Liver cancer (hepatocellular carcinoma)

Hepatocellular carcinoma (HCC, liver cancer) is the third most common cause of cancer-related death in the world. Furthermore, the incidence of this cancer appears to be increasing - in the United Kingdom there were 1.4 new diagnoses of HCC per 100,000 people in 1975, but this rose to an incidence of 3.9 new diagnoses per 100,000 people in 2006.

In 80-90% of cases, HCC develops in patients with underlying chronic liver disease (cirrhosis) (see picture 1). Worldwide, a patient with cirrhosis is more likely to die as a result of HCC than as a result of any other liver-related complication.

(picture 1, liver cirrhosis with hepatocellular carcinoma)(picture 1, liver cirrhosis with hepatocellular carcinoma)

Chronic infection with the viruses hepatitis B and hepatitis C is the most common underlying cause of liver disease that predisposes to HCC, although HCC can develop in patients with liver disease due to any cause. Another wellrecognised risk factor for HCC is a poison produced by the fungus Aspergillus. This fungus contaminated grain in West Africa and China, and if eaten by patients with Hepatitis B, it increases their risk of developing HCC by 5 times.

Lastly, liver disease due to alcohol and due to ‘fatty liver’ (an increasingly common cause of liver disease seen in people who do not drink alcohol but who are overweight, or have diabetes, high cholesterol or high blood pressure), is also a recognised risk factor for HCC, and this is particularly the case in the Western World where the prevalence of obesity and diabetes has increased significantly over the past decade.

Unfortunately, HCC usually presents late – in other words, patients can have no symptoms until the cancer is already advanced. It is usually diagnosed on the basis of a blood test called the alpha-fetoprotein, which is elevated in most people with HCC, and a lesion seen within the liver on ultrasound or computed tomography (CT) scanning (see picture 2). The outcome from this type of cancer is therefore poor; one study found an average survival of 17 months in 102 patients with cirrhosis and HCC. Furthermore, the cancer can grow rapidly, doubling in size over a period of between one month and one year. However, patients who are detected with early HCC (such as a single, small cancer and with liver disease that is still stable) have a much better outcome and are, for example, more likely to be able to undergo surgery for their cancer.(

(picture 2, CT scan showing hepatocellular carcinoma, arrow)(picture 2, CT scan showing hepatocellular carcinoma, arrow)

Therefore, in all patients with cirrhosis, it is recommended that regular blood tests and scans are performed every 6 months (even if the patient is well) in order to attempt to diagnose the HCC when it is still at a relatively early stage. This ‘screening’ approach has been shown to save lives in a large trial in China. This approach has also been shown to be cost-effective in the UK.

Various treatment options are available for patients diagnosed with HCC. In those who present with an early cancer, curative surgery may be possible in the form of resection of part of the liver or a liver transplant (see picture 3). This results in a more than 50% chance of surviving more than 5 years, although the cancer can recur. Otherwise, treatment with chemotherapy or locally destructive treatments may be offered, but these treatments would not result in a cure. New treatments are also emerging but at present these are largely experimental.

(picture 3, liver transplant scar)(picture 3, liver transplant scar)

The only way to prevent the development of this cancer would be by diagnosing the underlying liver condition at an earlier stage and attempting to treat the liver condition before it progresses to cirrhosis. For example, vaccination against the hepatitis B virus is offered to the entire population in countries where the prevalence of the virus is high (for example, Taiwan), and to people at high-risk of getting infected with the virus in other countries (for example, the vaccine is provided to all babies born to hepatitis B-positive mothers in the UK).

For patients with known liver disease (from whatever cause), treatment should be offered for the underlying cause of the liver disease (for example, antiviral therapy in patients with hepatitis B or hepatitis C). Furthermore, patients with cirrhosis should be identified as early as possible, so that they can be entered into a screening programme to detect an HCC at an early stage, when curative therapy may still be an option.

Currently, the identification of cirrhosis can only reliably be established by performing a liver biopsy. This involves removing a small sample of the liver using a special needle, and is performed under local anaesthetic. The sample is then analysed under the microscope to make a histological diagnosis of cirrhosis. A liver biopsy does carry a small but significant risk of complications (such as bleeding, the need for surgery and even death). Therefore, newer, non-invasive techniques are being evaluated that may permit the diagnosis of cirrhosis without the need for a liver biopsy. These techniques include specialised blood tests (called fibrosis markers) and a scan that measures the stiffness of the liver. This technique is called transient elastography and the scan involved is called a Fibroscan (see picture 4). The level of liver stiffness correlates well with the degree of liver damage and therefore allows a diagnosis of fibrosis or cirrhosis to be made with a high degree of confidence and without need for a liver biopsy.

(picture 4, Fibroscan machine in use)(picture 4, Fibroscan machine in use)

In summary, HCC is a leading cause of death worldwide and cirrhosis is the main risk factor. Prevention of cirrhosis would greatly reduce the incidence of this cancer. Early diagnosis of this cancer through screening of patients with cirrhosis has been shown to be cost-effective, and may result in a curative option. Newer, experimental treatments are emerging.

an article on liver cancer diagnosis from Dr. Saket Singhal.