الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
With ever-increasing demand for liver replacement, supply of organs is the limiting factor and a significant number of patients die while waiting. Living donor liver transplantation has emerged as an important option for many patients, particularly small pediatric patients and those adults that are disadvantaged by the current deceased donor allocation system.
Ideally there would be no need to subject perfectly healthy people in the prime of their lives to a potentially life-threatening operation to procure transplantable organs. Donor safety is imperative and cannot be compromised regardless of the implication for the intended recipient.
The evolution of split liver transplantation is the basis upon which live donor transplantation has become possible. The live donor procedures are considerably more complex than whole organ deceased donor transplantation and there are unique considerations involved in the assessment of any specific recipient and donor.
National standards for the selection of recipients (and donors) for LDLT have recently been published by several regulatory bodies. In general, to be considered ‘‘medically eligible’’ for LDLT, the patient must have an urgent need for an expedited transplantation. The MELD score is currently the basis by which patients are prioritized for transplantation. The higher the MELD score, the higher the 90-day mortality and the higher the priority for transplantation.
Although there are no standard recommendations for following recipients of living donor liver transplantation after hospital discharge, most large centers continue to follow the patients on an annual basis for life. Clearly, recipients should be seen frequently during the immediate-postoperative discharge period and then with less frequency over the following months and years. Liver function tests should be monitored at least until they normalize.
The spectrum of complications after LDLT is similar to deceased donor liver transplantation. However, some problems are more frequent in the LDLT recipients. The most common problem specific to the recipient of a LDLT is biliary complications, i.e. bile leak and biliary stricture, which are two- to three-fold more common compared with DD transplantation. Bile leak after surgery is common because thousands of biliary radicles are transected and exposed on the cut surface of the right hepatic lobe. Most studies reported that the postoperative biliary leaks are often self-limited and do not require interventions. Moreover, as surgical technique continues to improve, so should the rate of complications with LDLT.
The current range of available immunosuppressive agents allows some flexibility to tailor the regimen for the individual patient. At the same time, rejection and significant adverse effects continue to complicate the posttransplant period for many patients. Future work will include different combinations as well as development of new agents. Efforts will also focus on improving the balance of maximizing immunosuppression while minimizing adverse effects.
Although acute rejection occurs in approximately 30% of recipients of LDLT, the incidence of graft loss due to rejection has decreased significantly. The dramatic improvement in graft and recipient survival coincides with the introduction of calcineurin inhibitor-based immunosuppression protocols. Cyclosporine, tacrolimus, and the recently introduced sirolimus are the primary agents on which current protocols are based. The advantages of tacrolimus include the ability to wean posttransplant immunosuppression to a single agent as well to prevent and treat chronic rejection. Sirolimus is a renal sparing agent that also may prove efficacious in the treatment of chronic rejection.
The successful treatment of rejection demands a high index of suspicion, early evaluation with biopsy, and an aggressive, thorough course of treatment. Adopting these practices will continue to yield improvements in allograft function and, ultimately, increases in patient survival.
Vascular complications after LDLT represent an important source of morbidity and mortality. Prevention continues to be based on meticulous surgical technique. Early diagnosis is critical to graft salvage, and surgical intervention is the mainstay of management in the early postoperative period. However, in the late postoperative period, nonsurgical percutaneous interventions can maintain organ viability and extend patient survival.
HCV continues to be a major challenge in liver transplantation. Reinfection is common after transplantation, and progression of the disease leads to a dismal outcome. Pretransplant antiviral therapy with at least on-treatment virologic response at the time of transplantation would be desirable, but the tolerability and risk of therapy limits the applicability to patients with compensated or mildly decompensated liver disease (low MELD score). Preemptive treatment is also limited by frequent complications in the early post-transplant phase and a high rate of side effects. The use of combined peg-IFN and RBV therapy has increased the rate of viral clearance, but its intolerability in the majority of patients prevents its general application. The overall risk and benefit of the current strategy over the long term remains to be evaluated.
Prevention of Recurrence of HBV infection after LDLT plays a key role in the post-transplant outcomes of the patient and graft. In the setting of pretransplantation, LAM has been proposed to be downgraded from first- to second-line therapy because of its resistance profile. In contrast, ADV has been approved not only as first-line therapy, but also as rescue therapy for patients with LAM resistance. Furthermore, combination of ADV and LAM may result in lower risk of ADV resistance than ADV monotherapy. Other new drugs such as entecavir, telbivudine and tenofovir, are probably candidates for the treatment of HBsAg-positive patients awaiting liver transplantation, but long-term studies are needed to evaluate the safety and resistance of these new antiviral drugs.
In the post-transplantation setting, low-dose IM HBIG, in combination with LAM, is regarded as the most cost-effective regimen for the prevention of HBV recurrence in recipients without pretransplant LAM resistance, and is rapidly being accepted in many transplant centers. With the introduction of new antiviral drugs, new hepatitis B vaccine and its new adjuvants, post-transplant HBIG-free therapeutic regimens are promising, particularly in those patients with low risk of HBV recurrence.
Infectious complications remain important preventable causes of morbidity and mortality among recipients of LDLT. The vast majority of infections that occur during the immediate period after liver transplantation are often related either to surgical procedures, medical devices, or the need for prolonged hospitalization. During the highly intense period of immunosuppression, the most common opportunistic infections are cytomegalovirus and invasive fungal infections (candidiasis and less commonly aspergillosis). It is therefore essential to have in place an effective approach to prevention, based on predicted infection risk, local antimicrobial resistance patterns, and surveillance of specific risk factors. A better understanding of the common and important infectious complications is anticipated to improve quality of life and survival rate after liver transplantation.