Function of the liver
The liver is one of the largest organs in the body and receives one third of its blood supply (1500 ml/min). It has a left and a right lobe, and is divided into eight segments. The liver is located under the rib cage and fills the upper right part of the abdomen.
The liver has many complex functions. These include the formation of bile to help with the digestion of food, the production of enzymes to convert food to energy, the production of plasma proteins and blood clotting factors, and the filtering and detoxification of the blood.
Cancer: Cells normally grow, divide and replace old cells as they die. This is a highly regulated process with strict control mechanisms. Sometimes this process goes wrong and new cells are produced which the body does not require. These form a tumour that can either be benign or malignant.
Benign tumours are not cancer. They do not spread to other parts of the body and tend not to recur when surgically removed. Although considered less dangerous than malignant tumours, they can have serious effects due to their location or the pressure they exert.
Malignant tumours are cancer. Cancer cells can invade and damage adjacent tissues and are potentially life-threatening. They can spread to other parts of the body by direct extension, via the bloodstream or via the lymphatic system.
Liver cancer: Cancer that begins in the liver cells is known as primary liver cancer. Most begin in the hepatocytes (liver cells) and are known as a hepatocellular carcinoma (HCC) or a malignant hepatoma. HCC accounts for 80 percent of primary liver cancers and is the fifth most common malignancy worldwide and the third most common cause of cancer-related death.
The liver is a common site of spread for cancers from other parts of the body, such as the colon, lungs and breast. These are secondary cancers called metastases. They’re not liver cancer per se and will not be addressed in this article.
Who is at risk?
Certain risk factors increase one’s risk of developing liver cancer:
- Hepatitis B or hepatitis C infection: these viruses are passed from person to person through blood or sexual contact. An infected mother can also transfer the virus to her baby. A person with chronic infection has a 100-fold increased risk of liver cancer compared with an uninfected person.
- Cirrhosis: this is a disease in which liver cells are damaged and replaced by scar tissue. There are many causes, including infections, alcohol abuse, certain drugs and toxins. About 20 percent of people with cirrhosis will develop liver cancer.
- Aflatoxin: this is a poison produced by the Aspergillus mould on improperly stored foods like grain and nuts.
- Male gender: liver cancer is three times more common in men.
Although not shown to have a direct carcinogenic effect on liver cells, lifestyle habits such as smoking and alcohol abuse are thought to promote the cancer-forming process in conjunction with the other risk factors.
Liver cancer is often “silent” and does not cause symptoms in the early stage. As the cancer grows, it can cause the following problems:
- Pain or discomfort in the upper abdomen on the right side. The pain may extend to the back and right shoulder blade.
- A swelling on the right side below the rib cage
- Swelling of the abdomen (ascites)
- Intermittent nausea and vomiting
- Loss of weight and appetite
- Weakness or feeling generally unwell
If a patient's symptoms suggest liver cancer, the doctor will examine him or her and order special tests to help confirm or refute the diagnosis. These may include:
Ultrasound: the ultrasound machine produces sound waves which bounce off internal organs and produce echoes that are interpreted by a computer to produce an image. It can detect tumours in the liver as well as abnormal lymph nodes and abnormal fluid (ascites) in the abdomen. Doppler ultrasound can also show the relationship of important blood vessels in the liver with the tumour.
Computed tomography (CT) scan this uses X-rays linked to a computer to give a detailed picture of the organs and blood vessels in the abdomen.
Magnetic resonance imaging (MRI): a powerful magnet linked to a computer produces detailed pictures of the internal organs and blood vessels. It has the advantage over a CT scan in that the patient is not exposed to X-ray radiation.
Angiogram: dye is injected into the artery to show up the blood vessels of the liver. This can show a liver tumour as well as involvement of the portal vein, which drains blood to the liver. This test is not used routinely, as non-invasive tests such as ultrasound, MRI and CT scans can provide the information.
Blood tests can show how well the liver is working, but abnormalities are not specific to HCC. Alpha-fetoprotein (AFP) levels are raised in 90 percent of patients with HCC and, if elevated, could be a sign of liver cancer. Levels may also be raised in other liver diseases and cancers. Previous or current infection with the hepatitis B or C virus is also detectable.
A sample of tissue can be removed and examined under the microscope to look for cancer cells. This is usually done under ultrasound or CT scan guidance and can be performed using a thin needle (fine needle aspiration) or a thick needle (core biopsy). It can also be performed via laparoscopy or during an open operation.
Possible complications include bleeding and rupture of the tumour. There is also a small, but definite risk (1 percent) of tumour seeding in the needle biopsy tract, which would compromise the chance of curing the cancer by removing part of the liver. For this reason, routine biopsies of possibly cancerous liver lesions that could potentially be surgically removed are not recommended.
Treatment options and prognosis
Treatment options and chance of recovery are determined by:
- Stage of the disease: size of the tumour, how much of the liver has been affected, whether there is spread to other parts of the body
- Liver function: how well the liver is working, including whether or not there is underlying cirrhosis.
- The patient’s general health
- Effects of the treatment
When liver cancer is diagnosed, it is important to know the extent of the disease as this will help with planning the treatment. Staging determines the size of the tumour, whether it affects part of or the whole liver, and whether it has spread to other parts of the body. Staging will show if the tumour can be surgically removed.
The tests mentioned above provide much of the information needed to stage the disease. Additional tests may include a chest X-ray or CT scan of the chest to look for spread to the lungs, and a bone scan if there is suspected spread to the bone. A laparoscopy may also be used to look directly at the liver and adjacent organs.
Depending on the size of the tumour and evidence of spread to the lymph nodes and other parts of the body, liver cancer can be classified into stages. A number of staging systems for HCC exist, but most have limitations and none are universally accepted. International guidelines recommend particular roles for certain staging systems.
In terms of deciding on treatment, liver cancer can be staged as:
- Early-stage HCC: the cancer is localised to the liver, has not spread and can be completely removed by surgery. Potentially curable.
- Intermediate-stage HCC: the cancer is localised to the liver, has not spread, but cannot be completely removed by surgery. Treatment is still aimed at increasing life expectancy.
- Late-stage HCC: the cancer has spread throughout the liver or to other parts of the body. Incurable.
Treatment options are available for the management of hepatocellular carcinoma. These include:
- Liver transplantation
Local ablative procedures
- Radiofrequency thermal ablation (RFA)
- Percutaneous ethanol injection (PEI)
- Transarterial chemoembolization (TACE)
- Laser and microwave therapy
- Regional radiotherapy
- Targeted molecular therapy
- Symptomatic treatment
The choice of treatment depends on the stage of the cancer, the condition of the liver, and the age and general health of the patient. The patient’s personal values and the possible side effects of treatment are also taken into account.
Resection (partial hepatectomy): this involves removal of the part of the liver containing the cancer, a rim of normal tissue and maybe a wedge or a whole lobe or more than a lobe of liver tissue. A normal liver can tolerate up to 80 percent of resection of functional tissue. Partial hepatectomy is the choice of treatment for non-cirrhotic patients with HCC.Liver transplantation: the entire liver is removed and replaced with a healthy donated liver. This can only occur if the cancer is confined to the liver and a donor liver becomes available. Transplantation manages both the cancer and the underlying liver disease.
Surgical treatment options offer the only possibility of cure. Unfortunately, most liver cancers present late and are not amenable to surgical resection.
These techniques are used in patients with early- and intermediate-stage HCC who are not suitable for surgical treatment. They are usually performed by using imaging-guided ultrasound or computed tomography (CT).
Cryoablation: a probe is inserted into the tumour via laparoscopy or open surgery. Liquid nitrogen is passed through the probe to freeze and kill the cancer cells.
Radiofrequency thermal ablation (RFA): alternating current is passed through a probe inserted into the tumour. This results in ionic agitation, which produces heat and kills the cancer cells. It is limited by the size (smaller than 5 cm), number and location of tumours within the liver. The procedure can be done percutaneously using local anaesthetic or during laparoscopy or open surgery.
Percutaneous ethanol injection (PEI): alcohol is injected directly into the tumour to kill cancer cells. It is carried out under local anaesthetic using ultrasound to guide the needle to the correct position. It is used when the tumour is smaller than 3 cm and there are three or fewer.
Transarterial chemoembolization (TACE): Tiny beads called microspheres, are delivered to the hepatic artery, where they lodge and obstruct the blood flow. These beads are combined with chemotherapeutic agents, which can stay in the liver for longer because of the decreased blood flow, allowing them to kill off large HCC tumours. (Doctors call this necrosis of the tumours.) Although the hepatic artery is blocked, healthy liver tissue survives because it can still receive blood from the portal vein.
Transarterial radioembolization: this involves the administration of radiolabeled microspheres (tiny radioactive beads) via the hepatic artery to deliver radiation therapy to the tumour.
Other therapies that use heat to destroy cancer cells are laser and microwave therapy, but not much information is available on the success of these techniques.
Regional radiotherapy (radiation therapy) uses high-energy rays to kill cancer cells. It is used in advanced cancers to alleviate symptoms and slow progress of the cancer. In selected cases the tumour can be somewhat shrinked, but results are generally not very good.
Chemotherapy uses drugs to kill the cancer cells or to stop them from dividing. Normal cells like blood, hair and cells of the gastrointestinal tract are also affected, resulting in various side effects. The drugs can be injected into a vein, taken orally or be given directly into the liver (regional chemotherapy).
Liver cancer is relatively resistant to chemotherapy delivered via injection or orally. It has a low response rate of 15-20%, which is usually incomplete and lasts for only a short while. This therapy is used in advanced cancer to slow the progress of the disease.
When drugs are delivered directly to the liver via a catheter placed into the hepatic artery, it is called hepatic artery infusion. With this treatment, higher concentrations of the drugs go directly to the cancer cells in the liver with less effect on the normal cells of the body, but results have also been disappointing.
Targeted molecular therapy
Thanks to modern advances in the understanding of cancer, new systemic therapies have been developed that target the molecular pathways involved in the development and growth of the tumour. These drugs seek out and kill only the cancer cells, leaving surrounding healthy tissue unscathed. Sorafenib has been the first of these to show a prolonged survival and has been approved for the management of advanced HCC. Several other targeted therapies are in early stages of evaluation.
Supportive (palliative) care
Supportive treatment is an important aspect of management of patients with HCC. The aim is to enhance the patient’s quality of life as much as possible in his or her remaining short lifespan. The goals of palliative care are:
- Relief of pain and other symptoms
- Psychological and spiritual care for patients to allow them to come to terms with dying
- A support system to maintain personal integrity and self-esteem
- A system to support the family to cope with the patient’s final days and their bereavement
Although one can never be completely safe from HCC, the following steps will help reduce your risk of contracting the cancer.
- Be vaccinated against hepatitis B.
- Nuts and grains should be properly stored.
Lifestyle changes such as safe sexual practices, smoking cessation and drinking alcohol in moderation, will also reduce the risk of liver cancer.
Role of screening
The early detection of HCC undoubtedly results in a better prognosis. In high-risk groups such as patients with chronic liver disease or who are chronic carriers of hepatitis B or C, the lifetime risk of developing hepatocellular carcinoma ranges from 10-40 percent. These patients would certainly benefit from a screening programme using ultrasound examination and alpha-fetoprotein measurement. Because of the low yield, screening of the general population is however not an economically viable option.
Reviewed by Dr Pieter Barnardt, medical oncologist, Tygerberg Hospital and the University of Stellenbosch, 2010