Clinical symptoms resulting from biliary invasion or haemobilia are present in 2% of patients. Possible paraneoplastic syndromes associated with HCC include polyglobulia, hypercalcaemia and hypoglycaemia. Finally, in patients with underlying liver disease, a sudden onset or worsening ascites or liver decompensation may be the first evidence of HCC formation.

Serum α-fetoprotein (AFP) is the most widely recognised serum marker of HCC. It is secreted during fetal life but the residual levels are very low in the adult (0–20 ng/mL). It may increase in HCC patients and serum levels greater than 400 ng/mL can be considered as diagnostic for HCC, with 95% confidence. Levels may exceed 10 000 ng/mL in 5–10% of patients with HCC. Very high levels usually correlate with poor differentiation, tumour aggressiveness and vascular invasion. However, an AFP > surveillance programme using this cut-off value would miss 40% of tumours). If a value of > mL is used, 22% of tumours would be missed. Only 10% of small tumours are associated with raised levels whereas 30% of patients with chronic active hepatitis without an HCC have a moderately increased AFP. This usually correlates with the degree of histological activity and raised levels of transaminase, and it may therefore fluctuate. Tumours other than HCC can also be associated with increased AFP levels but these are rare (non-seminal germinal tumours, hepatoid gastric tumours, neuroendocrine tumours).

by vitamin K absence [PIVKA-II (>40 mAU/mL)] and AFP-L3 (>15%) have not come into common practice except in Japan, where they are covered under a national health insurance. A prospective cohort study in at-risk patients comparing the accuracy of AFP and DCP in the early detection of HCC showed that the combination of both markers increased the sensitivity, from 61% and 74% for each marker alone, to 91% for both markers combined.

most importantly heterogeneous. A hypoechoic peripheral rim corresponds to the capsule. The infiltrating type is usually very difficult to identify in a grossly heterogeneous cirrhotic liver. Besides echogenicity, the accuracy of US depends on the dimension and location of the tumour, as well as operator experience. A 1-cm diameter tumour can be visualised if it is deeply located, whereas the same lesion located on the surface of the liver can be missed. Similarly, tumours located in the upper liver segments or on the edge of the left lateral segment may be missed. Tumours detected at an advanced stage despite surveillance are frequently located at one of these two sites. Obesity may also prevent accurate assessment of the liver (thickened abdominal wall or steatotic liver). Doppler US may demonstrate a feeding artery and/or draining veins. US is also accurate in identifying vascular or biliary invasion and indirect evidence of cirrhosis such as segmental atrophy, splenomegaly, ascites or collateral veins. Tumour thrombosis is associated with enlargement of the vascular lumen, and an arterial signal may be detected by duplex Doppler.

Computed tomography (CT) is more accurate than US in identifying HCCs and their lobar or segmental distribution, particularly with the development of helical and multislice spiral scanners. Spiral CT is undertaken without contrast and during arterial (25–50 s), portal (60–65 s) and equilibrium (130–180 s) phases after contrast administration. In addition, it is useful for identifying features of underlying cirrhosis, accurately measuring liver and tumour volumes, and assessing extrahepatic tumour spread. HCCs are usually hypodense and spontaneous hyperdensity is usually associated with iron overload or fatty infiltration, which is seen in 2–20% of patients. Specific features are early uptake of contrast and a mosaic shape pattern. During the portal phase, the density diminishes sharply and results in washout (tumour is hypodense compared to adjacent parenchyma) during the late phase

Subsequent to these recommendations, several studies reported that contrast-enhanced US may provide a false-positive HCC diagnosis and cannot selectively differentiate intrahepatic cholangiocarcinoma from HCC. This technique has therefore been withdrawn from the diagnostic algorithm initially proposed by the American Association for the Study of Liver Diseases (AASLD).

There are limitations to screening programmes. Of patients presenting with HCC, 20–50% have previously undiagnosed cirrhosis and therefore escape surveillance. Access to medical care and compliance is a limitation in highly endemic areas, with 50% of patients with alcoholic cirrhosis defaulting from surveillance over 5years. US is highly operator-dependent, and the cost and invasiveness of CT and MRI make them unsuitable for screening. However, these latter modalities are particularly suited in patients with irregular background liver parenchyma or obesity. Physicians should also take into account the presence of comorbid disease, severity of liver disease and available treatment options when deciding whether or not to screen a cirrhotic patient. Screening of Child–Pugh C patients in particular is inappropriate if they are not potential liver transplant candidates.

Patients with HCC identified by surveillance usually present with smaller tumours and are more likely to benefit from a curative treatment. A recent population-based study raised a concern about the access to curative treatment in real-life practice. Despite full insurance coverage for all populations and standardised recommendations for HCC surveillance and management, only 22.8% of patients had curative treatment. Moreover, there were marked variations between areas in access to curative treatment.