Management of recurrent hepatocellular carcinoma after liver transplant

Abstract

Hepatocellular carcinoma (HCC) is the leading cause of deaths in patients with hepatitis B or C, and its incidence has increased considerably over the past decade and is still on the rise. Liver transplantation (LT) provides the best chance of cure for patients with HCC and liver cirrhosis. With the implementation of the MELD exception system for patients with HCC waitlisted for LT, the number of recipients of LT is increasing, so is the number of patients who have recurrence of HCC after LT. Treatments for intrahepatic recurrence after transplantation and after other kinds of surgery are more or less the same, but long-term cure of posttransplant recurrence is rarely seen as it is a "systemic" disease. Nonetheless, surgical resection has been shown to be effective in prolonging patient survival despite the technical difficulty in resecting graft livers. Besides surgical resection, different kinds of treatment are also in use, including transarterial chemoembolization, radiofrequency ablation, highintensity focused ultrasound ablation, and stereotactic body radiation therapy. Targeted therapy and modulation of immunosuppressants are also adopted to treat the deadly disease.

Late recurrence of hepatocellular carcinoma after liver transplantation

“…Other options for treatment include TACE, RFA, high-intensity focused ultrasound ablation, stereotactic body radiation therapy, and modulation of immunosuppressants. [34] Sorafenib, a multikinase inhibitor that improves progression-free and overall survival in patients with advanced HCC, has also shown promising results in treatment of HCC recurrence post-LT with a modest survival benefit and manageable adverse effects. [35,36] Combination therapy with sorafenib and an mTOR inhibitor such as everolimus has also been used in practice, though longer follow-up studies are needed to assess the benefits versus increased toxicity of such a regimen in recurrent HCC.…”

Long-term outcome of percutaneous radiofrequency ablation in recurrent hepatocellular carcinoma after liver transplantation

“…Currently, the management of recurrent HCC after LT seems to be a losing battle with the increase of LT. Surgical resection can be considered the most promising and potentially curative treatment (6). Unfortunately, poor functional liver reserve, widespread recurrent lesions, or severe postoperative adhesions seriously affected the operation [8].…”

“…Of these patients, 15 with 23 recurrent HCCs after LT enrolled in this study. The inclusion criteria for RFA were as follows: (1) a tumour size 6 cm and tumour number 4; (2) an absence of significant direct tumour invasion of adjacent organs or tumour thrombi in the main or lobar portal system; (3) a tumour not invading a main bile duct or being obviously exophytic; (4) a tumour accessible via a percutaneous approach; (5) an international standard ratio <1.6 and platelet count >50 000/ll; (6) no extrahepatic metastasis or local extrahepatic metastasis with good control before RFA and (7) a follow-up of at least one year after the first RFA treatment.…”

“…Currently, liver transplantation (LT) is regarded as the ideal treatment for the removal of existing tumours and replacement of chronically injured and multifocal precancerous livers [3,4]. However, there is a possibility of tumour recurrence after LT, and there has been an increasing trend in recurrence due to the expansion of LT criteria and immunosuppression intervention; the reported recurrence rates after LT are as high as 10-60% [5][6][7]. Poor liver function reserve, widespread recurrent lesions and severe postoperative adhesions usually become obstacles for reoperation for most LT patients with recurrent tumours [8,9].…”

Development of a radiofrequency ablation platform in a clinically relevant murine model of hepatocellular cancer

“…7 Liver transplantation is an effective treatment for cirrhosis and early tumors, but as recurrence is common in advanced disease and organs are scarce, most patients are not able to receive transplantation. 8 In 2008, the receptor tyrosine kinase inhibitor, sorafenib, became the first and only drug approved by the Food and Drug Administration (FDA) to treat unresectable HCC, after it was shown to increase the median overall survival of patients from 7.9 to 10.7 months. 9 This small but statistically significant therapeutic effect highlights the challenge in treating this devastating disease.…”