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Galicia-Moreno et al. Hepatoma Res 2020;6:20 I http://dx.doi.org/10.20517/2394-5079.2019.36 Page 11 of 18

diameter, or up to three HCCs with each < 3 cm in diameter; (2) absence of portal venous thrombosis; (3)
[88]
Child-Pugh A or B, and (4) no significant coagulopathy .

Finally, IRE is a novel, non-thermal form of tumor ablation that produces less collateral damage. IRE relies
on short pulses of high frequency energy to induce pores in the lipid bilayer of cells, leading to cell death
[89]
via apoptosis . Patients who are candidates for RFA or MWA, but have tumors adjacent to structures that
would cause either heat sink or collateral damage, can therefore be treated with IRE.

Palliative options, chemoembolization
This treatment consists of the administration of a chemotherapeutic agent into the tumor followed by an
[90]
embolizing agent. This process increases the survival rate to 41% in 2 years . TACE is the gold standard
in patients unsuitable for surgery and for percutaneous ablation techniques with multinodular HCC, but
have preserved liver function without vascular invasion or extrahepatic spread. This technique is based
on occlusion of the arterial blood supply of the target neoplastic lesion by embolizing microparticles, in
[80]
combination with an injection of chemotherapeutic drugs . A variety of chemotherapeutic agents have been
used, including monotherapy with doxorubicin or cisplatin, or a mixture with cisplatin, doxorubiicn and
mitomycin C. Contraindications to TACE include decompensated cirrhosis (Child-Pugh C), encephalopathy,
active infection and uncorrectable bleeding diathesis. Other relative contraindications include serum
bilirubin of 3-7 mg/dL, advanced cancer stage, portal vein thrombosis, iodinated contrast allergy, biliary
[90]
obstruction and renal insufficiency .

TARE is an important loco-regional treatment,used in patients with intermediate or advanced stages of
HCC who are not candidates for TACE or Sorafenib. TARE, also known as selective internal radiation
therapy, consists of intra-arterial delivery of a radioactive material to the tumor to limit systemic irradiation
90
and preserve healthy liver. Ytrium-90 ( Y) has suitable characteristics for the treatment of tumors. It is a
pure b emitter characterized by a short half-life (64.2 h) and has limited tissue penetration. Two types of
microspheres are available, TheraSphere which is made of glass, and SIR-Spheres made of resin, and both
[91]
have been demonstrated effective and safe in treating primary and secondary liver cancers . Emission of
90
90
a b particle with decay Y to Zr (zirconium) enables delivery of targeted radiation to the lesion, limiting
radiation exposure to normal parenchyma while reducing the risk of radiation exposure induced liver
[92]
disease .
According to the clinical practice guidelines for the management of HCC by the Latin American Association
for the Study of the Liver (LAASL), chemoembolization is an option for patients, particularly those who are
[5]
not candidates for resection, liver transplantation, or percutaneous ablation .

Systemic therapies
These are options for patients with the diagnosis of advanced stage HCC or in patients with tumor
[93]
progression after loco-regional therapy .

Sorafenib
[93]
This is considered and approved as first-line treatment for patients with advanced HCC . It is a multi-
kinase inhibitor that targets Raf-1, B-Raf, vascular endothelial growth factor receptor, platelet derived growth
factor receptor, and c-kit receptors. It inhibits tyrosine kinase activity and serine-threonine kinase receptor,
acting as an antiproliferative and anti-angiogenic agent. Its efficacy has been demonstrated in phase II and III
[93]
clinical trials .

HCC patients with Child-Pugh category A and advanced disease and with an Eastern Cooperative Oncology
[35]
Group score of 0-2 are eligible to receive Sorafenib . However, the main disadvantage is its high cost that
makes it non-affordable to most patients. A retrospective analysis of 127 HCC cases treated with sorafenib in