G

Fig. 8.08 Histological subtypes of hepatocellular carcinoma. A Pseudoglandular. B Clear cell. C Fatty change. D Spindle cell. E Scirrhous type. F Scirrhous type, Masson trichrome stain. G Poorly differentiated, with numerous mitotic figures. H Pleomorphic. I Multinucleated giant cell.

tion in codon 249 of the TP53 tumour suppressor gene, leading to an amino acid substitution of arginine to serine {188}. In Southern China and Subsaharan Africa, the two world regions with the highest levels of food contamination with AFB1, this mutation is present in > 40% of HCC {1265} and can be detected in serum DNA of patients with preneoplastic lesions and HCC {924}. In regions where AFB1 levels in food are very low or undetectable, codon 249 transversion mutations are either very rare or absent.

Clinical features

Symptoms and signs

Most HCC patients have a past or current history of chronic liver disease from different causes {1681}. The major clinical risk factor for HCC development is liver cirrhosis; 70-90% of HCCs develop in a macronodular cirrhosis {452}. The presenting symptoms in patients with HCC include abdominal pain, gen eral malaise, anorexia or weight loss, and nausea or vomiting. The symptoms are caused by the underlying chronic liver disease or cirrhosis and its clinical complications, or by the HCC itself. The most common clinical signs in HCC patients are hepatomegaly, ascites, fever, jaundice, and splenomegaly. The laboratory findings are in part determined by the underlying liver disease, which results in elevations of various liver enzymes, such as aspartate amino trans-ferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma-glutamyl-transpeptidase (GGT), and bilirubin. These laboratory parameters are not HCC-specific, however. A significantly raised level of alpha-fetopro-tein (AFP) of > 500 ng/ml, or continuously rising values even if less than 100 ng/ml, strongly suggest HCC. However, not all cases of HCC are associated with AFP elevation, and raised AFP may also be found in liver disease without HCC. Furthermore, in the early stages of HCC

development, AFP levels do not closely correlate with clinical HCC stage. AFP levels, therefore, have to be interpreted individually in the context of other clinical symptoms and signs as well as imaging studies. Another HCC-specific marker is des-gamma-carboxyprothrombin (DCP), which is roughly equivalent to AFP. Occasionally, HCC patients develop a paraneoplastic syndrome, with erythrocy-tosis, hypoglycaemia or hypercalcaemia.

Imaging

Imaging studies are important in patient management for the identification and localization of HCC. Useful techniques include ultrasonography of the liver and the abdomen, colour Doppler ultra-sonography, computed tomography (CT), lipiodol CT, magnetic resonance imaging, angiography, and possibly positron emission tomography. The standard imaging techniques are ultrasonog-raphy and CT. In most cases, these allow HCC detection and staging. In patients

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