Can exercise help to prevent or reverse fatty liver disease? Professor Stephen Twigg, head of endocrinology at the Royal Prince Alfred Hospital and the Kellion Professor of Endocrinology and Stan Clark Chair in Diabetes at the University of Sydney, is looking at whether certain types of exercise have an effect on a severe type of fatty liver disease common in people with type 2 diabetes.

Non-alcoholic steatohepatitis (known as NASH) is the most severe form of non-alcoholic fatty liver disease. “There is a very strong link between NASH and type 2 diabetes,” says Professor Twigg. “About 20 percent of patients with type 2 have severe NASH compared with less than five percent of the general population.”

He says exerts are not exactly sure why people with type 2 diabetes are more susceptible to developing non-alcoholic fatty liver disease. “We believe type 2 sets up an environment where the liver is hit with too much fat,” he says. “The body can’t store this fat, so high levels of fatty acids begin circulating in the blood.”

In more severe types of fatty liver disease, such as NASH, this leads to liver inflammation and scarring. Professor Twigg says there are links between NASH and heart disease and kidney problems and it also increases your risk of developing liver cancer.

He says in the early stages of NASH, there are often no symptoms, apart from general ones such as fatigue. It takes 10-15 years for the disease to progress and become more severe.

He says there is currently no established treatment for NASH, though some medications have shown promise. “Significant weight loss can help to stabilise and reverse it, but this weight loss needs to be about 10 percent of the patient’s body weight and most patients need bariatric surgery in order to achieve this,” he says.

Treating NASH with exercise would be far less invasive than surgery. “This is the first study in the world looking at exercise to treat or prevent NASH,” says Professor Twigg.

He says his team published a study about 10 years ago that looked at a mouse model of NASH that developed from type 2 diabetes. “Then, recently, we looked at different exercise models in mice. We had a good mouse model of NASH fibrosis and well-developed exercise models in mice, so we decided to put the two together to see if we can prevent or reverse NASH in diabetic mice.”

Professor Twigg was awarded a one-year Diabetes Australia Research Program grant to do this. Though his team lost six months last year due to COVID-19, they still managed to complete the study. He will be presenting his findings at the Australasian Diabetes Congress in August but he can reveal that “the model worked” and produced some “interesting results”.

“We also looked at different exercise models,” he says. “We looked at endurance exercise and high-intensity interval training (HIIT), which has become very trendy.”

Professor Twigg says it is difficult to do studies on lifestyle changes in humans as these studies have to be done over several years. It takes just 25 weeks for the mice to develop severe NASH compared with 10-15 years in humans.

However, he is hoping to move on to clinical trials in humans soon. “We believe our results can be translated to humans.”

He would also like to try combining his exercise model with various medications and/or weight loss and seeing what effects these have.

He says there is currently no regular national screening program for NASH, though there are recommendations overseas in countries such as the US for screening patients with type 2 who may be at risk of developing the disease. As a result, the condition is often only detected when it is too late.

“NASH is a ticking time bomb,” he says. “We believe our research is a very important line of enquiry.”