A common cancer

THE liver is the second largest organ in the body, and performs a variety of functions that are vital to life. These include the filtering and processing of blood; bile production; producing proteins, glucose and cholesterol; storing fat-soluble vitamins, glycogen and iron; metabolising drugs, glucose and haemoglobin; and even a role in immunity.

That’s an impressive resume, and it’s safe to say that when something adverse happens to the liver, life as we know it will never be the same.

Unfortunately, many things can go wrong in the liver, and probably the worst of the lot would be cancer.

In fact, liver cancer is the sixth most common cancer worldwide. Worse, it’s the third most common cause of cancer-related death. This is probably due to the fact that there are typically no symptoms of the disease until the cancer is in its later stages.

Dr Mellor ... Those living with hepatitis C, hepatitis B viral infection, as well as those with alcohol-related cirrhosis, are at most risk of developing chronic, cirrhotic liver disease. Hence, they are ultimately at higher risk for hepatocellular carcinoma (liver cancer).

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, and is responsible for about 90% of the primary malignant liver cancers seen in adults.

The current five-year survival rate for patients with liver cancer are as follows: Europe, 8.6%; United States, less than 10%; and Asia, less than 10%, for inoperable tumours. These are very depressing figures indeed.

According to consultant oncologist Dr Matin Mellor, approximately 75 to 80% of all HCC occurs in Asia. “In some parts of Asia and Africa, HCC is the leading cause of cancer mortality.”

Risk factors

It has been noted that liver cancer disproportionately affects men, with about three times as many men developing the disease as women.

Although the overall cancer incidence and mortality are decreasing in the United States, both the incidence and mortality of liver cancer are increasing worldwide.

There are a few major risk factors for the development of the disease, but the most significant one is chronic, cirrhotic liver disease. Cirrhosis is the widespread disruption of normal liver structure by fibrosis and the formation of regenerative nodules that is caused by various chronic progressive conditions affecting the liver, such as alcohol abuse.

“Those living with hepatitis C (HCV), hepatitis B viral infection (HBV), as well as those with alcohol-related cirrhosis, are at most risk of developing chronic, cirrhotic liver disease. Hence, they are ultimately at higher risk for HCC.

“Worldwide, 75 to 80% of HCC cases are related to chronic HBV or HCV infection,” noted Dr Mellor.

Other risk factors include:

·Obesity – non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

·Diabetes

·Long-term exposure to aflatoxins (naturally occurring toxins produced by many species of fungus that can be found in tree nuts, peanuts and other oilseeds).

·Tobacco use

·Long-term use of anabolic steroids.

·In some parts of the world, water contaminated with arsenic.

Symptoms and complications

It is often said that the symptoms of liver cancer only appear late into the disease. The signs and symptoms may include the following:

·Unexplainable weight loss

·Ongoing lack of appetite

·Feeling very full after a small meal

·A hard lump on the right side just below the rib cage

·Pain around the right shoulder blade

·Yellow-green colour to the skin and eyes (jaundice)

·Discomfort in the upper abdomen on the right side

·Unusual tiredness

·Nausea

Many of these symptoms can also be an indication of liver cirrhosis.

Liver cirrhosis leads to many complications. There can be fluid accumulation in the abdomen (ascites), risk of infection to the lining of the abdomen (bacterial peritonitis), enlarged spleen, distended and/or swollen veins, brain dysfunction (hepatic encephalopathy), malnutrition, and of course, HCC.

According to Dr Mellor, HCC usually presents in patients aged 40 to 50 years old, and about 40% of these patients do not show any symptoms during diagnosis.

“Diagnostic tests for HCC include a full history and examination, liver function tests, ultrasound and other forms of radiology such as CT or MRI scan, and tumour markers (in the case of HCC, it’s alpha-fetoprotein serology).

“Once a diagnosis is confirmed, the cancer is then staged. Staging is used to determine prognosis and guide treatment,” said Dr Mellor.

“Staging HCC is difficult because most patients have underlying liver disease, and key prognostic indicators are not clearly defined. In addition, there isn’t a universal satging system that is used worldwide. There are a few around, and it depends on the doctor’s personal choice as to which one is used.

“But in general, the guidelines recommend that HCC staging systems should consider the tumour stage, liver function, health status, and impact of treatment,” he added.

Prognosis and treatment

A person’s prognosis depends on both the extent of liver disease, as well as the cancer. In general, a majority of patients present with intermediate or advanced disease, which does not bode well for future prognosis.

Treatment options for liver cancer depend on the stage of the malignant disease, underlying liver function and the patient’s overall condition.

Surgery offers the best chance to cure patients with liver cancer. If the cancer is found at an early stage and the rest of the liver is healthy, surgery with or without liver transplantation may be curative. However, only about 15% of patients are operable.

“For early stage HCC, surgery (which could be partial or total removal of the liver), or other techniques such as percutaneous ablation (a needle probe is inserted into the liver tumour, usually under ultrasound, CT or MRI, and radio-frequency oscillations used to kill liver cancer cells).

“For the intermediate stage, transarterial chemoembolisation (TACE) is used,” Dr Mellor explained.

TACE exposes the tumour to high concentrations of chemotherapy and confine the agents locally as they are not carried away by the bloodstream. At the same time, this technique deprives the tumour of its needed blood supply, which can result in the damage or death of the tumour cells.

Treatment options for advanced patients are limited. There is a drug, sorafenib, which is the first approved systemic therapy for HCC, and the only one shown to significantly improve overall survival in patients with the disease.

References:

1. World Health Organization. Hepatitis B. Available at: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/. Accessed May 8, 2008.

2. Mayo Clinic. Liver Cancer. Available at: http://www.mayoclinic.com/invoke.cfm?objectid=C2850661-4805-4AD6-905AD30E9FC79DB2&dsection=5. Accessed May 8, 2008.

3. International Agency for Cancer Research. GLOBOCAN 2002. Available at: http://www-dep.iarc.fr. Accessed May 12, 2008.

4. Ferlay J, et al., GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No.5, Version 2.0. IARCPress, Lyon, 2004. Available at: http://www-dep.iarc.fr. Accessed May 12, 2008.

5. Berrino et al., “Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995-99: results of the EUROCARE-4 study.” The Lancet Oncology 2007: 8: 773-783.

6. American Cancer Society. What are the Key Statistics About Liver Cancer? Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_liver_cancer_25.asp?sitearea==. Accessed May 8, 2008.

7. Teo, T.K. and Fock, K.M. “Hepatocellular Carcinoma: An Asian Perspective.” Digestive Diseases 2001:19: 263-268.

8. National Cancer Institute. Cancer of the Liver and Intrahepatic Bile Duct. Available at: http://seer.cancer.gov/statfacts/html/livibd_print.html. Accessed Accessed May 8, 2008.

9. Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Horner MJ, Howlader N, Eisner MP, Reichman M, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2004, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2004/, based on November 2006 SEER data submission, posted to the SEER web site, 2007.

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