June 2015 | Issue 18

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Cross-disciplinary approach to fatty liver disease

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By Nicole Lim

Assistant Director, Communications & External Relations

​Gallbladder removal surgery is an everyday matter these days - most people suffering from gallstones would not think twice about having the keyhole procedure, known as a laparoscopic cholecystectomy. As a matter of fact, it is one of the most ​commonly performed surgeries in the world. But could this common solution to gallstones set you on the path to develop fatty liver disease? Or are the gallstones one of the consequences of fatty liver disease?

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Left to right: Prof Pettersson, Prof Chow and Prof Wahli

Professor Pierce Chow, Senior Consultant with the Division of Surgical Oncology at the National Cancer Centre Singapore (NCCS), regularly performs keyhole operations such as cholecystectomies. However, over time he noticed that a growing number of patients who came to see him with gallstones also had a fatty liver. "The incidence of fatty liver has just gone through the roof," he said.

Prof Chow, who is also Co-Director of NCCS's Comprehensive Liver Cancer Clinic, followed up his observation with a retrospective study by one of his medical students Mr Kevin Khaw from Duke-NUS, which shows that the incidence of fatty liver has doubled over the last ten years among people who come for cholecystectomies. In addition, some of these patients have gone on to develop cirrhosis and eventually liver cancer.

 

While the global rise in obesity plays a key role in the explosion of fatty liver disease, people without traditional risk factors are also affected.

Prof Chow approached his next-door office neighbours from the Academia Tower on Singapore General Hospital campus – LKCMedicine Professors of Metabolic Disease Sven Pettersson and Walter Wahli, who have been working together on host-microbiome interaction for the past five years, to explore ways to study this relationship. (The microbiome is defined as the collective genomes of the microbes - bacteria, bacteriophage, fungi, protozoa and viruses - that live inside and on the human body. The gut microbiome alone is made up of between 500 to 1,000 species of good bacteria that live inside the digestive tract, whose  composition and diversity change constantly. They are affected by what we eat, how old we are, our gender, our exercise habits, etc.)

Together they developed a systems biology approach to study the inter-organ communication that leads to fatty liver disease. "The two organs we're focusing on are the microbiome and the liver," said Prof Pettersson.

Prof Wahli added, "Eventually, we'd like to learn as much as possible so that we can be predictive. If we can predict the course of the disease, we can also be more preventive."

Understanding what drives fatty liver disease will certainly enable people to manage the disease itself, but may also have a beneficial knock-on effect in dealing with chronic diseases such as diabetes, high blood pressure and liver cirrhosis, which are often associated with a fatty liver.

Prof Wahli said, "A fatty liver can lead to insulin resistance, inflammation, fibrosis and eventually cancer. Adipose tissue and muscle tissue are also affected by these changes."

In their first project, the team aims to map the changes in gut flora before and after cholecystectomy in patients with and without fatty liver disease. They want to understand whether the changes in the microbiome contribute to metabolic changes that spur the development or progression of fatty liver disease.

"Whether the microbiome is a bystander or the real effector, that's what we hope to find out," said Prof Pettersson.

From there, the team plans to set up a much larger study that follows patients for years in order to fully elucidate the relationship between microbiome and the liver.

The hope one day is to be able to stratify patients whose fatty liver disease gives them a higher chance of developing serious consequences. Prof Chow said, "Our aim is to be able to offer personalised care plans for individuals to stop them from going on to develop diseases such as liver cancer."