

Intraoperative management by a knowledgeable anesthesiologist with experience in liver transplantation is critical for a successful technical result. The procedure presents the challenge of maintaining homeostasis of temperature, circulation (including oxygen-carrying capacity and coagulation competence), gluconeogenesis, and electrolyte concentration while establishing adequate anesthesia.

Successful engraftment of the organ begins with a controlled recipient hepatectomy. This can be a formidable task in patients with severe portal hypertension and extensive collateral formation or in those with multiple operative interventions. In general, extirpation follows the basic surgical guidelines of establishing proximal and distal vascular control combined with lysis of all ligamentous attachments. Specific technical concerns include retaining maximal length on all vessels. Mobilization of the common bile duct depends on the planned biliary reconstruction (choledochocholedochostomy versus choledochojejunostomy). Care to avoid injury to the right adrenal vein during caval dissection is important. If venovenous bypass is planned, cannulation of the left axillary, femoral, and portal veins is performed.

Acute Rejection.

As with other allografts, T-cell-mediated destruction of the liver is inevitable without immunosuppressive therapy. The primary targets for T-cell recognition are HLA antigens on the biliary epithelium and vascular endothelium. The characteristics of this rejection, termed acute rejection, are similar to those of kidney or heart in that it develops in most of the cases during the first 6 months after transplantation.

Chronic Rejection.

The development of liver allograft dysfunction over a period of months to years is termed chronic rejection and, like other allografts, is controversial and multifactorial in its etiology, and is usually not reversible. Histologically it appears as a paucity of bile duct epithelium without conspicuous lymphocytic infiltration and has thus been described as the "vanishing bile duct syndrome."

Immunosuppressive Pharmacology.

Manipulation of the immune system is required to avoid graft loss from rejection. Identifying a safe, effective, and minimally immunosuppressive regimen requires a careful balance aimed at reducing infectious and neoplastic complications without a resultant increase in allograft rejection and/or dysfunction. Thus, rational, selective use of several immunosuppressive agents is required to manage successfully the broad array of patients who are transplanted.

OUTCOMES

Clearly, liver transplantation is the most significant advancement in the treatment of end-stage liver disease this century. Diseases treated by OLT are by definition terminal with few exceptions, and as such are lethal without hepatic replacement. Survival of a patient with no other hope for survival.

Medical Perspective.

Despite the recent advances in all aspects of liver transplantation, the procedure remains one with considerable morbidity. Most patients have some complications that deviate from an ideal recovery, and all patients accept the trade of their liver disease for the disease of immunosuppression. These negative outcomes are generally remedied by prompt recognition of problems.

A negative sequel is an adverse effect inherent to the transplant procedure. Transplantation in general carries with it the risk of lifelong immunosuppression.

Failure to cure refers to pre-existing conditions that remain unchanged or recur after the transplant procedure. The likelihood of cure reflects the primary disease.

A complication is any other negative outcome that does not fit clearly into the definition of negative sequel or failure to cure. Complications of some kind occur in almost all patients.

Several common complications, such as acute and chronic rejection, have been discussed. Some complications deserve particular attention because of their seriousness and requirement for prompt intervention. PNF presents as a complete lack of synthetic function from the time of reperfusion.

Hepatic artery thrombosis remains a complication, especially in the pediatric population. This presents as a rapid rise in serum transaminase levels. The transplanted liver does not tolerate loss.

EMERGING TECHNIQUES

Living-Related Transplantation.

Arising from the success of reduced-size grafting, living-related transplantation has been initiated at selected centers. This involves a reduced-size graft usually derived from a donor left lobe (segments 2 and 3 or 2, 3, and 4). Technically, this has been quite successful and has the benefits.