Alpha-Fetoprotein (AFP)
Alpha-fetoprotein levels may be assessed by a blood test. Alpha-fetoprotein (AFP) is a tumor marker that is elevated in 60–70% of patients with hepatocellular carcinoma. Normally, levels of AFP are below 10 ng/ml, but marginal elevations (10–100) are common in patients with chronic hepatitis. However, all patients with elevated AFP should be screened (abdominal ultrasound, CT scan or MRI) for hepatocellular carcinoma, especially if there has been an increase from baseline levels. In our experience, a steadily rising AFP is almost diagnostic of hepatocellular carcinoma. The specificity of AFP is very high when the levels are above 400 ng/ml. Undifferentiated teratocarcinoma and embryonal cell carcinoma of the testis or ovary may give false-positive results and should be considered in the differential diagnosis of elevated AFP.

The doubling time of AFP is around 60–90 days. Therefore, it may be advisable to check AFP every 3–4 months to screen high-risk cirrhotic patients (hepatitis C, hepatitis B, and hemochromatosis) for hepatocellular carcinoma.

Radiographic Diagnosis
The diagnostic accuracy of ultrasound, CT , magnetic resonance imaging (MRI) and angiography is dependent on a number of variables: expertise of the operator (especially with ultrasound), sophistication of equipment and technique, presence of cirrhosis and, most importantly, experience of the interpreter. For small tumors (<2 cm), the diagnostic accuracy ranges from 60–80%. The diagnostic accuracy increases significantly with an increase in tumor size, ultimately reaching 100% with very large tumors with all modalities (Figure 6).

Figure 6. Computed tomography (CT) scan of hepatocellular carcinoma.

Liver Biopsy and Histological Grading
Liver biopsy is indicated when diagnosis is in doubt (Figure 7). If AFP is significantly elevated and a tumor is seen in the liver, it is reasonable to assume a diagnosis of hepatocellular carcinoma and a liver biopsy is not warranted.

Figure 7. A, Biopsy of focal tumor; B, histological appearance; C, percutaneous approach to the liver.

The World Health Organization has suggested that hepatocellular carcinoma might be classified into histological types based on the structural organization of tumor cells: trabecular or sinusoidal type, pseudoglandular or acinar type, and compact or scirrhous sclerosing agent type. The tumor could also be graded based on the degree of cell differentiation into well, moderately, and poorly differentiated.

Another well-known staging method is UICC (International Union Against Cancer) classification, which is based on tumor number, size, vascular invasion, and metastasis. Figure 8 details this staging method.

Because most liver cancers are observed in association with cirrhosis, it is important to consider the severity of liver disease before a treatment strategy is planned. Child-Pugh scoring determines the severity of liver disease on the basis of serum albumin, bilirubin, prothrombin time, ascites , and encephalopathy.

Table 2. Child-Turchotte-Pugh (CTP) Scoring System to Assess the Severity of Liver Disease