Bridge Therapy before Liver Transplant for Advanced Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be considered. Bridge therapies have been introduced in order to limit this issue. The aim of this study is to evaluate if bridge therapies in advanced hepatocellular carcinoma can improve overall survival and reduce de-listing. We selected 185 articles. The search was limited to English articles involving only adult patients. These were deduplicated and articles with incomplete text or irrelevant conclusions were excluded. Sorafenib is the standard of care for advanced hepatocellular carcinoma and increases overall survival without any significant drug toxicity. However, its survival benefit is limited. The combination of transarterial chemoembolization + sorafenib, instead, delays tumor progression, although its survival benefit is still uncertain. A few studies have shown that patients undergoing transarterial chemoembolization + radiation therapy have similar or even better outcomes than those undergoing transarterial chemoembolization or sorafenib alone for rates of histopathologic complete response (89% had no residual in the explant). Also, the combined therapy of transarterial chemoembolization + radiotherapy + sorafenib was compared to the association of transarterial chemoembolization + radiotherapy and was associated with a better survival rate (24 vs. 17 months). Moreover, immunotherapy revealed new encouraging perspectives. Combination therapies showed the most encouraging results and could become the gold standard as a bridge to transplant for patients with advanced hepatocellular carcinoma.

Keywords: hepatocellular carcinoma; orthotopic liver transplant; radiotherapy; sorafenib; transarterial chemoembolization.

Figure 1

PRISMA flow diagram.

Figure 2

Proposed treatment for different stages of HCC according to Child–Pugh grade. * Cryoablation if 3 nodules <3 cm with perivascular invasion and poor anesthesia candidate; MVA if 3 nodules <3 cm with perivascular invasion and good anesthesia candidate if 3–6 cm; and RFA if <3 cm and no perivascular invasion. OLT: orthotopic liver transplant; TARE: rransarterial radioembolization; TACE: rransarterial chemoembolization; and DEB: drug-eluting beads.

Figure 3

HCC nodule treated through TACE (A): CT scan of an HCC nodule; (B): TACE (B); and (C): re-evaluation one month after TACE (personal observation).