ReviewRecommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report
Introduction
Although liver transplantation was first done in human beings by Tom Starzl in 1963, the procedure did not begin to gain wide acceptance until the mid-1980s, when effective immunosuppression with ciclosporin became available. Currently, overall 1-year and 5-year survival after liver transplantation exceeds 85% and 70%, respectively, in most centres.1, 2
Hepatocellular carcinoma (HCC) is a major health problem worldwide, which continues to increase because of the association of HCC with hepatitis B and C viruses. HCC was one of the first indications for liver transplantation, because it was postulated that this approach would eliminate the tumour and cure the underlying liver disease. However, it soon became apparent that the success of liver transplantation depends on the tumour load; patients with extensive disease had very poor outcomes, whereas most patients with small tumours could be cured. This led to many controversies around the use of liver transplantation in patients with HCC, such as the selection of patients in the context of worldwide organ shortage, control of the tumour load while patients wait for a graft, use of living donors, and the choice of immunosuppression or adjuvant therapies.
The goal of liver transplantation, regardless of the underlying disease, is providing liver recipients with the maximum benefit possible from the limited resource of deceased and living donor organs, in a fair, ethical, and cost-effective manner. Thus, indications for the procedure and allocation of donor organs are closely scrutinised by all stakeholders in liver transplantation. With the endorsement of most international societies concerned with liver transplantation or HCC, we organised a conference that aimed to reach wide consensus throughout the medical and non-medical population on various aspects of the use of liver transplantation for patients with HCC, based on the best available evidence.
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Methods
An international consensus conference on liver transplantation for HCC was held on Dec 2–4, 2010, in Zurich, Switzerland, under the auspices of ten international societies focused on liver diseases or transplantation, with the aim of establishing a consensus regarding indications for liver transplantation in patients with HCC and to provide internationally accepted statements and guidelines for the conduct of liver transplantation programmes. For this purpose, we developed a novel format based
Assessment of candidates with HCC for liver transplantation
The purpose of cancer staging is to accurately predict prognosis and to link tumour stage with specific therapeutic interventions. The ideal staging system for HCC should take into account tumour stage, liver function, and functional status of the patient. Several staging systems have been developed over the past three decades, although none has gained worldwide acceptance (table 2).26, 27, 28, 29, 30, 31, 32, 33, 34 The Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian
Criteria for listing candidates with HCC in cirrhotic livers for deceased-donor liver transplantation
In the context of shortage of available grafts, decisions have to take into account the collective benefit of all potential liver recipients, in addition to the benefit for the individual patient. Liver transplantation achieves excellent results in patients with limited tumour load. Patients with solitary HCC of less than 5 cm or with up to three nodules of less than 3 cm (the Milan criteria40) have a 5-year survival of 70% after liver transplantation, with recurrence in less than 10%. This
Criteria for HCC candidates with non-cirrhotic livers
Although most HCC occurs in patients with liver cirrhosis, about 10% of cases arise in absence of cirrhosis. In such patients, diagnosis is often made at an advanced stage. Resection is currently the preferred therapeutic option, when feasible, since patients with good liver reserve have high tolerance for extensive liver resection.60 However, as in cirrhotic patients, the risk of local recurrence is high, ranging from 30 to 73%, and affects 5-year overall survival (25–81%) and disease-free
Role of downstaging of HCC
The goal of downstaging using locoregional therapy—eg, alcohol injection, radiofrequency ablation (RFA), transarterial chemoembolisation (TACE), transarterial radioembolisation (TARE), or liver resection—is to decrease the tumour size and number in patients initially presenting with tumours that do not meet locally acceptable criteria for liver transplantation.
Success in downstaging has been reported in many studies, although most of these are uncontrolled observational studies with no method
Managing patients on the waiting list
With increases in waiting times for liver transplantation in many centres, it has become common practice to monitor patients with HCC to ensure that they remain within the acceptability criteria for liver transplantation. Strategies have also been developed to treat patients whose HCC is at risk or shows signs of progression while waiting for a graft. There is no agreement about specific timing or optimum imaging methods to use for these patients, although a 3-month interval is common.
Role of living-donor liver transplantation for HCC
Living-donor liver transplantation (LDLT) using the right or left hemiliver of a healthy donor is the only option for liver transplantation in some countries, particularly in Asia, where there is limited or no availability of deceased-donor organs. LDLT has also been used in other countries with well established programmes for organ donation from brain dead or non-heart-beating donors, because of organ shortage, long waiting times associated with deaths on the waiting list, drop-out due to
Post-transplant management
The main concern after liver transplantation for HCC is the risk of tumour recurrence, which occurs in 8–20% of recipients.81 HCC recurrence is usually seen within the first 2 years after liver transplantation, and is associated with a median survival of less than 1 year (IQR 7–18 months) from the time of diagnosis.82 The adoption of routine imaging and α-fetoprotein monitoring has led to the detection of early recurrence, with a possibility of cure with ablation therapies in up to a third of
Conclusion
The 37 recommendations and statements presented here cover the most controversial topics surrounding liver transplantation for HCC, and may guide transplantation programmes around the world to improve management of their HCC patients. The phrasing of many recommendations permits adjustment according to variations in programme and regional circumstances, among which might be team experience and the availability of donor organs or living donation. Although the conference was not designed to
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