Rapidly emerging as a significant health threat across Asia, this silent epidemic is being driven by increasing rates of obesity and diabetes.
Non-alcoholic fatty liver disease (NAFLD), now more accurately termed metabolic dysfunction-associated steatotic liver disease (MASLD), is a silent health crisis sweeping through Southeast Asia, including Singapore and Malaysia.
The global prevalence of MASLD has been increasing over time, and is now recognised as the most common cause of chronic liver disease, affecting approximately 30% of the world population. Initially thought to be uncommon in Asia, the prevalence of fatty liver disease has grown rapidly, impacting between 29.6% to 31.6% of the Asian population, with the increase occurring in tandem with the global obesity and diabetes epidemics.
A study conducted in Kuala Lumpur in 2019 found that peak prevalence of the disease in Malaysia was highest among people aged 53 to 60 years, with a higher percentage among men at 48.3%, and Indians being the most affected at 61.1%. The prevalence in Singapore is similar, affecting around 40% of adults.
What is Fatty Liver Disease?
MASLD is a condition characterized by the accumulation of excess fat in the liver of people who consume little to no alcohol.
A healthy liver contains a small amount of fat, but when fat makes up more than 5% of the liver’s weight, in the absence of alcohol consumption, health problems will start to emerge. Fatty liver disease ranges from simple fatty liver or steatosis to metabolic dysfunction associated steatohepatitis (MASH), which is an aggressive form of liver inflammation, and can progress to fibrosis, cirrhosis, and liver cancer.
Although the cause of MASLD is unknown, it has been closely associated with obesity, type 2 diabetes or prediabetes, high blood pressure, certain metabolic disorders, as well as high levels of blood cholesterol and triglycerides.
Dr Ganesalingam Kanagasabai, Consultant Gastroenterologist at the Subang Jaya Medical Center explains, “In type 2 diabetes, insulin resistance prevents glucose from being effectively absorbed by cells, leading to higher levels of insulin and glucose in the blood. This excess insulin promotes fat storage in the liver cells, leading to fat accumulation and obesity. As well as causing inflammation and oxidative stress to the liver, type 2 diabetes can contribute to liver damage, exacerbate fatty liver disease, and is also likely to accelerate steatohepatitis progression to cirrhosis.”
Fatty liver disease is now also considered an independent risk factor for cardiovascular disease (CVD), non-liver malignancies, lung diseases, and chronic kidney disease (CKD).
Research has recently found specific genetic risk variants play a significant role in, and influence the severity of the disease and its outcomes. Both inherited and acquired genetic factors can contribute to, and increase risks of developing MASLD.
From NAFLD to MAFLD and MASLD: A Shift in Understanding
The nomenclature shift from NAFLD to MASLD underscores a critical change in how liver disease is perceived by healthcare practitioners and patients.
The renaming of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) and subsequently to metabolic dysfunction-associated steatotic liver disease (MASLD), was motivated by the need to improve accuracy in the description of the disease.
The significance of the disease on the patient was not fully appreciated in the past, says Dr Tan Chi Chiu, Consultant Gastroenterologist, Gastroenterology and Medicine International, Gleneages Medical Center, Singapore. He elaborates, "When the disease was known as NAFLD, the cause of the fatty liver disease was almost always attributed to being overweight or having high triglycerides or cholesterol in the blood. It was thought that by reducing weight or taking medicines to reduce cholesterol, the fatty liver would also get better. However, it was not understood that fatty liver disease has various other causes, which includes alcohol, that if not addressed correctly, can become much more severe, potentially leading to death."
“Cryptogenic cirrhosis, which has led to many liver transplants and whose cause was previously unknown, is now recognized as the result of fatty liver disease which has not been diagnosed in its early stages. This has significant implications today, and underscores the need for early detection and better screening of MASLD, so fatty liver does not progress to cirrhosis and we avoid the need for liver transplants.”
He adds, “Introduced in Singapore in 2023, the new nomenclature, MASLD, more appropriately represents the range of fatty liver diseases and their broader spectrum of contributing factors, which includes alcohol consumption, as well as the connections between fatty liver disease and other conditions such as diabetes and obesity.”
Additionally, the terms 'non-alcoholic' and 'fatty' in the old name implied patients must provide information on their alcohol use and excessive eating to healthcare practitioners, which could be confusing and stigmatizing, while the new terminologies and diagnostic criteria are non-stigmatizing, have garnered widespread support, and provide an all-inclusive platform from which healthcare practitioners can help reduce stigma, better detect disease, and speed up the development of biomarkers and drugs that can improve outcomes for patients.
The new term MASLD was endorsed by the Malaysian Society of Gastroenterology and Hepatology in 2022.
Detecting MAFLD/ MASLD
To prevent the disease from progressing, early detection is crucial. Unfortunately, the silent nature of the disease, which presents few if no symptoms, often leads to late diagnosis, when complications such as liver inflammation (MASH), fibrosis, and cirrhosis have already developed.
"It is important to emphasise patients with MASLD will almost always present no symptoms until there is liver decompensation, and this is when jaundice, swelling of the ankles, abdominal distension, and bleeding from the gut begin to emerge," Dr Ganesalingam warns.
MASLD is also underdiagnosed due to the lack of awareness in both the general population and even healthcare practitioners. The most common symptoms such as fatigue or discomfort in the upper right side of the abdomen, where the liver is located, are frequently misdiagnosed.
While there is no specific blood test for diagnosing MASLD, several markers can be assessed, including liver enzymes, blood sugar levels, and lipid profile. Although a liver biopsy remains the gold standard for diagnosis, the disease is diagnosed primarily through an ultrasound that confirms steatosis alongside the presence of one or more metabolic conditions, such as dyslipidaemia (abnormal lipid levels), hypertension, or diabetes.
“In Malaysia, FibroScan, a non-invasive imaging technique, is used to assess liver stiffness and steatosis, which are important in diagnosing and managing metabolic dysfunction-associated fatty liver disease. It helps estimate the degree of fibrosis and the amount of fat in the liver, facilitating early detection and monitoring of the disease,” Dr Ganesalingam says.
Managing MASLD
Lifestyle modifications remain the cornerstone of MASLD management. “Weight loss, regular physical activity which should include resistance training as well as cardio exercises, and a healthy diet rich in fruit, vegetables, and whole grains are essential to keep the disease at bay,” Dr Tan stresses.
He adds, "Losing weight and maintaining a healthy weight is essential to slow, stop or even reverse the fat accumulation in the liver in some patients. Reducing body weight by 3% to 5% by diet alone or in combination with increased physical activity can reverse liver fibrosis, while reducing body weight further to 10% by the same means can reduce liver fibrosis, even when there has been some scarring on the liver.”
"Smoking cessation is also important for managing MASLD. Quitting smoking may help reduce the incidence of, and improve the outcomes associated with MASLD as well as cardiovascular disease, as smoking is a significant risk factor for both conditions," adds Dr Ganesalingam.
In cases where lifestyle changes are not sufficient to manage the conditions, medications for diabetes and high cholesterol may be prescribed for their effects on metabolic processes.
Statins, used for managing cholesterol, have been shown to improve liver enzymes and may enhance survival in patients with MASLD, while metformin, a common diabetes medication, may reduce hepatic steatosis, inflammation, and fibrosis, and has been observed to decrease liver transaminase levels as well.
As obesity, MASLD, and type 2 diabetes share underlying pathophysiological mechanisms, including insulin resistance, it is expected that other treatments for type 2 diabetes, such as pioglitazone and glucagon-like peptide 1 or GLP-1 agonists, would demonstrate benefits in MASLD patients.
At the time of writing, while no drugs have been licensed yet in Singapore and Malaysia to specifically treat MASLD, the United States of Food and Drug Administration (USFDA) has recently approved resmetirom for the treatment of non-cirrhotic non-alcoholic steatohepatitis (NASH or MASH) with moderate to advanced liver scarring (fibrosis), to be used along with diet and exercise.
A dual-goal treatment plan of treating hyperglycaemia and obesity, as well as targeting liver disease in individuals with MASLD are often beneficial to the patient. Treatments that offer cardiovascular protection should also be considered, in view of cardiovascular disease being the leading cause of mortality of patients with fatty liver disease.
For patients with advanced liver diseases such as MASH or cirrhosis, more aggressive treatments may be necessary, including medications specifically targeting liver inflammation or fibrosis. In severe cases, liver transplantation may be a last resort.
Prevention is Key
The best way to prevent MASLD is adopting a healthy lifestyle. Both Dr Tan and Dr Ganesalingam agree that the most important steps in managing fatty liver disease are by regular exercise, adequate sleep, maintaining a healthy weight, consuming a balanced diet, reducing sugar intake, stopping smoking and limiting alcohol consumption.
“Educating primary care physicians on detecting the disease early is key,” advises Dr Ganesalingam. “Implementing public health programs such as nutrition education and providing exercise facilities which the public can access, and disseminating this information on social media can help raise awareness and promote a healthier population,” he says.
“The Healthier SG initiative in Singapore aims to shift the focus from treating illnesses to promoting health and preventing diseases, including MASLD. The initiative emphasizes lifestyle changes and managing metabolic health and involves community engagement, medical support, as well as ongoing health education,” Dr Tan adds.
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