There is a cancer that seems to have a frightening preference for Asian men. Eighty percent of all the world’s cases occur in Asia, and 90 percent of those patients are men.

In the first of a two-part article, Professor Choo Su Pin from the Duke-NUS Graduate Medical School Singapore tells us more about liver cancer, how it can be prevented, how to detect it early, the available treatment options, and how a new drug is significantly improving survival statistics.

Q: What is hepatocellular carcinoma?

A: Hepatocellular carcinoma (HCC) is the medical name for liver cancer. HCC is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism.

Like any other part of the body, the cells in the liver can undergo changes to form cancer. We think HCC possibly starts when hepatic stem cells in the liver responsible for repairing it start to multiply out of control in response to chronic liver damage but that remains the subject of investigation.

We call HCC liver cancer a primary malignancy because it starts with mutation and proliferation of cells in the liver. Cancerous cells that start from other parts of the body and spread to the liver, for example, colon cancer that has spread, does not constitute liver cancer in the strictest sense. These are known as secondary liver tumours or metastatic cancers to the liver.

Q: Would it be fair to say HCC is an Asian disease?

A: Almost 80 percent of cases of HCC and about 70 to 80 percent of the deaths from HCC occur in Asia, you could say that it is an Asian disease.

The figures may be even higher than that as there are some countries in Asia which have very high incidence of the disease but no effective registries or records; countries like Myanmar and Laos have no accurate source of data. Others, like Indonesia, have national registries which fairly accurately cover the big cities but do not effectively cover the less developed rural areas. So I suspect there may be even more HCC in Asia and that people are dying in rural areas without HCC ever being identified as the cause.

Q: Why does HCC target Asian men in particular and are Asians genetically more prone to HCC?

A: HCC tends to occur in men 4 times more than in women. We do not really understand why. People have postulated that it has to do with hormones or genetics. As I said earlier, liver cancer occurs predominantly in Asia as we have the highest rates of hepatitis B infection.

Q: Why is it so deadly, why is life expectancy so poor after diagnosis?

A: That requires a two-part answer. The reason HCC can be deadly is that our liver is vital to life; it’s one of our major organs and carries out many important functions such as manufacturing various essential proteins, processing and storing nutrients like glucose and ketones, and detoxifying harmful substances in your body.

The reason the prognosis upon diagnosis is often poor is because many patients are not diagnosed until the cancer is quite advanced which then limits our treatment options. If detected early; i.e. before it has spread and invaded blood vessels, we can perform a resection, called a partial hepatectomy, to remove the tumour. With successful curative surgery, the chance of survival beyond five years is more than 40 percent. Sometimes, a liver transplant is recommended as it both removes the cancer as well as the underlying diseased liver. Fiver-year survival after transplant can be as high as 70 percent

Unfortunately the majority of patients are not suitable for surgery as their cancer is too far advanced by the time it is discovered. In its early stages, HCC is largely asymptomatic; people simply do not show any signs of illness such as fever, pain or swelling. Very often HCC is only picked up by chance when patients are being treated and examined for something else.

Screening is the other big issue. Many high-risk patients, even those who know they are hepatitis B carriers, don’t get regularly screened. Some tell me they did not think it was important, others say no one ever told them they should be screened. There is a need for more education among high-risk groups and also general practitioners to encourage regular screening.

Q: What are the main risk factors for HCC?

A: Chronic hepatitis B and hepatitis C, non-alcoholic fatty liver disease, alcoholic liver cirrhosis, non-alcoholic causes of cirrhosis, Non-alcoholic Steatohepatitis (NASH) which is an advanced form of non-alcoholic fatty liver disease, tobacco smoking, obesity, and diabetes. Worldwide hepatitis infection is responsible for 65 percent of HCC cases but in Asia it more like 80 percent while in Europe and the United States the majority of cases are due to lifestyle risk factors such as alcohol drinking, obesity, smoking, and hepatitis C infection from shared drug paraphernalia. Use of anabolic steroids is also a risk factor.

Mongolia as an example of a perfect storm of risk factors. It has the highest per capita rates of HCC in the world because it has very high rates of hepatitis B and C infection and a lot of alcohol problems.

When we can reduce the hepatitis infection rates, especially hepatitis B, we start to see a decline in the number of HCC cases. Taiwan has reported a decrease in the number of HCC cases in recent years due to the fall in hepatitis B rates since they started vaccinating new born babies in the 1980s.

Singapore also introduced vaccination for babies in the 1980s and the benefits are already becoming apparent. It will take another generation or even two to really get it under control but already we are seeing fewer cases of HCC in young people under 40. Babies being infected by their mothers is the most common cause of hepatitis B infection so screening at birth and vaccination is the best way to reduce rates.

Thirty years ago hepatitis B was responsible for 80 percent of the HCC in Singapore just like in the rest of Asia. Today it is only responsible for about 50 percent of the cases here. In Singapore we have seen a decline in the number of HCC cases; especially the hepatitis B related cases but unfortunately we are now seeing an increase in the number of cases related to lifestyle such as non-alcoholic fatty liver disease and NASH-related cases due to increasing numbers of overweight and obese people. Fatty liver disease is now the second most common cause of HCC in Singapore responsible for far more cases than hepatitis C and alcoholic cirrhosis put together.

Even people who are not visibly obese can develop fatty liver disease because it is related to the amount of visceral fat, the fat stored around the internal organs rather than the subcutaneous fat stored just beneath the skin. Indicators of high levels of visceral fat are the apple body shape or having a pronounced and quite firm pot belly. Subcutaneous fat is what causes fleshy thighs, love handles and other pinchable inches.

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 Watch this space for Part 2 of this article!