Fourth Forum on Liver Transplantation Hepatocellular carcinoma: where are the controversies?☆
Article Outline
Hepatocellular carcinoma (HCC) currently constitutes more than 10% of the indications for orthotopic liver transplantation (OLT) according to the USA (UNOS) and European (ELTR) registries; this figure may reach 30% in areas endemic with hepatitis B or C, which are often associated with this tumor. The accepted, or so called standard, criteria for eligibility for OLT in most centers worldwide rely on a study published a decade ago from the group in Milan, Italy, i.e.; one tumor of 5
cm or less in diameter in patients with a single tumor, and no more than three tumor nodules, each 3cm or less in diameter, in patients with multiple tumors [1]. However, many questions have remained open such as whether these criteria are still adequate, and particularly whether we may accept less stringent criteria, when a living donor is available? Should we biopsy each lesion suspicious of HCC prior to OLT? Should the immunosuppression be tailored to this population of patients to minimize the risk of recurrence, and how should recurrent HCC be treated? These controversies have persisted due to the shortcomings in reporting series of HCC, such as the lack of standardized staging system for HCC enabling convincing comparisons among various studies [2]. It is paramount to address the issues raised in this forum as only patients with HCC who benefit from OLT should be listed on waiting lists using a formula that somewhat arbitrarily gives them a higher priority that the severity of disease would allow [3].
We included six articles in this fourth Forum on Liver Transplantation. The first controversy in HCC is whether a biopsy is necessary prior to transplantation. Wallis Marsh and Igor Dvorchik recommend routine biopsy mostly to secure the diagnosis and thereby offer appropriate listing and timing for liver transplantation. In contrast, Stigliano and Burroughs argue against biopsy as this rarely changes the indication of transplantation, provides a false negative result in 10% of the cases, and yields a 2% risk of seeding. The previous Forum on Liver Transplantation focused on living donor liver transplantation (LDLT), and it was suggested that one of the most cost effective indications for living donation is HCC [4]. Here, we triggered a debate about whether or not criteria for transplanting patients with HCC using living donors should be expanded beyond the ‘Milan’ criteria. Chris Broelsch, Andrea Frilling and Massimo Malago provide arguments in favor mostly because the ‘Milan criteria’ miss a number of patients who may benefit from OLT, while Jonathan Hiatt, Ian Carmody and Ron Busuttil argue against any variation in criteria due the current lack of convincing data enabling worthwhile changes, and ethical issues related to living donation for marginal indications. Another open question relates the optimal immunosuppressive regimen for this population of patients. Until the ultimate goal of selective tolerance toward the graft is reached, obviating the need for any immunosuppressive agent, Drs Pietro Majno, Emiliano Giostra and Gilles Mentha provide a well balanced discussion concluding that the best strategy should probably mostly focus on an attempt to lower immunosuppression as much as feasible. While sirolimus or everolimus interfere at a variety of steps in cancer formation and thereby yields promises, further data is still necessary before recommending the routine use of these drugs in patients with HCC. However, in the meantime, many centers are already using these drugs in the presence of adverse tumor characteristics (e.g. vascular invasion) or recurrent disease after OLT. Finally, Myron Schwartz, Susan Roayaie, and Josep Llovet address the difficult issue of managing patients with recurrent HCC after OLT. They argue for an aggressive approach similar to the non-transplant population including resection, when feasible. Retransplant is however not an option. Unfortunately, apart from chemo-embolization, ablation therapy, and resection in very selective patients, no strategies have been shown to control or minimize the disease prior to transplantation. Majno et al. recently reviewed this topic in a supplement of the Journal of Hepatology [5].
While these debates may fail to give a definitive answer, they represent a valuable tool to enable our own judgment in controversial areas, where evidence based data is absent.
References
- Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–699
- . Critical evaluation of the different staging systems for hepatocellular carcinoma. Brit J Surg. 2004;91:400–408
- . MELD: the holy grail of organ allocation? first forum on liver transplantation. J Hepatol. 2005;42:16–20
- . Is living donor liver transplantation cost-effective? Third forum on liver transplantation. J Hep. 2005;43:27–32
- . Management of hepatocellular carcinoma in the waiting list before liver transplantation. J Hepatol. 2005;42(Suppl. 1):S134–S143
☆ In January 2006 the Journal of Hepatology will publish the Concise Statement of the Monothematic Conference on Hepatocellular Carcinoma and Molecular Profiling of Clinical Management by EASL, AASLD and the JSH which was held in Barcelona, June 10–12, 2005.
PII: S0168-8278(05)00503-9
doi:10.1016/j.jhep.2005.07.013
© 2005 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
