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EASL Clinical Practice Guidelines Liver Transplantation [2015]

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EASL Clinical Practice Guidelines: Liver transplantation q European Association for the Study of the Liver ⇑ Introduction The first human orthotopic liver transplantation (LT) in Europe was performed by Sir Roy Calne in Cambridge in 1968  [1] , only one year after the first successful human liver transplantation reported by Thomas Starzl in the United States  [2]. Since then LT has evolved rapidly, becoming the standard therapy for acute and chronic liver failure of all aetiologies, with more than 80,000 procedures performed to date. Survival rates have improved sig- nificantly in the last 25 years, achieving rates of 96% and 71% at 1 and 10 years after LT respectively  [3] . This great success is mostly attributable to several advances such as the introduction of new immunosuppressive agents and prese rvati on solu tions , to the impro veme nts in surgi cal techniques and to the early diagnosis and management of com- plications after LT [4] . As a consequence of these achievements, indications for LT have been expanded resulting in a growing demand for transplantable grafts and in a dramatic organ short- age. Therefore, one of the main ongoing challenges the transplant community is facing is to expand the donor pool in order to min- imize the rate of patient death on the waiting list  [5]. On the other hand, liver transplanted patients are surviving longer after the operation and long-term outcomes are becoming the main concern for clinicians, who have to deal with direct and indirect side effects of immunosuppressive therapy. This Clinical Practice Guideline (CPG) has been developed to assist physicians and other healthcare providers during the eval- uation process of candidates for LT and to help them in the cor- rect management of patients after LT. The evidence and recommendations in these guidelines have been graded acc ording to the Grading of Rec ommendations Asse ssme nt Deve lopme nt and Evalu ation (GRADE) syst em  [6]. The strength of recommendations reflects the quality of underly- ing evidence . The principl es of the GRADE system have been enunciated. The GRADE system offers two grades of recommen- dation: strong (1) or weak (2) (Table 1). The CPGs thus consider the quality of evidence: the higher the quality of evidence, the more likely a strong recommendation is warranted; the greater the variability in values and preferences, or the greater the uncer- tainty, the more likely a weaker recommendation is warranted.  The candidate to liver transplantation Indications to liver transplantation LT should be considered in any patient with end-stage liver dis- ease, in whom the LT would extend life expectancy beyond what the natural history of underlying liver disease would predict or in whom LT is likely to improve the quality of life (QoL). Patients should be selected if expected survival in the absence of trans- plantation is one year or less, or if the patient had an unaccept- able QoL because of liver disease. A detailed medical evaluation is performed to ensure the feasibility of LT. LT is indicated in patients with end-stage liver disease, in patie nts with the devel opme nt of hepat ocell ular carci noma (HCC) and in patients with acute liver failure. The most common indication to LT for end-stage liver disease in adults is cirrhosis. Patie nts should be referred to trans plan t centres when major complications of cirrhosis, such as variceal haemorrhage, ascites, hepatorenal syndrome and encephalopathy occur. Conversely, acute liver failure represents an urgent indication to LT  [7]. Viruses (especially hepatitis viruses A and B), drugs (acetaminophen), and toxic agents are the most common causes of acute liver failure, with the proportions varying between coun- tries. Seronegative hepatitis is also an important cause of LT for acute liver failure, being the most common indication for LT in acute liver failure in the UK  [8].  Prognosis is essentially deter- mined by neurological status, but is also rapidly affected by dam- age to other organs. LT has revolutionized the prognosis of acute liver failure, causing survival to increase from 10–20% (all causes combined) to 75–80% at 1 year and 70% at 5 years. Indications for LT in Europe are summarized in  Fig. 1. In recent years, an extension of indications has been observed, but in contra st, the trans plan t community is curre ntly facing organ short ages. Act ual ly, limited organ ava ila bility and an increasing demand for organ transplantation has extended trans- plant waiting times and thus increased morbidity and mortality for potential recipients on these waiting lists. This has led to increased pressure on organ allocation programs. Since a success- ful outcome requires optimal patient selection and timing, the issue of which patients to list for LT and when to transplant cir- rhotic patients has generated great interest as well as consider- able controversy.  Journal of Hepatology 2015 vol. xxx  j xxx–xxx Received 8 October 2015; accepted 8 October 2015 q Contributors. Coordinator:  Patrizia Burra;  Panel members:  Andrew Burroughs y , Ivo Graz iadei , Jacq ues Piren ne, Juan Carlos Valde casas, Paol o Muie san, Didier Samuel, Xavier Forns. y Andrew Burroughs passed away during the preparation of this chapter. We would like to acknowledge Giacomo Germani and Emmanuel Tsochatzis, who contributed to its completion. ⇑ Correspondence: EASL Office, 7 Rue Daubin, CH 1203 Geneva, Switzerland. E-mail address:  easloffice@ea sloffice.eu. Clinical Practice Guidelines Please cite this article in press as: EASL Clinical Practice Guidelines: Liver transplantation .J Hepatol (2015),  http://dx.doi.or g/10.1016/j.jhep.201 5.10.006
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