**2.3.1 Hepatocellular carcinoma (HCC)**

It is the most common liver malignancy (Parkin et al, 2005). It develops secondary to cirrhosis (in approx. 80% of cases) (Llovet et al, 2003) therefore, ultrasound examination every 6 months combined with alpha fetoprotein (AFP) determination is an effective method for early detection and treatment monitoring for this type of tumor (Bruix & Sherman 2005; Llovet & Bruix 2008). Clinically, HCC overlaps with advanced liver cirrhosis (long evolution, repeated vascular and parenchymal decompensation, sometimes bleeding due to variceal leakage) in addition to accelerated weight loss in the recent past and lack of appetite.

HCC appearance on 2D ultrasound is that of a solid tumor, with imprecise delineation, with heterogeneous structure, uni- or multilocular (encephaloid form). An "infiltrative" type is also described which is difficult to discriminate from liver nodular reconstruction in cirrhosis. Typically HCC invades liver vessels, primarily the portal veins but also the hepatic veins (Badea R. & Badea Gh, 1991). Doppler examination detects a high speed arterial flow and low impedance index (correlated with described changes in tumor angiogenesis). The spatial distribution of the vessels is irregular, disordered. CEUS examination shows hyperenhancement of the lesion during the arterial phase. During the portal venous phase there is a specific "wash out" of ultrasound contrast agent (UCA) and the tumor appears hypoechoic during the late phase. Poorly differentiated tumors may have a stronger wash out leading to an isoechoic appearance to the liver parenchyma during portal venous phase. This appearance was found in approx. 30% of cases (Nicolau et al, 2004). The described changes have diagnostic value in liver nodules larger than 2 cm.

Fig. 6. Encephaloid hepatocellular carcinoma (CEUS). Contrast tumor enhancement is observed on the left during arterial phase. The "wash-out" phenomenon can be seen on the right, during portal venous phase.

Ultrasound is useful in HCC detection, stadialization and assessing therapeutic efficacy. In terms of staging related to therapy effectiveness, the Barcelona classification is used (Llovet et al, 1999) which identifies five HCC stages. Curative therapy is indicated in early stages, which include very early stage (single nodule <2 cm), curable by surgical resection (survival 50-70% five years after surgical resection) (Llovet et al, 2003) and early stage (single nodule of 2-5 cm, or up to 3 nodules <3 cm) which can be treated by radiofrequency ablation (RFA) and liver transplantation. Intermediate stage (polinodular, without portal invasion) and advanced stage (N1, M1, with portal invasion) undergo palliative therapies (TACE and sorafenib systemic therapy) and in the end stage only symptomatic therapy applies.
