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and the close geographic correlation between incidence and mortality reflects the dismal prognosis. However, longer survival can be reached in early diagnosed and properly treated cases. Awareness of the risk factors of HCC is helpful both in diagnostics and in order to set up the surveillance. Liver cirrhosis is the main risk factor; surveillance is indicated in these patients. A tumour found in cirrhotic liver is more likely to be HCC than metastasis or liver adenoma.

The other risk factors act mainly through inducing cirrhosis although a fraction of HCC can precede the development of cirrhosis in a patient affected by chronic liver disease or develop in non-fibrotic liver. Thus, the complete list of the risk factors of HCC includes chronic active hepatitis B or C, liver damage by alcohol and/or aflatoxins, as well as NASH. The risk factors can act synergistically. Evaluating the HCC risk in any patient, the relative risk must be considered in accordance to the risk factors that are identified in that individual. However, to estimate the expected cancer burden in the population, population attributable fractions are of importance; these parameters depend both on relative risk and population frequency of each

Non-invasive radiological approach is the gold standard in the diagnostics of HCC in contrast with most of other malignant tumours necessitating confirmation by a biopsy. Biopsy is indicated only in radiologically controversial cases or to prove HCC in non-cirrhotic liver.

Ultrasonography is used for surveillance and the initial step of diagnostics. For surveillance of cirrhotic patient, US is carried out once in 6 months. If a suspicious focus is disclosed, the further approach is based on the size. Either CT or MRI is indicated for mass lesions larger than 20 mm, while both methods are recommended for a nodule measuring between 10 and 20 mm. Nodules that are smaller than 1 cm are followed up by US once in 4 months. Hypervascularity is a characteristic trait of HCC in CT and MRI. PET and CEUS may have additional role in HCC

If biopsy is carried out, HCC can be diagnosed if both signs of hepatocellular differentiation and cellular atypia or invasion are present. Low-grade tumours must be differentiated from dysplastic nodule, focal nodular hyperplasia and adenoma while high-grade HCC must be distinguished from metastasis. Mass lesion in cirrhotic liver is most probably a dysplastic nodule or HCC while adenomas and metastases usually develop in non-cirrhotic liver. In a Western patient, clearly malignant tumour in a non-cirrhotic liver has higher probability to

Regarding immunohistochemistry, arginase-1 and HepPar antigen are reasonable hepatocellular markers that are used to distinguish HCC from metastases. Novel immunohistochemical markers of HCC include bile salt export pump protein and heavy chain of clathrin. Glypican should be used with caution due to the reported expression in a wide range of extrahepatic tumours. In order to discriminate between low-grade HCC and FNH, reticulin network, glypican-3 and heat shock protein 70 can be assessed. The differential diagnosis between high grade dysplastic nodule and low grade HCC can be very complicated as both processes share several morphological features and can coexist, biologically representing subsequent stages of HCC development. The features favouring malignancy over dysplastic nodule, include (1)

However, the differential diagnosis includes a dysplastic cirrhotic nodule.

38 Hepatocellular Carcinoma - Advances in Diagnosis and Treatment

particular factor.

diagnostics.

represent a metastatic carcinoma.

Dzeina Mezale<sup>1</sup> , Ilze Strumfa<sup>1</sup> \*, Andrejs Vanags<sup>2</sup> , Arturs Kalva1 , Dainis Balodis1 , Boriss Strumfs3 , Ilze Fridrihsone<sup>1</sup> , Arnis Abolins<sup>1</sup> and Janis Gardovskis<sup>2</sup>

\*Address all correspondence to: ilze.strumfa@rsu.lv

