Fat accumulation in the liver might not seem like such a big problem, but beware the consequences, which include scarring, and ultimately, even liver cancer.

FATTY liver is a condition where excess fats are deposited in liver cells. While this phenomenon is generally not harmful, excessive fat accumulation (when it exceeds 5% of the liver’s weight) can lead to inflammation and liver tissue scarring (fibrosis).

While heavy drinkers could end up having lots of fat deposits in their liver, teetotallers or light drinkers are not immune from this scourge, which, in this case, is called non-alcoholic fatty liver disease (NAFLD).

NAFLD is reported to be an independent risk factor for cardiovascular disease (CVD), with one study stating that suspected NAFLD in the 45-54 years age group is a strong independent risk factor for cardiovascular death, and justifies further cardiovascular risk management measures.

Those who are overweight and have high blood cholesterol have the tendency to accumulate fat in the liver, and this will affect liver function.

On the rise

There is a rising incidence of diabetes and obesity in Malaysia, and these two conditions have strong links. Diabetics who have poor blood sugar control are at increased risk of having liver disease. Similarly, patients who are overweight and have high blood cholesterol also have the tendency to accumulate fat in the liver, and this will affect the cells, as well as liver function.

Very often, the symptoms of liver disease are not obvious, and can be as non-specific as tiredness, or a general feeling of being unwell.

The prevalence of NAFLD is disturbingly high worldwide, with the prevalence rate in the general adult population reported to be between 15% and 30% in Western countries. In Japan, is believed to range from 18 to 30%, and about 14% in Thailand.

Most patients don’t show many visible symptoms, and NAFLD is usually discovered incidentally when doctors pick up abnormal liver function test readings, or find an enlarged liver in the course of looking for something unrelated.

Dr Enrico Magosso… Based on our research, USM filed a patent in February for the use of tocotrienols in the prevention of liver diseases.

“No agency has ever conducted a systematic study on the prevalence of NAFLD here, hence the data on the prevalence of fatty liver can only be estimated,” said Dr Enrico Magosso of Universiti Sains Malaysia’s (USM) Advanced Medical & Dental Institute, who did an estimate based on the prevalence of other metabolic diseases that are commonly associated with fatty liver, such as diabetes (type II), hypertension and obesity.

“In conjunction with the data from our study on patients with high cholesterol, we can say that the prevalence of NAFLD in Malaysia could be approximately 15-30% of the general adult population. This projection is based on the high prevalence of other metabolic diseases in the Malaysian population that are commonly associated with NAFLD, such as high blood sugar (10.5%), hypertension (34.7%), and a staggering 44.2% of overweight adults, of which 14% are classified as obese.

“Our previous epidemiological study showed that about 60% of Malaysian with slightly elevated cholesterol levels have NAFLD,” said Dr Magosso.

A safe bet?

There is no drug that can effectively cure NAFLD at the moment, though some scientists are now placing their bets on tocotrienols, a form of vitamin E that is found in relative abundance in palm oil.

It takes roughly 10 tonnes of palm oil to produce 4kg of tocotrie-nols, a substance that is showing some promise after encouraging trials in animals and small-scale human studies.

A few years ago, a group of USM scientists (Dr Magosso being among them) found that the administration of a high fat and high sugar diet for six months caused NAFLD in a group of mice, but a second group of mice that received the same diet fortified with a dose of tocotrienols did not exhibit any signs of NAFLD, thus providing grounds to believe that tocotrienols are beneficial for prevention of NAFLD in humans.

“Based on our research, USM filed a patent in February for the use of tocotrienols in prevention of liver diseases,” said Dr Magosso, who added that USM (along with its Advanced Medical and Dental Institute) is now involved in a tripartite collaboration with the Malaysian Palm Oil Board (MPOB) and Hovid Bhd to conduct large scale human clinical trials to validate the value of tocotrienols in preventing or curing NAFLD.

It takes roughly 10 tonnes of palm oil to produce 4kg of tocotrienols, a substance that is showing some promise of fighting fatty livers after encouraging trials in animals and small-scale human studies.

“The major aim of the patent is actually to prevent our findings from being hijacked from other countries, thus protecting a Malaysian product. There are already several cases in which specific tocotrienol uses have been patented, with the latest for radiation protection, filed by the United States Army.”

Recently, the team from USM, headed by Prof Yuen Kah Hay, MPOB and Hovid completed a two-year double-blind placebo-controlled study on about 200 patients to evaluate the neuroprotective properties of tocotrienols previously reported in cell culture and animal studies. The clinical component of the trial was concluded in 2011, and the final manuscript is now being readied for publication.

Prof Dr Ibrahim Lutfi Shuaib from USM’s Advanced Medical and Dental Institute also just completed a two-year study on 1,000 people with white matter lesions — neuronal damage in the brain that is related to stroke.

Although the full study results are not yet ready, it is understood that some patients treated with tocotrienols showed improvements as far as white matter lesion measurement is concerned.

The effects of tocotrienols on stroke patients is also another option to be explored in future studies. It is understood that USM had submitted a research proposal to the Performance Management and Delivery Unit (Pemandu) to further fund clinical studies in patients with fatty liver, including the more advanced stage called non-alcoholic steatohepatitis, or NASH, but was turned down.

National resource

“We are confident that our proposed study on NAFLD will be given due consideration by Pemandu for support, amidst growing medical and public interest in fatty liver. Tocotrienols are a national resource and a priority for the palm oil industry, so I think we can wait for the next round of funding,” said Dr Magosso.

Last November, Pemandu announced that it will be giving a RM20mil grant for six clinical trials involving palm-based tocotrienols with different researchers in the United States, Singapore and Malaysia. The funding is in line with Malaysia’s aim to expedite growth in the food and health-based downstream segment under the Palm Oil National Key Economic Area.

The trials are intended to determine whether tocotrienols can prevent the recurrence of stroke, breast cancer tumour progression and colorectal cancer, as well as the enhancement of the survival rate of patients with prostate cancer.

The grants are parceled out to researchers from the Ohio State University Medical Center, the MD Anderson Cancer Center of the University of Texas, Singapore-based Davos Life Science, MPOB, Universiti Malaya, USM, and Penang Medical College.

It is hoped that these trials will lead to the production of supplements that will be approved by the US Food and Drug Administration (FDA), as well as the European Medicines Agency.

In April 2009, the FDA approved tocotrienols as a food additive, and the substance can now be found in some margarines, salad dressings, mayonnaise, and even potato chips.

Dr Magosso, an Italian who has called Malaysia home for the past 10 years, said that fatty liver is expected to be a major health problem in Malaysia due to increasingly affluent lifestyles and poor dietary habits.

“These factors have led to the increasing prevalence of overweight and obesity amongst Malaysians. Fatty livers that are not well managed can progress to liver scarring, hardening, and also, liver cancer,” he added.

While waiting for medical breakthroughs, the only sensible solution is lifestyle modifications like exercising and watching one’s diet.