Recurrent hepatocellular carcinoma after liver transplantation - an emerging clinical challenge

Abstract

Summary In western countries, hepatocellular carcinoma (HCC) is a major reason for orthotopic liver transplantation (OLT) with estimated recurrence rates between 15% and 20%. This selective literature review addresses follow‐up care after OLT in HCC and current treatment options. Recurrence prediction is based on pathological tumor stage, vascular invasion, serum alfafetoprotein levels, and histological differentiation, but further advances are expected by molecular profiling techniques. Lower levels of immunosuppressive agents are associated with a lower risk for HCC recurrence. Retrospective studies indicate that mammalian target of rapamycin (mTOR) inhibitors as immunosuppression reduce the risk of HCC recurrence. However, prospective studies supporting this potential advantage of mTOR inhibitors are still lacking, and higher rejection rates were reported for sirolimus after OLT in HCC. Prognosis is poor in recurrent HCC, a longer interval between OLT and recurrence and feasibility of surgical resection are associated with improved survival. Systemic treatment with sorafenib is the current standard of care in patients with advanced‐stage HCC not suitable for locoregional therapy. After OLT, combination of an mTOR inhibitor with sorafenib is feasible and frequently used in clinical practice. As safety and efficacy data are still limited, close clinical monitoring is mandatory.

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“…13 Currently, HCC is one of the major indications for OLT, with expected recurrence rates between 15% to 20% and less than 10% in patients who meet the Milan criteria, and overall survival rate of patients within Milan criteria is over than 70% after liver transplant. 10,14 In patients in our study, the tumorfree survival rate for tumors within Milan criteria was 83.9% and beyond Milan criteria was 69.2%. However, in our study there was no significant difference in survival of patients who were within or beyond Milan criteria; this finding could be explained by small sample size.…”

“…Proposals to expand the selection criteria from transplant centers include UCSF criteria, Hangzhou criteria, and up to 7 criteria, and these have made patients with larger tumors eligible for liver transplant. 9,10 The OLT also is limited by a shortage of donors, which facilitates tumor progression while waiting for transplant and might lead to poor patient survival. 2 Although the expanded criteria (UCSF criteria) for liver transplant have provided satisfactory results in several consensus studies, several unclear issues remain for discussion.…”

Hepatocellular carcinoma and living donor liver transplantation; the factors associated with recurrence and survival of patients. A single center experience

“…Bizim çalışmamızda görülen %14.7 oranındaki nüks ve nüks gelişen hastalardaki düşük sağkalım oranlarının literatürde yayınlanan önceki çalışmalarla uyumlu olduğu görüldü (3,6,15).…”

“…Ancak, karaciğer nakli olan hastalarda en önemli risk ise nakil sonrası görülen %10-30 oranındaki kanser nüksleridir (5). Kanser nüksünün, hasta sağkalım oranlarını belirgin bir şekilde azalttığı gösterilmiştir (6). Nüks gelişen hastalarda ise tedavi imkanı oldukça sınırlıdır.…”

Hepatocellular carcinoma treatment strategies – a case-based review

“…Nevertheless, specific conditions have to be taken into consideration: influence of immunosuppression, anatomic characteristics of vascular anastomoses, risk of stenosis of the hepatic artery by transarterial techniques, and potential pharmacological interactions between antineoplastic and immunosuppressive drugs and hepatotoxicity of systemic treatments like the multikinase inhibitor sorafenib [33] .…”